2,123 research outputs found
Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses.
CTL are held to be an important host defense mechanism in persistent herpes-virus infections. We have therefore studied the nature and specificity of human cytomegalovirus (HCMV)-specific CTL in normal persistently infected individuals. This was achieved by using vaccinia recombinants encoding viral genes expressed at different stages of the virus replicative cycle, a structural glycoprotein gB (vac.gB) and the major 72-kD immediate early nonstructural protein (vac.IE) of HCMV, combined with limiting dilution analysis of the CTL response. In two subjects, 43 and 58% of HCMV CTL precursors (CTLp) lysed vac.IE-infected cells, in contrast to less than 6% lysing gB-infected cells. HCMV-specific CTL could also be generated by secondary in vitro stimulation with vac.gB- but not vac.IE-infected autologous fibroblasts. The high frequency of 72-kD IE protein-specific CTL suggests that this is at least a major recognition element for the HCMV-specific CTL response in asymptomatic persistently infected individuals, and CTL with this specificity may be important in maintaining the normal virus/host equilibrium
Training Load and Carbohydrate Periodization Practices of Elite Male Australian Football Players: Evidence of Fueling for the Work Required.
The authors aimed to quantify (a) the periodization of physical loading and daily carbohydrate (CHO) intake across an in-season weekly microcycle of Australian Football and (b) the quantity and source of CHO consumed during game play and training. Physical loading (via global positioning system technology) and daily CHO intake (via a combination of 24-hr recall, food diaries, and remote food photographic method) were assessed in 42 professional male players during two weekly microcycles comprising a home and away fixture. The players also reported the source and quantity of CHO consumed during all games (n = 22 games) and on the training session completed 4 days before each game (n = 22 sessions). The total distance was greater (p < .05) on game day (GD; 13 km) versus all training days. The total distance differed between training days, where GD-2 (8 km) was higher than GD-1, GD-3, and GD-4 (3.5, 0, and 7 km, respectively). The daily CHO intake was also different between training days, with reported intakes of 1.8, 1.4, 2.5, and 4.5 g/kg body mass on GD-4, GD-3, GD-2, and GD-1, respectively. The CHO intake was greater (p < .05) during games (59 ± 19 g) compared with training (1 ± 1 g), where in the former, 75% of the CHO consumed was from fluids as opposed to gels. Although the data suggest that Australian Football players practice elements of CHO periodization, the low absolute CHO intakes likely represent considerable underreporting in this population. Even when accounting for potential underreporting, the data also suggest Australian Football players underconsume CHO in relation to the physical demands of training and competition
Muscle Glycogen Utilisation during an Australian Rules Football Game.
PURPOSE: To better understand the carbohydrate (CHO) requirement of Australian Football (AF) match play by quantifying muscle glycogen utilisation during an in-season AF match. METHODS: After a 24 h CHO loading protocol of 8 g/kg and 2 g/kg in the pre-match meal, two elite male forward players had biopsies sampled from m. vastus lateralis before and after participation in a South Australian Football League game. Player A (87.2kg) consumed water only during match play whereas player B (87.6kg) consumed 88 g CHO via CHO gels. External load was quantified using global positioning system technology. RESULTS: Player A completed more minutes on the ground (115 vs. 98 min) and covered greater total distance (12.2 vs. 11.2 km) than Player B, though with similar high-speed running (837 vs. 1070 m) and sprinting (135 vs. 138 m), respectively. Muscle glycogen decreased by 66% in Player A (Pre-: 656, Post-: 223 mmol∙kg-1 dw) and 24% in Player B (Pre-: 544, Post-: 416 mmol∙kg-1 dw), respectively. CONCLUSION: Pre-match CHO loading elevated muscle glycogen concentrations (i.e. >500 mmol.kg-1 dw), the magnitude of which appears sufficient to meet the metabolic demands of elite AF match play. The glycogen cost of AF match play may be greater than soccer and rugby and CHO feeding may also spare muscle glycogen use. Further studies using larger sample sizes are now required to quantify the inter-individual variability of glycogen cost of match play (including muscle and fibre-type specific responses) as well examine potential metabolic and ergogenic effects of CHO feeding
Casting Light on Dark Matter
The prospects for detecting a candidate supersymmetric dark matter particle
at the LHC are reviewed, and compared with the prospects for direct and
indirect searches for astrophysical dark matter. The discussion is based on a
frequentist analysis of the preferred regions of the Minimal supersymmetric
extension of the Standard Model with universal soft supersymmetry breaking (the
CMSSM). LHC searches may have good chances to observe supersymmetry in the near
future - and so may direct searches for astrophysical dark matter particles,
whereas indirect searches may require greater sensitivity, at least within the
CMSSM.Comment: 16 pages, 13 figures, contribution to the proceedings of the LEAP
2011 Conferenc
Dark-adapted red flash ERGs in healthy adults
Purpose: The x-wave of the dark-adapted (DA) ERG to a red flash reflects DA cone function. This exploratory study of healthy adults aimed to investigate changes in the DA red ERG with flash strength and during dark adaptation to optimise visualisation and therefore quantification of the x-wave.
Methods: The effect of altering red flash strength was investigated in four subjects by recording ERGs after 20 minutes dark adaptation to red flashes (0.2–2.0 cd s m-2) using skin electrodes and natural pupils. The effect of dark adaptation duration was investigated in 16 subjects during 20 minutes in the dark, by recording DA 1.5 red ERGs at 1, 2, 3, 4, 5, 10, 15 and 20 minutes.
Results: For a dark adaption period of 20 minutes, the x-wave was more clearly visualised to weaker (< 0.6 cd s m-2) red flash strengths: to stronger flashes it became obscured by the b-wave. For red flashes of 1.5 cd s m-2, the x-wave was most prominent in ERGs recorded after 1–5 minutes of dark adaptation: with longer dark-adaptation, it was subsumed into the b-wave’s rising edge.
Conclusions: This small study suggests that x-wave visibility in healthy subjects after 20 minutes dark adaptation is improved by using flashes weaker than around 0.6 cd s m-2; for flash strengths of 1.5 cd s m-2, x-wave visibility is enhanced by recording after only around 5 minutes of dark adaptation. No evidence was found that interim red flash ERGs affecting the dark-adapted state of the normal retina
Targeted prevention of common mental health disorders in university students: randomised controlled trial of a transdiagnostic trait-focused web-based intervention
Background:
A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders.<p></p>
Aims:
To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students.<p></p>
Method:
Students were recruited online (n = 1047, age: M = 21.8, SD = 4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n = 519) or a control intervention (n = 528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes.<p></p>
Results:
Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p<.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p = .018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating.<p></p>
Conclusions
This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention
A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus
The innate immune system is critical in the response to infection by pathogens and it is activated by pattern recognition receptors (PRRs) binding to pathogen associated molecular patterns (PAMPs). During viral infection, the direct recognition of the viral nucleic acids, such as the genomes of DNA viruses, is very important for activation of innate immunity. Recently, DNA-dependent protein kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA that is important for the innate immune response to intracellular DNA and DNA virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit this function of DNA-PK by expression of a highly conserved protein called C16, which was known to contribute to virulence but by an unknown mechanism. Data presented show that C16 binds directly to the Ku heterodimer and thereby inhibits the innate immune response to DNA in fibroblasts, characterised by the decreased production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA-PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing. The C-terminal region of C16 is sufficient for binding Ku and this activity is conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of 5 amino acids in this domain is enough to knockout this function from the attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV mutant lacking C16 induced higher levels of cytokines and chemokines early after infection compared to control viruses, confirming the role of this virulence factor in attenuating the innate immune response. Overall this study describes the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to the evidence that DNA-PK is a critical component of innate immunity to DNA viruses
The what and where of adding channel noise to the Hodgkin-Huxley equations
One of the most celebrated successes in computational biology is the
Hodgkin-Huxley framework for modeling electrically active cells. This
framework, expressed through a set of differential equations, synthesizes the
impact of ionic currents on a cell's voltage -- and the highly nonlinear impact
of that voltage back on the currents themselves -- into the rapid push and pull
of the action potential. Latter studies confirmed that these cellular dynamics
are orchestrated by individual ion channels, whose conformational changes
regulate the conductance of each ionic current. Thus, kinetic equations
familiar from physical chemistry are the natural setting for describing
conductances; for small-to-moderate numbers of channels, these will predict
fluctuations in conductances and stochasticity in the resulting action
potentials. At first glance, the kinetic equations provide a far more complex
(and higher-dimensional) description than the original Hodgkin-Huxley
equations. This has prompted more than a decade of efforts to capture channel
fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of
these approaches, while intuitively appealing, produce quantitative errors when
compared to kinetic equations; others, as only very recently demonstrated, are
both accurate and relatively simple. We review what works, what doesn't, and
why, seeking to build a bridge to well-established results for the
deterministic Hodgkin-Huxley equations. As such, we hope that this review will
speed emerging studies of how channel noise modulates electrophysiological
dynamics and function. We supply user-friendly Matlab simulation code of these
stochastic versions of the Hodgkin-Huxley equations on the ModelDB website
(accession number 138950) and
http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl
Unconstrained three-dimensional reaching in Rhesus monkeys
To better understand normative behavior for quantitative evaluation of motor recovery after injury, we studied arm movements by non-injured Rhesus monkeys during a food-retrieval task. While seated, monkeys reached, grasped, and retrieved food items. We recorded three-dimensional kinematics and muscle activity, and used inverse dynamics to calculate joint moments due to gravity, segmental interactions, and to the muscles and tissues of the arm. Endpoint paths showed curvature in three dimensions, suggesting that maintaining straight paths was not an important constraint. Joint moments were dominated by gravity. Generalized muscle and interaction moments were less than half of the gravitational moments. The relationships between shoulder and elbow resultant moments were linear during both reach and retrieval. Although both reach and retrieval required elbow flexor moments, an elbow extensor (triceps brachii) was active during both phases. Antagonistic muscles of both the elbow and hand were co-activated during reach and retrieval. Joint behavior could be described by lumped-parameter models analogous to torsional springs at the joints. Minor alterations to joint quasi-stiffness properties, aided by interaction moments, result in reciprocal movements that evolve under the influence of gravity. The strategies identified in monkeys to reach, grasp, and retrieve items will allow the quantification of prehension during recovery after a spinal cord injury and the effectiveness of therapeutic interventions
A review of elliptical and disc galaxy structure, and modern scaling laws
A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their
models to describe the radial distribution of stars in `nebulae'. This article
reviews the progress since then, providing both an historical perspective and a
contemporary review of the stellar structure of bulges, discs and elliptical
galaxies. The quantification of galaxy nuclei, such as central mass deficits
and excess nuclear light, plus the structure of dark matter halos and cD galaxy
envelopes, are discussed. Issues pertaining to spiral galaxies including dust,
bulge-to-disc ratios, bulgeless galaxies, bars and the identification of
pseudobulges are also reviewed. An array of modern scaling relations involving
sizes, luminosities, surface brightnesses and stellar concentrations are
presented, many of which are shown to be curved. These 'redshift zero'
relations not only quantify the behavior and nature of galaxies in the Universe
today, but are the modern benchmark for evolutionary studies of galaxies,
whether based on observations, N-body-simulations or semi-analytical modelling.
For example, it is shown that some of the recently discovered compact
elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to
appear in "Planets, Stars and Stellar
Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references
incl. many somewhat forgotten, pioneer papers. Original submission to
Springer: 07-June-201
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