bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Amino Terminus of Herpes Simplex Virus Type 1 Glycoprotein K (gK) Modulates gB-Mediated Virus-Induced Cell Fusion and Virion Egress
Authors: Chouljenko Vladimir N. , Iyer Arun V. , Chowdhury Sona , Chouljenko Dmitry V. , Kousoulas Konstantin G. 
Published: October 2009

ABSTRACT
Herpes simplex virus type 1 (HSV-1)-induced cell fusion is mediated by viral glycoproteins and other membrane proteins expressed on infected cell surfaces. Certain mutations in the carboxyl terminus of HSV-1 glycoprotein B (gB) and in the amino terminus of gK cause extensive virus-induced cell fusion. Although gB is known to be a fusogenic glycoprotein, the mechanism by which gK is involved in virus-induced cell fusion remains elusive. To delineate the amino-terminal domains of gK involved in virus-induced cell fusion, the recombinant viruses gKΔ31-47, gKΔ31-68, and gKΔ31-117, expressing gK carrying in-frame deletions spanning the amino terminus of gK immediately after the gK signal sequence (amino acids [aa] 1 to 30), were constructed. Mutant viruses gKΔ31-47 and gKΔ31-117 exhibited a gK-null (ΔgK) phenotype characterized by the formation of very small viral plaques and up to a 2-log reduction in the production of infectious virus in comparison to that for the parental HSV-1(F) wild-type virus. The gKΔ31-68 mutant virus formed substantially larger plaques and produced 1-log-higher titers than the gKΔ31-47 and gKΔ31-117 mutant virions at low multiplicities of infection. Deletion of 28 aa from the carboxyl terminus of gB (gBΔ28syn) caused extensive virus-induced cell fusion. However, the gBΔ28syn mutation was unable to cause virus-induced cell fusion in the presence of the gKΔ31-68 mutation. Transient expression of a peptide composed of the amino-terminal 82 aa of gK (gKa) produced a glycosylated peptide that was efficiently expressed on cell surfaces only after infection with the HSV-1(F), gKΔ31-68, ΔgK, or UL20-null virus. The gKa peptide complemented the gKΔ31-47 and gKΔ31-68 mutant viruses for infectious-virus production and for gKΔ31-68/gBΔ28syn-mediated cell fusion. These data show that the amino terminus of gK modulates gB-mediated virus-induced cell fusion and virion egress.
The African Swine Fever Virus Virion Membrane Protein pE248R Is Required for Virus Infectivity and an Early Postentry Event
Authors: Rodríguez Irene , Nogal María L. , Redrejo-Rodríguez Modesto , Bustos María J. , Salas María L. 
Published: October 2009

ABSTRACT
The African swine fever virus (ASFV) protein pE248R, encoded by the gene E248R, is a late structural component of the virus particle. The protein contains intramolecular disulfide bonds and has been previously identified as a substrate of the ASFV-encoded redox system. Its amino acid sequence contains a putative myristoylation site and a hydrophobic transmembrane region near its carboxy terminus. We show here that the protein pE248R is myristoylated during infection and associates with the membrane fraction in infected cells, behaving as an integral membrane protein. Furthermore, the protein localizes at the inner envelope of the virus particles in the cytoplasmic factories. The function of the protein pE248R in ASFV replication was investigated by using a recombinant virus that inducibly expresses the gene E248R. Under repressive conditions, the ASFV polyproteins pp220 and pp62 are normally processed and virus particles with morphology indistinguishable from that of those produced in a wild-type infection or under permissive conditions are generated. Moreover, the mutant virus particles can exit the cell as does the parental virus. However, the infectivity of the pE248R-deficient virions was reduced at least 100-fold. An investigation of the defect of the mutant virus indicated that neither virus binding nor internalization was affected by the absence of the protein pE248R, but a cytopathic effect was not induced and early and late gene expression was impaired, indicating that the protein is required for some early postentry event.
The Polymerase Acidic Protein Gene of Influenza A Virus Contributes to Pathogenicity in a Mouse Model
Authors: Song Min-Suk , Pascua Philippe Noriel Q. , Lee Jun Han , Baek Yun Hee , Lee Ok-Jun , Kim Chul-Joong , Kim Hyunggee , Webby Richard J. , Webster Robert G. , Choi Young Ki 
Published: October 2009

ABSTRACT

Adaptation of influenza A viruses to a new host species usually involves the mutation of one or more of the eight viral gene segments, and the molecular basis for host range restriction is still poorly understood. To investigate the molecular changes that occur during adaptation of a low-pathogenic avian influenza virus subtype commonly isolated from migratory birds to a mammalian host, we serially passaged the avirulent wild-bird H5N2 strain A/Aquatic bird/Korea/W81/05 (W81) in the lungs of mice. The resulting mouse-adapted strain (ma81) was highly virulent (50% mouse lethal dose = 2.6 log
10
50% tissue culture infective dose) and highly lethal. Nonconserved mutations were observed in six viral genes (those for PB2, PB1, PA, HA, NA, and M). Reverse genetic experiments substituting viral genes and mutations demonstrated that the PA gene was a determinant of the enhanced virulence in mice and that a Thr-to-Iso substitution at position 97 of PA played a key role. In growth kinetics studies, ma81 showed enhanced replication in mammalian but not avian cell lines; the PA
97I
mutation in strain W81 increased its replicative fitness in mice but not in chickens. The high virulence associated with the PA
97I
mutation in mice corresponded to considerably enhanced polymerase activity in mammalian cells. Furthermore, this characteristic mutation is not conserved among avian influenza viruses but is prevalent among mouse-adapted strains, indicating a host-dependent mutation. To our knowledge, this is the first study that the isoleucine residue at position 97 in PA plays a key role in enhanced virulence in mice and is implicated in the adaptation of avian influenza viruses to mammalian hosts.
Role of ORF74-Encoded Viral G Protein-Coupled Receptor in Human Herpesvirus 8 Lytic Replication
Authors: Sandford Gordon , Choi Young Bong , Nicholas John 
Published: October 2009

ABSTRACT

The human herpesvirus 8 (HHV-8) viral G protein-coupled receptor (vGPCR) has been implicated in virus-associated disease pathogenesis due principally to its ability to induce the production of angiogenic cytokines involved in this process. However, the role of the vGPCR in normal virus biology is understudied and remains unknown. Here we provide evidence from vGPCR gene knockout and depletion experiments that vGPCR is a positive regulator of HHV-8 productive replication and, through experimental utilization of Gα-coupling variants of vGPCR, that signaling via Gα
q
activation and targeted mitogen-activated protein kinase pathways is of particular relevance to this activity.
Dengue Virus Infection Induces Upregulation of GRP78, Which Acts To Chaperone Viral Antigen Production
Authors: Wati S. , Soo M.-L. , Zilm P. , Li P. , Paton A. W. , Burrell C. J. , Beard M. , Carr J. M. 
Published: October 2009

ABSTRACTDengue virus (DENV) pathogenesis is related to the host responses to viral infection within target cells, and therefore, this study assessed intracellular changes in host proteins following DENV infection. Two-dimensional gel electrophoresis and mass spectrometry identified upregulation of the host endoplasmic reticulum (ER) chaperone GRP78 in K562 cells following DENV infection, in the absence of virus-induced cell death. Upregulation of GRP78 in DENV-infected cells was confirmed by immunostaining and confocal microscopy and by Western blot analysis and was also observed in DENV-infected primary monocyte-derived macrophages, a natural target cell type for DENV infection. GRP78 was upregulated in both DENV antigen-positive and -negative cells in the DENV-infected culture, suggesting a bystander effect, with the highest GRP78 levels coincident with high-level DENV antigen production and infectious-virus release. Transfection of target cells to express GRP78 prior to DENV challenge did not affect subsequent DENV infection, but cleavage of GRP78 with the SubAB toxin, during an established DENV infection, yielded a 10- to 100-fold decrease in infectious-virus release, loss of intracellular DENV particles, and a dramatic decrease in intracellular DENV antigen. However, DENV RNA levels were unchanged, indicating normal DENV RNA replication but altered DENV antigen levels in the absence of GRP78. Thus, GRP78 is upregulated by DENV infection and is necessary for DENV antigen production and/or accumulation. This may be a common requirement for viruses such as flaviviruses that depend heavily on the ER for coordinated protein production and processing.
Antimigratory and antimetastatic effect of heparin-derived 4–18 unit oligosaccharides in a preclinical human melanoma metastasis model
Authors: Kenessey István , Simon Erika , Futosi Krisztina , Bereczky Bíborka , Kiss Andrea , Erdödi Ferenc , Gallagher John , Tímár József , Tóvári József 
Published: October 2009

SummaryHeparin and its derivatives have been shown to inhibit angiogenesis and metastasis formation. Accordingly, we investigated the effect of heparin fragments containing 4 to 22 monomers on human melanoma cell proliferation, migration and invasion in vitro as well as on the in vivo metastatic potential in a SCID mouse model. Only oligosaccharide dp18 had significant inhibitory effect on cell proliferation. In contrast, cell migration was inhibited by all oligosaccharides studied except dp8 and dp22. Anti CD44v3 antibody stimulated cell migration and invasion, and this effect could be attenuated by oligosaccharides dp4 and dp18. These fragments also inhibited the catalytic activity of myosin light chain phosphatase as well. Moreover, oligosaccharides dp4 and dp18 reduced the number of lung colonies formed in SCID mice intravenously injected with human melanoma cells, while dp22 proved to be ineffective in this respect.These studies revealed that fragments of heparin have an antimigratory and antimetastatic potential. These fragments lack the haemostatic effect of heparin, suggesting that they are potential specific antimetastatic agents in anticancer therapy.
Megakaryocyte and platelet abnormalities in a patient with a W33C mutation in the conserved SH3-like domain of myosin heavy chain IIA
Authors: Savoia Anna , Pluthero Fred , Li Ling , Christensen Hilary , De Rocco Daniela , Traivaree Chanchai , Butchart Sheila , Curtin Julie , Stollar Elliott , Forman-Kay Julie , Blanchette Victor , Kahr Walter 
Published: October 2009

SummaryHeterozygous mutations in MYH9, which encodes non-muscle myosin heavy chain IIA (MHC-IIA),result in autosomal dominant inherited MYH9-related disorders characterised by macrothrombocytopenia, granulocyte inclusions, variable sensorineural deafness, cataracts and nephritis. MHC-IIA is assembled into a complex consisting of two pairs of light chains and two heavy chains, where the latter contain a neck region, SH3-like, motor and rod domains. We describe a patient with a Trp33Cys missense mutation in the SH3-like domain of MHC-IIA. Abnormal platelet function was observed using platelet aggregometry with the agonists epinephrine and adenosine diphosphate (ADP). Patient granulocytes and megakaryocytes, but not platelets, contained abnormal MHC-IIA inclusions visualised by confocal immunofluorescence or electron microscopy. Megakaryocytes grown in culture were smaller and contained hypolobulated nuclei compared to controls. Bone marrow-derived megakaryocytes revealed a preponderance of immature forms, the presence of structurally diverse inclusion bodies, and frequent emperipolesis as assessed by electron microscopy. Platelets and leukocytes contained indistinguishable amounts of total MHCIIA determined by immunoblotting. Molecular modelling studies indicated that mutation of Trp33 destabilises the interface between the SH3-like and motor domain of MHC-IIA, which is close to previously described motor domain mutations, implying an important structural and/or functional role for this region in MHC-IIA.
Infection of the endothelium by members of the order Rickettsiales
Authors: Walker David , Valbuena Gustavo 
Published: October 2009

SummaryThe vascular endothelium is the main target of a limited number of infectious agents; Rickettsia, Ehrlichia ruminantium, and Orientia tsutsugamushi are among them. These arthropod-transmitted obligately-intracellular bacteria cause serious systemic diseases that are not infrequently lethal. In this review, we discuss the bacterial biology, vector biology, and clinical aspects of these conditions with particular emphasis on the interactions of these bacteria with the vascular endothelium and how it responds to intracellular infection. The study of these bacteria in relevant in vivo models is likely to offer new insights into the physiology of the endothelium that have not been revealed by other models.
Antimicrobial and immunoregulatory effector mechanisms in human endothelial cells
Authors: Schmidt Silvia , Heseler Kathrin , Spekker Katrin , MacKenzie Colin , Däubener Walter 
Published: October 2009

SummaryIn infectious diseases, interferon-gamma (IFN-γ) is generally accepted as one of the most important inducers of antimicrobial and immunoregulatory effects, and both seemingly contradictory effects, can be mediated by the same effector molecules. In detail, several IFN-γ induced enzymes such as the inducible nitric oxide synthase (iNOS) as well as the indoleamine 2,3-dioxygenase (IDO) also exert this double function. In this review we focus on antimicrobial and immunoregulatory properties of both enzymes expressed by human endothelial cells, which are prominent players in infectious diseases, tumour immunology and transplant medicine.
Alteration of fibrin clot properties by ultrafine particulate matter
Authors: Metassan Sofian , Charlton Alexander , Routledge Michael , Scott D. Julian , Ariëns Robert 
Published: October 2009

SummaryBoth long- and short-term (1–2 hours) exposure to particulate matter (PM) are associated with morbidity and mortality caused by cardiovascular diseases. One of the underlying mechanisms may be due to changes to blood coagulability upon exposure to PM. We investigated this possibility by measuring differences in blood clots formed in the presence of particulate matter in vitro. Total (T)PM increased the permeation of clots in a dose-dependant manner. Filtered (F)PM (17 μg/ml) also produced a significant increase in permeation. Turbidity measured as maximum optical density (ODmax) was increased in a dose-dependant manner with increasing concentration of TPM and FPM. Turbidity measurements also showed a significantly faster rate of polymerisation in the presence of 68 μg/ml FPM. Laser scanning confocal microscopy (LSCM) showed a decrease in fibre density without a significant increase in fibre diameter. However, LSCM showed increased clot heterogeneity due to fibre clustering, creating areas of denser fibrin network surrounded by looser network. The presence of reactive oxygen species (ROS) scavenger mannitol inhibited the effects on fibre clustering. Our data show that TPM and FPM cause alterations in fibrin clot structure, likely through the formation of ROS. These changes in fibrin clot structure may play a role in thromboembolic events upon PM exposure.
Platelet-endothelial cell interactions in cerebral malaria: The end of a cordial understanding
Authors: Faille Dorothée , El-Assaad Fatima , Alessi Marie-Christine , Fusai Thierry , Combes Valéry , Grau Georges 
Published: October 2009

SummaryCerebral malaria is an acute encephalopathy evolving from an infection with Plasmodium falciparum which kills more than one million people each year. Brain tissues from patients who died with cerebral malaria revealed multifocal capillary obstruction by parasitised red blood cells, platelets, and leukocytes. Many studies are unified in their proposal of two major hypotheses consisting of cell adhesion to the brain endothelium and excessive immune stimulation resulting in further vascular inflammation, prothrombotic cell activation, mechanical obstruction of cerebral capillaries and, consequently, blood-brain barrier disruption. Platelets and endothelial cells communicate on multiple levels. Infection-induced changes in platelets and endothelial cells occur in cerebral malaria, resulting in their concomitant activation, increased interactions between these two cell types, and a secondary procoagulant or hypercoagulable state. Here we review evidence for these mechanisms and highlight the possible role of platelets as effectors of endothelial damage in cerebral malaria. A better understanding of the complex regulation of these various interactions between brain endothelial cells and platelets in the context of cerebral malaria may prove useful in the development of new approaches to the treatment of this disease.
Gender as a risk factor for pulmonary embolism after air travel
Authors: Le Toumelin Philippe , Chassery Carine , Galinski Michel , Ameur Lydia , Jabre Patricia , Lapandry Claude , Adnet Frédéric , Lapostolle Frédéric 
Published: October 2009

SummaryIt was the objective of this study to confirm the hypothesis that women experience an increased risk of pulmonary embolism (PE) and/or thromboembolic events after long-distance air travel. We systematically reviewed the records of all patients with confirmed pulmonary embolism after arrival at Roissy-Charles-de-Gaulle (CDG) Airport (Paris, France) during a 13-year period.The incidence of PE was calculated as a function of distance travelled and gender using Bayesian conditional probabilities obtained in part from a control population of long-distance travellers arriving in French Polynesia (Tahiti). A total of 287.6 million passengers landed at CDG airport during the study period. The proportion of male to female long-distance travellers was estimated to be 50.5% to 49.5%. Overall, 116 patients experienced PE after landing [90 females (78%), 26 males (22%)]. The estimated incidence of PE was 0.61 (0.61–0.61) cases per million passengers in females and 0.2 (0.20–0.20) in males, and reached 7.24 (7.17–7.31) and 2.35 (2.33–2.38) cases, respectively, in passengers travelling over 10,000 km. Our study strongly suggests that there is a relationship between risk of PE after air travel and gender.This relationship needs to be confirmed in order to develop the best strategy for prophylaxis.
Management of Antithrombotic Therapy in Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome and/or Undergoing Percutaneous Coronary Intervention/ Stenting
Authors: Huber Kurt , Andreotti Felicita , Arnesen Harald , Airaksinen K. Juhani , Cuisset Thomas , Kirchhof Paulus , Marín Francisco , Lip Gregory 
Published: October 2009

SummaryThere remains uncertainty over optimal antithrombotic management strategy for patients with atrial fibrillation (AF) presenting with an acute coronary syndrome and/or undergoing percutaneous coronary intervention/stenting. Clinicians need to balance the risk of stroke and thromboembolism against the risk of recurrent cardiac ischaemia and/ or stent thrombosis, and the risk of bleeding. This consensus document comprehensively reviews the published evidence and presents a consensus statement on a ‘best practice’ antithrombotic therapy guideline for the management of antithrombotic therapy in such AF patients.
Musical Theory and Philosophy: The Case of Archestratus
Authors: Barker Andrew 
Published: October 2009

AbstractLittle is known about the harmonic theorist Archestratus (probably early 3rd century BC). Our only substantial information comes from Porphyry, who quotes a brief comment by a certain Didymus on his epistemological stance, and seeks to justify it through reflection on a rather startling technical doctrine which Archestratus propounded; and from Philodemus, who comments scathingly on his view of the relation between harmonic theory and philosophy. Neither passage is easy to interpret; this paper tries to make sense of them, and to set them in an intelligible relation to one another. It argues that the doctrine recorded by Porphyry becomes comprehensible when it is placed against the background of Aristoxenus' work in harmonics, and it discusses Porphyry's inferences about the way in which his epistemological position diverged from that of Aristoxenus. It argues that Philodemus' report gives evidence of Archestratus' interest in issues of central concern to philosophy and in particular of an engagement with Aristotelian thought; it tries to identify some specific questions which attracted his attention, and to explain how he seems to have answered them, and why. It suggests that the two reports can be brought together as elements in a single, though fragmentary picture, and finally that Archestratus can be assigned an interesting though minor role in the history of Peripatetic philosophy and science.
The Political Economy of Academic Publishing
Authors: Pirie Iain 
Published: October 2009

AbstractThe digitisation of academic journals has created the technical possibility that research can be made available to any interested party free of charge. This possibility has been undermined by the proprietary control that commercial publishers exercise over the majority of this material. The control of commercial publishers over publicly-funded research has been criticised by charitable bodies, politicians and academics themselves. While the existing critical literature on academic publishers has considerable value, it fails to link questions of control within the journal-industry to the wider restructuring of economic and social relations that has taken place over the last three decades. This article seeks to complement this literature by highlighting how broader profitability pressures and the subsequent attempts by state-managers to expand the social space for capitalist accumulation have structured the development of the journal-industry.
Egyptian Family Courts: A Pathway of Women's Empowerment?
Authors: Al-Sharmani Mulki 
Published: October 2009

AbstractA significant new law was passed by Egyptian legislators in 2004 introducing family courts to arbitrate family conflict in an effort to promote non-adversarial legal mechanisms. The aim of this paper is to examine how this new legal system is working for female plaintiffs. Through an analysis of court practices in a number of divorce and maintenance cases, this essay will make two central arguments: First, I will argue that the benefits family courts are currently providing to female plaintiffs are limited due to a number of gaps and shortcomings in the legislation, mechanisms of implementation, resources, and the capacity and the training of court personnel. In addition, the legal process in the new courts as well as the substantive family laws that are being implemented continue to reflect gender inequality and biases against women. Secondly, I will argue that the shortcomings of the new court system also result from the approach of addressing gender inequalities through the piecemeal approach of fragmented procedural reforms as well as the contradictions arising from the divergent agendas of the alliances built between different reform actors (e.g. women's rights organizations, government bodies, and legal institution).