Effects of acute fatigue on the volitional and magnetically-evoked electromechanical delay of the knee flexors in males and females

Neuromuscular performance capabilities, including those measured by evoked responses, may be adversely affected by fatigue; however, the capability of the neuromuscular system to initiate muscle force rapidly under these circumstances is yet to be established. Sex-differences in the acute responses of neuromuscular performance to exercise stress may be linked to evidence that females are much more vulnerable to ACL injury than males. Optimal functioning of the knee flexors is paramount to the dynamic stabilisation of the knee joint, therefore the aim of this investigation was to examine the effects of acute maximal intensity fatiguing exercise on the voluntary and magnetically-evoked electromechanical delay in the knee flexors of males and females. Knee flexor volitional and magnetically-evoked neuromuscular performance was assessed in seven male and nine females prior to and immediately after: (i) an intervention condition comprising a fatigue trial of 30-seconds maximal static exercise of the knee flexors, (ii) a control condition consisting of no exercise. The results showed that the fatigue intervention was associated with a substantive reduction in volitional peak force (PFV) that was greater in males compared to females (15.0%, 10.2%, respectively, p < 0.01) and impairment to volitional electromechanical delay (EMDV) in females exclusively (19.3%, p < 0.05). Similar improvements in magnetically-evoked electromechanical delay in males and females following fatigue (21%, p < 0.001), however, may suggest a vital facilitatory mechanism to overcome the effects of impaired voluntary capabilities, and a faster neuromuscular response that can be deployed during critical times to protect the joint system

Underperforming policy networks : the biopesticides network in the United Kingdom

Loosely integrated and incomplete policy networks have been neglected in the literature. They are important to consider in terms of understanding network underperformance. The effective delivery and formulation of policy requires networks that are not incomplete or underperforming. The biopesticides policy network in the United Kingdom is considered and its components identified with an emphasis on the lack of integration of retailers and environmental groups. The nature of the network constrains the actions of its agents and frustrates the achievement of policy goals. A study of this relatively immature policy network also allows for a focus on network formation. The state, via an external central government department, has been a key factor in the development of the network. Therefore, it is important to incorporate such factors more systematically into understandings of network formation. Feedback efforts from policy have increased interactions between productionist actors but the sphere of consumption remains insufficiently articulated

A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila

Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens

A statistical approach to quantitative data validation focused on the assessment of students' perceptions about biotechnology

Student awareness levels are frequently used to evaluate the effectiveness of educational policies to promote scientific literacy. Over the last years several studies have been developed to assess students' perceptions towards science and technology, which usually rely on quantitative methods to achieve broad characterizations, and obtain quantifiable and comparable data. Although the usefulness of this information depends on its validity and reliability, validation is frequently neglected by researchers with limited background in statistics. In this context, we propose a guideline to implement a statistical approach to questionnaire validation, combining exploratory factor analysis and reliability analysis. The work focuses on the psychometric analysis of data provided by a questionnaire assessing 1196 elementary and high school students' perceptions about biotechnology. Procedural guidelines to enhance the efficiency of quantitative inquiry surveys are given, by discussing essential methodological aspects and relevant criteria to integrate theory into practice.The authors are grateful to all the participant teachers and students that contributed to gather the data presented and to Catarina L. Santos for useful comments and suggestions on the manuscript. Maria Joao Fonseca was supported by the FCT fellowship SFRH/BD/37389/2007 and this work was sponsored by a research grant (PTDC/AGR-PRO/111857/2009) from Fundacao para a Ciencia e Tecnologia (FCT, Portugal)

An expanded global inventory of allelic variation in the most extremely polymorphic region of Plasmodium falciparum merozoite surface protein 1 provided by short read sequence data.

BACKGROUND: Within Plasmodium falciparum merozoite surface protein 1 (MSP1), the N-terminal block 2 region is a highly polymorphic target of naturally acquired antibody responses. The antigenic diversity is determined by complex repeat sequences as well as non-repeat sequences, grouping into three major allelic types that appear to be maintained within populations by natural selection. Within these major types, many distinct allelic sequences have been described in different studies, but the extent and significance of the diversity remains unresolved. METHODS: To survey the diversity more extensively, block 2 allelic sequences in the msp1 gene were characterized in 2400 P. falciparum infection isolates with whole genome short read sequence data available from the Pf3K project, and compared with the data from previous studies. RESULTS: Mapping the short read sequence data in the 2400 isolates to a reference library of msp1 block 2 allelic sequences yielded 3815 allele scores at the level of major allelic family types, with 46% of isolates containing two or more of these major types. Overall frequencies were similar to those previously reported in other samples with different methods, the K1-like allelic type being most common in Africa, MAD20-like most common in Southeast Asia, and RO33-like being the third most abundant type in each continent. The rare MR type, formed by recombination between MAD20-like and RO33-like alleles, was only seen in Africa and very rarely in the Indian subcontinent but not in Southeast Asia. A combination of mapped short read assembly approaches enabled 1522 complete msp1 block 2 sequences to be determined, among which there were 363 different allele sequences, of which 246 have not been described previously. In these data, the K1-like msp1 block 2 alleles are most diverse and encode 225 distinct amino acid sequences, compared with 123 different MAD20-like, 9 RO33-like and 6 MR type sequences. Within each of the major types, the different allelic sequences show highly skewed geographical distributions, with most of the more common sequences being detected in either Africa or Asia, but not in both. CONCLUSIONS: Allelic sequences of this extremely polymorphic locus have been derived from whole genome short read sequence data by mapping to a reference library followed by assembly of mapped reads. The catalogue of sequence variation has been greatly expanded, so that there are now more than 500 different msp1 block 2 allelic sequences described. This provides an extensive reference for molecular epidemiological genotyping and sequencing studies, and potentially for design of a multi-allelic vaccine

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

Biases in the Explore-Exploit Tradeoff in Addictions: The Role of Avoidance of Uncertainty.

We focus on exploratory decisions across disorders of compulsivity, a potential dimensional construct for the classification of mental disorders. Behaviors associated with the pathological use of alcohol or food, in alcohol use disorders (AUD) or binge-eating disorder (BED), suggest a disturbance in explore-exploit decision-making, whereby strategic exploratory decisions in an attempt to improve long-term outcomes may diminish in favor of more repetitive or exploitatory choices. We compare exploration vs exploitation across disorders of natural (obesity with and without BED) and drug rewards (AUD). We separately acquired resting state functional MRI data using a novel multi-echo planar imaging sequence and independent components analysis from healthy individuals to assess the neural correlates underlying exploration. Participants with AUD showed reduced exploratory behavior across gain and loss environments, leading to lower-yielding exploitatory choices. Obese subjects with and without BED did not differ from healthy volunteers but when compared with each other or to AUD subjects, BED had enhanced exploratory behaviors particularly in the loss domain. All subject groups had decreased exploration or greater uncertainty avoidance to losses compared with rewards. More exploratory decisions in the context of reward were associated with frontal polar and ventral striatal connectivity. For losses, exploration was associated with frontal polar and precuneus connectivity. We further implicate the relevance and dimensionality of constructs of compulsivity across disorders of both natural and drug rewards.The study was funded by the Wellcome Trust Fellowship grant for VV (093705/Z/10/Z) and Cambridge NIHR Biomedical Research Centre. VV and NAH are Wellcome Trust (WT) intermediate Clinical Fellows. LSM is in receipt of an MRC studentship. The BCNI is supported by a WT and MRC grant. MF is funded by NIMH and NSF grants and is consultant for Hoffman LaRoche pharmaceuticals. The remaining authors declare no competing financial interests.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/npp.2015.20

Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity

Positive-strand RNA (+RNA) viruses rearrange cellular membranes during replication, possibly in order to concentrate and arrange viral replication machinery for efficient viral RNA synthesis. Our previous work showed that in addition to the conserved coronavirus double membrane vesicles (DMVs), Beau-R, an apathogenic strain of avian Gammacoronavirus infectious bronchitis virus (IBV), induces regions of ER that are zippered together and tethered open-necked double membrane spherules that resemble replication organelles induced by other +RNA viruses. Here we compared structures induced by Beau-R with the pathogenic lab strain M41 to determine whether membrane rearrangements are strain dependent. Interestingly, M41 was found to have a low spherule phenotype. We then compared a panel of pathogenic, mild and attenuated IBV strains in ex vivo tracheal organ culture (TOC). Although the low spherule phenotype of M41 was conserved in TOCs, each of the other tested IBV strains produced DMVs, zippered ER and spherules. Furthermore, there was a significant correlation for the presence of DMVs with spherules, suggesting that these structures are spatially and temporally linked. Our data indicate that virus induced membrane rearrangements are fundamentally linked to the viral replicative machinery. However, coronavirus replicative apparatus clearly has the plasticity to function in different structural contexts

A whole-genome shotgun approach for assembling and anchoring the hexaploid bread wheat genome

Citation: Chapman, J. A., Mascher, M., Buluç, A., Barry, K., Georganas, E., Session, A., . . . Rokhsar, D. S. (2015). A whole-genome shotgun approach for assembling and anchoring the hexaploid bread wheat genome. Genome Biology, 16(1). doi:10.1186/s13059-015-0582-8Polyploid species have long been thought to be recalcitrant to whole-genome assembly. By combining high-throughput sequencing, recent developments in parallel computing, and genetic mapping, we derive, de novo, a sequence assembly representing 9.1 Gbp of the highly repetitive 16 Gbp genome of hexaploid wheat, Triticum aestivum, and assign 7.1 Gb of this assembly to chromosomal locations. The genome representation and accuracy of our assembly is comparable or even exceeds that of a chromosome-by-chromosome shotgun assembly. Our assembly and mapping strategy uses only short read sequencing technology and is applicable to any species where it is possible to construct a mapping population. © 2015 Chapman et al. licensee BioMed Central.Additional Authors: Muehlbauer, G. J.;Stein, N.;Rokhsar, D. S

Qualitative meta-synthesis of user experience of computerised therapy for depression and anxiety

Objective: Computerised therapies play an integral role in efforts to improve access to psychological treatment for patients with depression and anxiety. However, despite recognised problems with uptake, there has been a lack of investigation into the barriers and facilitators of engagement. We aimed to systematically review and synthesise findings from qualitative studies of computerised therapies, in order to identify factors impacting on engagement. Method: Systematic review and meta-synthesis of qualitative studies of user experiences of computer delivered therapy for depression and/or anxiety. Results: 8 studies were included in the review. All except one were of desktop based cognitive behavioural treatments. Black and minority ethnic and older participants were underrepresented, and only one study addressed users with a comorbid physical health problem. Through synthesis, we identified two key overarching concepts, regarding the need for treatments to be sensitive to the individual, and the dialectal nature of user experience, with different degrees of support and anonymity experienced as both positive and negative. We propose that these factors can be conceptually understood as the ‘non-specific’ or ‘common’ factors of computerised therapy, analogous to but distinct from the common factors of traditional face-to-face therapies. Conclusion: Experience of computerised therapy could be improved through personalisation and sensitisation of content to individual users, recognising the need for users to experience a sense of ‘self’ in the treatment which is currently absent. Exploiting the common factors of computerised therapy, through enhancing perceived connection and collaboration, could offer a way of reconciling tensions due to the dialectal nature of user experience. Future research should explore whether the findings are generalisable to other patient groups, to other delivery formats (such as mobile technology) and other treatment modalities beyond cognitive behaviour therapy. The proposed model could aid the development of enhancements to current packages to improve uptake and support engagement