bluuebunny/crossref_metadata_2025_split huggingface dataset:
CARDIOVASCULAR DISEASE IN RENAL TRANSPLANT RECIPIENTS
Authors: McQuarrie Emily P. , Fellström Bengt C. , Holdaas Hallvard , Jardine Alan G. 
Published: May 2010

SUMMARYRenal transplant recipients have a markedly increased risk of premature cardiovascular disease (CVD) compared with the general population, although considerably lower than that of patients receiving maintenance haemodialysis. CVD in transplant recipients is poorly characterised and differs from the nonrenal population, with a much higher proportion of fatal to nonfatal cardiac events. In addition to traditional ischaemic heart disease risk factors such as age, gender, diabetes and smoking, there are additional factors to consider in this population such as the importance of hypertension, left ventricular hypertrophy and uraemic cardiomyopathy. There are factors specific to transplantation such immunosuppressive therapies and graft dysfunction which contribute to this altered risk profile. However, understanding and treatment is limited by the absence of large randomised intervention trials addressing risk factor modification, with the exception of the ALERT study. The approach to managing these patients should begin early and be multifactorial in nature.
ATHEROSCLEROTIC RENOVASCULAR DISEASE AND THE HEART
Authors: Chrysochou Constantina , Kalra Philip A. 
Published: May 2010

SUMMARYThe detrimental link between cardiac and renal pathophysiology in atherosclerotic renovascular disease (ARVD) is well described. Patients with ARVD usually have significant atherosclerotic disease in other vascular beds including the coronary circulation, and structural and functional cardiac changes are highly prevalent. This excess cardiovascular burden probably contributes to the increased cardiac morbidity and mortality seen in these patients.In this review we describe the associations of cardiovascular disease and ARVD and treatment thereof. The clinical debate of which patients are offered any additional advantage by revascularisation over medications alone remains to be answered. The close link between cardiac and renal pathophysiology in ARVD raises the possibility that renal revascularisation might confer a benefit to cardiac morphology and function. This is the subject of ongoing randomised controlled trials.
THE DIABETIC CKD PATIENT—A MAJOR CARDIOVASCULAR CHALLENGE
Authors: Van Der Meer Irene M. , Ruggenenti Piero , Remuzzi Giuseppe 
Published: May 2010

SUMMARYThe diabetic patient with chronic kidney disease (CKD) is at very high risk of cardiovascular disease (CVD). Primary and secondary CVD prevention is of major importance and should be targeted at both traditional cardiovascular risk factors and risk factors specific for patients with CKD, such as albuminuria, anaemia and CKD—mineral and bone disorder. However, treatment goals have largely been derived from clinical trials including patients with no or only mild CKD and may not be generalisable to patients with advanced renal disease. Moreover, in patients on renal replacement therapy, the association between traditional CVD risk factors and the incidence of CVD may be reversed, and pharmaceutical interventions that are beneficial in the general population may be ineffective or even harmful in this high‐risk population. Those involved in the delivery of care to patients with diabetes and CKD need to be aware of these issues and should adopt an individualised approach to treatment.
Differences of genetic diversity and antibiotics susceptibility of Pseudomonas aeruginosa isolated from hospital, river and coastal seawater
Authors: Nonaka Lisa , Inubushi Ayumi , Shinomiya Hiroto , Murase Mitsuharu , Suzuki Satoru 
Published: May 2010

Summary Pseudomonas aeruginosa is an opportunistic pathogen, and ubiquitously found in natural environments. However, details on difference between clinical and environmental isolates have not been reported enough. In this study, we defined existence of marine specific genogroup and different drug susceptibility among isolates from clinical, river and coastal seawaters. Pseudomonas aeruginosa were isolated by using cetrimide kanamycin nalidixic acid agar media and incubation at 42°C, which was specific selection method of this bacterium from the natural aquatic samples. Pulse field gel electrophoresis analysis showed that the levels of genetic variation within P. aeruginosa were different among environmental sites. Pulse field gel electrophoresis also showed a lower diversity within P. aeruginosa in the coastal waters; and coastal strains isolated different sampling points were positioned closely in the same cluster. Most of the aquatic isolates were sensitive to most of the drugs tested and ‘intermediate’ to panipenem on the contrast to the clinical isolates, suggesting that the clinical use of antibiotics affect significantly to the emergence of the drug‐resistant P. aeruginosa.
EXPERIENCES AS COMPLEX EVENTS
Authors: Jacovides Michael 
Published: May 2010

abstractIt is argued that experiences are complex events that befall their subjects. Each experience has a single subject and depends on the state or the event that it is of. The constituents of an experience are (or underlie) its subject, its grounding event or state, and everything that the subject is aware of during that time that's relevant to the telling of the story of how it was to participate in that event or be put in that state. The experience occurs where the person having the experience is. An experience of an event or state occurs when that event or state makes a difference to its possessor's conscious life, where this difference is either a matter of really knowing what's happening or merely a matter of being affected.
POLITICAL LIBERALISM, BASIC LIBERTIES, AND LEGAL PATERNALISM
Authors: Glod William 
Published: May 2010

abstractThis essay argues that neutral paternalism (NP) is problematic for antiperfectionist liberal theories. Section 2 raises textual evidence that Rawlsian liberalism does not oppose and may even support NP. In section 3, I cast doubt on whether NP should have a place in political liberalism by defending a partially comprehensive conception of the good I call “moral capacity at each moment,” or MCEM, that is inconsistent with NP. I then explain why MCEM is a reasonable conception on Rawls's account of reasonableness. In section 4, I handle concerns that showing NP fails the test of Rawlsian public justification is a nonstarter since NP does not threaten any of our basic liberties. I sketch an argument that, if this is so, the burden is on political liberalism to defend its particular account of basic liberties, since MCEM is reasonable on Rawlsian grounds. More precisely, MCEM is a conception that challenges the way Rawls characterizes basic liberties; that is, his list of basic liberties should be more inclusive by political liberalism's own structural commitments, including Rawls's “liberal principle of legitimacy.” On this revised account, political liberalism can mount a strong opposition to hard legal paternalism.
Aichi Virus IgG Seroprevalence in Tunisia Parallels Genomic Detection and Clinical Presentation in Children with Gastroenteritis
Authors: Sdiri-Loulizi Khira , Hassine Mouna , Bour Jean-Baptiste , Ambert-Balay Katia , Mastouri Maha , Aho Ludwig-Serge , Gharbi-Khelifi Hakima , Aouni Zaidoun , Sakly Nabil , Chouchane Slaheddine , Neji-Guédiche Mohamed , Pothier Pierre , Aouni Mahjoub 
Published: May 2010

ABSTRACTAichi virus has been described as a novel causative agent of gastroenteritis in humans. In this study, we report the seroprevalence distribution of Aichi virus in Tunisia. A panel of 1,000 sera was screened by applying an enzyme-linked immunosorbent assay for immunoglobulin G specific for Aichi virus. A considerable prevalence (92%) of antibody to Aichi virus was found across all age groups. The specific anti-Aichi virus antibodies increased with age, from a high rate (68.8%) in children under 10 years old to about 100% in persons more than 60 years old. We found a statistically significant increase in levels of antibody to Aichi virus according to the age of patients. Immunoglobulin M antibodies were detected among five children. A high frequency of Aichi virus monoinfections in hospitalized children with severe gastroenteritis was previously observed in Tunisia. Aichi virus causes diarrhea with dehydration, fever, and vomiting. This work is the first to establish a correlation between the high seroprevalence of specific Aichi virus antibodies, clinical presentation, and a high frequency of isolation of Aichi virus by genomic characterization in stools of children suffering from gastroenteritis. Our data show the importance and emerging character of Aichi virus in the viral etiology of pediatric gastroenteritis.
Interacting Roles of Immune Mechanisms and Viral Load in the Pathogenesis of Crimean-Congo Hemorrhagic Fever
Authors: Saksida Ana , Duh Darja , Wraber Branka , Dedushaj Isuf , Ahmeti Salih , Avšič-Županc Tatjana 
Published: May 2010

ABSTRACT
Until now, the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) has not been well described. However, it has been hypothesized that it could be a result of the direct injury of virus-infected tissues in combination with the indirect effects of host immune responses, including cytokines. To shed more light on the role of viral load and cytokines, differential influences of CCHF virus (CCHFV) RNA load, antibody response, and cytokine production on severity and outcome of the disease were studied in sera of 46 patients with confirmed acute CCHF from Kosovo. In this study, viral load proved to be strongly related to the severity and outcome of the disease, with higher viral loads detected in patients with fatal outcomes than in surviving patients. Also, patients with fatal outcome had on average a weaker antibody response, if one was present at all. High levels of interleukin-10 (IL-10), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) were associated with poor outcome, since detected concentrations were highest in patients with fatal outcome and lowest in patients with moderate disease course. Additionally, a positive linear dependence between viral load and these cytokines was observed. Interestingly, reduced levels of IL-12 were detected in all CCHF patients. Our study favors the hypothesis that CCHF could be a result of a delayed and downregulated immune response caused by IL-10, which leads to an increased replication and spread of CCHFV throughout the body. This consequently triggers increased production of IFN-γ and TNF-α, cytokines mediating vascular dysfunction, disseminated intravascular coagulation, organ failure, and shock.
Differential Activation of NK Cells by Influenza A Pseudotype H5N1 and 1918 and 2009 Pandemic H1N1 Viruses
Authors: Du Ning , Zhou Jianfang , Lin Xiaojing , Zhang Yonghui , Yang Xiaoxing , Wang Yue , Shu Yuelong 
Published: May 2010

ABSTRACTNatural killer (NK) cells are the effectors of innate immunity and are recruited into the lung 48 h after influenza virus infection. Functional NK cell activation can be triggered by the interaction between viral hemagglutinin (HA) and natural cytotoxicity receptors NKp46 and NKp44 on the cell surface. Recently, novel subtypes of influenza viruses, such as H5N1 and 2009 pandemic H1N1, transmitted directly to the human population, with unusual mortality and morbidity rates. Here, the human NK cell responses to these viruses were studied. Differential activation of heterogeneous NK cells (upregulation of CD69 and CD107a and gamma interferon [IFN-γ] production as well as downregulation of NKp46) was observed following interactions with H5N1, 1918 H1N1, and 2009 H1N1 pseudotyped particles (pps), respectively, and the responses of the CD56dimsubset predominated. Much stronger NK activation was triggered by H5N1 and 1918 H1N1 pps than by 2009 H1N1 pps. The interaction of pps with NK cells and subsequent internalization were mediated by NKp46 partially. The NK cell activation by pps showed a dosage-dependent manner, while an increasing viral HA titer attenuated NK activation phenotypes, cytotoxicity, and IFN-γ production. The various host innate immune responses to different influenza virus subtypes or HA titers may be associated with disease severity.
Proteasome-Dependent Degradation of Daxx by the Viral E1B-55K Protein in Human Adenovirus-Infected Cells
Authors: Schreiner Sabrina , Wimmer Peter , Sirma Hüseyin , Everett Roger D. , Blanchette Paola , Groitl Peter , Dobner Thomas 
Published: May 2010

ABSTRACTThe death-associated protein Daxx found in PML (promyelocytic leukemia protein) nuclear bodies (PML-NBs) is involved in transcriptional regulation and cellular intrinsic antiviral resistence against incoming viruses. We found that knockdown of Daxx in a nontransformed human hepatocyte cell line using RNA interference (RNAi) techniques results in significantly increased adenoviral (Ad) replication, including enhanced viral mRNA synthesis and viral protein expression. This Daxx restriction imposed upon adenovirus growth is counteracted by early protein E1B-55K (early region 1B 55-kDa protein), a multifunctional regulator of cell-cycle-independent Ad5 replication. The viral protein binds to Daxx and induces its degradation through a proteasome-dependent pathway. We show that this process is independent of Ad E4orf6 (early region 4 open reading frame 6), known to promote the proteasomal degradation of cellular p53, Mre11, DNA ligase IV, and integrin α3 in combination with E1B-55K. These results illustrate the importance of the PML-NB-associated factor Daxx in virus growth restriction and suggest that E1B-55K antagonizes innate antiviral activities of Daxx and PML-NBs to stimulate viral replication at a posttranslational level.
Redirecting Lentiviral Vectors Pseudotyped with Sindbis Virus-Derived Envelope Proteins to DC-SIGN by Modification of N-Linked Glycans of Envelope Proteins
Authors: Morizono Kouki , Ku Amy , Xie Yiming , Harui Airi , Kung Sam K. P. , Roth Michael D. , Lee Benhur , Chen Irvin S. Y. 
Published: May 2010

ABSTRACTRedirecting the tropism of viral vectors enables specific transduction of selected cells by direct administration of vectors. We previously developed targeting lentiviral vectors by pseudotyping with modified Sindbis virus envelope proteins. These modified Sindbis virus envelope proteins have mutations in their original receptor-binding regions to eliminate their natural tropisms, and they are conjugated with targeting proteins, including antibodies and peptides, to confer their tropisms on target cells. We investigated whether our targeting vectors interact with DC-SIGN, which traps many types of viruses and gene therapy vectors by binding to the N-glycans of their envelope proteins. We found that these vectors do not interact with DC-SIGN. When these vectors were produced in the presence of deoxymannojirimycin, which alters the structures of N-glycans from complex to high mannose, these vectors used DC-SIGN as their receptor. Genetic analysis demonstrated that the N-glycans at E2 amino acid (aa) 196 and E1 aa 139 mediate binding to DC-SIGN, which supports the results of a previous report of cryoelectron microscopy analysis. In addition, we investigated whether modification of the N-glycan structures could activate serum complement activity, possibly by the lectin pathway of complement activation. DC-SIGN-targeted transduction occurs in the presence of human serum complement, demonstrating that high-mannose structure N-glycans of the envelope proteins do not activate human serum complement. These results indicate that the strategy of redirecting viral vectors according to alterations of their N-glycan structures would enable the vectors to target specific cells types expressing particular types of lectins.
The Ubiquitin-Proteasome System Plays an Important Role during Various Stages of the Coronavirus Infection Cycle
Authors: Raaben Matthijs , Posthuma Clara C. , Verheije Monique H. , te Lintelo Eddie G. , Kikkert Marjolein , Drijfhout Jan W. , Snijder Eric J. , Rottier Peter J. M. , de Haan Cornelis A. M. 
Published: May 2010

ABSTRACTThe ubiquitin-proteasome system (UPS) is a key player in regulating the intracellular sorting and degradation of proteins. In this study we investigated the role of the UPS in different steps of the coronavirus (CoV) infection cycle. Inhibition of the proteasome by different chemical compounds (i.e., MG132, epoxomicin, and Velcade) appeared to not only impair entry but also RNA synthesis and subsequent protein expression of different CoVs (i.e., mouse hepatitis virus [MHV], feline infectious peritonitis virus, and severe acute respiratory syndrome CoV). MHV assembly and release were, however, not appreciably affected by these compounds. The inhibitory effect on CoV protein expression did not appear to result from a general inhibition of translation due to induction of a cellular stress response by the inhibitors. Stress-induced phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) generally results in impaired initiation of protein synthesis, but the sensitivity of MHV infection to proteasome inhibitors was unchanged in cells lacking a phosphorylatable eIF2α. MHV infection was affected not only by inhibition of the proteasome but also by interfering with protein ubiquitination. Viral protein expression was reduced in cells expressing a temperature-sensitive ubiquitin-activating enzyme E1 at the restrictive temperature, as well as in cells in which ubiquitin was depleted by using small interfering RNAs. Under these conditions, the susceptibility of the cells to virus infection was, however, not affected, excluding an important role of ubiquitination in virus entry. Our observations reveal an important role of the UPS in multiple steps of the CoV infection cycle and identify the UPS as a potential drug target to modulate the impact of CoV infection.
Role of the Endoplasmic Reticulum Chaperone BiP, SUN Domain Proteins, and Dynein in Altering Nuclear Morphology during Human Cytomegalovirus Infection
Authors: Buchkovich Nicholas J. , Maguire Tobi G. , Alwine James C. 
Published: May 2010

ABSTRACT
The process of assembly and egress of human cytomegalovirus (HCMV) virions requires significant morphological alterations of the nuclear and cytoplasmic architecture. In the studies presented we show that the nuclear periphery is dramatically altered, especially near the cytoplasmic assembly compartment, where the nuclear lamina is specifically rearranged, the outer nuclear membrane is altered, and the nucleus becomes permeable to large molecules. In addition, the tethering of the inner and outer nuclear membranes is lost during infection due to a decrease in levels of the SUN domain proteins. We previously demonstrated that the endoplasmic reticulum protein BiP functions as a component of the assembly compartment and disruption of BiP causes the loss of assembly compartment integrity. In this study we show that the depletion of BiP, and the loss of assembly compartment integrity, results in the loss of virally induced lamina rearrangement and morphology of the nucleus that is characteristic of HCMV infection. BiP functions in lamina rearrangement through its ability to affect lamin phosphorylation. Depletion of BiP and disruption of the assembly compartment result in the loss of lamin phosphorylation. The dependency of lamin phosphorylation on BiP correlates with an interaction between BiP and UL50. Finally, we confirm previous data (S. V. Indran, M. E. Ballestas, and W. J. Britt, J. Virol. 84:3162-3177, 2010) suggesting an involvement of dynein in assembly compartment formation and extend this observation by showing that when dynein is inhibited, the nuclear morphology characteristic of an HCMV infection is lost. Our data suggest a highly integrated assembly-egress continuum.
Safety and Immunogenicity of Novel Recombinant BCG and Modified Vaccinia Virus Ankara Vaccines in Neonate Rhesus Macaques
Authors: Rosario Maximillian , Fulkerson John , Soneji Shamit , Parker Joe , Im Eung-Jun , Borthwick Nicola , Bridgeman Anne , Bourne Charles , Joseph Joan , Sadoff Jerald C. , Hanke Tomáš 
Published: May 2010

ABSTRACTAlthough major inroads into making antiretroviral therapy available in resource-poor countries have been made, there is an urgent need for an effective vaccine administered shortly after birth, which would protect infants from acquiring human immunodeficiency virus type 1 (HIV-1) through breast-feeding.BacillusCalmette-Guérin (BCG) is given to most infants at birth, and its recombinant form could be used to prime HIV-1-specific responses for a later boost by heterologous vectors delivering the same HIV-1-derived immunogen. Here, two groups of neonate Indian rhesus macaques were immunized with either novel candidate vaccine BCG.HIVA401or its parental strain AERAS-401, followed by two doses of recombinant modified vaccinia virus Ankara MVA.HIVA. The HIVA immunogen is derived from African clade A HIV-1. All vaccines were safe, giving local reactions consistent with the expected response at the injection site. No systemic adverse events or gross abnormality was seen at necropsy. Both AERAS-401 and BCG.HIVA401induced high frequencies of BCG-specific IFN-γ-secreting lymphocytes that declined over 23 weeks, but the latter failed to induce detectable HIV-1-specific IFN-γ responses. MVA.HIVA elicited HIV-1-specific IFN-γ responses in all eight animals, but, except for one animal, these responses were weak. The HIV-1-specific responses induced in infants were lower compared to historic data generated by the two HIVA vaccines in adult animals but similar to other recombinant poxviruses tested in this model. This is the first time these vaccines were tested in newborn monkeys. These results inform further infant vaccine development and provide comparative data for two human infant vaccine trials of MVA.HIVA.
Feline Lectin Activity Is Critical for the Cellular Entry of Feline Infectious Peritonitis Virus
Authors: Regan Andrew D. , Ousterout David G. , Whittaker Gary R. 
Published: May 2010

ABSTRACTFeline infectious peritonitis is a lethal disease of felids caused by systemic infection with a feline coronavirus. Here, we report identification and analysis of the feline homologue to the human lectin DC-SIGN and show that it is a coreceptor for virulent strains of serotype 1 and serotype 2 feline coronaviruses.