bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanical and Electromyographic Comparisons of Isometric Trunk Flexor Endurance Test Postures: Prone Plank Versus V-Sit
Authors: Musalem Lindsay L. , Stankovic Tatjana , Glisic Drazen , Cook Gillian E. , Beach Tyson A.C.
Published: August 2015

The objective of this study was to investigate why holding times on 2 different tests of isometric trunk flexor endurance capacity (prone plank and v-sit) are weakly correlated. Body position and ground reaction force data from 10 men and 10 women were used to conduct static biomechanical analyses of both test postures, and bilateral activations of the rectus abdominis, internal and external obliques, latissimus dorsi, and lumbar and thoracic erector spinae were measured in a second sample of 15 men and 15 women while holding the test postures. No between-posture differences in net low back flexor moments were found (P = .111), but the lumbar spine was 28° more flexed in the v-sit than in the plank (P < .001). No between-posture differences were detected in the rectus abdominis (P = .397), external obliques (P = .204), internal obliques (P = .226), or lumbar erector spinae (P = .116) activation levels, but those of the thoracic erector spinae (P = .0253) and latissimus dorsi (P < .001) were greater in the plank than in the v-sit. Altogether, the findings suggest that differences between plank and v-sit holding times are most likely related to between-test differences in lumbar spine postures and shoulder demands.
The Effects of a Lateral Wedge Insole on Knee and Ankle Joints During Slope Walking
Authors: Uto Yuki , Maeda Tetsuo , Kiyama Ryoji , Kawada Masayuki , Tokunaga Ken , Ohwatashi Akihiko , Fukudome Kiyohiro , Ohshige Tadasu , Yoshimoto Yoichi , Yone Kazunori
Published: August 2015

The purpose of this study was to determine whether a lateral wedge insole reduces the external knee adduction moment during slope walking. Twenty young, healthy subjects participated in this study. Subjects walked up and down a slope using 2 different insoles: a control flat insole and a 7° lateral wedge insole. A three-dimensional motion analysis system and force plate were used to examine the knee adduction moment, the ankle valgus moment, and the moment arm of the ground reaction force to the knee joint center in the frontal plane. The lateral wedge insole significantly decreased the moment arm of the ground reaction force, resulting in a reduction of the knee adduction moment during slope walking, similar to level walking. The reduction ratio of knee adduction moment by the lateral wedge insole during the early stance of up-slope walking was larger than that of level walking. Conversely, the lateral wedge insole increased the ankle valgus moment during slope walking, especially during the early stance phase of up-slope walking. Clinicians should examine the utilization of a lateral wedge insole for knee osteoarthritis patients who perform inclined walking during daily activity, in consideration of the load on the ankle joint.
Effect of Electrode Location on Task-Dependent Electromyography Responses Within the Human Biceps Femoris Muscle
Authors: Watanabe Kohei , Kouzaki Motoki , Moritani Toshio
Published: August 2015

In some muscles, nonuniform surface electromyography (EMG) responses have been demonstrated within a muscle, meaning that the electrode location could be critical in the results of surface EMG. The current study investigated possible region-specific EMG responses within the human biceps femoris (BF) muscle. Surface EMG was recorded from various regions along the longitudinal axis of the BF muscle with 20 electrodes. Ten healthy men performed maximal isometric contractions of hip extension and knee flexion, which involve the BF muscle. The ratio of the EMG amplitude between hip extension and knee flexion tasks (HE/KF) was calculated and compared among the regions. There were no significant differences in HE/KF among the regions along the BF muscle (P > .05). This suggests that the entire superficial region of the BF muscle is equally regulated in the 2 different tasks. We suggest that the electrode location is not critical in estimating the activation properties and/or functional role of the superficial region, which corresponds with approximately 50% of the muscle length of the BF muscle, using surface EMG during maximal contraction.
Australia and Other Nations Are Failing to Meet Sedentary Behaviour Guidelines for Children: Implications and a Way Forward
Authors: Straker Leon , Howie Erin Kaye , Cliff Dylan Paul , Davern Melanie T. , Engelen Lina , Gomersall Sjaan R. , Ziviani Jenny , Schranz Natasha K. , Olds Tim , Tomkinson Grant Ryan
Published: August 2015

Background:

Australia has joined a growing number of nations that have evaluated the physical activity and sedentary behavior status of their children. Australia received a “D minus” in the first Active Healthy Kids Australia Physical Activity Report Card.

Methods:

An expert subgroup of the Australian Report Card Research Working Group iteratively reviewed available evidence to answer 3 questions: (a) What are the main sedentary behaviors of children? (b) What are the potential mechanisms for sedentary behavior to impact child health and development? and (c) What are the effects of different types of sedentary behaviors on child health and development?

Results:

Neither sedentary time nor screen time is a homogeneous activity likely to result in homogenous effects. There are several mechanisms by which various sedentary behaviors may positively or negatively affect cardiometabolic, neuromusculoskeletal, and psychosocial health, though the strength of evidence varies. National surveillance systems and mechanistic, longitudinal, and experimental studies are needed for Australia and other nations to improve their grade.

Conclusions:

Despite limitations, available evidence is sufficiently convincing that the total exposure and pattern of exposure to sedentary behaviors are critical to the healthy growth, development, and wellbeing of children. Nations therefore need strategies to address these common behaviors.
The Effect of Footrest on Standing Postural Control
Authors: Ganesan Mohan , Lee Yun-Ju , Aruin Alexander S.
Published: August 2015

The use of a footrest while performing activity in standing is frequently associated with improvement of a user’s well-being however no information exists on the role of a footrest in improving postural stability. The aim of the study was to evaluate the effects of using a footrest in postural control. Twenty healthy young volunteers were tested using three experimental conditions: standing with two feet on the force platform and standing on the force platform when one foot was placed on a 15 cm footrest positioned in front or laterally. The mean and root mean square distance, range and velocity of the center of pressure (COP) were calculated in the anterior-posterior (AP) and medio-lateral (ML) directions using the force platform data. The COP displacements in AP and ML directions increased in conditions of standing with one foot placed on the footrest regardless of its location. Standing with eyes closed increased COP displacements further. The outcome of the study suggests the importance of using COP measures for evaluation of postural stability and provides additional information needed for optimization of working conditions involving standing with a footrest.
The Effects of 8-Week Plyometric Training on Physical Performance in Young Tennis Players
Authors: Fernandez-Fernandez Jaime , De Villarreal Eduardo Sáez , Sanz-Rivas David , Moya Manuel
Published: August 2015

Objectives:

The aim of this study was to analyze the effects of an 8-week (conducted biweekly for a total of 16 sessions) plyometric training program (PT) (e.g., upper- and lower-body exercises) combined with regular tennis training on physical qualities in young tennis players.

Design:

Sixty tennis players between the ages of 12 and 13 years (age 12.5 ± 0.3 years, weight 44.2 ± 7.0 kg, height 156.6 ± 7.1 cm) were allocated to either the control group (standard in-season regimen) (CG; n = 30) or the experimental group, which received an additional PT (TG; n = 30) for 30–60 min as a substitute for some tennis training within the usual 90-min practice.

Methods:

Pre- and posttests included: anthropometric measures; vertical countermovement jump (CMJ); standing long jump (SLJ); 20 m sprint time (with 5 and 10 m splits); a modified 505 agility test; overhead medicine ball throw; and serve velocity test.

Results:

After the training intervention, the TG showed significant (p < .01) improvements in all the parameters analyzed, with percentages of change and effect sizes ranging from 3.1% to 10.1% and 0.4 (small) to 1.3 (moderate), respectively. No significant changes were observed in the CG after the training intervention.

Conclusions:

PT was shown as an important stimulus for enhancing explosive actions in young tennis players.
The Development of Activity Profiles in Adolescent Females and their Association with Adiposity
Authors: Dowd Kieran , Harrington Deidre , Hannigan Ailish , Purtill Helen , Kelly Sarah M. , Macken Alan P. , Moyna Niall , O’Gorman Clodagh S. , Donnelly Alan E.
Published: August 2015

Objectives:

This study aims to (1) use the objective activPAL activity monitor to assess physical activity behaviors, including sitting/lying, standing, and both light (LIPA) and moderate-to-vigorous physical activity (MVPA); (2) to develop distinct activity profiles based on time spent in each behavior in a sample of adolescent females; and (3) examine whether levels of adiposity differ across these activity profiles.

Methods:

Female adolescents (n = 195; 14–18 y) had body mass index (median = 21.7 [IQR = 5.2] kg/m2) and 4-site skinfold thickness (median 62.0 mm; IQR = 37.1) measured. Physical activity behaviors were measured using the activPAL. Hierarchical cluster analysis grouped participants into activity profiles based on similar physical activity characteristics. Linear mixed models explored differences in body composition across activity profiles.

Results:

Three activity profiles were identified, a low (n = 35), moderate (n = 110), and a high activity profile (n = 50). Significant differences across activity profiles were observed for skinfold thickness (p = .046), with higher values observed in the low activity profile compared with the high activity profile.

Conclusions:

Profiling free-living activity using behaviors from across the activity intensity continuum may account for more of the variability in energy expenditure then examining specific activity intensities, such as MVPA alone. The use of activity profiles may enable the identification of individuals with unhealthy activity behaviors, leading to the development and implementation of more targeted interventions.
The brain's identity crisis
Authors: Underwood Emily
Published: August 2015

Will new tools for classifying neurons put a 150-year-long debate to rest?
The reusable holdout: Preserving validity in adaptive data analysis
Authors: Dwork Cynthia , Feldman Vitaly , Hardt Moritz , Pitassi Toniann , Reingold Omer , Roth Aaron
Published: August 2015

Testing hypotheses privately

Large data sets offer a vast scope for testing already-formulated ideas and exploring new ones. Unfortunately, researchers who attempt to do both on the same data set run the risk of making false discoveries, even when testing and exploration are carried out on distinct subsets of data. Based on ideas drawn from differential privacy, Dworket al.now provide a theoretical solution. Ideas are tested against aggregate information, whereas individual data set components remain confidential. Preserving that privacy also preserves statistical inference validity.

Science, this issue p.636
The next century of ecology
Authors: Inouye David W.
Published: August 2015

The science of ecology is about relationships—among organisms and habitats, on all scales—and how they provide information that helps us better understand our world. In the past 100 years, the field has moved from observations to experiments to forecasting. Next week, the Ecological Society of America (ESA), the world's largest ecological society, celebrates its centennial in Baltimore, an opportunity to reflect on the field's past and future. The gathering of international scientists, policy-makers, and students will not only explore the knowledge in hand, but consider what else is needed to chart a course over the next century in which humanity sustains and even improves the relationships that underpin life on Earth.
Profiling risk and sustainability in coastal deltas of the world
Authors: Tessler Z. D. , Vörösmarty C. J. , Grossberg M. , Gladkova I. , Aizenman H. , Syvitski J. P. M. , Foufoula-Georgiou E.
Published: August 2015

Deltas are growing centers of risk

Population growth, urbanization, and rising sea levels are placing populations living in delta regions under increased risk. The future resiliency and potential for adaptation by these populations depend on a number of socioeconomic and geophysical factors. Tessler
et al.
examined 48 deltas from around the globe to assess changes in regional vulnerability (see the Perspective by Temmerman). Some deltas in countries with a high gross domestic product will be initially more resilient to these changes, because they can perform expensive maintenance on infrastructure. However, short-term policies will become unsustainable if unaccompanied by long-term investments in all delta regions.

Science
, this issue p.
638
; see also p.
588
Deepwater Horizon, 5 years on
Authors: Joye Samantha B.
Published: August 2015

Baseline environmental data are crucial for understanding the impacts of oil spills
Plasmons at the interface
Authors: Kale Matthew J. , Christopher Phillip
Published: August 2015

Extraction of light-induced electrons is enhanced by interface control

[Also see Report by

Wu
et al.

]
Multivalent Pneumococcal Protein Vaccines Comprising Pneumolysoid with Epitopes/Fragments of CbpA and/or PspA Elicit Strong and Broad Protection
Authors: Chen Austen , Mann Beth , Gao Geli , Heath Richard , King Janice , Maissoneuve Jeff , Alderson Mark , Tate Andrea , Hollingshead Susan K. , Tweten Rodney K. , Briles David E. , Tuomanen Elaine I. , Paton James C.
Published: August 2015

Immunization with the pneumococcal proteins pneumolysin (Ply), choline binding protein A (CbpA), or pneumococcal surface protein A (PspA) elicits protective responses against invasive pneumococcal disease in animal models. In this study, we used different mouse models to test the efficacy of a variety of multivalent protein-based vaccines that comprised various combinations of full-length or peptide regions of the immunogens Ply, CbpA, or PspA: Ply toxoid with the L460D substitution (referred to herein as L460D); L460D fused with protective peptide epitopes from CbpA (YPT-L460D-NEEK [YLN]); L460D fused with the CD2 peptide containing the proline-rich region (PRR) of PspA (CD2-L460D); a combination of L460D and H70 (L460D+H70), a slightly larger PspA-derived peptide containing the PRR and the SM1 region; H70+YLN; and other combinations. Each mouse was immunized either intraperitoneally (i.p.) or subcutaneously (s.c.) with three doses (at 2-week intervals) of the various antigen combinations in alum adjuvant and then challenged in mouse models featuring different infection routes with multiple
Streptococcus pneumoniae
strains. In the i.p. infection sepsis model, H70+YLN consistently provided significant protection against three different challenge strains (serotypes 1, 2, and 6A); the CD2+YLN and H70+L460D combinations also elicited significant protection. Protection against intravenous (i.v.) sepsis (type 3 and 6A challenge strains) was largely dependent on PspA-derived antigen components, and the most protection was elicited by H70 with or without L460D or YLN. In a type 4 intratracheal (i.t.) challenge model that results in progression to meningitis, antigen combinations that contained YLN elicited the strongest protection. Thus, the trivalent antigen combination of H70+YLN elicited the strongest and broadest protection in diverse pneumococcal challenge models.
Quantitative Microplate-Based Growth Assay for Determination of Antifungal Susceptibility of Histoplasma capsulatum Yeasts
Authors: Goughenour Kristie D. , Balada-Llasat Joan-Miquel , Rappleye Chad A.
Published: August 2015

Standardized methodologies for determining the antifungal susceptibility of fungal pathogens is central to the clinical management of invasive fungal disease. Yeast-form fungi can be tested using broth macrodilution and microdilution assays. Reference procedures exist for
Candida
species and
Cryptococcus
yeasts; however, no standardized methods have been developed for testing the antifungal susceptibility of yeast forms of the dimorphic systemic fungal pathogens. For the dimorphic fungal pathogen
Histoplasma capsulatum
, susceptibility to echinocandins differs for the yeast and the filamentous forms, which highlights the need to employ
Histoplasma
yeasts, not hyphae, in antifungal susceptibility tests. To address this, we developed and optimized methodology for the 96-well microtiter plate-based measurement of
Histoplasma
yeast growth
in vitro
. Using optical density, the assay is quantitative for fungal growth with a dynamic range greater than 30-fold. Concentration and assay reaction time parameters were also optimized for colorimetric (MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] reduction) and fluorescent (resazurin reduction) indicators of fungal vitality. We employed this microtiter-based assay to determine the antifungal susceptibility patterns of multiple clinical isolates of
Histoplasma
representing different phylogenetic groups. This methodology fulfills a critical need for the ability to monitor the effectiveness of antifungals on
Histoplasma
yeasts, the morphological form present in mammalian hosts and, thus, the form most relevant to disease.
Hepatitis C Virus Envelope Glycoprotein E1 Forms Trimers at the Surface of the Virion
Authors: Falson Pierre , Bartosch Birke , Alsaleh Khaled , Tews Birke Andrea , Loquet Antoine , Ciczora Yann , Riva Laura , Montigny Cédric , Montpellier Claire , Duverlie Gilles , Pécheur Eve-Isabelle , le Maire Marc , Cosset François-Loïc , Dubuisson Jean , Penin François
Published: August 2015

In hepatitis C virus (HCV)-infected cells, the envelope glycoproteins E1 and E2 assemble as a heterodimer. To investigate potential changes in the oligomerization of virion-associated envelope proteins, we performed SDS-PAGE under reducing conditions but without thermal denaturation. This revealed the presence of SDS-resistant trimers of E1 in the context of cell-cultured HCV (HCVcc) as well as in the context of HCV pseudoparticles (HCVpp). The formation of E1 trimers was found to depend on the coexpression of E2. To further understand the origin of E1 trimer formation, we coexpressed in bacteria the transmembrane (TM) domains of E1 (TME1) and E2 (TME2) fused to reporter proteins and analyzed the fusion proteins by SDS-PAGE and Western blotting. As expected for strongly interacting TM domains, TME1–TME2 heterodimers resistant to SDS were observed. These analyses also revealed homodimers and homotrimers of TME1, indicating that such complexes are stable species. The N-terminal segment of TME1 exhibits a highly conserved GxxxG sequence, a motif that is well documented to be involved in intramembrane protein-protein interactions. Single or double mutations of the glycine residues (Gly354 and Gly358) in this motif markedly decreased or abrogated the formation of TME1 homotrimers in bacteria, as well as homotrimers of E1 in both HCVpp and HCVcc systems. A concomitant loss of infectivity was observed, indicating that the trimeric form of E1 is essential for virus infectivity. Taken together, these results indicate that E1E2 heterodimers form trimers on HCV particles, and they support the hypothesis that E1 could be a fusion protein.

IMPORTANCE
HCV glycoproteins E1 and E2 play an essential role in virus entry into liver cells as well as in virion morphogenesis. In infected cells, these two proteins form a complex in which E2 interacts with cellular receptors, whereas the function of E1 remains poorly understood. However, recent structural data suggest that E1 could be the protein responsible for the process of fusion between viral and cellular membranes. Here we investigated the oligomeric state of HCV envelope glycoproteins. We demonstrate that E1 forms functional trimers after virion assembly and that in addition to the requirement for E2, a determinant for this oligomerization is present in a conserved GxxxG motif located within the E1 transmembrane domain. Taken together, these results indicate that a rearrangement of E1E2 heterodimer complexes likely occurs during the assembly of HCV particles to yield a trimeric form of the E1E2 heterodimer. Gaining structural information on this trimer will be helpful for the design of an anti-HCV vaccine.
Identification of Host Cell Factors Associated with Astrovirus Replication in Caco-2 Cells
Authors: Murillo Andrea , Vera-Estrella Rosario , Barkla Bronwyn J. , Méndez Ernesto , Arias Carlos F.
Published: August 2015

Astroviruses are small, nonenveloped viruses with a single-stranded positive-sense RNA genome causing acute gastroenteritis in children and immunocompromised patients. Since positive-sense RNA viruses have frequently been found to replicate in association with membranous structures, in this work we characterized the replication of the human astrovirus serotype 8 strain Yuc8 in Caco-2 cells, using density gradient centrifugation and free-flow zonal electrophoresis (FFZE) to fractionate cellular membranes. Structural and nonstructural viral proteins, positive- and negative-sense viral RNA, and infectious virus particles were found to be associated with a distinct population of membranes separated by FFZE. The cellular proteins associated with this membrane population in infected and mock-infected cells were identified by tandem mass spectrometry. The results indicated that membranes derived from multiple cell organelles were present in the population. Gene ontology and protein-protein interaction network analysis showed that groups of proteins with roles in fatty acid synthesis and ATP biosynthesis were highly enriched in the fractions of this population in infected cells. Based on this information, we investigated by RNA interference the role that some of the identified proteins might have in the replication cycle of the virus. Silencing of the expression of genes involved in cholesterol (
DHCR7
,
CYP51A1
) and fatty acid (
FASN
) synthesis, phosphatidylinositol (
PI4KIIIβ
) and inositol phosphate (
ITPR3
) metabolism, and RNA helicase activity (
DDX23
) significantly decreased the amounts of Yuc8 genomic and antigenomic RNA, synthesis of the structural protein VP90, and virus yield. These results strongly suggest that astrovirus RNA replication and particle assembly take place in association with modified membranes potentially derived from multiple cell organelles.

IMPORTANCE
Astroviruses are common etiological agents of acute gastroenteritis in children and immunocompromised patients. More recently, they have been associated with neurological diseases in mammals, including humans, and are also responsible for different pathologies in birds. In this work, we provide evidence that astrovirus RNA replication and virus assembly occur in contact with cell membranes potentially derived from multiple cell organelles and show that membrane-associated cellular proteins involved in lipid metabolism are required for efficient viral replication. Our findings provide information to enhance our knowledge of astrovirus biology and provide information that might be useful for the development of therapeutic interventions to prevent virus replication.
Turnover Rate of NS3 Proteins Modulates Bluetongue Virus Replication Kinetics in a Host-Specific Manner
Authors: Ftaich Najate , Ciancia Claire , Viarouge Cyril , Barry Gerald , Ratinier Maxime , van Rijn Piet A. , Breard Emmanuel , Vitour Damien , Zientara Stephan , Palmarini Massimo , Terzian Christophe , Arnaud Frédérick
Published: August 2015

Bluetongue virus (BTV) is an arbovirus transmitted to livestock by midges of the
Culicoides
family and is the etiological agent of a hemorrhagic disease in sheep and other ruminants. In mammalian cells, BTV particles are released primarily by virus-induced cell lysis, while in insect cells they bud from the plasma membrane and establish a persistent infection. BTV possesses a ten-segmented double-stranded RNA genome, and NS3 proteins are encoded by segment 10 (Seg-10). The viral nonstructural protein 3 (NS3) plays a key role in mediating BTV egress as well as in impeding the
in vitro
synthesis of type I interferon in mammalian cells. In this study, we asked whether genetically distant NS3 proteins can alter BTV-host interactions. Using a reverse genetics approach, we showed that, depending on the NS3 considered, BTV replication kinetics varied in mammals but not in insects. In particular, one of the NS3 proteins analyzed harbored a proline at position 24 that leads to its rapid intracellular decay in ovine but not in
Culicoides
cells and to the attenuation of BTV virulence in a mouse model of disease. Overall, our data reveal that the genetic variability of Seg-10/NS3 differentially modulates BTV replication kinetics in a host-specific manner and highlight the role of the host-specific variation in NS3 protein turnover rate.

IMPORTANCE
BTV is the causative agent of a severe disease transmitted between ruminants by biting midges of
Culicoides
species. NS3, encoded by Seg-10 of the BTV genome, fulfills key roles in BTV infection. As Seg-10 sequences from various BTV strains display genetic variability, we assessed the impact of different Seg-10 and NS3 proteins on BTV infection and host interactions. In this study, we revealed that various Seg-10/NS3 proteins alter BTV replication kinetics in mammals but not in insects. Notably, we found that NS3 protein turnover may vary in ovine but not in
Culicoides
cells due to a single amino acid residue that, most likely, leads to rapid and host-dependent protein degradation. Overall, this study highlights that genetically distant BTV Seg-10/NS3 influence BTV biological properties in a host-specific manner and increases our understanding of how NS3 proteins contribute to the outcome of BTV infection.
Establishment of a Zebrafish Infection Model for the Study of Wild-Type and Recombinant European Sheatfish Virus
Authors: Martín Verónica , Mavian Carla , López Bueno Alberto , de Molina Antonio , Díaz Eduardo , Andrés Germán , Alcami Antonio , Alejo Alí
Published: August 2015

Amphibian-like ranaviruses include pathogens of fish, amphibians, and reptiles that have recently evolved from a fish-infecting ancestor. The molecular determinants of host range and virulence in this group are largely unknown, and currently fish infection models are lacking. We show that European sheatfish virus (ESV) can productively infect zebrafish, causing a lethal pathology, and describe a method for the generation of recombinant ESV, establishing a useful model for the study of fish ranavirus infections.
Host Determinants of Prion Strain Diversity Independent of Prion Protein Genotype
Authors: Crowell Jenna , Hughson Andrew , Caughey Byron , Bessen Richard A.
Published: August 2015

Phenotypic diversity in prion diseases can be specified by prion strains in which biological traits are propagated through an epigenetic mechanism mediated by distinct PrP
Sc
conformations. We investigated the role of host-dependent factors on phenotypic diversity of chronic wasting disease (CWD) in different host species that express the same prion protein gene (
Prnp
). Two CWD strains that have distinct biological, biochemical, and pathological features were identified in transgenic mice that express the Syrian golden hamster (SGH)
Prnp
. The CKY strain of CWD had a shorter incubation period than the WST strain of CWD, but after transmission to SGH, the incubation period of CKY CWD was ∼150 days longer than WST CWD. Limited proteinase K digestion revealed strain-specific PrP
Sc
polypeptide patterns that were maintained in both hosts, but the solubility and conformational stability of PrP
Sc
differed for the CWD strains in a host-dependent manner. WST CWD produced PrP
Sc
amyloid plaques in the brain of the SGH that were partially insoluble and stable at a high concentration of protein denaturant. However, in transgenic mice, PrP
Sc
from WST CWD did not assemble into plaques, was highly soluble, and had low conformational stability. Similar studies using the HY and DY strains of transmissible mink encephalopathy resulted in minor differences in prion biological and PrP
Sc
properties between transgenic mice and SGH. These findings indicate that host-specific pathways that are independent of
Prnp
can alter the PrP
Sc
conformation of certain prion strains, leading to changes in the biophysical properties of PrP
Sc
, neuropathology, and clinical prion disease.

IMPORTANCE
Prions are misfolded pathogenic proteins that cause neurodegeneration in humans and animals. Transmissible prion diseases exhibit a spectrum of disease phenotypes and the basis of this diversity is encoded in the structure of the pathogenic prion protein and propagated by an epigenetic mechanism. In the present study, we investigated prion diversity in two hosts species that express the same prion protein gene. While prior reports have demonstrated that prion strain properties are stable upon infection of the same host species and prion protein genotype, our findings indicate that certain prion strains can undergo dramatic changes in biological properties that are not dependent on the prion protein. Therefore, host factors independent of the prion protein can affect prion diversity. Understanding how host pathways can modify prion disease phenotypes may provide clues on how to alter prion formation and lead to treatments for prion, and other, human neurodegenerative diseases of protein misfolding.
Hydrodynamic and Membrane Binding Properties of Purified Rous Sarcoma Virus Gag Protein
Authors: Dick Robert A. , Datta Siddhartha A. K. , Nanda Hirsh , Fang Xianyang , Wen Yi , Barros Marilia , Wang Yun-Xing , Rein Alan , Vogt Volker M.
Published: August 2015

Previously, no retroviral Gag protein has been highly purified in milligram quantities and in a biologically relevant and active form. We have purified Rous sarcoma virus (RSV) Gag protein and in parallel several truncation mutants of Gag and have studied their biophysical properties and membrane interactions
in vitro
. RSV Gag is unusual in that it is not naturally myristoylated. From its ability to assemble into virus-like particles
in vitro
, we infer that RSV Gag is biologically active. By size exclusion chromatography and small-angle X-ray scattering, Gag in solution appears extended and flexible, in contrast to previous reports on unmyristoylated HIV-1 Gag, which is compact. However, by neutron reflectometry measurements of RSV Gag bound to a supported bilayer, the protein appears to adopt a more compact, folded-over conformation. At physiological ionic strength, purified Gag binds strongly to liposomes containing acidic lipids. This interaction is stimulated by physiological levels of phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and by cholesterol. However, unlike HIV-1 Gag, RSV Gag shows no sensitivity to acyl chain saturation. In contrast with full-length RSV Gag, the purified MA domain of Gag binds to liposomes only weakly. Similarly, both an N-terminally truncated version of Gag that is missing the MA domain and a C-terminally truncated version that is missing the NC domain bind only weakly. These results imply that NC contributes to membrane interaction
in vitro
, either by directly contacting acidic lipids or by promoting Gag multimerization.

IMPORTANCE
Retroviruses like HIV assemble at and bud from the plasma membrane of cells. Assembly requires the interaction between thousands of Gag molecules to form a lattice. Previous work indicated that lattice formation at the plasma membrane is influenced by the conformation of monomeric HIV. We have extended this work to the more tractable RSV Gag. Our results show that RSV Gag is highly flexible and can adopt a folded-over conformation on a lipid bilayer, implicating both the N and C termini in membrane binding. In addition, binding of Gag to membranes is diminished when either terminal domain is truncated. RSV Gag membrane association is significantly less sensitive than HIV Gag membrane association to lipid acyl chain saturation. These findings shed light on Gag assembly and membrane binding, critical steps in the viral life cycle and an untapped target for antiretroviral drugs.
Role for a Zinc Finger Protein (Zfp111) in Transformation of 208F Rat Fibroblasts by Jaagsiekte Sheep Retrovirus Envelope Protein
Authors: Hsu Tom , Phung An , Choe Kevin , Kim Jung Woo , Fan Hung
Published: August 2015

The native envelope gene (
env
) of Jaagsiekte sheep retrovirus (JSRV) also acts as an oncogene. To investigate the mechanism of transformation, we performed yeast 2-hybrid screening for cellular proteins that interact with Env. Among several candidates, we identified mouse or rat zinc finger protein 111 (
zfp111
). The interaction between Env and Zfp111 was confirmed through
in vivo
coimmunoprecipitation assays. Knockdown of endogenous Zfp111 caused a decrease in cell transformation by JSRV Env, while overexpression of Zfp111 increased overall Env transformation, supporting a role for Zfp111 in Env transformation. Knockdown of Zfp111 had no effect on the growth rate of parental rat 208F cells, while it decreased the proliferation rate of JSRV-transformed 208F cells, suggesting that JSRV-transformed cells became dependent on Zfp111. In addition, Zfp111 preferentially bound to a higher-mobility form of JSRV Env that has not been described previously. The higher-mobility form of Env (P70

env

) was found exclusively in the nuclear fraction, and size of its polypeptide backbone was the same as that of the cytoplasmic Env polyprotein (Pr80

env

). The differences in glycosylation between the two versions of Env were characterized. These results identify a novel cellular protein, Zfp111, that binds to the JSRV Env protein, and this binding plays a role in Env transformation. These results indicate that JSRV transformation also involves proteins and interactions in the nucleus.

IMPORTANCE
The envelope protein (Env) of Jaagsiekte sheep retrovirus (JSRV) is an oncogene, but its mechanism of cell transformation is still unclear. Here we identified seven candidate cellular proteins that can interact with JSRV Env by yeast two-hybrid screening. This study focused on one of the seven candidates, zinc finger protein 111 (Zfp111). Zfp111 was shown to interact with JSRV Env in cells and to be involved in JSRV transformation. Moreover, coexpression of JSRV Env and Zfp111 led to the identification of a novel nuclear form of the JSRV Env protein that binds Zfp111. Nuclear Env was found to differ by glycosylation from the cytoplasmic Env precursor to the virion envelope proteins. These results suggest that JSRV Env transformation may involve nuclear events such as an alteration in transcription mediated by Env-Zfp111 interactions.
Soluble Envelope Glycoprotein Trimers from a CD4-Independent HIV-1 Elicit Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies in Guinea Pigs
Authors: Murray Marta K. , Teran Victor A. , Chapleau Jean-Philippe , Wang Baomin , Kim Su Hyon , LaBranche Celia C. , Richard Jonathan , Montefiori David C. , Finzi Andrés , Yuan Wen
Published: August 2015

CD4-independent HIV-1 variants can infect coreceptor-expressing cells lacking CD4. The envelope (Env) glycoproteins on these HIV-1 variants expose a coreceptor binding site that overlaps some CD4-induced (CD4i) epitopes. Reports have demonstrated that CD4i antibodies mediate antibody-dependent cellular cytotoxicity (ADCC). Here we investigated the immunogenicity of soluble Env trimers (sgp140) from a CD4-independent HIV-1 in guinea pigs and found that the sgp140 elicited ADCC-mediating antibodies. Therefore, these sgp140 might be useful in vaccine regimens aimed at eliciting ADCC responses.
Structural and Functional Diversity of Nairovirus-Encoded Nucleoproteins
Authors: Wang Wenming , Liu Xiang , Wang Xu , Dong Hui , Ma Chao , Wang Jingmin , Liu Baocheng , Mao Yonghong , Wang Ying , Li Ting , Yang Cheng , Guo Yu
Published: August 2015

The nairoviruses include assorted tick-borne bunyaviruses that are emerging as causative agents of infectious diseases among humans and animals. As negative-sense single-stranded RNA (−ssRNA) viruses, nairoviruses encode nucleoprotein (NP) that encapsidates the genomic RNA and further forms ribonucleoprotein (RNP) complex with viral RNA-dependent RNA polymerase (RdRp). We previously revealed that the monomeric NP encoded by Crimean-Congo hemorrhagic fever virus (CCHFV) presents a racket-shaped structure and shows unusual DNA-specific endonuclease activity. To examine the structural and biological variation of nairovirus-encoded NPs, here, we systematically solved the crystal structures of NPs encoded by various nairoviruses, including Hazara virus (HAZV), Kupe virus (KUPV), and Erve virus (ERVEV). Combined with biochemical analysis, our results generate a clearer picture to aid in the understanding of the functional diversity of nairovirus-encoded NPs and the formation of nairovirus RNPs.

IMPORTANCE
Nairoviruses comprise several tick-borne bunyaviruses that are emerging as causative agents of infectious diseases among humans and animals; however, little is known of the nairovirus genome assembly and transcription mechanisms. Based on the previous study of CCHFV NP reported by different research groups, we systematically investigate here the structural and functional diversity among three different nairoviruses. This work provides important information on nairovirus nucleoprotein function and the formation of RNPs.
Suppressor of Cytokine Signaling 3 Is an Inducible Host Factor That Regulates Virus Egress during Ebola Virus Infection
Authors: Okumura Atsushi , Rasmussen Angela L. , Halfmann Peter , Feldmann Friederike , Yoshimura Akihiko , Feldmann Heinz , Kawaoka Yoshihiro , Harty Ronald N. , Katze Michael G.
Published: August 2015

Ebola virus (EBOV) initially targets monocytes and macrophages, which can lead to the release of proinflammatory cytokines and chemokines. These inflammatory cytokines are thought to contribute to the development of circulatory shock seen in fatal EBOV infections. The VP40 matrix protein is a key viral structural protein that is critical for virion egress. Physical and functional interactions between VP40 and host proteins such as Tsg101 and Nedd4 facilitate efficient release of VP40-driven virus-like particles (VLPs) and infectious virus. Here, we show that host suppressor of cytokine signaling 3 (SOCS3) can also bind to EBOV VP40, leading to enhanced ubiquitinylation and egress of VP40. Indeed, titers of infectious EBOV derived from SOCS3 knockout mouse embryonic fibroblasts (MEFs) were significantly reduced compared to those from wild-type (WT) MEFs at 24 and 48 h postinfection. Importantly, this reduced virus yield could be rescued back to WT levels by exogenously expressing SOCS3. Lastly, we show that SOCS3 expression is induced by EBOV glycoprotein (GP) expression and that VLPs containing EBOV VP40 and GP induced production of proinflammatory cytokines, which induced SOCS3 for negative-feedback regulation. These data indicate that host innate immune protein SOCS3 may play an important role in budding and pathogenesis of EBOV.

IMPORTANCEThe VP40 matrix protein is a key structural protein critical for Ebola virus budding. Physical and functional interactions between VP40 and host proteins such as Tsg101 and Nedd4 facilitate efficient release of VLPs and infectious virus. We reported that host TLR4 is a sensor for Ebola GP on VLPs and that the resultant TLR4 signaling pathways lead to the production of proinflammatory cytokines. Host SOCS3 regulates the innate immune response by controlling and limiting the proinflammatory response through negative-feedback inhibition of cytokine receptors. We present evidence that Ebola virus VLPs stimulate induction of SOCS3 as well as proinflammatory cytokines, and that expression of human SOCS3 enhances budding of Ebola VLPs and infectious virus via a mechanism linked to the host ubiquitinylation machinery.
Infections on Cruise Ships
Authors: Kak Vivek
Published: August 2015

The modern cruise ship is a small city on the seas, with populations as large as 5,000 seen on large ships. The growth of the cruise ship industry has continued in the twenty-first century, and it was estimated that nearly 21.3 million passengers traveled on cruise ships in 2013, with the majority of these sailing from North America. The presence of large numbers of individuals in close proximity to each other facilitates transmission of infectious diseases, often through person-to-person spread or via contaminated food or water. An infectious agent introduced into the environment of a cruise ship has the potential to be distributed widely across the ship and to cause significant morbidity. The median cruise ship passenger is over 45 years old and often has chronic medical problems, so it is important that, to have a safe cruise ship experience, any potential for the introduction of an infecting agent as well as its transmission be minimized. The majority of cruise ship infections involve respiratory and gastrointestinal infections. This article discusses infectious outbreaks on cruise ships and suggests preventative measures for passengers who plan to travel on cruise ships.
The Role of Vibrios in Diseases of Corals
Authors: Munn Colin B.
Published: August 2015

The tissue, skeleton, and secreted mucus of corals supports a highly dynamic and diverse community of microbes, which play a major role in the health status of corals such as the provision of essential nutrients or the metabolism of waste products. However, members of the
Vibrio
genus are prominent as causative agents of disease in corals. The aim of this chapter is to review our understanding of the spectrum of disease effects displayed by coral-associated vibrios, with a particular emphasis on the few species where detailed studies of pathogenicity have been conducted. The role of
Vibrio shilonii
in seasonal bleaching of
Oculina patagonica
and the development of the coral probiotic hypothesis is reviewed, pointing to unanswered questions about this phenomenon. Detailed consideration is given to studies of
V. coralliilyticus
and related pathogens and changes in the dominance of vibrios associated with coral bleaching. Other
Vibrio
-associated disease syndromes discussed include yellow band/blotch disease and tissue necrosis in temperate gorgonian corals. The review includes analysis of the role of enzymes, resistance to oxidative stress, and quorum sensing in virulence of coral-associated vibrios. The review concludes that we should probably regard most—possibly all—vibrios as “opportunistic” pathogens which, under certain environmental conditions, are capable of overwhelming the defense mechanisms of appropriate hosts, leading to rapid growth and tissue destruction.
Allergic bronchopulmonary aspergillosis in an adult with Kartagener syndrome
Authors: Sehgal Inderpaul Singh , Dhooria Sahajal , Bal Amanjit , Agarwal Ritesh
Published: August 2015

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder resulting from immune responses directed against inhaledAspergillus fumigatusantigens. It manifests with poorly controlled asthma, fleeting pulmonary opacities and structural lung damage in the form of bronchiectasis. Initially defined in individuals suffering from bronchial asthma and cystic fibrosis, it has also been described in patients with other structural lung disorders such as chronic obstructive pulmonary disease, pulmonary tuberculosis, idiopathic bronchiectasis and others. Kartagener syndrome is a manifestation of primary ciliary dyskinesia characterised by the presence of dextrocardia, bronchiectasis and chronic sinusitis. We report a case of ABPA in an adult suffering from Kartagener syndrome. We also performed a systematic review of the literature on the association between Kartagener syndrome and ABPA.
Relationship between education levels and booster counselling sessions on smoking cessation among Chinese smokers
Authors: Wu Lei , He Yao , Jiang Bin , Zuo Fang , Liu Qinghui , Zhang Li , Zhou Changxi , Liu Miao , Chen Hongyan
Published: August 2015

Objectives

Although various effective interventions are available to help individuals quit smoking, the effect of educational levels on cessation rates has rarely been studied, and of the few intervention studies on this topic, the results have been conflicting.

Design and setting

From October 2008 to August 2013, a partly retrospective non-randomised study was conducted in a smoking cessation clinic of a large general hospital in Beijing, China.

Participants

In total, 547 Chinese smokers who sought treatment were divided into two groups: a face-to-face counselling group (FC, n=149) and an FC group subjected to four telephone follow-up sessions (FCF, n=398).

Outcomes

We evaluated self-reported cessation rates by day 7 and after 6 and 12 months and stratified the two groups by education levels.

Results

The 7-day and 6-month and 12-month continuous cessation rates of smokers of low education levels in the FC group at the time of the 12-month follow-up were 12.5%, 7.1% and 7.1%, respectively, which were lower than those of the highly educated smokers (16.1%, 12.9% and 9.7%, respectively). The results were opposite for the FCF group. The corresponding results for the highly educated smokers of the FCF group were 25.0%, 17.2% and 10.3%, respectively, which were lower than those for the smokers of low education levels (28.3%, 22.9% and 18.1%, respectively). However, significant differences were observed only among the FCF group participants who had experienced 12 months of continuous abstinence, and the crude OR for these individuals was recorded at 0.52 (0.29 to 0.93), p=0.03. A stepwise logistic regression showed that education levels may play a role in various intervention methods. Being married and higher Fagerström test scores were also predictors of cessation tendencies.

Conclusions

Education levels may affect the benefits of booster counselling sessions on smoking cessation among Chinese smokers.