bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete Genome and Clinicopathological Characterization of a Virulent Newcastle Disease Virus Isolate from South America
Authors: Diel Diego G. , Susta Leonardo , Cardenas Garcia Stivalis , Killian Mary L. , Brown Corrie C. , Miller Patti J. , Afonso Claudio L. 
Published: December 2011

ABSTRACT

Newcastle disease (ND) is one of the most important diseases of poultry, negatively affecting poultry production worldwide. The disease is caused by Newcastle disease virus (NDV) or avian paramyxovirus type 1 (APMV-1), a negative-sense single-stranded RNA virus of the genus
Avulavirus
, family
Paramyxoviridae
. Although all NDV isolates characterized to date belong to a single serotype of APMV-1, significant genetic diversity has been described between different NDV isolates. Here we present the complete genome sequence and the clinicopathological characterization of a virulent Newcastle disease virus isolate (NDV-Peru/08) obtained from poultry during an outbreak of ND in Peru in 2008. Phylogenetic reconstruction and analysis of the evolutionary distances between NDV-Peru/08 and other isolates representing established NDV genotypes revealed the existence of large genomic and amino differences that clearly distinguish this isolate from viruses of typical NDV genotypes. Although NDV-Peru/08 is a genetically distinct virus, pathogenesis studies conducted with chickens revealed that NDV-Peru/08 infection results in clinical signs characteristic of velogenic viscerotropic NDV strains. Additionally, vaccination studies have shown that an inactivated NDV-LaSota/46 vaccine conferred full protection from NDV-Peru/08-induced clinical disease and mortality. This represents the first complete characterization of a virulent NDV isolate from South America.
Seasonal H1N1 Influenza Virus Infection Induces Cross-Protective Pandemic H1N1 Virus Immunity through a CD8-Independent, B Cell-Dependent Mechanism
Authors: Fang Yuan , Banner David , Kelvin Alyson A. , Huang Stephen S. H. , Paige Christopher J. , Corfe Steven A. , Kane Kevin P. , Bleackley R. Chris , Rowe Thomas , Leon Alberto J. , Kelvin David J. 
Published: December 2011

ABSTRACT

During the 2009 H1N1 influenza virus pandemic (pdmH1N1) outbreak, it was found that most individuals lacked antibodies against the new pdmH1N1 virus, and only the elderly showed anti-hemagglutinin (anti-HA) antibodies that were cross-reactive with the new strains. Different studies have demonstrated that prior contact with the virus can confer protection against strains with some degree of dissimilarity; however, this has not been sufficiently explored within the context of a pdmH1N1 virus infection. In this study, we have found that a first infection with the A/Brisbane/59/2007 virus strain confers heterologous protection in ferrets and mice against a subsequent pdmH1N1 (A/Mexico/4108/2009) virus infection through a cross-reactive but non-neutralizing antibody mechanism. Heterologous immunity is abrogated in B cell-deficient mice but maintained in CD8
−/−
and perforin-1
−/−
mice. We identified cross-reactive antibodies from A/Brisbane/59/2007 sera that recognize non-HA epitopes in pdmH1N1 virus. Passive serum transfer showed that cross-reactive sH1N1-induced antibodies conferred protection in naive recipient mice during pdmH1N1 virus challenge. The presence or absence of anti-HA antibodies, therefore, is not the sole indicator of the effectiveness of protective cross-reactive antibody immunity. Measurement of additional antibody repertoires targeting the non-HA antigens of influenza virus should be taken into consideration in assessing protection and immunization strategies. We propose that preexisting cross-protective non-HA antibody immunity may have had an overall protective effect during the 2009 pdmH1N1 outbreak, thereby reducing disease severity in human infections.
Human Herpesvirus 8 Viral Interleukin-6 Interacts with Splice Variant 2 of Vitamin K Epoxide Reductase Complex Subunit 1
Authors: Chen Daming , Cousins Emily , Sandford Gordon , Nicholas John 
Published: December 2011

ABSTRACT

Viral interleukin-6 (vIL-6) specified by human herpesvirus 8 is, unlike its cellular counterpart, secreted very inefficiently and can signal via vIL-6
2
:gp130
2
signaling complexes from the endoplasmic reticulum (ER) compartment. Intracellular, autocrine activities of vIL-6 are important for proproliferative and prosurvival activities of the viral cytokine in latently infected primary effusion lymphoma (PEL) cells. However, the molecular determinants of vIL-6 ER localization and function are unclear. Using yeast two-hybrid analysis, we identified the database-documented but uncharacterized splice variant of vitamin K epoxide reductase complex subunit 1 (VKORC1), termed VKORC1 variant 2 (VKORC1v2), as a potential interaction partner of vIL-6. In transfected cells, epitope-tagged VKORC1v2 was found to localize to the ER, to adopt a single-transmembrane (TM) topology placing the C tail in the ER lumen, and to bind vIL-6 via these sequences. Deletion mutagenesis and coprecipitation assays mapped the vIL-6-binding domain (vBD) of VKORC1v2 to TM-proximal residues 31 to 39. However, while sufficient to confer vIL-6 binding to a heterologous protein, vBD was unable to induce vIL-6 secretion when fused to (secreted) hIL-6, suggesting a VKORC1v2-independent mechanism of vIL-6 ER retention. In functional assays, overexpression of ER-directed vBD led to suppression of PEL cell proliferation and viability, effects also mediated by VKORC1v2 depletion and, as reported previously, by vIL-6 suppression. The growth-inhibitory and proapoptotic effects of VKORC1v2 depletion could be rescued by transduced wild-type VKORC1v2 but not by a vIL-6-refractory vBD-altered variant, indicating the functional relevance of the vIL-6–VKORC1v2 interaction. Notably, gp130 signaling was unaffected by VKORC1v2 or vBD overexpression or by VKORC1v2 depletion, suggesting an alternative pathway of vIL-6 activity via VKORC1v2. Combined, our data identify a novel and functionally significant interaction partner of vIL-6 that could potentially be targeted for therapeutic benefit.
Proline-Serine-Threonine Phosphatase-Interacting Protein 2 (PSTPIP2), a Host Membrane-Deforming Protein, Is Critical for Membranous Web Formation in Hepatitis C Virus Replication
Authors: Chao Ti-Chun , Su Wen-Chi , Huang Jing-Ying , Chen Yung-Chia , Jeng King-Song , Wang Horng-Dar , Lai Michael M. C. 
Published: December 2011

ABSTRACT
Hepatitis C virus (HCV) reorganizes intracellular membranes to establish sites of replication. How viral and cellular proteins target, bind, and rearrange specific membranes into the replication factory remains a mystery. We used a lentivirus-based RNA interference (RNAi) screening approach to identify the potential cellular factors that are involved in HCV replication. A protein with membrane-deforming activity, proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2), was identified as a potential factor. Knockdown of PSTPIP2 in HCV subgenomic replicon-harboring and HCV-infected cells was associated with the reduction of HCV protein and RNA expression. PSTPIP2 was localized predominantly in detergent-resistant membranes (DRMs), which contain the RNA replication complex. PSTPIP2 knockdown caused a significant reduction of the formation of HCV- and NS4B-induced membranous webs. A PSTPIP2 mutant defective in inducing membrane curvature failed to support HCV replication, confirming that the membrane-deforming ability of PSTPIP2 is essential for HCV replication. Taking these results together, we suggest that PSTPIP2 facilitates membrane alterations and is a key player in the formation of the membranous web, which is the site of the HCV replication complex.
Dengue-1 Virus Clade Replacement in Thailand Associated with Enhanced Mosquito Transmission
Authors: Lambrechts Louis , Fansiri Thanyalak , Pongsiri Arissara , Thaisomboonsuk Butsaya , Klungthong Chonticha , Richardson Jason H. , Ponlawat Alongkot , Jarman Richard G. , Scott Thomas W. 
Published: December 2011

ABSTRACT

Dengue viruses (DENV) are characterized by extensive genetic diversity and can be organized in multiple, genetically distinct lineages that arise and die out on a regular basis in regions where dengue is endemic. A fundamental question for understanding DENV evolution is the relative extent to which stochastic processes (genetic drift) and natural selection acting on fitness differences among lineages contribute to lineage diversity and turnover. Here, we used a set of recently collected and archived low-passage DENV-1 isolates from Thailand to examine the role of mosquito vector-virus interactions in DENV evolution. By comparing the ability of 23 viruses isolated on different dates between 1985 and 2009 to be transmitted by a present-day
Aedes aegypti
population from Thailand, we found that a major clade replacement event in the mid-1990s was associated with virus isolates exhibiting increased titers in the vector's hemocoel, which is predicted to result in a higher probability of transmission. This finding is consistent with the hypothesis that selection for enhanced transmission by mosquitoes is a possible mechanism underlying major DENV clade replacement events. There was significant variation in transmission potential among isolates within each clade, indicating that in addition to vector-driven selection, other evolutionary forces act to maintain viral genetic diversity. We conclude that occasional adaptive processes involving the mosquito vector can drive major DENV lineage replacement events.
A comparison of the relationship of 14 performance-based measures with frailty in older women
Authors: Theou Olga , Jones Gareth R. , Jakobi Jennifer M. , Mitnitski Arnold , Vandervoort Anthony A. 
Published: December 2011

The purpose of this study was to determine which performance measures of physical function are most closely related to frailty and whether physical function is different across levels of frailty. Fifty-three community-dwelling Greek women (63–100 years) participated in this study. Participants were divided into 3 tertiles based on level of frailty as calculated from a frailty index (FI): lowest FI group (<0.19 FI), intermediate FI group (0.19–0.36 FI), and highest FI group (>0.36 FI). Performance measures tested were handgrip and knee extension muscle strength and fatigue, upper and lower body muscular endurance, walking performance, agility, and dynamic balance. The greatest proportion of variance in the FI was explained by combining all performance-based measures of physical function. The performance measures that were most closely related to frailty yet different across levels of frailty were ambulatory mobility, lower body muscular endurance, and nondominant handgrip strength. Walking at a preferred pace had the strongest relationship to frailty rather than walking at maximal pace. Grip strength of the nondominant hand had a stronger correlation with frailty compared with the dominant hand. The FI was a better predictor of physical function than chronological age. The decline in physical function accelerated after the intermediate FI tertile. Definitions of frailty need to combine performance-based measures that can identify impairments in various domains of physical function. The assessment protocols of these measures are important.
Functional Interaction between Responses to Lactic Acidosis and Hypoxia Regulates Genomic Transcriptional Outputs
Authors: Tang Xiaohu , Lucas Joseph E. , Chen Julia Ling-Yu , LaMonte Gregory , Wu Jianli , Wang Michael Changsheng , Koumenis Constantinos , Chi Jen-Tsan 
Published: December 2011

Abstract
Within solid tumor microenvironments, lactic acidosis, and hypoxia each have powerful effects on cancer pathophysiology. However, the influence that these processes exert on each other is unknown. Here, we report that a significant portion of the transcriptional response to hypoxia elicited in cancer cells is abolished by simultaneous exposure to lactic acidosis. In particular, lactic acidosis abolished stabilization of HIF-1α protein which occurs normally under hypoxic conditions. In contrast, lactic acidosis strongly synergized with hypoxia to activate the unfolded protein response (UPR) and an inflammatory response, displaying a strong similarity to ATF4-driven amino acid deprivation responses (AAR). In certain breast tumors and breast tumor cells examined, an integrative analysis of gene expression and array CGH data revealed DNA copy number alterations at the ATF4 locus, an important activator of the UPR/AAR pathway. In this setting, varying ATF4 levels influenced the survival of cells after exposure to hypoxia and lactic acidosis. Our findings reveal that the condition of lactic acidosis present in solid tumors inhibits canonical hypoxia responses and activates UPR and inflammation responses. Furthermore, these data suggest that ATF4 status may be a critical determinant of the ability of cancer cells to adapt to oxygen and acidity fluctuations in the tumor microenvironment, perhaps linking short-term transcriptional responses to long-term selection for copy number alterations in cancer cells. Cancer Res; 72(2); 491–502. ©2011 AACR.
A Climatology of the Mesoscale Environment Associated with Heavily Precipitating Events over a Northwestern Mediterranean Area
Authors: Ricard Didier , Ducrocq Véronique , Auger Ludovic 
Published: December 2011

AbstractA climatological approach is developed to characterize the mesoscale environment in which heavily precipitating events (HPEs) grow over a mountainous Mediterranean area. This climatology that is based on three-dimensional variational data assimilation (3D-Var) mesoscale analyses is performed for a 5-yr period, considering cases with daily precipitation of >150 mm occurring over southern France during autumn. Different diagnostics are used to document the time evolution of mesoscale features associated with the HPEs for initiation, mature, and dissipation stages. To underline differences according to the location of precipitation, four subdomains are also considered: Languedoc-Roussillon, Cévennes-Vivarais, South Alps, and Corsica. Composite analyses show that these events are driven by some common features (slowly evolving trough–ridge pattern and diffluent midlevel flow). Instability and moisture are transported by the low-level jet (LLJ) toward the target area from their sources, which are located upstream over the Mediterranean Sea. Strong moisture convergence is located within the left exit of the LLJ. These parameters reach a maximum during the mature stage. During the life cycle of the HPEs, the low-level winds rotate clockwise. Composite analyses also show that the synoptic and mesoscale patterns can differ greatly as a function of the location of the precipitation. Indeed, the LLJ varies from southeasterly to southwesterly. The midlevel flow varies from southerly to southwesterly. The areas of high moisture and instability are stretched in different orientations. Long-lasting events are associated with a more pronounced quasi-stationary trough–ridge pattern, higher values of CAPE, a wetter troposphere, and faster LLJ. The most-heavily precipitating events are found to be in general associated with higher values of these parameters or with a low-level inflow that is closer to perpendicular to the relief.
Regulation of hepcidin expression at high altitude
Authors: Talbot Nick P. , Lakhal Samira , Smith Thomas G. , Privat Catherine , Nickol Annabel H. , Rivera-Ch Maria , León-Velarde Fabiola , Dorrington Keith L. , Mole David R. , Robbins Peter A. 
Published: December 2011

Abstract
Enhanced erythropoietic drive and iron deficiency both influence iron homeostasis through the suppression of the iron regulatory hormone hepcidin. Hypoxia also suppresses hepcidin through a mechanism that is unknown. We measured iron indices and plasma hepcidin levels in healthy volunteers during a 7-day sojourn to high altitude (4340 m above sea level), with and without prior intravenous iron loading. Without prior iron loading, a rapid reduction in plasma hepcidin was observed that was almost complete by the second day at altitude. This occurred before any index of iron availability had changed. Prior iron loading delayed the decrease in hepcidin until after the transferrin saturation, but not the ferritin concentration, had normalized. We conclude that hepcidin suppression by the hypoxia of high altitude is not driven by a reduction in iron stores.
Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin
Authors: Lebensburger Jeffrey D. , Howard Thad , Hu Yunming , Pestina Tamara I. , Gao Geli , Johnson Melissa , Zakharenko Stanislav S. , Ware Russell E. , Tuomanen Elaine I. , Persons Derek A. , Rosch Jason W. 
Published: December 2011

AbstractSickle cell anemia is characterized by chronic hemolysis coupled with extensive vascular inflammation. This inflammatory state also mechanistically promotes a high risk of lethal, invasive pneumococcal infection. Current treatments to reduce vaso-occlusive complications include chronic hydroxyurea therapy to induce fetal hemoglobin. Because hydroxyurea also reduces leukocytosis, an understanding of the impact of this treatment on pneumococcal pathogenesis is needed. Using a sickle cell mouse model of pneumococcal pneumonia and sepsis, administration of hydroxyurea was found to significantly improve survival. Hydroxyurea treatment decreased neutrophil extravasation into the infected lung coincident with significantly reduced levels of E-selectin in serum and on pulmonary epithelia. The protective effect of hydroxyurea was abrogated in mice deficient in E-selectin. The decrease in E-selectin levels was also evident in human sickle cell patients receiving hydroxyurea therapy. These data indicate that in addition to induction of fetal hemoglobin, hydroxyurea attenuates leukocyte–endothelial interactions in sickle cell anemia, resulting in protection against lethal pneumococcal sepsis.
Coincidence theorems and minimax inequalities in abstract convex spaces
Authors: Je Cho Yeol , Delavar Mohsen Rostamian , Mohammadzadeh Seyed Asghar , Roohi Mehdi 
Published: December 2011

Abstract
In this paper, we deal with the notion of abstract convex spaces via minimal spaces as an extended version of other forms of convexity and establish some well-known results such as coincidence theorems for the classes m-KKM and ms-KKM of multimaps and Ky Fan's type minimax inequality.

Mathematics Subject Classification (2000)

26A51; 26B25; 54H25; 55M20; 47H10; 54A05.
Prolonged morphine administration alters protein expression in the rat myocardium
Authors: Drastichova Zdenka , Skrabalova Jitka , Neckar Jan , Kolar Frantisek , Novotny Jiri 
Published: December 2011

Abstract

Background
Morphine is used in clinical practice as a highly effective painkiller as well as the drug of choice for treatment of certain heart diseases. However, there is lack of information about its effect on protein expression in the heart. Therefore, here we aimed to identify the presumed alterations in rat myocardial protein levels after prolonged morphine treatment.

Methods
Morphine was administered to adult male Wistar rats in high doses (10 mg/kg per day) for 10 days. Proteins from the plasma membrane- and mitochondria-enriched fractions or cytosolic proteins isolated from left ventricles were run on 2D gel electrophoresis, scanned and quantified with specific software to reveal differentially expressed proteins.

Results
Nine proteins were found to show markedly altered expression levels in samples from morphine-treaded rats and these proteins were identified by mass spectrometric analysis. They belong to different cell pathways including signaling, cytoprotective, and structural elements.

Conclusions
The present identification of several important myocardial proteins altered by prolonged morphine treatment points to global effects of this drug on heart tissue. These findings represent an initial step toward a more complex view on the action of morphine on the heart.
Revealing the functionality of hypothetical protein KPN00728 from Klebsiella pneumonia e MGH78578: molecular dynamics simulation approaches
Authors: Choi Sy Bing , Normi Yahaya M , Wahab Habibah A 
Published: December 2011

Abstract

Background
Previously, the hypothetical protein, KPN00728 from Klebsiella pneumoniae MGH78578 was the Succinate dehydrogenase (SDH) chain C subunit via structural prediction and molecular docking simulation studies. However, due to limitation in docking simulation, an in-depth understanding of how SDH interaction occurs across the transmembrane of mitochondria could not be provided.

Results
In this present study, molecular dynamics (MD) simulation of KPN00728 and SDH chain D in a membrane was performed in order to gain a deeper insight into its molecular role as SDH. Structural stability was successfully obtained in the calculation for area per lipid, tail order parameter, thickness of lipid and secondary structural properties. Interestingly, water molecules were found to be highly possible in mediating the interaction between Ubiquinone (UQ) and SDH chain C via interaction with Ser27 and Arg31 residues as compared with earlier docking study. Polar residues such as Asp95 and Glu101 (KPN00728), Asp15 and Glu78 (SDH chain D) might have contributed in the creation of a polar environment which is essential for electron transport chain in Krebs cycle.

Conclusions
As a conclusion, a part from the structural stability comparability, the dynamic of the interacting residues and hydrogen bonding analysis had further proved that the interaction of KPN00728 as SDH is preserved and well agreed with our postulation earlier.
Near-membrane ensemble elongation in the proline-rich LRP6 intracellular domain may explain the mysterious initiation of the Wnt signaling pathway
Authors: Liu Chengcheng , Yao Mingxi , Hogue Christopher WV 
Published: December 2011

AbstractBackgroundLRP6 is a membrane protein crucial in the initiation of canonical Wnt/β-catenin signalling. Its function is dependent on its proline-serine rich intracellular domain. LRP6 has five PPP(S/T)P motifs that are phosphorylated during activation, starting with the site closest to the membrane. Like all long proline rich regions, there is no stable 3D structure for this isolated, contiguous region.ResultsIn our study, we use a computational simulation tool to sample the conformational space of the LRP6 intracellular domain, under the spatial constraints imposed by (a) the membrane and (b) the close approach of the neighboring intracellular molecular complex, which is assembled on Frizzled when Wnt binds to both LRP6 and Frizzled on the opposite side of the membrane. We observe that an elongated form dominates in the LRP6 intracellular domain structure ensemble. This elongation could relieve conformational auto-inhibition of the PPP(S/T)PX(S/T) motif binding sites and allow GSK3 and CK1 to approach their phosphorylation sites, thereby activating LRP6 and the downstream pathway.ConclusionsWe propose a model in which the conformation of the LRP6 intracellular domain is elongated before activation. This is based on the intrusion of the Frizzled complex into the ensemble space of the proline rich region of LRP6, which alters the shape of its available ensemble space. To test whether this observed ensemble conformational change is sequence dependent, we did a control simulation with a hypothetical sequence with 50% proline and 50% serine in alternating residues. We confirm that this ensemble neighbourhood-based conformational change is independent of sequence and conclude that it is likely found in all proline rich sequences. These observations help us understand the nature of proline rich regions which are both unstructured and which seem to evolve at a higher rate of mutation, while maintaining sequence composition.