bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation of a Single Envelope N-Linked Glycosylation Site Enhances the Pathogenicity of Bovine Leukemia Virus
Authors: de Brogniez Alix , Bouzar Amel Baya , Jacques Jean-Rock , Cosse Jean-Philippe , Gillet Nicolas , Callebaut Isabelle , Reichert Michal , Willems Luc 
Published: June 2015

ABSTRACT

Viruses have coevolved with their host to ensure efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is exemplified by the bovine leukemia virus (BLV) system in which lymphoproliferative disorders develop in ruminants after latency periods of several years. In principle, the equilibrium reached between the virus and its host could be disrupted by emergence of more pathogenic strains. Intriguingly but fortunately, such a hyperpathogenic BLV strain was never observed in the field or designed
in vitro
. In this study, we sought to understand the role of envelope N-linked glycosylation with the hypothesis that this posttranslational modification could either favor BLV infection by allowing viral entry or allow immune escape by using glycans as a shield. Using reverse genetics of an infectious molecular provirus, we identified a N-linked envelope glycosylation site (N230) that limits viral replication and pathogenicity. Indeed, mutation N230E unexpectedly leads to enhanced fusogenicity and protein stability.

IMPORTANCE
Infection by retroviruses requires the interaction of the viral envelope protein (SU) with a membrane-associated receptor allowing fusion and release of the viral genomic RNA into the cell. We show that N-linked glycosylation of the bovine leukemia virus (BLV) SU protein is, as expected, essential for cell infection
in vitro
. Consistently, mutation of all glycosylation sites of a BLV provirus destroys infectivity
in vivo
. However, single mutations do not significantly modify replication
in vivo
. Instead, a particular mutation at SU codon 230 increases replication and accelerates pathogenesis. This unexpected observation has important consequences in terms of disease control and managing.
Phylodynamics of Enterovirus A71-Associated Hand, Foot, and Mouth Disease in Viet Nam
Authors: Geoghegan Jemma L. , Tan Le Van , Kühnert Denise , Halpin Rebecca A. , Lin Xudong , Simenauer Ari , Akopov Asmik , Das Suman R. , Stockwell Timothy B. , Shrivastava Susmita , Ngoc Nghiem My , Uyen Le Thi Tam , Tuyen Nguyen Thi Kim , Thanh Tran Tan , Hang Vu Thi Ty , Qui Phan Tu , Hung Nguyen Thanh , Khanh Truong Huu , Thinh Le Quoc , Nhan Le Nguyen Thanh , Van Hoang Minh Tu , Viet Do Chau , Tuan Ha Manh , Viet Ho Lu , Hien Tran Tinh , Chau Nguyen Van Vinh , Thwaites Guy , Grenfell Bryan T. , Stadler Tanja , Wentworth David E. , Holmes Edward C. , Van Doorn H. Rogier 
Published: June 2015

ABSTRACT

Enterovirus A71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011 and 2013 and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (R
e
) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the R
e
of subgenogroup C4 decreased during the time frame of sampling, whereas that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated area of endemicity. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia.

IMPORTANCE
EV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a potential EV-A71 vaccine, there is no current prevention and little is known about the patterns and dynamics of EV-A71 spread. In this study, we utilize full-length genome sequence data obtained from HFMD patients in Viet Nam, a geographical region where the disease has been endemic since 2003, to characterize the phylodynamics of this important emerging virus.
Partial Attenuation of Respiratory Syncytial Virus with a Deletion of a Small Hydrophobic Gene Is Associated with Elevated Interleukin-1β Responses
Authors: Russell Ryan F. , McDonald Jacqueline U. , Ivanova Maria , Zhong Ziyun , Bukreyev Alexander , Tregoning John S. 
Published: June 2015

ABSTRACTThe small hydrophobic (SH) gene of respiratory syncytial virus (RSV), a major cause of infant hospitalization, encodes a viroporin of unknown function. SH gene knockout virus (RSV ΔSH) is partially attenuatedin vivo, but notin vitro, suggesting that the SH protein may have an immunomodulatory role. RSV ΔSH has been tested as a live attenuated vaccine in humans and cattle, and here we demonstrate that it protected against viral rechallenge in mice. We compared the immune response to infection with RSV wild type and RSV ΔSHin vivousing BALB/c mice andin vitrousing epithelial cells, neutrophils, and macrophages. Strikingly, the interleukin-1β (IL-1β) response to RSV ΔSH infection was greater than to wild-type RSV, in spite of a decreased viral load, and when IL-1β was blockedin vivo, the viral load returned to wild-type levels. A significantly greater IL-1β response to RSV ΔSH was also detectedin vitro, with higher-magnitude responses in neutrophils and macrophages than in epithelial cells. Depleting macrophages (with clodronate liposome) and neutrophils (with anti-Ly6G/1A8) demonstrated the contribution of these cells to the IL-1β responsein vivo, the first demonstration of neutrophilic IL-1β production in response to viral lung infection. In this study, we describe an increased IL-1β response to RSV ΔSH, which may explain the attenuationin vivoand supports targeting the SH gene in live attenuated vaccines.IMPORTANCEThere is a pressing need for a vaccine for respiratory syncytial virus (RSV). A number of live attenuated RSV vaccine strains have been developed in which the small hydrophobic (SH) gene has been deleted, even though the function of the SH protein is unknown. The structure of the SH protein has recently been solved, showing it is a pore-forming protein (viroporin). Here, we demonstrate that the IL-1β response to RSV ΔSH is greater in spite of a lower viral load, which contributes to the attenuationin vivo. This potentially suggests a novel method by which viruses can evade the host response. As allPneumovirinaeand someParamyxovirinaecarry similar SH genes, this new understanding may also enable the development of live attenuated vaccines for both RSV and other members of theParamyxoviridae.
Assembly of Epstein-Barr Virus Capsid in Promyelocytic Leukemia Nuclear Bodies
Authors: Wang Wen-Hung , Kuo Chung-Wen , Chang Li-Kwan , Hung Chen-Chia , Chang Tzu-Hsuan , Liu Shih-Tung 
Published: June 2015

ABSTRACT

The Epstein-Barr virus (EBV) capsid contains a major capsid protein, VCA; two minor capsid proteins, BDLF1 and BORF1; and a small capsid protein, BFRF3. During the lytic cycle, these capsid proteins are synthesized and imported into the host nucleus for capsid assembly. This study finds that EBV capsid proteins colocalize with promyelocytic leukemia (PML) nuclear bodies (NBs) in P3HR1 cells during the viral lytic cycle, appearing as nuclear speckles under a confocal laser scanning microscope. In a glutathione
S
-transferase pulldown study, we show that BORF1 interacts with PML-NBs
in vitro
. BORF1 also colocalizes with PML-NBs in EBV-negative Akata cells after transfection and is responsible for bringing VCA and the VCA-BFRF3 complex from the cytoplasm to PML-NBs in the nucleus. Furthermore, BDLF1 is dispersed throughout the cell when expressed alone but colocalizes with PML-NBs when BORF1 is also present in the cell. In addition, this study finds that knockdown of PML expression by short hairpin RNA does not influence the intracellular levels of capsid proteins but reduces the number of viral particles produced by P3HR1 cells. Together, these results demonstrate that BORF1 plays a critical role in bringing capsid proteins to PML-NBs, which may likely be the assembly sites of EBV capsids. The mechanisms elucidated in this study are critical to understanding the process of EBV capsid assembly.

IMPORTANCE
Capsid assembly is an important event during the Epstein-Barr virus (EBV) lytic cycle, as this process is required for the production of virions. In this study, confocal microscopy revealed that the EBV capsid protein BORF1 interacts with promyelocytic leukemia (PML) nuclear bodies (NBs) in the host nucleus and is responsible for transporting the other EBV capsid proteins, including VCA, BDLF1, and BFRF3, to these subnuclear locations prior to initiation of capsid assembly. This study also found that knockdown of PML expression by short hairpin RNA significantly reduces EBV capsid assembly capabilities. This enhanced understanding of capsid assembly offers potential for the development of novel antiviral strategies and therapies that can prevent the propagation and spread of EBV.
Maternal Deworming Research Study (MADRES) protocol: a double-blind, placebo-controlled randomised trial to determine the effectiveness of deworming in the immediate postpartum period
Authors: Mofid Layla S , Casapía Martín , Montresor Antonio , Rahme Elham , Fraser William D , Marquis Grace S , Vercruysse Jozef , Allen Lindsay H , Gyorkos Theresa W 
Published: June 2015

IntroductionSoil-transmitted helminth infections are endemic in 114 countries worldwide, and cause the highest burden of disease among all neglected tropical diseases. The WHO includes women of reproductive age as a high-risk group for infection. The primary consequence of infection in this population is anaemia. During lactation, anaemia may contribute to reduced quality and quantity of milk, decreasing the duration of exclusive breastfeeding and lowering the age at weaning. To date, no study has investigated the effects of maternal postpartum deworming on infant or maternal health outcomes.Methods and analysisA single-centre, parallel, double-blind, randomised, placebo-controlled trial will be carried out in Iquitos, Peru, to assess the effectiveness of integrating single-dose 400 mg albendazole into routine maternal postpartum care. A total of 1010 mother-infant pairs will be randomised to either the intervention or control arm, following inhospital delivery and prior to discharge. Participants will be visited in their homes at 1, 6, 12 and 24 months following delivery for outcome ascertainment. The primary outcome is infant mean weight gain between birth and 6 months of age. Secondary outcomes include other infant growth indicators and morbidity, maternal soil-transmitted helminth infection and intensity, anaemia, fatigue, and breastfeeding practices. All statistical analyses will be performed on an intention-to-treat basis.Ethics and disseminationResearch ethics board approval has been obtained from the McGill University Health Centre (Canada), the Asociación Civil Impacta Salud y Educación (Peru) and the Instituto Nacional de Salud (Peru). A data safety and monitoring committee is in place to oversee study progression and evaluate adverse events. The results of the analyses will be published in peer-reviewed journals, and presented at national and international conferences.Trial registration numberClinicaltrials.gov:NCT01748929.
A longitudinal study of poor performance and subclinical respiratory viral activity in Standardbred trotters
Authors: Back Helena , Penell Johanna , Pringle John , Isaksson Mats , Ronéus Nils , Treiberg Berndtsson Louise , Ståhl Karl 
Published: June 2015

IntroductionWhile clinical respiratory disease is considered a main cause of poor performance in horses, the role of subclinical respiratory virus infections is less clear and needs further investigation.Aims and objectivesIn this descriptive longitudinal study the relationship of markers of subclinical respiratory viral activity to occurrence of poor performance in racing Standardbred trotters was investigated.Material and methods66 elite Standardbred trotters were followed for 13 months by nasal swabs analysed with qPCR for equine influenza virus, equine arteritis virus, equine rhinitis B virus (ERBV), equine herpesvirus type 1(EHV‐1) and equine herpesvirus type 4 (EHV‐4) and serology to equine rhinitis A virus (ERAV), ERBV, EHV‐1 and EHV‐4, as well as the acute phase protein serum amyloid A (SAA). Findings on lab analyses were subsequently assessed for possible correlations to workload performance and trainer opinion measures of poor performance.ResultsDespite occurrence of poor performance and subclinical viral activity the authors were unable to detect association neither between subclinical viral activity and poor performance, nor between SAA elevations and either viral activity or poor performance.ConclusionsConsistent with earlier study results, antibody titres to ERBV remained high for at least a year and few horses two years or older were seronegative to either ERAV or ERBV. In absence of clinical signs, serology to common respiratory viruses appears to have little diagnostic benefit in evaluation of poor performance in young athletic horses.
Magnetization carriers of grey to red deep-water limestones in the GSSP of the Givetian–Frasnian boundary (Puech de la Suque, France): signals influenced by moderate diagenetic overprinting
Authors: Devleeschouwer Xavier , Riquier Laurent , Bábek Ondřej , De Vleeshouwer David , Petitclerc Estelle , Sterckx Sarane , Spassov Simo 
Published: June 2015

Abstract
Limestones at the Puech de la Suque Global Boundary Stratotype Section and Point (GSSP) of the Givetian–Frasnian boundary show a drastic change towards much higher magnetic susceptibility values in the Givetian rocks. Different rock magnetic parameters indicate that ferromagnetic minerals are the main controlling factor. The ferromagnetic fraction is composed of low- (magnetite-type) and high-coercivity (hematite and goethite) phases. Confirmed by the spectral reflectance, high coercivity minerals are fluctuating along the section with a higher abundance in the basal Frasnian. These phases may be of secondary origin and produced during burial stage. The magnetite-type phase contains two different grain-size populations. The identified that Stable Single-domain/Superparamagnetic (SSD/SP) particles are of diagenetic origin and their amount decreases slightly upwards. A second group of magnetite grains correspond to coarse-grained particles identified using the squareness v. coercive force plot. It is tentatively suggested here that these particles present throughout the section are of primary origin. On the contrary, the paramagnetic minerals underwent a clear diagenetic overprinting and may represent secondary minerals. The presence of a primary ferromagnetic carrier allowed the use of spectral analyses, leading to the detection of spectral peaks at 1.25 and 4 cycles/m, which can be interpreted as the result of 405-kyr and 100-kyr eccentricity forcing, respectively.
Short-term Peripheral Auditory Effects of Cranial Irradiation
Authors: Gasser Rutledge Krysta L. , Prasad Kumar G. , Emery Kara R. , Mikulec Anthony A. , Varvares Mark , Gratton Michael Anne 
Published: June 2015

Objectives: Assess postcranial irradiation: (1) short-term threshold shift, (2) short-term peripheral auditory histopathology, and (3) the mouse as an experimental model. Methods: Adult mice were exposed to single-dose radiation of 10 to 60 Gy. Pre- and post-irradiation (baseline, 2-8 days) audiometric brainstem response data were recorded with analysis of cochlear ultrastructure. Results: Significant threshold shift occurred at all test frequencies in mice exposed to ≥20 Gy at 4 to 6 days post-irradiation. Ultrastructurally in Rosenthal’s canal and the spiral lamina, neuronal density and extracellular matrix decreased dramatically. There was overall preservation of hair cells, stria vascularis, and vasculature. No difference within Gy group was noted in the frequency or severity of pathology along the length of the cochlea. Conclusions: The initial impact of radiation in the first week post-exposure focuses on spiral ganglion cell bodies and peripheral projections, resulting in significant threshold shift for irradiation dosages ≥20 Gy. This study demonstrates that the mouse is a viable model for study of short-term peripheral auditory effects using single-dose cranial irradiation. Additionally, with access to a precise animal irradiator, the mouse may be used as an experimental model for a fractionated irradiation dosage of 10 Gy, simulating stereotactic therapeutic cranial irradiation.
Effect of Nasal Corticosteroid on Secretory Immunoglobulin A Measured in Rat Nasal Lavage
Authors: Aksoy Fadlullah , Dogan Remzi , Kocak Ilker , Veyseller Bayram , Ozturan Orhan , Incir Said 
Published: June 2015

ObjectiveIn this study, we aimed to experimentally investigate the effects of nasal corticosteroids on the levels of secretory immunoglobulin A (sIgA) in nasal mucosa in rats.Study DesignProspective, randomized control trial.SettingResearch laboratory.Subject and MethodsTwenty‐four male Sprague Dawley rats were included in our study. The rats were randomized into 3 groups. In group 1, nasal mometasone furoate was applied to the rats for 30 days. Saline was applied to group 2 for 30 days. Group 3 was the control group and received no treatment throughout the study period. Nasal lavage was conducted on both nasal openings of all rats in the 3 groups at the beginning of the study and on days 15 and 30, and the lavage solution (distilled water) was collected by aspiration.ResultsIn group 1, the sIgA value was significantly higher at day 15 than at baseline. No significant difference was found between the sIgA values on day 15 and day 30. In groups 2 and 3, there were no significant differences in sIgA values at baseline, day 15, and day 30. The sIgA value of group 1 on day 15 was significantly higher than the values of groups 2 and 3. The sIgA value of group 1 on day 30 was significantly higher than the values of groups 2 and 3.ConclusionTopical corticosteroids (mometasone furoate) applied to the nasal mucosa significantly increase nasal sIgA levels.
National Institutes of Health Funding for Obstructive Sleep Apnea
Authors: Gouveia Christopher J. , Qureshi Hannan A. , Kern Robert C. , Shintani Smith Stephanie 
Published: June 2015

ObjectiveTo describe current levels and trends of funding for the National Institutes of Health (NIH) in obstructive sleep apnea (OSA) and to recognize the current status of otolaryngologists in OSA research.Study DesignScientometric analysis.MethodsThe NIH RePORTER database was queried for the search term “obstructive sleep apnea” for all available years. Sex, degree, academic department, NIH funding source, geography, funding totals and years, and h‐index of principal investigators (PIs) were collected and summarized.ResultsA total of 397 projects spanning 1242 total funding years were funded. Of the 273 individual PIs, 33.3% (91/273) were female. Regarding credentials, 52.4% of PIs (143/273) were MD or MD/PhD, and 41.0% (112/273) were PhD alone. Academic departments of PIs were most often medicine (34.1%), pediatrics (12.1%), cell biology/physiology (10.6%), and psychiatry (7.7%). Seven otolaryngology faculty members had received NIH funding for OSA research (2.6% of total PIs) since 2000. They accounted for 8 grants (0.25% of total grants) and $7,235,729 (1.5% of total dollars) of research funding.ConclusionDespite studies showing increasing levels of OSA surgery being performed and major areas of research and clinical opportunity, otolaryngologists represent a small minority of OSA research funding. This information may help direct our specialty when setting priorities regarding research funding, as research into the basic science and clinical management of OSA represents a broad and interdisciplinary pursuit.
Personal Projects Analysis in occupational therapy research: A scoping review
Authors: Arcand-Dusseault Caroline , Egan Mary 
Published: June 2015

Introduction Personal Projects Analysis has been used in occupational therapy research to better understand occupation. The purpose of this scoping review is to describe Personal Projects Analysis and examine how it has been used in occupational therapy research. Method Occupational therapy studies using Personal Projects Analysis were identified and described in terms of sample, research question, design, use of Personal Projects Analysis, and results. Findings Fifteen studies in which Personal Projects Analysis was used in occupational therapy research were retrieved. Three of the four Personal Projects Analysis modules have been used in occupational therapy research on project characteristics and subjective well-being, types of projects affected by health problems, and occupational balance. Only one paper described a clinical use of Personal Projects Analysis in occupational therapy. Conclusion Personal Projects Analysis is a useful evaluation for occupational therapy research and a potential tool for practice.
Headaches after traumatic spinal cord injury in Estonia
Authors: Sabre Liis , Rugo Mariann , Asser Toomas , Kõrv Janika , Braschinsky Mark 
Published: June 2015

Background Patients with traumatic spinal cord injury (TSCI) often suffer from different types of pain. However, headaches after TSCI have not been studied. Aim The aim of this article is to examine the occurrence of headache among patients with TSCI. Methods This cross-sectional study included individuals with TSCI from 1997 to 2012 in Estonia. Patients with TSCI were interviewed via telephone. The interview was based on a questionnaire specifically designed to identify headache type using the International Classification of Headache Disorders, third edition (beta version). Results There were 73 patients with a mean age 37.1 ± 10.6 years. The mean time since TSCI was 7.5 ± 4.0 years. The most frequently mentioned pain was headache (71%), followed by back pain (60%) and pain in neck (44%). Headaches were more frequent after the trauma compared with the headaches before TSCI (71% vs 51%, p = 0.02). Headaches that arose after TSCI were not related to the concomitant brain injury ( p = 0.15). The occurrence of headache did not depend on the severity or the level of the TSCI. Eighty-five percent of patients had not contacted any physician and headache was not diagnosed. Conclusions This is the first study that evidentially shows that headache is the most prevalent pain condition after TSCI. Despite this, the majority of patients never consult a physician, nor is their headache diagnosed or appropriately managed. This indicates that further studies are needed to provide evidence regarding the prevalence and causes of headache and its impact on quality of life.