bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated Levels of Innate Immune Modulators in Lymph Nodes and Blood Are Associated with More-Rapid Disease Progression in Simian Immunodeficiency Virus-Infected Monkeys
Authors: Durudas Andre , Milush Jeffrey M. , Chen Hui-Ling , Engram Jessica C. , Silvestri Guido , Sodora Donald L. 
Published: September 2009

ABSTRACT

Cytokines and chemokines are critical for establishing tissue-specific immune responses and play key roles in modulating disease progression in simian immunodeficiency virus (SIV)-infected macaques and human immunodeficiency virus (HIV)-infected humans. The goal here was to characterize the innate immune response at different tissue sites and to correlate these responses to clinical outcome, initially focusing on rhesus macaques orally inoculated with SIV and monitored until onset of simian AIDS. Cytokine and chemokine mRNA transcripts were assessed at lymph nodes (LN) and peripheral blood cells utilizing quantitative real-time PCR at different time points postinfection. The mRNA expression of four immune modulators—alpha interferon (IFN-α), oligoadenylate synthetase (OAS), CXCL9, and CXCL10—was positively associated with disease progression within LN tissue. Elevated cytokine/chemokine expression in LN did not result in any observed beneficial outcome since the numbers of CXCR3
+
cells were not increased, nor were the SIV RNA levels decreased. In peripheral blood, increased OAS and CXCL10 expression were elevated in SIV
+
monkeys that progress the fastest to simian AIDS. Our results indicate that higher IFN-α, OAS, CXCL9, and CXCL10 mRNA expression in LN was associated with rapid disease progression and a LN environment that may favor SIV replication. Furthermore, higher expression of CXCL10 and OAS in peripheral blood could potentially serve as a diagnostic marker for hosts that are likely to progress to AIDS. Understanding the expression patterns of key innate immune modulators will be useful in assessing the disease state and potential rates of disease progression in HIV
+
patients, which could lead to novel therapy and vaccine approaches.
Fusion between Perinuclear Virions and the Outer Nuclear Membrane Requires the Fusogenic Activity of Herpes Simplex Virus gB
Authors: Wright Catherine C. , Wisner Todd W. , Hannah Brian P. , Eisenberg Roselyn J. , Cohen Gary H. , Johnson David C. 
Published: September 2009

ABSTRACT
Herpesviruses cross nuclear membranes (NMs) in two steps, as follows: (i) capsids assemble and bud through the inner NM into the perinuclear space, producing enveloped virus particles, and (ii) the envelopes of these virus particles fuse with the outer NM. Two herpes simplex virus (HSV) glycoproteins, gB and gH (the latter, likely complexed as a heterodimer with gL), are necessary for the second step of this process. Mutants lacking both gB and gH accumulate in the perinuclear space or in herniations (membrane vesicles derived from the inner NM). Both gB and gH/gL are also known to act directly in fusing the virion envelope with host cell membranes during HSV entry into cells, i.e., both glycoproteins appear to function directly in different aspects of the membrane fusion process. We hypothesized that HSV gB and gH/gL also act directly in the membrane fusion that occurs during virus egress from the nucleus. Previous studies of the role of gB and gH/gL in nuclear egress involved HSV gB and gH null mutants that could potentially also possess gross defects in the virion envelope. Here, we produced recombinant HSV-expressing mutant forms of gB with single amino acid substitutions in the hydrophobic “fusion loops.” These fusion loops are thought to play a direct role in membrane fusion by insertion into cellular membranes. HSV recombinants expressing gB with any one of four fusion loop mutations (W174R, W174Y, Y179K, and A261D) were unable to enter cells. Moreover, two of the mutants, W174Y and Y179K, displayed reduced abilities to mediate HSV cell-to-cell spread, and W174R and A261D exhibited no spread. All mutant viruses exhibited defects in nuclear egress, enveloped virions accumulated in herniations and in the perinuclear space, and fewer enveloped virions were detected on cell surfaces. These results support the hypothesis that gB functions directly to mediate the fusion between perinuclear virus particles and the outer NM.
Mixed Infections ofPepino Mosaic VirusStrains Modulate the Evolutionary Dynamics of this Emergent Virus
Authors: Gómez P. , Sempere R. N. , Elena S. F. , Aranda M. A. 
Published: September 2009

ABSTRACTPepino mosaic virus(PepMV) is an emerging pathogen that causes severe economic losses in tomato crops (Solanum lycopersicumL.) in the Northern hemisphere, despite persistent attempts of control. In fact, it is considered one of the most significant viral diseases for tomato production worldwide, and it may constitute a good model for the analysis of virus emergence in crops. We have combined a population genetics approach with an analysis of in planta properties of virus strains to explain an observed epidemiological pattern. Hybridization analysis showed that PepMV populations are composed of isolates of two types (PepMV-CH2 and PepMV-EU) that cocirculate. The CH2 type isolates are predominant; however, EU isolates have not been displaced but persist mainly in mixed infections. Two molecularly cloned isolates belonging to each type have been used to examine the dynamics of in planta single infections and coinfection, revealing that the CH2 type has a higher fitness than the EU type. Coinfections expand the range of susceptible hosts, and coinfected plants remain symptomless several weeks after infection, so a potentially important problem for disease prevention and management. These results provide an explanation of the observed epidemiological pattern in terms of genetic and ecological interactions among the different viral strains. Thus, mixed infections appear to be contributing to shaping the genetic structure and dynamics of PepMV populations.
Origin and Phylodynamics of Rabbit Hemorrhagic Disease Virus
Authors: Kerr Peter J. , Kitchen Andrew , Holmes Edward C. 
Published: September 2009

ABSTRACT

To determine the origin, phylogenetic relationships, and evolutionary dynamics of rabbit hemorrhagic disease virus (RHDV), we examined 210 partial and complete capsid gene nucleotide sequences. Using a Bayesian Markov chain Monte Carlo approach, we estimated that these sequences evolved at a rate of 3.9 × 10
−4
to 11.9 × 10
−4
nucleotide substitutions per site per year. This rate was consistent across subsets of data, was robust in response to recombination, and casts doubt on the provenance of viral strains isolated from the 1950s to the 1970s, which share strong sequence similarity to modern isolates. Using the same analysis, we inferred that the time to the most recent common ancestor for a joint group of RHDV and rabbit calicivirus sequences was <550 years ago and was <150 years ago for the RHDV isolates that have spread around the world since 1984. Importantly, multiple lineages of RHDV were clearly circulating before the major Chinese outbreak of 1984, a finding indicative of an early evolution of RHDV virulence. Four phylogenetic groups within RHDV were defined and analyzed separately. Each group shared a common ancestor in the mid-1960s or earlier, and each showed an expansion of populations starting before 1984. Notably, the group characterized by the antigenic variant RHDVa harbors the greatest genetic diversity, compatible with an elevated fitness. Overall, we contend that the high virulence of RHDV likely evolved once in the early part of the 20th century, well before the documented emergence of rabbit hemorrhagic disease in 1984.
The Pre-S1 and Antigenic Loop Infectivity Determinants of the Hepatitis B Virus Envelope Proteins Are Functionally Independent
Authors: Le Duff Yann , Blanchet Matthieu , Sureau Camille 
Published: September 2009

ABSTRACT

The hepatitis B virus (HBV) envelope proteins bear two determinants of viral entry: a receptor-binding site (RBS) in the pre-S1 domain of the large envelope protein and a conformation-dependent determinant, of unknown function, in the antigenic loop (AGL) of the small, middle, and large envelope proteins. Using an in vitro infection assay consisting of susceptible HepaRG cells and the hepatitis delta virus (HDV) as a surrogate of HBV, we first investigated whether subelements of the pre-S1 determinant (amino acids 2 to 75), i.e., the N-terminal myristoyl anchor, subdomain 2-48 (RBS), and subdomain 49-75, were functionally separable. In transcomplementation experiments, coexpression of two distinct infectivity-deficient pre-S1 mutants at the surface of HDV virions failed to restore infectivity, indicating that the myristoyl anchor, the 2-48 RBS, and the 49-75 sequence, likely cooperate in
cis
at viral entry. Furthermore, we showed that as much as 52% of total pre-S1 in the HDV envelope could bear infectivity-deficient lesions without affecting entry, indicating that a small number of pre-S1 polypeptides—estimated at three to four per virion—is sufficient for infectivity. We next investigated the AGL activity in the small or large envelope protein background (S- and L-AGL, respectively) and found that lesions in S-AGL were more deleterious to infectivity than in L-AGL, a difference that reflects the relative stoichiometry of the small and large envelope proteins in the viral envelope. Finally, we showed that C147S, an AGL infectivity-deficient substitution, exerted a dominant-negative effect on infectivity, likely reflecting an involvement of C147 in intermolecular disulfide bonds.
Association of the pr Peptides with Dengue Virus at Acidic pH Blocks Membrane Fusion
Authors: Yu I.-M. , Holdaway H. A. , Chipman P. R. , Kuhn R. J. , Rossmann M. G. , Chen J. 
Published: September 2009

ABSTRACT

Flavivirus assembles into an inert particle that requires proteolytic activation by furin to enable transmission to other hosts. We previously showed that immature virus undergoes a conformational change at low pH that renders it accessible to furin (I. M. Yu, W. Zhang, H. A. Holdaway, L. Li, V. A. Kostyuchenko, P. R. Chipman, R. J. Kuhn, M. G. Rossmann, and J. Chen, Science 319:1834-1837, 2008). Here we show, using cryoelectron microscopy, that the structure of immature dengue virus at pH 6.0 is essentially the same before and after the cleavage of prM. The structure shows that after cleavage, the proteolytic product pr remains associated with the virion at acidic pH, and that furin cleavage by itself does not induce any major conformational changes. We also show by liposome cofloatation experiments that pr retention prevents membrane insertion, suggesting that pr is present on the virion in the
trans
-Golgi network to protect the progeny virus from fusion within the host cell.
Interaction of ICP34.5 with Beclin 1 Modulates Herpes Simplex Virus Type 1 Pathogenesis through Control of CD4+T-Cell Responses
Authors: Leib David A. , Alexander Diane E. , Cox Douglas , Yin Jiyi , Ferguson Thomas A. 
Published: September 2009

ABSTRACTAutophagy is an important component of host innate and adaptive immunity to viruses. It is critical for the degradation of intracellular pathogens and for promoting antigen presentation. Herpes simplex virus type 1 (HSV-1) infection induces an autophagy response, but this response is antagonized by the HSV-1 neurovirulence gene product, ICP34.5. This is due, in part, to its interaction with the essential autophagy protein Beclin 1 (Atg6) via the Beclin-binding domain (BBD) of ICP34.5. Using a recombinant virus lacking the BBD, we examined pathogenesis and immune responses using mouse models of infection. The BBD-deficient virus (Δ68H) replicated equivalently to its marker-rescued counterpart (Δ68HR) at early times but was cleared more rapidly than Δ68HR from all tissues at late times following corneal infection. In addition, the infection of the cornea with Δ68H induced less ocular disease than Δ68HR. These results suggested that Δ68H was attenuated due to its failure to control adaptive rather than innate immunity. In support of this idea, Δ68H stimulated a significantly stronger CD4+T-cell-mediated delayed-type hypersensitivity response and resulted in significantly more production of gamma interferon and interleukin-2 from HSV-specific CD4+T cells than Δ68HR. Taken together, these data suggest a role for the BBD of ICP34.5 in precluding autophagy-mediated class II antigen presentation, thereby enhancing the virulence and pathogenesis of HSV-1.
Chloroquine Administration Does Not Prevent Nipah Virus Infection and Disease in Ferrets
Authors: Pallister Jackie , Middleton Deborah , Crameri Gary , Yamada Manabu , Klein Reuben , Hancock Tim J. , Foord Adam , Shiell Brian , Michalski Wojtek , Broder Christopher C. , Wang Lin-Fa 
Published: September 2009

ABSTRACT

Hendra virus and Nipah virus, two zoonotic paramyxoviruses in the genus
Henipavirus
, have recently emerged and continue to cause sporadic disease outbreaks in humans and animals. Mortality rates of up to 75% have been reported in humans, but there are presently no clinically licensed therapeutics for treating henipavirus-induced disease. A recent report indicated that chloroquine, used in malaria therapy for over 70 years, prevented infection with Nipah virus in vitro. Chloroquine was assessed using a ferret model of lethal Nipah virus infection and found to be ineffective against Nipah virus infection in vivo.
Catheter exchange technique for the Wingspan stent: technical note
Authors: Lesley W S , Rangaswamy R 
Published: September 2009

Background and purposeThe only Food and Drug Administration-approved implant for managing intracranial stenosis is the Wingspan stent. Modification of the standard Wingspan stent delivery procedure has not been previously reported.Material and methodsRetrospective, single-patient, technical report.ResultsFollowing uneventful balloon angioplasty, a symptomatic intracranial vertebral artery stenosis was inaccessible to Wingspan stent delivery using standard procedural protocol because of poor proximal guide catheter purchase. After placing a Renegade Hi-Flo microcatheter across the stenosis, the Wingspan stent was transferred to this catheter and advanced to the lesion using a Neuroform stabilizer. Unsheathing of the stent yielded uncomplicated, precise placement of the stent with a good clinical result.ConclusionThe Wingspan stent transfer technique can be used successfully in the management of intracranial stenotic disease.
從 〔社會排斥〕 到 〔社會融合〕 談中國社會福利政策的取向：
Authors: 蘇 細清 
Published: September 2009

本文通過對歐洲社會福利政策研究中社會排斥和社會融合取向的作用進行簡要的歷史回顧，並反思社會排斥為主的福利政策研究取向對中國福利政策研究的影響。通過對有關農民工社會福利制度現狀的研究文獻綜述，筆者發現，大多數的研究實際上都是取自社會排斥角度，在探討社會排斥研究模式可能在中國社會福利研究體系中可能存在的困難和不足，筆者提出重新整合社會排斥和社會融合的必要性。第一，整合社會融合的研究模式與中國政府提出的社會和諧目的相一致；第二，整合社會融合的研究模式凸顯社會資本在幫助農民工融入城市的重要作用，有利於減少社會因福利支出而增加的經濟負擔，容易為政府所接受；第三，整合社會融合的研究模式可以進一步促進福利主體間的合作，包括與政府的合作，市民社會之間的協作和融合等；第四，整合社會融合的研究模式有助於政策研究者有技巧和彈性地與政府溝通，有助於政策的落實與實現；最後，整合社會融合的研究模式有助於發展農民工在城市中的代言人，如社會工作者隊伍和 NGO 機構等。 This article begins with historical review on the roles of social exclusion and social inclusion in social welfare policy research in European area. And then critical reflect on the difficulties of social-exclusion-focused research model which domains the Chinese social welfare policy area. Basing on the literature review, through discussing on the current difficulties and insufficiencies of peasant workers' social welfare in China, the integrated model which should view social inclusion and social exclusion as one whole to be social welfare policy research model was proposed to meet the ultimate goal of social welfare policy. The importance of the integrated model was also discussed in the article as: First, integrating social inclusion perspective is consistent with the social harmony tenet which is highlighted by government; Second, integrating social inclusion perspective pays more attention on the functions of social capitals which may play an important role in facilitating peasant workers to adapt to urban cities, at the same time, social capitals may reduce the social welfare economic burden which can be easily accepted by government and facilitate the collaboration with government. Third, integrating social inclusion into social welfare policy research may facilitate the collaboration with government and reduce the tension between urban and rural. Forth, under the integrated model, social welfare policy researches may communicate with government flexibly and get more government support to make the policy realized; and finally, the agencies who can stand for the voices of peasant workers, such as social work team, NGO institutions can be developed rapidly.
On Estimating Hurricane Return Periods
Authors: Emanuel Kerry , Jagger Thomas 
Published: September 2009

Abstract
Interest in hurricane risk usually focuses on landfalling events of the highest intensity, which cause a disproportionate amount of hurricane-related damage. Yet assessing the long-term risk of the most intense landfalling events is problematic because there are comparatively few of them in the historical record. For this reason, return periods of the most intense storms are usually estimated by first fitting standard probability distribution functions to records of lower-intensity events and then using such fits to estimate the high-intensity tails of the distributions. Here the authors attempt a modest improvement over this technique by making use of the much larger set of open-ocean hurricane records and postulating that hurricanes make landfall during a random stage of their open-ocean lifetime. After testing the validity of this assumption, an expression is derived for the probability density of maximum winds. The probability functions so derived are then used to estimate hurricane return periods for several highly populated regions, and these are compared with return periods calculated both from historical data and from a set of synthetic storms generated using a recently published downscaling technique. The resulting return-period distributions compare well to those estimated from extreme-value theory with parameter fitting using a peaks-over-threshold model, but they are valid over the whole range of hurricane wind speeds.
Elevated levels of serum antibodies against Saccharomyces cerevisiae mannan in patients with systemic lupus erythematosus
Authors: Dai H , Li Z , Zhang Y , Lv P , Gao XM 
Published: September 2009

This study was undertaken to investigate whether levels of anti- Saccharomyces cerevisiae mannan antibodies (ASCMAs), a serological marker for Crohn’s disease, seronegative spondyloarthritis and Behcet’s disease, also correlate with systemic lupus erythematosus (SLE) in humans. Serum samples from healthy volunteers ( n = 152) and patients with SLE ( n = 40) were compared for ASCMA-IgA, -IgG and -IgM levels using enzyme linked immunosorbent assays. ASCMA-IgG, but not IgM and IgA, prevalence was significantly raised in active SLE patients (57.5%) compared with healthy controls (8.5%). ASCMA-IgG levels in SLE patients during remission were relatively lower, indicating a possible correlation with disease activity. These results differ from a previous study, which did not detect a difference between ASCMA levels in SLE patients and healthy control. It remains to be evaluated whether elevated ASCMA-levels are common to all rheumatic disorders.
Metabolic syndrome in Argentinean patients with systemic lupus erythematosus
Authors: Bellomio V , Spindler A , Lucero E , Berman A , Sueldo R , Berman H , Santana M , Molina MJ , Góngora V , Cassano G , Paira S , Saurit V , Retamozo G , Alvarellos A , Caerio F , Alba P , Gotero M , Velozo EJ , Ceballos F , Soriano E , Catoggio L , García MA , Eimon A , Agüero S ,   SLE Study Group of the Argentinean Society of Rheumatology
Published: September 2009

The objective was to determine the prevalence of the metabolic syndrome (MS) in patients with systemic lupus erythematosus (SLE) in Argentina, to assess the factors associated to it, and to compare the results with a control group with non-inflammatory disorders. The study included 147 patients with SLE and 119 controls. MS was defined according to criteria by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) Scientific Statement. Demographic characteristics, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) were assessed as well as administration, maximum dose and cumulative dose of prednisone and hydroxychloroquine (HCQ). MS prevalence was 28.6% (CI 95%: 21.4–36.6) in patients with SLE and 16% in controls ( P = 0.0019). Patients with SLE presented higher arterial hypertension frequency compared with controls (43 vs 25%, P = 0.007). When comparing lupus patients with MS ( n = 41) and without MS ( n = 106), no significant differences were observed regarding duration of the disease, SLEDAI or cumulative prednisone dose. Cumulative damage was associated independently with MS (OR 1.98; P = 0.021), whereas HCQ use was found to be protective (OR 0.13; P = 0.015). Patients with lupus presented higher MS prevalence than controls with non-inflammatory disorders, and occurrence of arterial hypertension was also higher. MS was associated with cumulative damage; the use of HCQ showed to be protective against presence of MS.
Renal cell apoptosis in human lupus nephritis: a histological study
Authors: Faurschou M , Penkowa M , Andersen CB , Starklint H , Jacobsen S 
Published: September 2009

Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any of the control or nephritis biopsies. Scarce apoptotic tubular cells were seen in 13 of 35 (37%) of the nephritis specimens and in two of five (40%) of the control sections. Within the SLE cohort, patients with TUNEL-positive tubular cells in their renal biopsies had significantly higher activity index scores for tubulointerstitial mononuclear cell infiltration than patients without apoptotic tubular cells in their biopsies ( P = 0.01). Furthermore, the level of tubular cell apoptosis displayed a statistically significant, positive correlation with the activity index score for mononuclear cell infiltration (rs = 0.472, P = 0.004) but not with scores for other activity or chronicity index components. These observations indicate that the degree of tubular cell apoptosis correlates with the severity of tubulointerstitial inflammation in SLE-associated nephritis. However, our findings do not suggest that apoptotic renal cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis.