bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Early Protective Thymus-Independent Antibody Response to Foot-and-Mouth Disease Virus Is Mediated by Splenic CD9+B Lymphocytes
Authors: Ostrowski Matias , Vermeulen Monica , Zabal Osvaldo , Zamorano Patricia I. , Sadir Ana M. , Geffner Jorge R. , Lopez Osvaldo J. 
Published: June 2007

ABSTRACTInfection of mice with cytopathic foot-and-mouth disease virus (FMDV) induces a rapid and specific thymus-independent (TI) neutralizing antibody response that promptly clears the virus. Herein, it is shown that FMDV-infected dendritic cells (DCs) directly stimulate splenic innate-like CD9+B lymphocytes to rapidly (3 days) produce neutralizing anti-FMDV immunoglobulin M antibodies without T-lymphocyte collaboration. In contrast, neither follicular (CD9−) B lymphocytes from the spleen nor B lymphocytes from lymph nodes efficiently respond to stimulation with FMDV-infected DCs. The production of these protective neutralizing antibodies is dependent on DC-derived interleukin-6 (IL-6) and on CD9+cell-derived IL-10 secretion. In comparison, DCs loaded with UV-inactivated FMDV are significantly less efficient in directly stimulating B lymphocytes to secrete TI antibodies. A critical role of the spleen in the early production of anti-FMDV antibodies in infected mice was also demonstrated in vivo. Indeed, either splenectomy or functional disruption of the marginal zone of the spleen delays and reduces the magnitude of the TI anti-FMDV antibody response in infected mice. Together, these results indicate that in addition to virus localization, the FMDV-mediated modulation of DC functionality is a key parameter that collaborates in the induction of a rapid and protective TI antibody response against this virus.
Downregulation of Class I Major Histocompatibility Complex Surface Expression by Varicella-Zoster Virus Involves Open Reading Frame 66 Protein Kinase-Dependent and -Independent Mechanisms
Authors: Eisfeld Amie J. , Yee Michael B. , Erazo Angela , Abendroth Allison , Kinchington Paul R. 
Published: June 2007

ABSTRACTWe show here that the varicella-zoster virus (VZV) open reading frame 66 (ORF66) protein kinase is one mechanism employed to reduce class I major histocompatibility complex (MHC-I) surface expression in VZV-infected cells. Cells expressing enhanced green fluorescent protein-tagged functional and inactivated ORF66 (GFP-66 and GFP-66kd) from replication-defective adenovirus vectors revealed that ORF66 reduced MHC-I surface levels in a manner dependent on kinase activity. Cells infected with recombinant VZV expressing GFP-66 exhibited a significantly greater reduction in MHC-I surface expression than that observed in cells infected with VZV disrupted in GFP-66 expression. MHC-I maturation was delayed in its transport from the endoplasmic reticulum through the Golgi in both adenovirus-transduced cells expressing only GFP-66 and in VZV-infected cells expressing high levels of GFP-66, and this was predominantly kinase dependent. MHC-I levels were reduced in VZV-infected cells, and analyses of intracellular MHC-I revealed accumulation of folded MHC-I in the Golgi region, irrespective of ORF66 expression. Thus, the ORF66 kinase is important for VZV-mediated MHC-I downregulation, but additional mechanisms also may be involved. Analyses of the VZV ORF9a protein, the ortholog of the bovine herpesvirus 1 transporter associated with antigen processing inhibitor UL49.5 revealed no effects on MHC-I. These results establish a new role for viral protein kinases in immune evasion and suggest that VZV utilizes unique mechanisms to inhibit antigen presentation.
Heterosubtypic Immunity to Influenza A Virus Infection Requires a Properly Diversified Antibody Repertoire
Authors: Nguyen Huan H. , Zemlin Michael , Ivanov Ivaylo I. , Andrasi Judit , Zemlin Cosima , Vu Huong L. , Schelonka Robert , Schroeder Harry W. , Mestecky Jiri 
Published: June 2007

ABSTRACTHeterosubtypic immunity (HSI) is defined as cross-protection to infection with an influenza A virus serotype other than the one used for primary infection. Although HSI has been thought to be mediated by serotype cross-reactive cytotoxic T lymphocytes (CTL) that recognize conserved epitopes of structural proteins, recent studies suggest that antibodies (Abs) may make a significant contribution. In this study, we provide further evidence for the role of Abs in HSI using transgenic mice lacking terminal deoxyribonucleotidyltransferase (TdT), which adds N nucleotides to V-D and D-J junctions of the complementary determining region 3 (CDR3) (TdT−/−) and mice with altered Ab repertoires due to replacement of the complete locus of heavy chain diversity segments (DH) with an altered DHsegment (namely, ΔD-iD). Both types of mice failed to generate complete HSI, although they were able to mount protective immunity to a homologous challenge. Lower levels of virus-specific antibodies along with more severely impaired HSI were observed in TdT−/−mice compared to those in ΔD-iD mice, while CTL activity remained unchanged in both types of mice. These findings indicate that a properly diversified antibody repertoire is required for HSI and that N addition by TdT is a more effective mechanism in the induction of a properly diversified antibody repertoire and, therefore, complete HSI. The results suggest that the diversity of the antibody repertoire as determined by the composition of the D region of HCDR3 and by N addition are among the mechanisms selected for in evolution to create a favorable environment to resolve infections with mutated viruses.
Activation of Cellular Arf GTPases by Poliovirus Protein 3CD Correlates with Virus Replication
Authors: Belov George A. , Habbersett Courtney , Franco David , Ehrenfeld Ellie 
Published: June 2007

ABSTRACT
We have previously shown that synthesis of poliovirus protein 3CD in uninfected HeLa cell extracts induces an increased association with membranes of the cellular Arf GTPases, which are key players in cellular membrane traffic. Arfs cycle between an inactive, cytoplasmic, GDP-bound form and an active, membrane-associated, GTP-bound form. 3CD promotes binding of Arf to membranes by initiating recruitment to membranes of guanine nucleotide exchange factors (GEFs), BIG1 and BIG2. GEFs activate Arf by replacing GDP with GTP. In poliovirus-infected cells, there is a dramatic redistribution of cellular Arf pools that coincides with the reorganization of membranes used to form viral RNA replication complexes. Here we demonstrate that Arf translocation in vitro can be induced by purified recombinant 3CD protein; thus, concurrent translation of viral RNA is not required. Coexpression of 3C and 3D proteins was not sufficient to target Arf to membranes. 3CD expressed in HeLa cells was retained after treatment of the cells with digitonin, indicating that it may interact with a membrane-bound host factor. A F441S mutant of 3CD was shown previously to have lost Arf translocation activity and was also defective in attracting the corresponding GEFs to membranes. A series of other mutations were introduced at 3CD residue F441. Mutations that retained Arf translocation activity of 3CD also supported efficient growth of virus, regardless of their effects on 3D polymerase elongation activity. Those that abrogated Arf activation by 3CD generated quasi-infectious RNAs that produced some plaques from which revertants that always restored the Arf activation property of 3CD were rescued.
Functionally Distinct Transmission of Human Immunodeficiency Virus Type 1 Mediated by Immature and Mature Dendritic Cells
Authors: Wang Jian-Hua , Janas Alicia M. , Olson Wendy J. , Wu Li 
Published: June 2007

ABSTRACTDendritic cells (DCs) potently stimulate the transmission of human immunodeficiency virus type 1 (HIV-1) to CD4+T cells. Immature DCs (iDCs) located in submucosal tissues can capture HIV-1 and migrate to lymphoid tissues, where they become mature DCs (mDCs) for effective antigen presentation. DC maturation promotes HIV-1 transmission; however, the underlying mechanisms remain unclear. Here we have compared monocyte-derived iDCs and mDCs for their efficiencies and mechanisms of HIV-1 transmission. We have found that mDCs significantly facilitate HIV-1 endocytosis and efficiently concentrate HIV-1 at virological synapses, which contributes to mDC-enhanced viral transmission, at least in part. mDCs were more efficient than iDCs in transferring HIV-1 to various types of target cells independently of C-type lectins, which partially accounted for iDC-mediated HIV-1 transmission. Efficient HIV-1trans-infection mediated by iDCs and mDCs required contact between DCs and target cells. Moreover, rapid HIV-1 degradation occurred in both iDCs and mDCs, which correlated with the lack of HIV-1 retention-mediated long-term viral transmission. Our results provide new insights into the mechanisms underlying DC-mediated HIV-1 transmission, suggesting that HIV-1 exploits mDCs to facilitate its dissemination within lymphoid tissues.
Fusion Promotion by a Paramyxovirus Hemagglutinin-Neuraminidase Protein: pH Modulation of Receptor Avidity of Binding Sites I and II
Authors: Palermo Laura M. , Porotto Matteo , Greengard Olga , Moscona Anne 
Published: June 2007

ABSTRACT
Paramyxoviruses, including the childhood respiratory pathogen human parainfluenza virus type 3 (HPIV3), possess an envelope protein hemagglutinin-neuraminidase (HN) that has receptor-cleaving (neuraminidase), as well as receptor-binding, activity. HN is a type II transmembrane glycoprotein, present on the surface of the virus as a tetramer composed of two dimers. HN is also essential for activating the fusion protein (F) to mediate merger of the viral envelope with the host cell membrane. This initial step of viral entry occurs at the host cell surface at neutral pH. The HN molecule carries out these three different critical activities at specific points in the process of viral entry, and understanding the regulation of these activities is key for the design of strategies that block infection. One bifunctional site (site I) on the HN of HPIV3 possesses both receptor binding and neuraminidase activities, and we recently obtained experimental evidence for a second receptor binding site (site II) on HPIV3 HN. Mutation of HN at specific residues at this site, which is next to the HN dimer interface, confers enhanced fusion properties, without affecting neuraminidase activity or receptor binding at neutral pH. We now demonstrate that mutations at this site II, as well as at site I, confer pH dependence on HN′s receptor avidity. These mutations permit pH to modulate the binding and fusion processes of the virus, potentially providing regulation at specific stages of the viral life cycle.
Ebola Virus VP30 Is an RNA Binding Protein
Authors: John Sinu P. , Wang Tan , Steffen Scott , Longhi Sonia , Schmaljohn Connie S. , Jonsson Colleen B. 
Published: June 2007

ABSTRACT

The Ebola virus (EBOV) genome encodes for several proteins that are necessary and sufficient for replication and transcription of the viral RNAs in vitro; NP, VP30, VP35, and L. VP30 acts in
trans
with an RNA secondary structure upstream of the first transcriptional start site to modulate transcription. Using a bioinformatics approach, we identified a region within the N terminus of VP30 with sequence features that typify intrinsically disordered regions and a putative RNA binding site. To experimentally assess the ability of VP30 to directly interact with the viral RNA, we purified recombinant EBOV VP30 to >90% homogeneity and assessed RNA binding by UV cross-linking and filter-binding assays. VP30 is a strongly acidophilic protein; RNA binding became stronger as pH was decreased. Zn
2+
, but not Mg
2+
, enhanced activity. Enhancement of transcription by VP30 requires a RNA stem-loop located within nucleotides 54 to 80 of the leader region. VP30 showed low binding affinity to the predicted stem-loop alone or to double-stranded RNA but showed a good binding affinity for the stem-loop when placed in the context of upstream and downstream sequences. To map the region responsible for interacting with RNA, we constructed, purified, and assayed a series of N-terminal deletion mutations of VP30 for RNA binding. The key amino acids supporting RNA binding activity map to residues 26 to 40, a region rich in arginine. Thus, we show for the first time the direct interaction of EBOV VP30 with RNA and the importance of the N-terminal region for binding RNA.
An Attenuated Strain of Enterovirus 71 Belonging to Genotype A Showed a Broad Spectrum of Antigenicity with Attenuated Neurovirulence in Cynomolgus Monkeys
Authors: Arita Minetaro , Nagata Noriyo , Iwata Naoko , Ami Yasushi , Suzaki Yuriko , Mizuta Katsumi , Iwasaki Takuya , Sata Tetsutaro , Wakita Takaji , Shimizu Hiroyuki 
Published: June 2007

ABSTRACT
Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also sometimes associated with serious neurological disorders. In this study, we characterized the antigenicity and tissue specificity of an attenuated strain of EV71 [EV71(S1-3′)], which belongs to genotype A, in a monkey infection model. Three cynomolgus monkeys were inoculated with EV71(S1-3′), followed by lethal challenge with the parental virulent strain EV71(BrCr-TR) via an intravenous route on day 45 postinoculation of EV71(S1-3′). Monkeys inoculated with EV71(S1-3′) showed a mild neurological symptom (tremor) but survived lethal challenge by virulent EV71(BrCr-TR) without exacerbation of the symptom. The immunized monkey sera showed a broad spectrum of neutralizing activity against different genotypes of EV71, including genotypes A, B1, B4, C2, and C4. For the strains examined, the sera showed the highest neutralization activity against the homotype (genotype A) and the lowest neutralization activity against genotype C2. The order of decreasing neutralization activity of sera was as follows: A > B1 > C4 > B4 > C2. To examine the tissue specificity of EV71(S1-3′), two monkeys were intravenously inoculated with EV71(S1-3′), followed by examination of virus distribution in the central nervous system (CNS) and extraneural tissues. In the CNS, EV71(S1-3′) was isolated only from the spinal cord. These results indicate that EV71(S1-3′) acts as an effective antigen, although this attenuated strain was still neurotropic when inoculated via the intravenous route.
Injuries on offshore cruising sailboats: analysis for means of prevention
Authors: Rouvillain J-L , Mercky F , Lethuillier D 
Published: June 2007

Objective:No studies have been performed on cruising sailors who spend most of the year on offshore cruising sailboats. To gain a better understanding of this population, traumatic events occurring in this group of sailors were studied to define appropriate means of prevention.Design, setting and patients:Primary care data were collected prospectively using a questionnaire during in-depth interviews by one of the authors (FM) of 100 cruising sailboat crews that called at Martinique between December 2001 and May 2002.Main outcome measurements:In total, 56 injuries were reported: 20 involved the upper limb, 20 the lower limb, and 7 the head and neck. There were also 19 burns, 11 of which were photoinduced and 8 accidental. There were 16 skin infections, 3 of which were complicated by arthritis.Results:After analysis, we found that most of these injuries could be prevented if the following recommendations were applied. Wearing shoes would avoid foot injuries. A hatch cover would effectively protect from cranial trauma caused by the boom. To protect from the sun, a bimini top (cover to shield the cockpit) would be most effective. A windlass would avoid hand injuries and acute lower back pain. Lastly, meticulous wound care until complete healing would prevent the common complications of skin superinfections.Conclusions:Injuries to professional seafarers and ocean racers are well described, but the increasingly growing cruising sailor population has not been well studied. Development of easy and inexpensive worldwide network connection will allow better follow-up of this mobile population.
Experiences of Australian professional female tennis players returning to competition from injury
Authors: Young Janet A , Pain Michelle D , Pearce Alan J 
Published: June 2007

Background:This study examined the experiences of professional female tennis players returning to competition from injury.Methods:In a study commissioned by Tennis Australia, 55 Australian professional female tennis players responded anonymously to a questionnaire developed for the purposes of this study. The questionnaire consisted of open and closed questions that assessed a player’s attribution style, the occurrence and effect of minor and major injuries, frequency and type of treatment sought, attitudinal chances following injury and preventative injury factors.Results:The quantitative and qualitative analyses of participants’ responses revealed players generally displayed an internal attribution style with the majority of minor injuries involving lower limb injuries (attributed to playing on hard surfaces). Players reported these injuries were addressed in a variety of ways including self-treatment. The majority of severe injuries were upper limb/shoulder and these were generally treated at tournament sites with some requiring surgery.Conclusions:Players adopted a range of measures to assist recovery from severe injury including the services of health professionals. In further findings, a player’s attribution style was not a predictive variable, except in terms of the number of tournaments missed for minor injuries. Implications of the study’s results and future research directions for cross-cultural studies are highlighted.
Effects of the playing surface on plantar pressures and potential injuries in tennis
Authors: Girard O , Eicher F , Fourchet F , Micallef J P , Millet G P 
Published: June 2007

Objectives:To examine the influence of different playing surfaces on in-shoe loading patterns during tennis-specific movements.Methods:Ten experienced male players performed two types of tennis-specific displacements (serve and volley (SV) and baseline play (BA)) on two different playing surfaces; eg, clay vs Greenset. Maximum and mean force and pressure, contact time, contact area and relative load were recorded by an insole with 99 sensors (X-Pedar system) divided into 9 areas.Results:Regarding the whole foot, mean (SD) force (SV: 615 (91) vs 724 (151) N; −12.4%, p<0.05 and BA: 614 (73) vs 717 (133) N; −11.6%, p<0.05) was lower on clay than on Greenset, whereas contact time was longer (SV: 299 (113) vs 270 (148) ms; +16.5%, NS and BA: 354 (72) vs 272 (60) ms; +30.3%, p<0.001). Greenset induced higher loading in the hallux (SV: +15.3%, p<0.05 and BA: +11.4%, not significant) and lesser toes areas (SV: +12.6%, p<0.05 and BA: +18.0%, p<0.01). In contrast, the relative load on the medial (SV: +27.4%, p<0.05 and BA: +16.1%, p = 0.06) and lateral midfoot (SV: +23.3%, p<0.05 and BA: +28.3%, p<0.01) was higher on clay.Conclusions:This study demonstrates that playing surface affects plantar loading in tennis: Greenset induced higher loading in the hallux (SV: +15.3%, p<0.05 and BA: +11.4%, NS) and lesser toes areas (SV: +12.6%, p<0.05 and BA: +18.0%, p<0.01) but lower relative load on the medial (SV: −27.4%, p<0.05 and BA: −16.1%, p = 0.06) and lateral midfoot (SV: −23.3%, p<0.05 and BA: −28.3%, p<0.01) than clay.
Association of rear seat safety belt use with death in a traffic crash: a matched cohort study
Authors: Zhu Motao , Cummings Peter , Chu Haitao , Cook Lawrence J 
Published: June 2007

Objective:To estimate the association of rear seat safety belt use with death in a traffic crash.Design:Matched cohort study.Setting:The US during 2000 through 2004.Subjects:Drivers (10 427) and rear seat passengers (15 922) in passenger vehicles that crashed and had at least one driver or rear passenger death. Data from the Fatality Analysis Reporting System.Main outcome measures:The adjusted relative risk (aRR) of death for a belted rear seat passenger compared with an otherwise similar unbelted rear passenger.Results:Safety belt use was associated with a reduced risk of death for rear car occupants: outboard rear seat aRR 0.42 (95% CI 0.38 to 0.46), and center rear seat aRR 0.30 (95% CI 0.20 to 0.44). For rear occupants of light trucks, vans, and utility vehicles, the estimates were: outboard aRR 0.25 (95% CI 0.21 to 0.29), center aRR 0.34 (95% CI 0.24 to 0.48).Conclusions:If the authors’ estimates are causal, traffic crash mortality can be reduced for rear occupants by approximately 55–75% if they use safety belts.
Risk factors for childhood drowning in rural regions of a developing country: a case–control study
Authors: Yang Li , Nong Quan-Qing , Li Chun-Ling , Feng Qi-Ming , Lo Sing Kai 
Published: June 2007

Background:Descriptive epidemiological studies have shown that childhood drowning rates are higher in developing countries, with an increasing trend in rural areas.Aim:To examine risk factors associated with childhood drowning in rural China.Methods:Participants included parents of all children aged 1–14 years who died of drowning between 2002 and 2004 in 20 districts in GuangXi Province, and two age- and gender-matched controls each. Behavioral characteristics of the child and the children’s caregivers were collected using a questionnaire and analyzed using logistic regression.Results:Boys (60%) and children aged 1–4 years (48%) were over-represented among the cases; 62% occurred within 500 m of the school or home. Protective fencing or warning signs were found at only two sites. None of the children’s caregivers knew how to perform cardiopulmonary resuscitation. For children aged 1–4 years significant risk factors included poor health of the caregiver (OR 3.1; 95% CI 1.9 to 5.8), not using flotation devices (OR 2.3; 95% CI 1.4 to 4.5) and no proper swimming lessons (OR 1.8; 95% CI 1.1 to 5.5). For children aged 5–14 years, the main risk factors were that the child did not have the experience of playing near or in water regularly (OR 2.7; 95% CI 1.8 to 7.4) and lack of close supervision (OR 1.9; 95% CI 1.3 to 5.6).Conclusion:Risk factors identified in this study suggest that childhood drowning in rural areas in developing countries could be prevented by providing safety educational programs, which should focus on constant adult supervision and the use of flotation devices when children play in and near water.