bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions
Authors: Giroud Charline , Marin Mariana , Hammonds Jason , Spearman Paul , Melikyan Gregory B. 
Published: July 2015

ABSTRACT
HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env.

IMPORTANCE
Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF279, is due to the blocking of virus interactions with both the CXCR4 and CCR5 coreceptors. The ability of NF279 to abrogate cellular calcium signaling induced by the respective chemokines showed that this compound acts as a dual-coreceptor antagonist. P2X1 receptor antagonists could thus represent a new class of dual-coreceptor inhibitors with a structure and a mechanism of action that are distinct from those of known HIV-1 coreceptor antagonists.
A Coronavirus E Protein Is Present in Two Distinct Pools with Different Effects on Assembly and the Secretory Pathway
Authors: Westerbeck Jason W. , Machamer Carolyn E. 
Published: July 2015

ABSTRACT

Coronaviruses (CoVs) assemble by budding into the lumen of the early Golgi complex prior to exocytosis. The small CoV envelope (E) protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi complex membranes, and has cation channel activity
in vitro
. However, the precise functions of the CoV E protein during infection are still enigmatic. Structural data for the severe acute respiratory syndrome (SARS)-CoV E protein suggest that it assembles into a homopentamer. Specific residues in the HD regulate the ion-conducting pore formed by SARS-CoV E in artificial bilayers and the pathogenicity of the virus during infection. The E protein from the avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system which require residues in the HD. Here, we use the known structural data from SARS-CoV E to infer the residues important for ion channel activity and the oligomerization of IBV E. We present biochemical data for the formation of two distinct oligomeric pools of IBV E in transfected and infected cells and the residues required for their formation. A high-order oligomer of IBV E is required for the production of virus-like particles (VLPs), implicating this form of the protein in virion assembly. Additionally, disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity.

IMPORTANCE
CoVs are important human pathogens with significant zoonotic potential, as demonstrated by the emergence of SARS-CoV and Middle East respiratory syndrome (MERS)-CoV. Progress has been made toward identifying potential vaccine candidates in mouse models of CoV infection, including the use of attenuated viruses that lack the CoV E protein or express E-protein mutants. However, no approved vaccines or antiviral therapeutics exist. We previously reported that the hydrophobic domain of the IBV E protein, a putative viroporin, causes disruption of the mammalian secretory pathway when exogenously expressed in cells. Understanding the mechanism of this disruption could lead to the identification of novel antiviral therapeutics. Here, we present biochemical evidence for two distinct oligomeric forms of IBV E, one essential for assembly and the other with a role in disruption of the secretory pathway. Discovery of two forms of CoV E protein will provide additional targets for antiviral therapeutics.
Plasmids from
Euryarchaeota
Authors: Forterre Patrick , Krupovic Mart , Raymann Kasie , Soler Nicolas 
Published: July 2015

ABSTRACT

Many plasmids have been described in
Euryarchaeota
, one of the three major archaeal phyla, most of them in salt-loving haloarchaea and hyperthermophilic
Thermococcales
. These plasmids resemble bacterial plasmids in terms of size (from small plasmids encoding only one gene up to large megaplasmids) and replication mechanisms (rolling circle or theta). Some of them are related to viral genomes and form a more or less continuous sequence space including many integrated elements. Plasmids from
Euryarchaeota
have been useful for designing efficient genetic tools for these microorganisms. In addition, they have also been used to probe the topological state of plasmids in species with or without DNA gyrase and/or reverse gyrase. Plasmids from
Euryarchaeota
encode both DNA replication proteins recruited from their hosts and novel families of DNA replication proteins.
Euryarchaeota
form an interesting playground to test evolutionary hypotheses on the origin and evolution of viruses and plasmids, since a robust phylogeny is available for this phylum. Preliminary studies have shown that for different plasmid families, plasmids share a common gene pool and coevolve with their hosts. They are involved in gene transfer, mostly between plasmids and viruses present in closely related species, but rarely between cells from distantly related archaeal lineages. With few exceptions (e.g., plasmids carrying gas vesicle genes), most archaeal plasmids seem to be cryptic. Interestingly, plasmids and viral genomes have been detected in extracellular membrane vesicles produced by
Thermococcales
, suggesting that these vesicles could be involved in the transfer of viruses and plasmids between cells.
Plasmid-Encoded Iron Uptake Systems
Authors: Di Lorenzo Manuela , Stork Michiel 
Published: July 2015

ABSTRACT
Plasmids confer genetic information that benefits the bacterial cells containing them. In pathogenic bacteria, plasmids often harbor virulence determinants that enhance the pathogenicity of the bacterium. The ability to acquire iron in environments where it is limited, for instance the eukaryotic host, is a critical factor for bacterial growth. To acquire iron, bacteria have evolved specific iron uptake mechanisms. These systems are often chromosomally encoded, while those that are plasmid-encoded are rare. Two main plasmid types, ColV and pJM1, have been shown to harbor determinants that increase virulence by providing the cell with essential iron for growth. It is clear that these two plasmid groups evolved independently from each other since they do not share similarities either in the plasmid backbones or in the iron uptake systems they harbor. The siderophores aerobactin and salmochelin that are found on ColV plasmids fall in the hydroxamate and catechol group, respectively, whereas both functional groups are present in the anguibactin siderophore, the only iron uptake system found on pJM1-type plasmids. Besides siderophore-mediated iron uptake, ColV plasmids carry additional genes involved in iron metabolism. These systems include ABC transporters, hemolysins, and a hemoglobin protease. ColV- and pJM1-like plasmids have been shown to confer virulence to their bacterial host, and this trait can be completely ascribed to their encoded iron uptake systems.
The Hidden World within Plants: Ecological and Evolutionary Considerations for Defining Functioning of Microbial Endophytes
Authors: Hardoim Pablo R. , van Overbeek Leonard S. , Berg Gabriele , Pirttilä Anna Maria , Compant Stéphane , Campisano Andrea , Döring Matthias , Sessitsch Angela 
Published: July 2015

SUMMARYAll plants are inhabited internally by diverse microbial communities comprising bacterial, archaeal, fungal, and protistic taxa. These microorganisms showing endophytic lifestyles play crucial roles in plant development, growth, fitness, and diversification. The increasing awareness of and information on endophytes provide insight into the complexity of the plant microbiome. The nature of plant-endophyte interactions ranges from mutualism to pathogenicity. This depends on a set of abiotic and biotic factors, including the genotypes of plants and microbes, environmental conditions, and the dynamic network of interactions within the plant biome. In this review, we address the concept of endophytism, considering the latest insights into evolution, plant ecosystem functioning, and multipartite interactions.
Immediate procedural outcomes in 44 consecutive Pipeline Flex cases: the first North American single-center series
Authors: Colby Geoffrey P , Lin Li-Mei , Caplan Justin M , Jiang Bowen , Huang Judy , Tamargo Rafael J , Coon Alexander L 
Published: July 2015

BackgroundFlow diversion is an established technique for treatment of cerebral aneurysms. The Pipeline embolization device (PED) is the only FDA-approved flow diverting stent in the USA. A second-generation device, PED Flex, has recently been released with modifications to the delivery system. Published reports of experience with this new device are limited.ObjectiveTo describe the initial outcomes from the first North American series using the PED Flex—a single-center experience of 44 cases.MethodsAll patients consecutively treated with the PED Flex embolization device from February 2015 through April 2015 were included in the study. Data were collected for patient demographics, aneurysm characteristics, technical procedural details, and early outcomes.ResultsPED Flex treatment was attempted in 42 patients (mean 56.6±2.0 years) with 44 aneurysms (mean size 6.5±0.6 mm), 41/44 (93%) of which were anterior circulation and 3/44 (7%) were posterior circulation. PED Flex was successfully implanted in 43/44 cases (98%). A single device was used in 41/43 cases (95%), with a mean of 1.07±0.05 devices implanted per case. Resheathing was performed in 4/44 cases (9%). Mean postprocedure hospital length of stay was 1.3±0.2 days. One significant neurological complication (2.3%) occurred, which was a stroke in a patient non-compliant with the prescribed antiplatelet regimen.ConclusionsPipeline Flex is a second-generation flow diverter with enhanced features compared with the first-generation PED. These modifications allow for more reliable deployment with continued improvements in procedural safety.
Poly (I:C) downregulates platelet production and function through type I interferon
Authors: Rivadeneyra Leonardo , Pozner Roberto Gabriel , Meiss Roberto , Fondevila Carlos , Gómez Ricardo Martin , Schattner Mirta 
Published: July 2015

SummaryThrombocytopenia is a frequent complication of viral infections; the underlying mechanisms appear to depend on the identity of the virus involved. Previous research, including reports from our group, indicates that as well as having antiviral activity type I interferons (IFN I) selectively downregulate platelet production. In this study we extended understanding of the role of endogenous IFN I in megakaryo/ thrombopoiesis by evaluating platelet and megakaryocyte physiology in mice treated with polyinosinic:polycytidylic acid [poly (I:C)], a synthetic analogue of double-stranded RNA, Toll-like receptor-3 ligand and strong IFNp inducer. Mice-treated with poly (I:C) showed thrombocytopaenia, an increase in mean platelet volume and abnormal haemostatic and inflammatory platelet-mediated functionality, indicated by decreased fibrinogen binding and platelet adhesion, prolonged tail bleeding times and impaired P-Selectin externalisation, RANTES release and thrombin-induced platelet-neutrophil aggregate formation. These changes were associated with an increase in size and an abnormal distribution of bone marrow megakaryocytes within the vascular niche and were directly correlated with the plasmatic and bone marrow IFNp levels. All these effects were absent in genetically modified mice lacking the IFN I receptor. Our results suggest that IFN I is the central mediator of poly (I:C)-induced thrombocytopenia and platelet dysfunction and indicate that these abnormalities are due to changes in the last stages of megakaryocyte development. These data provide new evidence for the role of IFN I in megakaryocyte distribution in the bone marrow niches and its influence on thrombopoiesis and haemostasis.
Beneficial Effect on Cardiac Resynchronization From Left Ventricular Endocardial Pacing Is Mediated by Early Access to High Conduction Velocity Tissue
Authors: Hyde Eoin R. , Behar Jonathan M. , Claridge Simon , Jackson Tom , Lee Angela W.C. , Remme Espen W. , Sohal Manav , Plank Gernot , Razavi Reza , Rinaldi Christopher A. , Niederer Steven A. 
Published: July 2015

Background—
Cardiac resynchronization therapy (CRT) delivered via left ventricular (LV) endocardial pacing (ENDO-CRT) is associated with improved acute hemodynamic response compared with LV epicardial pacing (EPI-CRT). The role of cardiac anatomy and physiology in this improved response remains controversial. We used computational electrophysiological models to quantify the role of cardiac geometry, tissue anisotropy, and the presence of fast endocardial conduction on myocardial activation during ENDO-CRT and EPI-CRT.

Methods and Results—

Cardiac activation was simulated using the monodomain tissue excitation model in 2-dimensional (2D) canine and human and 3D canine biventricular models. The latest activation times (LATs) for LV endocardial and biventricular epicardial tissue were calculated (LVLAT and TLAT), as well the percentage decrease in LATs for endocardial (en) versus epicardial (ep) LV pacing (defined as %dLV=100×(LVLAT
ep
−LVLAT
en
)/LVLAT
ep
and %dT=100×(TLAT
ep
−TLAT
en
)/TLAT
ep
, respectively). Normal canine cardiac anatomy is responsible for %dLV and %dT values of 7.4% and 5.5%, respectively. Concentric and eccentric remodeled anatomies resulted in %dT values of 15.6% and 1.3%, respectively. The 3D biventricular-paced canine model resulted in %dLV and %dT values of −7.1% and 1.5%, in contrast to the experimental observations of 16% and 11%, respectively. Adding fast endocardial conduction to this model altered %dLV and %dT to 13.1% and 10.1%, respectively.

Conclusions—
Our results provide a physiological explanation for improved response to ENDO-CRT. We predict that patients with viable fast-conducting endocardial tissue or distal Purkinje network or both, as well as concentric remodeling, are more likely to benefit from reduced ATs and increased synchrony arising from endocardial pacing.
Hypervolume Subset Selection in Two Dimensions: Formulations and Algorithms
Authors: Kuhn Tobias , Fonseca Carlos M. , Paquete Luís , Ruzika Stefan , Duarte Miguel M. , Figueira José Rui 
Published: July 2015

The hypervolume subset selection problem consists of finding a subset, with a given cardinality k, of a set of nondominated points that maximizes the hypervolume indicator. This problem arises in selection procedures of evolutionary algorithms for multiobjective optimization, for which practically efficient algorithms are required. In this article, two new formulations are provided for the two-dimensional variant of this problem. The first is a (linear) integer programming formulation that can be solved by solving its linear programming relaxation. The second formulation is a k-link shortest path formulation on a special digraph with the Monge property that can be solved by dynamic programming in [Formula: see text] time. This improves upon the result of [Formula: see text] in Bader ( 2009 ), and slightly improves upon the result of [Formula: see text] in Bringmann et al. ( 2014b ), which was developed independently from this work using different techniques. Numerical results are shown for several values of n and k.
Maximizing Submodular Functions under Matroid Constraints by Evolutionary Algorithms
Authors: Friedrich Tobias , Neumann Frank 
Published: July 2015

Many combinatorial optimization problems have underlying goal functions that are submodular. The classical goal is to find a good solution for a given submodular function f under a given set of constraints. In this paper, we investigate the runtime of a simple single objective evolutionary algorithm called ([Formula: see text]) EA and a multiobjective evolutionary algorithm called GSEMO until they have obtained a good approximation for submodular functions. For the case of monotone submodular functions and uniform cardinality constraints, we show that the GSEMO achieves a [Formula: see text]-approximation in expected polynomial time. For the case of monotone functions where the constraints are given by the intersection of [Formula: see text] matroids, we show that the ([Formula: see text]) EA achieves a ([Formula: see text])-approximation in expected polynomial time for any constant [Formula: see text]. Turning to nonmonotone symmetric submodular functions with [Formula: see text] matroid intersection constraints, we show that the GSEMO achieves a [Formula: see text]-approximation in expected time [Formula: see text].
Lectotypification of the name Aconitum naviculare (Ranunculaceae)
Authors: Agnihotri Priyanka , Husain Danish , Husain Tariq 
Published: July 2015

Aconitum naviculare was first described by Brühl in Brühl & King (1896) as a variety of Aconitum ferox Wall. ex Ser. i.e. Aconitum ferox var. navicularis. Later on, Stapf (1905) published the new combination, citing Brühl’s var. navicularis as the basionym. This taxon is distributed in the alpine zones of India, China, Nepal and Bhutan. During revisionary studies on the tribe Delphineae from India, it was found that no type has been designated for this taxon. Therefore, a lectotype for A. naviculare is selected here from amongst the original material.
A CloudSat–CALIPSO View of Cloud and Precipitation Properties across Cold Fronts over the Global Oceans
Authors: Naud Catherine M. , Posselt Derek J. , van den Heever Susan C. 
Published: July 2015

Abstract
The distribution of cloud and precipitation properties across oceanic extratropical cyclone cold fronts is examined using four years of combined CloudSat radar and CALIPSO lidar retrievals. The global annual mean cloud and precipitation distributions show that low-level clouds are ubiquitous in the postfrontal zone while higher-level cloud frequency and precipitation peak in the warm sector along the surface front. Increases in temperature and moisture within the cold front region are associated with larger high-level but lower mid-/low-level cloud frequencies and precipitation decreases in the cold sector. This behavior seems to be related to a shift from stratiform to convective clouds and precipitation. Stronger ascent in the warm conveyor belt tends to enhance cloudiness and precipitation across the cold front. A strong temperature contrast between the warm and cold sectors also encourages greater post-cold-frontal cloud occurrence. While the seasonal contrasts in environmental temperature, moisture, and ascent strength are enough to explain most of the variations in cloud and precipitation across cold fronts in both hemispheres, they do not fully explain the differences between Northern and Southern Hemisphere cold fronts. These differences are better explained when the impact of the contrast in temperature across the cold front is also considered. In addition, these large-scale parameters do not explain the relatively large frequency in springtime postfrontal precipitation.
Evaluating Environmental Impacts on Tropical Cyclone Rapid Intensification Predictability Utilizing Statistical Models
Authors: Kaplan John , Rozoff Christopher M. , DeMaria Mark , Sampson Charles R. , Kossin James P. , Velden Christopher S. , Cione Joseph J. , Dunion Jason P. , Knaff John A. , Zhang Jun A. , Dostalek John F. , Hawkins Jeffrey D. , Lee Thomas F. , Solbrig Jeremy E. 
Published: July 2015

Abstract
New multi-lead-time versions of three statistical probabilistic tropical cyclone rapid intensification (RI) prediction models are developed for the Atlantic and eastern North Pacific basins. These are the linear-discriminant analysis–based Statistical Hurricane Intensity Prediction Scheme Rapid Intensification Index (SHIPS-RII), logistic regression, and Bayesian statistical RI models. Consensus RI models derived by averaging the three individual RI model probability forecasts are also generated. A verification of the cross-validated forecasts of the above RI models conducted for the 12-, 24-, 36-, and 48-h lead times indicates that these models generally exhibit skill relative to climatological forecasts, with the eastern Pacific models providing somewhat more skill than the Atlantic ones and the consensus versions providing more skill than the individual models. A verification of the deterministic RI model forecasts indicates that the operational intensity guidance exhibits some limited RI predictive skill, with the National Hurricane Center (NHC) official forecasts possessing the most skill within the first 24 h and the numerical models providing somewhat more skill at longer lead times. The Hurricane Weather Research and Forecasting Model (HWRF) generally provides the most skillful RI forecasts of any of the conventional intensity models while the new consensus RI model shows potential for providing increased skill over the existing operational intensity guidance. Finally, newly developed versions of the deterministic rapid intensification aid guidance that employ the new probabilistic consensus RI model forecasts along with the existing operational intensity model consensus produce lower mean errors and biases than the intensity consensus model alone.