bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding Interactions between the Encephalomyocarditis Virus Leader and Protein 2A
Authors: Petty Ryan V. , Basta Holly A. , Bacot-Davis Valjean R. , Brown Bradley A. , Palmenberg Ann C. 
Published: September 2014

ABSTRACT

The leader (L) and 2A proteins of cardioviruses are the primary antihost agents produced during infection. For encephalomyocarditis virus (EMCV), the prototype of the genus
Cardiovirus
, these proteins interact independently with key cellular partners to bring about inhibition of active nucleocytoplasmic trafficking and cap-dependent translation, respectively. L and 2A also bind each other and require this cooperation to achieve their effects during infection. Recombinant L and 2A interact with 1:1 stoichiometry at a

K
D

(equilibrium dissociation constant) of 1.5 μM. The mapped contact domains include the amino-proximal third of 2A (first 50 amino acids) and the central hinge region of L. This contact partially overlaps the L segment that makes subsequent contact with Ran GTPase in the nucleus, and Ran can displace 2A from L. The equivalent proteins from Theiler's murine encephalomyelitis virus (TMEV; BeAn) and Saffold virus interact similarly in any subtype combination, with various affinities. The data suggest a mechanism whereby L takes advantage of the nuclear localization signal in the COOH region of 2A to enhance its trafficking to the nucleus. Once there, it exchanges partners in favor of Ran. This required cooperation during infection explains many observed codependent phenotypes of L and 2A mutations.

IMPORTANCE
Cardiovirus pathogenesis phenotypes vary dramatically, from asymptomatic, to mild gastrointestinal (GI) distress, to persistent demyelination and even encephalitic death. Leader and 2A are the primary viral determinants of pathogenesis, so understanding how these proteins cooperate to induce such a wide variety of outcomes for the host is of great important and interest to the field of virology, especially to those who use TMEV as a murine model for multiple sclerosis.
Specific Cells in the Primary Salivary Glands of the Whitefly Bemisia tabaci Control Retention and Transmission of Begomoviruses
Authors: Wei Jing , Zhao Juan-Juan , Zhang Tong , Li Fang-Fang , Ghanim Murad , Zhou Xue-Ping , Ye Gong-Yin , Liu Shu-Sheng , Wang Xiao-Wei 
Published: September 2014

ABSTRACT

The majority of plant viruses are vectored by arthropods via persistent-circulative or noncirculative transmission. Previous studies have shown that specific binding sites for noncirculative viruses reside within the stylet or foregut of insect vectors, whereas the transmission mechanisms of circulative viruses remain ambiguous. Here we report the critical roles of whitefly primary salivary glands (PSGs) in the circulative transmission of two begomoviruses. The Middle East Asia Minor 1 (MEAM1) species of the whitefly
Bemisia tabaci
complex efficiently transmits both
Tomato yellow leaf curl China virus
(TYLCCNV) and
Tomato yellow leaf curl virus
(TYLCV), whereas the Mediterranean (MED) species transmits TYLCV but not TYLCCNV. PCR and fluorescence
in situ
hybridization experiments showed that TYLCCNV efficiently penetrates the PSGs of MEAM1 but not MED whiteflies. When a fragment of the coat protein of TYLCCNV was exchanged with that of TYLCV, mutated TYLCCNV accumulated in the PSGs of MED whiteflies, while mutant TYLCV was nearly undetectable. Confocal microscopy revealed that virion transport in PSGs follows specific paths to reach secretory cells in the central region, and the accumulation of virions in the secretory region of PSGs was correlated with successful virus transmission. Our findings demonstrate that whitefly PSGs, in particular the cells around the secretory region, control the specificity of begomovirus transmission.

IMPORTANCE
Over 75% of plant viruses are transmitted by insects. However, the mechanisms of virus transmission by insect vectors remain largely unknown. Begomoviruses and whiteflies are a complex of viruses and vectors which threaten many crops worldwide. We investigated the transmission of two begomoviruses by two whitefly species. We show that specific cells of the whitefly primary salivary glands control viral transmission specificity and that virion transport in the glands follows specific paths to reach secretory cells in the central region and then to reach the salivary duct. Our results indicate that the secretory cells in the central region of primary salivary glands determine the recognition and transmission of begomoviruses. These findings set a foundation for future research not only on circulative plant virus transmission but also on other human and animal viruses transmitted by arthropod vectors.
Hallmarks of Hepatitis C Virus in Equine Hepacivirus
Authors: Tanaka Tomohisa , Kasai Hirotake , Yamashita Atsuya , Okuyama-Dobashi Kaori , Yasumoto Jun , Maekawa Shinya , Enomoto Nobuyuki , Okamoto Toru , Matsuura Yoshiharu , Morimatsu Masami , Manabe Noboru , Ochiai Kazuhiko , Yamashita Kazuto , Moriishi Kohji 
Published: September 2014

ABSTRACT

Equine hepacivirus (EHcV) has been identified as a closely related homologue of hepatitis C virus (HCV) in the United States, the United Kingdom, and Germany, but not in Asian countries. In this study, we genetically and serologically screened 31 serum samples obtained from Japanese-born domestic horses for EHcV infection and subsequently identified 11 PCR-positive and 7 seropositive serum samples. We determined the full sequence of the EHcV genome, including the 3′ untranslated region (UTR), which had previously not been completely revealed. The polyprotein of a Japanese EHcV strain showed approximately 95% homology to those of the reported strains. HCV-like
cis
-acting RNA elements, including the stem-loop structures of the 3′ UTR and kissing-loop interaction were deduced from regions around both UTRs of the EHcV genome. A comparison of the EHcV and HCV core proteins revealed that Ile
190
and Phe
191
of the EHcV core protein could be important for cleavage of the core protein by signal peptide peptidase (SPP) and were replaced with Ala and Leu, respectively, which inhibited intramembrane cleavage of the EHcV core protein. The loss-of-function mutant of SPP abrogated intramembrane cleavage of the EHcV core protein and bound EHcV core protein, suggesting that the EHcV core protein may be cleaved by SPP to become a mature form. The wild-type EHcV core protein, but not the SPP-resistant mutant, was localized on lipid droplets and partially on the lipid raft-like membrane in a manner similar to that of the HCV core protein. These results suggest that EHcV may conserve the genetic and biological properties of HCV.

IMPORTANCE
EHcV, which shows the highest amino acid or nucleotide homology to HCV among hepaciviruses, was previously reported to infect horses from Western, but not Asian, countries. We herein report EHcV infection in Japanese-born horses. In this study, HCV-like RNA secondary structures around both UTRs were predicted by determining the whole-genome sequence of EHcV. Our results also suggest that the EHcV core protein is cleaved by SPP to become a mature form and then is localized on lipid droplets and partially on lipid raft-like membranes in a manner similar to that of the HCV core protein. Hence, EHcV was identified as a closely related homologue of HCV based on its genetic structure as well as its biological properties. A clearer understanding of the epidemiology, genetic structure, and infection mechanism of EHcV will assist in elucidating the evolution of hepaciviruses as well as the development of surrogate models for the study of HCV.
HBZ Stimulates Brain-Derived Neurotrophic Factor/TrkB Autocrine/Paracrine Signaling To Promote Survival of Human T-Cell Leukemia Virus Type 1-Infected T Cells
Authors: Polakowski Nicholas , Terol Marie , Hoang Kimson , Nash Isabelle , Laverdure Sylvain , Gazon Hélène , Belrose Gilda , Mesnard Jean-Michel , Césaire Raymond , Péloponèse Jean-Marie , Lemasson Isabelle 
Published: September 2014

ABSTRACTBrain-derived neurotrophic factor (BDNF) is a neurotrophin that promotes neuronal proliferation, survival, and plasticity. These effects occur through autocrine and paracrine signaling events initiated by interactions between secreted BDNF and its high-affinity receptor, TrkB. A BDNF/TrkB autocrine/paracrine signaling loop has additionally been implicated in augmenting the survival of cells representing several human cancers and is associated with poor patient prognosis. Adult T-cell leukemia (ATL) is a fatal malignancy caused by infection with the complex retrovirus human T-cell leukemia virus type 1 (HTLV-1). In this study, we found that the HTLV-1-encoded protein HBZ activates expression of BDNF, and consistent with this effect, BDNF expression is elevated in HTLV-1-infected T-cell lines compared to uninfected T cells. Expression of TrkB is also higher in HTLV-1-infected T-cell lines than in uninfected T cells. Furthermore, levels of both BDNF and TrkB mRNAs are elevated in peripheral blood mononuclear cells (PBMCs) from ATL patients, and ATL patient sera contain higher concentrations of BDNF than sera from noninfected individuals. Finally, chemical inhibition of TrkB signaling increases apoptosis in HTLV-1-infected T cells and reduces phosphorylation of glycogen synthase kinase 3β (GSK-3β), a downstream target in the signaling pathway. These results suggest that HBZ contributes to an active BDNF/TrkB autocrine/paracrine signaling loop in HTLV-1-infected T cells that enhances the survival of these cells.IMPORTANCEInfection with human T-cell leukemia virus type 1 (HTLV-1) can cause a rare form of leukemia designated adult T-cell leukemia (ATL). Because ATL patients are unresponsive to chemotherapy, this malignancy is fatal. As a retrovirus, HTLV-1 integrates its genome into a host cell chromosome in order to utilize host factors for replication and expression of viral proteins. However, in infected cells from ATL patients, the viral genome is frequently modified to block expression of all but a single viral protein. This protein, known as HBZ, is therefore believed to modulate cellular pathways necessary for the leukemic state and the chemotherapeutic resistance of the cell. Here we provide evidence to support this hypothesis. We found that HBZ promotes a BDNF/TrkB autocrine/paracrine signaling pathway that is known to enhance the survival and chemotherapeutic resistance of other types of cancer cells. It is possible that inhibition of this pathway may improve treatments for ATL.
Characterization of a Broadly Neutralizing Monoclonal Antibody That Targets the Fusion Domain of Group 2 Influenza A Virus Hemagglutinin
Authors: Tan Gene S. , Lee Peter S. , Hoffman Ryan M. B. , Mazel-Sanchez Beryl , Krammer Florian , Leon Paul E. , Ward Andrew B. , Wilson Ian A. , Palese Peter 
Published: September 2014

ABSTRACT

Due to continuous changes to its antigenic regions, influenza viruses can evade immune detection and cause a significant amount of morbidity and mortality around the world. Influenza vaccinations can protect against disease but must be annually reformulated to match the current circulating strains. In the development of a broad-spectrum influenza vaccine, the elucidation of conserved epitopes is paramount. To this end, we designed an immunization strategy in mice to boost the humoral response against conserved regions of the hemagglutinin (HA) glycoprotein. Of note, generation and identification of broadly neutralizing antibodies that target group 2 HAs are rare and thus far have yielded only a few monoclonal antibodies (MAbs). Here, we demonstrate that mouse MAb 9H10 has broad and potent
in vitro
neutralizing activity against H3 and H10 group 2 influenza A subtypes. In the mouse model, MAb 9H10 protects mice against two divergent mouse-adapted H3N2 strains, in both pre- and postexposure administration regimens.
In vitro
and cell-free assays suggest that MAb 9H10 inhibits viral replication by blocking HA-dependent fusion of the viral and endosomal membranes early in the replication cycle and by disrupting viral particle egress in the late stage of infection. Interestingly, electron microscopy reconstructions of MAb 9H10 bound to the HA reveal that it binds a similar binding footprint to MAbs CR8020 and CR8043.

IMPORTANCE
The influenza hemagglutinin is the major antigenic target of the humoral immune response. However, due to continuous antigenic changes that occur on the surface of this glycoprotein, influenza viruses can escape the immune system and cause significant disease to the host. Toward the development of broad-spectrum therapeutics and vaccines against influenza virus, elucidation of conserved regions of influenza viruses is crucial. Thus, defining these types of epitopes through the generation and characterization of broadly neutralizing monoclonal antibodies (MAbs) can greatly assist others in highlighting conserved regions of hemagglutinin. Here, we demonstrate that MAb 9H10 that targets the hemagglutinin stalk has broadly neutralizing activity against group 2 influenza A viruses
in vitro
and
in vivo
.
Variation in access to community rehabilitation services and length of stay in hospital following a hip fracture: a cross-sectional study
Authors: Neuburger Jenny , Harding Karen A , Bradley Rachel J D , Cromwell David A , Gregson Celia L 
Published: September 2014

ObjectivesTo assess variation in access to and use of community rehabilitation services for patients with a hip fracture, and whether this affects length of stay in hospital.DesignCross-sectional study using administrative patient-level data from Hospital Episode Statistics (HES) and organisational survey data.SettingA regional health economy in South West England served by four acute National Health Service (NHS) hospital trusts and six former Primary Care Trusts (PCTs).Population1230 hip fracture patients treated in an acute hospital between 1 April 2011 and 29 February 2012.Main outcomesInformation about access to community rehabilitation services for each acute hospital and PCT, reported by organisational survey. Rates of patients transferred from acute hospital to community rehabilitation hospitals (CRH) across eight groups with varying access; determined by acute hospital and PCT. Median lengths of stay in the acute hospital, and in the acute hospital plus CRH combined. Associations between the rate of transfer to a CRH and median lengths of stay assessed using Spearman's rank correlation coefficient (rs).ResultsAccess to community rehabilitation services varied, including the number of CRH inpatient beds, formal access criteria and waiting times. In one PCT, no home-based rehabilitation service was available. The percentage of patients transferred to a CRH ranged from 2.1% to 54.7%. A higher transfer rate was associated with a shorter median length of stay in the acute hospital (rs=−0.8; p=0.01), but a longer median combined length of stay in the acute hospital and CRH (rs=+0.7; p=0.04).ConclusionsWithin one geographical area, there was wide variation in availability and use of community rehabilitation services for patients discharged from an acute hospital following a hip fracture. Reliance on transfers to community rehabilitation hospitals was associated with a longer length of stay in the NHS.
Reduced risk of pre-eclampsia with organic vegetable consumption: results from the prospective Norwegian Mother and Child Cohort Study
Authors: Torjusen Hanne , Brantsæter Anne Lise , Haugen Margaretha , Alexander Jan , Bakketeig Leiv S , Lieblein Geir , Stigum Hein , Næs Tormod , Swartz Jackie , Holmboe-Ottesen Gerd , Roos Gun , Meltzer Helle Margrete 
Published: September 2014

ObjectiveLittle is known about the potential health effects of eating organic food either in the general population or during pregnancy. The aim of this study was to examine associations between organic food consumption during pregnancy and the risk of pre-eclampsia among nulliparous Norwegian women.DesignProspective cohort study.SettingNorway, years 2002–2008.Participants28 192 pregnant women (nulliparous, answered food frequency questionnaire and general health questionnaire in mid-pregnancy and no missing information on height, body weight or gestational weight gain).Main outcome measureRelative risk was estimated as ORs by performing binary logistic regression with pre-eclampsia as the outcome and organic food consumption as the exposure.ResultsThe prevalence of pre-eclampsia in the study sample was 5.3% (n=1491). Women who reported to have eaten organic vegetables ‘often’ or ‘mostly’ (n=2493, 8.8%) had lower risk of pre-eclampsia than those who reported ‘never/rarely’ or ‘sometimes’ (crude OR=0.76, 95% CI 0.61 to 0.96; adjusted OR=0.79, 95% CI 0.62 to 0.99). The lower risk associated with high organic vegetable consumption was evident also when adjusting for overall dietary quality, assessed as scores on a healthy food pattern derived by principal component analysis. No associations with pre-eclampsia were found for high intake of organic fruit, cereals, eggs or milk, or a combined index reflecting organic consumption.ConclusionsThese results show that choosing organically grown vegetables during pregnancy was associated with reduced risk of pre-eclampsia. Possible explanations for an association between pre-eclampsia and use of organic vegetables could be that organic vegetables may change the exposure to pesticides, secondary plant metabolites and/or influence the composition of the gut microbiota.
Creating spaces in intensive care for safe communication: a video-reflexive ethnographic study
Authors: Hor Su-yin , Iedema Rick , Manias Elizabeth 
Published: September 2014

BackgroundThe built environment in acute care settings is a new focus in patient safety research, with few studies focusing primarily on the design of ward environments and the location and choice of material objects such as light fittings and hand-washing basins.MethodsWe report on an interventionist video-reflexive ethnographic (VRE) study that explored how clinicians used the built environment to achieve safe communication in an intensive care unit (ICU) in a metropolitan Sydney hospital. We conducted 40 semistructured interviews, 5 weeks of observation and four reflexive focus groups with a total of 87 participants (including medical, nursing, allied health and clerical staff).ResultsWe found that the accessibility of staff and patients in the open spaces of the ICU was both a safety feature and a safety risk, enabling safe communication flow, but also allowing potentially unsafe interruptions. Staff managed interruptions while allowing for a safe degree of accessibility by creating temporary protected spaces, using physical markers such as curtains, tape and signs as well as behavioural cues, movement and the development of policies restricting activities at certain areas. Furthermore, clinicians were able to use the VRE method to gain insight into their own practices and problems, and to develop meaningful solutions for other problematic spaces.ConclusionsICU staff enable safe communication in their wards by creating temporary spaces that are both ‘connected’ and ‘protected’. The flexibility of these ‘soft’ strategies is especially well suited to the fast-paced clinical context of intensive care.
Preterm delivery among first-time Mexico-born mothers: a binational population-based comparison of deliveries in California and Mexico
Authors: Guendelman Sylvia , Thornton Dorothy , Perez-Cuevas Ricardo , Walsh Julia 
Published: September 2014

BackgroundWhile studies have attributed the favourable birth outcomes of Mexico-born mothers in the USA to a ‘healthy immigrant effect’ that confers protection to immigrants, a comparison of immigrants with the source population in Mexico has been lacking. We compared preterm delivery (PTD) rates of Mexico-born immigrants who delivered in California with Mexico-born women who delivered in Mexico (WIMX) and with a subgroup who delivered in the five top immigrant sending states in Mexico.MethodsUsing 2009 birth records, we selected all live-born singletons of primiparous WIMX (699 129) and immigrants in California (33 251). We examined the unadjusted and adjusted association between place of delivery and any PTD (<37 weeks gestation), including PTD subcategories (early, moderate, late), using relative risks (RR) and 95% CIs. Multivariate models controlled for demographic and health system characteristics.ResultsPTD rates were higher among immigrants in California (6.7%) than WIMX (5.8%) and compared to women in the sending states (5.5%). The unadjusted risk of any PTD (RR=1.17 (1.12 to 1.22)), early/moderate PTD (<34 weeks gestation; RR=1.27 (1.18 to 1.38)) and late PTD (34–36 weeks; RR=1.14 (1.08 to 1.19)) was higher for immigrants than for WIMX and remained higher when controlling for age, education and healthcare variables. Birth weight <1500 g was also higher among immigrants (RR=1.27 (1.14 to 1.44)). Similar patterns were observed when comparing women in the sending states.ConclusionsWe found no evidence of a ‘healthy immigrant effect’. Further research must assess the comparability of gestational-age data in Mexican and Californian birth certificates.
Vitamin D status is a determinant of atorvastatin effect on carotid intima medial thickening progression rate in children with lupus: an Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) substudy
Authors: Robinson Angela Byun , Tangpricha Vin , Yow Eric , Gurion Reut , Schanberg Laura E , McComsey Grace A 
Published: September 2014

ObjectiveEpidemiological associations suggest that vitamin D status may play a role in inflammation and progression of atherosclerosis. Using frozen serum, carotid intima medial thickness (CIMT) measurements and other existing data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed interactions between serum 25-hydroxyvitamin D (25(OH)D), atorvastatin randomisation and CIMT progression rate.MethodsParticipants in the 3-year APPLE trial were randomised to placebo or atorvastatin and CIMT progression rate was measured. Baseline frozen serum was used to measure 25(OH)D concentrations. Mixed effect longitudinal models for CIMT progression at 3 years were used to evaluate interaction between vitamin D deficiency (serum 25(OH)D <20 ng/mL) at baseline and atorvastatin or placebo treatment, adjusting for key systemic lupus erythematosus disease variables and cardiovascular risk factors.Results201/221 APPLE participants had available samples and were included in this analysis; 61/201 (30%) had vitamin D deficiency at baseline. In adjusted longitudinal modelling, there was significant interaction between baseline vitamin D deficiency and atorvastatin randomisation in 3-year progression of mean-max CIMT. In four out of six carotid segments, there was a greater decrease in mean-max CIMT progression rate in subjects who were treated with atorvastatin compared with placebo if they had baseline serum 25(OH)D levels ≥20 ng/mL.ConclusionsSubjects with serum 25(OH)D ≥20 ng/mL had less mean-max CIMT progression following 3 years of atorvastatin treatment. Results from secondary analyses must be interpreted cautiously, but findings suggest that underlying vitamin D deficiency may be involved in response to atorvastatin in atherosclerosis prevention.Trial registration numberNCT00065806.