bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of Cytoskeletal Transport during Egress Critically Attenuates Ectromelia Virus Infection
In Vivo
Authors: Lynn Helena , Horsington Jacquelyn , Ter Lee Kuan , Han Shuyi , Chew Yee Lian , Diefenbach Russell J. , Way Michael , Chaudhri Geeta , Karupiah Gunasegaran , Newsome Timothy P. 
Published: April 2012

ABSTRACT

Egress of wrapped virus (WV) to the cell periphery following vaccinia virus (VACV) replication is dependent on interactions with the microtubule motor complex kinesin-1 and is mediated by the viral envelope protein A36. Here we report that ectromelia virus (ECTV), a related orthopoxvirus and the causative agent of mousepox, encodes an A36 homologue (ECTV-Mos-142) that is highly conserved despite a large truncation at the C terminus. Deleting the ECTV A36R gene leads to a reduction in the number of extracellular viruses formed and to a reduced plaque size, consistent with a role in microtubule transport. We also observed a complete loss of virus-associated actin comets, another phenotype dependent on A36 expression during VACV infection. ECTV ΔA36R was severely attenuated when used to infect the normally susceptible BALB/c mouse strain. ECTV ΔA36R replication and spread from the draining lymph nodes to the liver and spleen were significantly reduced in BALB/c mice and in Rag-1-deficient mice, which lack T and B lymphocytes. The dramatic reduction in ECTV ΔA36R titers early during the course of infection was not associated with an augmented immune response. Taken together, these findings demonstrate the critical role that subcellular transport pathways play not only in orthopoxvirus infection in an
in vitro
context but also during orthopoxvirus pathogenesis in a natural host. Furthermore, despite the attenuation of the mutant virus, we found that infection nonetheless induced protective immunity in mice, suggesting that orthopoxvirus vectors with A36 deletions may be considered another safe vaccine alternative.
Isoflavone Agonists of IRF-3 Dependent Signaling Have Antiviral Activity against RNA Viruses
Authors: Bedard Kristin M. , Wang Myra L. , Proll Sean C. , Loo Yueh-Ming , Katze Michael G. , Gale Michael , Iadonato Shawn P. 
Published: April 2012

ABSTRACT
There is a growing need for novel antiviral therapies that are broad spectrum, effective, and not subject to resistance due to viral mutations. Using high-throughput screening methods, including computational docking studies and an interferon-stimulated gene 54 (ISG54)-luciferase reporter assay, we identified a class of isoflavone compounds that act as specific agonists of innate immune signaling pathways and cause activation of the interferon regulatory factor (IRF-3) transcription factor. The isoflavone compounds activated the ISG54 promoter, mediated nuclear translocation of IRF-3, and displayed highly potent activity against hepatitis C virus (HCV) and influenza virus. Additionally, these agonists efficiently activated IRF-3 in the presence of the HCV protease NS3-4A, which is known to blunt the host immune response. Furthermore, genomic studies showed that discrete innate immune pathways centered on IRF signaling were regulated following agonist treatment without causing global changes in host gene expression. Following treatment, the expression of only 64 cellular genes was significantly induced. This report provides the first evidence that innate immune pathways dependent on IRF-3 can be successfully targeted by small-molecule drugs for the development of novel broad-spectrum antiviral compounds.
Dynamic Interactions between Bombyx mori Nucleopolyhedrovirus and Its Host Cells Revealed by Transcriptome Analysis
Authors: Xue Jian , Qiao Nan , Zhang Wei , Cheng Ruo-Lin , Zhang Xiao-Qin , Bao Yan-Yuan , Xu Yi-Peng , Gu Lin-Zhu , Han Jing-Dong Jackie , Zhang Chuan-Xi 
Published: April 2012

ABSTRACT

Although microarray and expressed sequence tag (EST)-based approaches have been used to profile gene expression during baculovirus infection, the response of host genes to baculovirus infection and the interaction between baculovirus and its host remain largely unknown. To determine the host response to
Bombyx mori
nucleopolyhedrovirus infection and the dynamic interaction between the virus and its host, eight digital gene expression libraries were examined in a Bm5 cell line before infection and at 1.5, 3, 6, 12, 24, 48, and 96 h postinfection. Gene set enrichment analysis of differentially expressed genes at each time point following infection showed that gene sets including cytoskeleton, transcription, translation, energy metabolism, iron ion metabolism, and the ubiquitin-proteasome pathway were altered after viral infection. In addition, a time course depicting protein-protein interaction networks between the baculovirus and the host were constructed and revealed that viral proteins interact with a multitude of cellular machineries, such as the proteasome, cytoskeleton, and spliceosome. Several viral proteins, including IE2, CG30, PE38, and PK-1/2, were predicted to play key roles in mediating virus-host interactions. Based on these results, we tested the role of the ubiquitin-proteasome pathway and iron ion metabolism in the viral infection cycle. Treatment with a proteasome inhibitor and deferoxamine mesylate
in vitro
and
in vivo
confirmed that these pathways regulate viral infection. Taken together, these findings provide new insights into the interaction between the baculovirus and its host and identify molecular mechanisms that can be used to block viral infection and improve baculovirus expression systems.
Hepatitis C Virus Attachment Mediated by Apolipoprotein E Binding to Cell Surface Heparan Sulfate
Authors: Jiang Jieyun , Cun Wei , Wu Xianfang , Shi Qing , Tang Hengli , Luo Guangxiang 
Published: April 2012

ABSTRACT

Viruses are known to use virally encoded envelope proteins for cell attachment, which is the very first step of virus infection. In the present study, we have obtained substantial evidence demonstrating that hepatitis C virus (HCV) uses the cellular protein apolipoprotein E (apoE) for its attachment to cells. An apoE-specific monoclonal antibody was able to efficiently block HCV attachment to the hepatoma cell line Huh-7.5 as well as primary human hepatocytes. After HCV bound to cells, however, anti-apoE antibody was unable to inhibit virus infection. Conversely, the HCV E2-specific monoclonal antibody CBH5 did not affect HCV attachment but potently inhibited HCV entry. Similarly, small interfering RNA-mediated knockdown of the key HCV receptor/coreceptor molecules CD81, claudin-1, low-density lipoprotein receptor (LDLr), occludin, and SR-BI did not affect HCV attachment but efficiently suppressed HCV infection, suggesting their important roles in HCV infection at postattachment steps. Strikingly, removal of heparan sulfate from the cell surface by treatment with heparinase blocked HCV attachment. Likewise, substitutions of the positively charged amino acids with neutral or negatively charged residues in the receptor-binding region of apoE resulted in a reduction of apoE-mediating HCV infection. More importantly, mutations of the arginine and lysine to alanine or glutamic acid in the receptor-binding region ablated the heparin-binding activity of apoE, as determined by an
in vitro
heparin pulldown assay. HCV attachment could also be inhibited by a synthetic peptide derived from the apoE receptor-binding region. Collectively, these findings demonstrate that apoE mediates HCV attachment through specific interactions with cell surface heparan sulfate.
Spinal Nerve Root Electroacupuncture for Symptomatic Treatment of Lumbar Spinal Canal Stenosis Unresponsive to Standard Acupuncture: A Prospective Case Series
Authors: Inoue Motohiro , Nakajima Miwa , Hojo Tatsuya , Kitakoji Hiroshi , Itoi Megumi 
Published: April 2012

Objective To study the effectiveness of electroacupuncture of the spinal nerve root using a selective spinal nerve block technique for the treatment of lumbar and lower limb symptoms in patients with lumbar spinal canal stenosis. Methods Subjects were 17 patients with spinal canal stenosis who did not respond to 2 months of general conservative treatment and conventional acupuncture. Under x-ray fluoroscopy, two acupuncture needles were inserted as close as possible to the relevant nerve root, as determined by subjective symptoms and x-ray and MRI findings, and low-frequency electroacupuncture stimulation was performed (10 Hz, 10 min). Patients received 3–5 once-weekly treatments, and were evaluated immediately before and after each treatment and 3 months after completion of treatment. Results After the first nerve root electroacupuncture stimulation, scores for lumbar and lower limb symptoms improved significantly (low back pain, p<0.05; lower limb pain, p<0.05; lower limb dysaesthesia, p<0.01) with some improvement in continuous walking distance. Symptom scores and continuous walking distance showed further improvement before the final treatment (p<0.01), and a significant sustained improvement was observed 3 months after completion of treatment (p<0.01). Conclusion Lumbar and lower limb symptoms, for which conventional acupuncture and general conservative treatment had been ineffective, improved significantly during a course of electroacupuncture to the spinal nerve root, showing sustained improvement even 3 months after completion of treatment. The mechanisms of these effects may involve activation of the pain inhibition system and improvement of nerve blood flow.
The FEeding Support Team (FEST) randomised, controlled feasibility trial of proactive and reactive telephone support for breastfeeding women living in disadvantaged areas
Authors: Hoddinott Pat , Craig Leone , Maclennan Graeme , Boyers Dwayne , Vale Luke 
Published: April 2012

ObjectiveTo assess the feasibility of implementing a dedicated feeding support team on a postnatal ward and pilot the potential effectiveness and cost-effectiveness of team (proactive) and woman-initiated (reactive) telephone support after discharge.DesignRandomised controlled trial embedded within a before-and-after study. Participatory approach and mixed-method process evaluation.SettingA postnatal ward in Scotland.SampleWomen living in disadvantaged areas initiating breast feeding.MethodsEligible women were recruited to a before-and-after intervention study, a proportion of whom were independently randomised after hospital discharge to intervention: daily proactive and reactive telephone calls for ≤14 days or control: reactive telephone calls ≤ day 14. Intention-to-treat analysis compared the randomised groups on cases with complete outcomes at follow-up.Main outcome measuresPrimary outcome: any breast feeding at 6–8 weeks assessed by a telephone call from a researcher blind to group allocation. Secondary outcomes: exclusive breast feeding, satisfaction with care, NHS costs and cost per additional woman breast feeding.ResultsThere was no difference in feeding outcomes for women initiating breast feeding before the intervention (n=413) and after (n=388). 69 women were randomised to telephone support: 35 intervention (32 complete cases) and 34 control (26 complete cases). 22 intervention women compared with 12 control women were giving their baby some breast milk (RR 1.49, 95% CI 0.92 to 2.40) and 17 intervention women compared with eight control women were exclusively breast feeding (RR 1.73, 95% CI 0.88 to 3.37) at 6–8 weeks after birth. The incremental cost of providing proactive calls was £87 per additional woman breast feeding and £91 per additional woman exclusively breast feeding at 6–8 weeks; costs were sensitive to service organisation.ConclusionsProactive telephone care delivered by a dedicated feeding team shows promise as a cost-effective intervention for improving breastfeeding outcomes. Integrating the FEeding Support Team (FEST) intervention into routine postnatal care was feasible.Trial registration numberISRCTN27207603. The study protocol and final report are available on request.
Inclusion criteria provide heterogeneity in baseline profiles of patients with mild cognitive impairment: comparison of two prospective cohort studies
Authors: Kawashima Shoji , Ito Kengo , Kato Takashi ,   the SEAD-J Study Group
Published: April 2012

BackgroundMild cognitive impairment (MCI) is considered to represent a transitional stage between ageing and Alzheimer's disease (AD). To aim at identifying neuroimaging measures associated with cognitive changes in healthy elderly and MCI patients, longitudinal multicentre studies are ongoing in several countries. The patient profiles of each study are based on unique inclusion criteria.ObjectivesThe purpose of the study is to clarify differences in baseline profiles of MCI patients between Studies on Diagnosis of Early Alzheimer's Disease—Japan (SEAD-J) and Alzheimer's Disease Neuroimaging Initiative (ADNI) and to examine the association between baseline profiles and risk of early conversion to AD.DesignProspective cohort study.Setting and participantsSEAD-J recruited 114 patients from nine facilities in Japan. A total of 200 patients in ADNI with fluorodeoxyglucose–positron emission tomography (FDG-PET) were enrolled from the USA.MethodsBaseline profiles were statistically analysed. For FDG-PET at a time of inclusion, associations between each profile and cerebral metabolic rate for glucose (CMRgl) were examined using SPM5 software. In each study, the ratio of conversion to AD within the 1-year and 2-year period after inclusion was investigated and differences in baseline profiles between AD converters and non-converters were analysed.ResultsSEAD-J included MCI patients with more severe verbal memory deficits and extracted patients with higher depressive tendencies. These differences were likely to be associated with criteria. SEAD-J exhibited a higher rate of conversion within 1 year compared with ADNI (24.5% vs 13.5%). In FDG-PET analyses of SEAD-J, AD converters within 1 year showed more severe decrease of FDG uptake in bilateral inferior parietal regions compared with non-converters.ConclusionsDifferent inclusion criteria provided differences in baseline profiles. The severity of memory deficit might cause increase of the AD conversion within 1 year. Clinical outcomes of multicentre studies for early diagnosis of AD should be interpreted carefully considering profiles of patients.
Process evaluation for the FEeding Support Team (FEST) randomised controlled feasibility trial of proactive and reactive telephone support for breastfeeding women living in disadvantaged areas
Authors: Hoddinott Pat , Craig Leone , MacLennan Graeme , Boyers Dwayne , Vale Luke 
Published: April 2012

ObjectiveTo assess the feasibility, acceptability and fidelity of a feeding team intervention with an embedded randomised controlled trial of team-initiated (proactive) and woman-initiated (reactive) telephone support after hospital discharge.DesignParticipatory approach to the design and implementation of a pilot trial embedded within a before-and-after study, with mixed-method process evaluation.SettingA postnatal ward in Scotland.SampleWomen initiating breast feeding and living in disadvantaged areas.MethodsQuantitative data: telephone call log and workload diaries. Qualitative data: interviews with women (n=40) with follow-up (n=11) and staff (n=17); ward observations 2 weeks before and after the intervention; recorded telephone calls (n=16) and steering group meetings (n=9); trial case notes (n=69); open question in a telephone interview (n=372). The Framework approach to analysis was applied to mixed-method data.Main outcome measuresQuantitative: telephone call characteristics (number, frequency, duration); workload activity. Qualitative: experiences and perspectives of women and staff.ResultsA median of eight proactive calls per woman (n=35) with a median duration of 5 min occurred in the 14 days following hospital discharge. Only one of 34 control women initiated a call to the feeding team, with women undervaluing their own needs compared to others, and breast feeding as a reason to call. Proactive calls providing continuity of care increased women's confidence and were highly valued. Data demonstrated intervention fidelity for woman-centred care; however, observing an entire breast feed was not well implemented due to short hospital stays, ward routines and staff–team–woman communication issues. Staff pragmatically recognised that dedicated feeding teams help meet women's breastfeeding support needs in the context of overstretched and variable postnatal services.ConclusionsImplementing and integrating the FEeding Support Team (FEST) trial within routine postnatal care was feasible and acceptable to women and staff from a research and practice perspective and shows promise for addressing health inequalities.Trial registrationISRCTN27207603. The study protocol and final report is available on request.
Physical and mechanical properties of black locust (Robinia pseudoacacia) wood grown in Belgium
Authors: Pollet C. , Verheyen C. , Hébert J. , Jourez B. 
Published: April 2012

The objective of this study was to characterize black locust ( Robinia pseudoacacia L.) wood on the basis of its physical and mechanical properties. The results are compared with those reported in the literature for English oak ( Quercus robur L.), teak ( Tectona grandis L. f.), and afzelia ( Afzelia sp.), since black locust is likely to be used for the same purposes as the former species. The variations between sites, trees, and radial positions in the trunk were also studied. The physical and mechanical properties of black locust wood were evaluated on clear wood specimens taken from 27 trees distributed over five sites in Wallonia (Belgium) according to Belgian and French standards. Most of the black locust’s mechanical properties are higher than those of oak and teak. The black locust is classified as a “mid-heavy” (734 kg·m–3) and “half-hard” (5.22) wood type with very high resilience (17.2 J·cm–2), modulus of elasticity (15 700 MPa), and tensile strength in static bending (138 MPa). Its resilience is exceptional, higher than that of teak and afzelia, while its modulus of elasticity and bending strength, which surpass those of teak, are comparable with those of afzelia. Black locust shows high total volumetric shrinkage (16%), placing it in the “nervous” class, average tangential (8.8%) and radial shrinkage (5.5%) as well as average axial compressive (63 MPa) and splitting strength (17.8 N·mm–1). No technological incompatibilities would prevent the use of this wood for many value-added purposes (floor, deck, exterior woodwork, and furniture); however, significant shrinkage makes it necessary to condition the wood to its service moisture.
Bending strength and stiffness of in-grade Douglas-fir and southern pine No. 2 2 × 4 lumber
Authors: Dahlen Joseph , Jones P. David , Seale R. Daniel , Shmulsky Rubin 
Published: April 2012

Douglas-fir ( Psuedotsuga menziesii (Mirb.) Franco) (DF) and southern pine ( Pinus spp.) (SP) trees are increasingly grown on intensively managed plantation forests that yield excellent growth. Lumber cut from these trees often contains a large percentage of juvenile wood, which negatively impacts its strength and stiffness. Design values of lumber must accurately reflect the available forest resource, and because the design values were determined over 25 years ago, questions exist whether wood quality has declined. To help address this, 1488 samples of commercial-grade No. 2 2 × 4 DF and SP lumber were destructively tested in edgewise bending. Mean stiffness of DF and SP was 11.51 and 10.89 GPa, respectively, comparing favorably with the 11.02 GPa mean design values; however, variation for SP was higher than in previous studies. The nonparametric 5th percentile bending strengths for DF and SP were 8.30 and 9.06 MPa, respectively. Both DF and SP tested at less than their design values, 9.3 and 10.34 MPa, respectively. Stiffness explained 66% and 52%, respectively, of the variability in strength for DF and SP. Because this relationship seems only moderately predictive, it may be prudent to couple stiffness with additional measures of quality when predicting bending strength.
Climate–growth relationships at different stem heights in silver fir and Norway spruce
Authors: van der Maaten-Theunissen Marieke , Bouriaud Olivier 
Published: April 2012

We investigated the effect of climate on variations in annual ring-area increment along the stem of dominant silver fir ( Abies alba Mill.) and Norway spruce ( Picea abies (L.) Karst.) trees in the Black Forest, southwestern Germany, to test the hypothesis that growth allocation changes as a result of climate fluctuations. Stem discs were taken at three different stem heights: 1.30, 11.50, and 16.70 m. For each site and stem height, average annual ring-area increment chronologies were computed. In addition, we calculated ratios between ring-area increment of the upper stem discs and the disc at breast height to compare growth variations along the stem. Pearson correlation coefficients revealed a highly similar growth pattern at different stem heights, where the two upper discs were most similar. Bootstrapped correlation coefficients between the ring-area increment chronologies, ratios, and monthly temperature, precipitation, and self-calibrated Palmer drought sensitivity index data were calculated to analyze differences in climate response. High temperatures in early summer were found to reduce growth of high-altitude fir in the upper stem parts, whereas high temperatures in summer limit growth of high-altitude fir and spruce, especially at breast height. For low-altitude trees, high temperatures as well as low precipitation amounts during summer were found to reduce growth at all stem heights, but more strongly at breast height. Growth at breast height seems to be biased, as it over- or underestimates annual ring-area increments along the stem (and thereby volume increment), particularly during warm and dry climate conditions.
Effects of elevated temperature and [CO2] on photosynthesis, leaf respiration, and biomass accumulation of Pinus taeda seedlings at a cool and a warm site within the species’ current range
Authors: Wertin Timothy M. , McGuire Mary Anne , van Iersel Marc , Ruter John M. , Teskey Robert O. 
Published: April 2012

We examined the influence of elevated temperature (ambient +2 °C) and atmospheric CO2 concentration ([CO2]) (700 µmol·mol–1), applied singly and in combination, on biomass accumulation and the temperature response of net photosynthesis (Anet) and leaf respiration (Rd) of loblolly pine ( Pinus taeda L.) seedlings grown simultaneously at a northern and a southern site within the species’ range. We used this experimental approach to determine if the response to future climate conditions would differ between a warm and cool location within a species’ range. Seedling biomass accumulation and the temperature responses of Anet and Rd were measured throughout the growing season. Biomass accumulation was substantially greater at the warmer site compared with the cooler site regardless of treatment. At each site, biomass accumulation was greater in the elevated temperature treatment compared with the ambient treatment. There was substantial acclimation of Rd, but not Anet, to site and to temperature treatment at each site. Elevated [CO2] increased biomass accumulation and Anet at both sites and in both temperature treatments. Our study provides an indication that future projected increases in [CO2] and air temperature of 700 µmol·mol–1 and +2 °C, respectively, are likely to increase loblolly pine growth in most, if not all, of its current range.