18 research outputs found

    Biomechanical measures of short-term maximal cycling on an ergometer: a test-retest study.

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    An understanding of test-retest reliability is important for biomechanists, such as when assessing the longitudinal effect of training or equipment interventions. Our aim was to quantify the test-retest reliability of biomechanical variables measured during short-term maximal cycling. Fourteen track sprint cyclists performed 3 × 4 s seated sprints at 135 rpm on an isokinetic ergometer, repeating the session 7.6 ± 2.5 days later. Joint moments were calculated via inverse dynamics, using pedal forces and limb kinematics. EMG activity was measured for 9 lower limb muscles. Reliability was explored by quantifying systematic and random differences within- and between-session. Within-session reliability was better than between-sessions reliability. The test-retest reliability level was typically moderate to excellent for the biomechanical variables that describe maximal cycling. However, some variables, such as peak knee flexion moment and maximum hip joint power, demonstrated lower reliability, indicating that care needs to be taken when using these variables to evaluate biomechanical changes. Although measurement error (instrumentation error, anatomical marker misplacement, soft tissue artefacts) can explain some of our reliability observations, we speculate that biological variability may also be a contributor to the lower repeatability observed in several variables including ineffective crank force, ankle kinematics and hamstring muscles' activation patterns

    Effects of strength training on the biomechanics and coordination of short-term maximal cycling.

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    The aim was to investigate the effects of a gym-based strength training intervention on biomechanics and intermuscular coordination patterns during short-term maximal cycling. Twelve track sprint cyclists performed 3 × 4 s seated sprints at 135 rpm, interspersed with 2 × 4 s seated sprints at 60 rpm on an isokinetic ergometer, repeating the session 11.6 ± 1.4 weeks later following a training programme that included two gym-based strength training sessions per week. Joint moments were calculated via inverse dynamics, using pedal forces and limb kinematics. EMG activity was measured for 9 lower limb muscles. Track cyclists 'leg strength" increased (7.6 ± 11.9 kg, P = 0.050 and ES = 0.26) following the strength training intervention. This was accompanied by a significant increase in crank power over a complete revolution for sprints at 135 rpm (26.5 ± 36.2 W, P = 0.028 and ES = 0.29). The increase in leg strength and average crank power was associated with a change in biceps femoris muscle activity, indicating that the riders successfully adapted their intermuscular coordination patterns to accommodate the changes in personal constraints to increase crank power

    Engineering pan–HIV-1 neutralization potency through multispecific antibody avidity

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    Deep mining of B cell repertoires of HIV-1-infected individuals has resulted in the isolation of dozens of HIV-1 broadly neutralizing antibodies (bNAbs). Yet, it remains uncertain whether any such bNAbs alone are sufficiently broad and potent to deploy therapeutically. Here, we engineered HIV-1 bNAbs for their combination on a single multispecific and avid molecule via direct genetic fusion of their Fab fragments to the human apoferritin light chain. The resulting molecule demonstrated a remarkable median IC50 value of 0.0009 g/mL and 100% neutralization coverage of a broad HIV-1 pseudovirus panel (118 isolates) at a 4 g/mL cutoff-a 32-fold enhancement in viral neutralization potency compared to a mixture of the corresponding HIV-1 bNAbs. Importantly, Fc incorporation on the molecule and engineering to modulate Fc receptor binding resulted in IgG-like bioavailability invivo. This robust plug-and-play antibody design is relevant against indications where multispecificity and avidity are leveraged simultaneously to mediate optimal biological activity.The following reagents were obtained through the NIH AIDS Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases: TZM-bl cells (ARP-8129; contributed by Dr. John C. Kappes and Dr. Xiaoyun Wu); anti–HIV-1 gp160 monoclonal antibody (N6/ PGDM1400x10E8v4) (ARP-13390; contributed by Drs. Ling Xu and Gary Nabel); HIV-1 NL4-3 ΔEnv Vpr luciferase reporter vector (pNL4-3.Luc.R-E-) (ARP-3418; contributed by Dr. Nathaniel Landau and Aaron Diamond); plasmids pcDNA3.1 D/V5-His TOPO-expressing HIV-1 Env/Rev (ARP-11017, ARP-11018, ARP-11024, and ARP-11022; contributed by Drs. David Montefiori, Feng Gao, and Ming Li); plasmid pcDNA3.1(+)-expressing HIV-1 Env/Rev (ARP-11037; contributed by Drs. B. H. Hahn and D. L. Kothe); plasmid pcDNA3.1 D/V5-His TOPO-expressing HIV-1 Env/Rev (ARP-11308; contributed by Drs. D. Montefiori, F. Gao, C. Wil- liamson, and S. Abdool Karim); plasmid pcDNA3.1 V5-His TOPO-expressing HIV-1 Env/Rev (ARP-11309; contributed by Drs. B. H. Hahn, Y. Li, and J. F. Sala- zar-Gonzalez); HIV-1 BG505 Env expression vector (BG505.W6M.ENV.C2) (ARP- 11518; contributed by Dr. Julie Overbaugh); HIV-1 Env expression vector (CRF02_AG clone 257) (ARP-11599; contributed by Drs. D. Ellenberger, B. Li, M. Callahan, and S. Butera); plasmid pcDNA3.1 V5-His TOPO-expressing HIV-1 CNE8 Env (ARP-12653; contributed by Drs. Linqi Zhang, Hong Shang, David Montefiori, Tsinghua University (Beijing, China), China Medical University (Bei- jing, China), and Duke University (Durham, NC); HIV-1 SF162 gp160 expression vector (ARP-10463; contributed by Drs. Leonidas Stamatatos and Cecilia Cheng- Mayer); plasmid pcDNA3.1 V5-His TOPO-expressing HIV-1 Env/Rev (ARP-11034; contributed by Drs. B. H. Hahn, X. Wei, and G. M. Shaw); plasmid pcDNA3.1/V5- His TOPO-expressing HIV Env/Rev (ARP-11038; contributed by Drs. B. H. Hahn and D. L. Kothe); plasmid pcDNA3.1 V5-His TOPO-expressing HIV-1 Env/Rev (ARP-11310; contributed by Drs. B. H. Hahn, Y. Li, and J. F. Salazar-Gonzalez); HIV-1 Env expression vector (p16845 env) (ARP-11503; contributed by Drs. R. Paranjape, S. Kulkarni, and D. Montefiori); HIV-1 1054 Env expression vector (p1054.TC4.1499) (ARP-11561) and 6244 Env expression vector (p6244_13.B5.4576) (ARP-11566; contributed by Drs. Beatrice H. Hahn, Brandon F. Keele, and George M. Shaw); HIV-1 ZM246F Env expression vector (pZM246F_C1G) (ARP-11830; contributed by Dr. Beatrice Hahn); HIV-1 Env expression vector (CRF02_AG clone 278) (ARP-11605; contributed by Drs. Michael Thomson, Ana Revilla, Elena Delgado, David Montefiori, Sonia P erez Castro, Centro Nacional de Microbiologia, Instituto de Salud Carlos III (Majada- honda, Madrid, Spain), Complejo Hospitalario Santa Mar ıa Madre (Orense, Spain), Duke University (Durham, NC), and the CAVD; and NL4-3 Env expression vector (pDOLHIVenv) (from Dr. Eric Freed and Dr. Rex Risser). The following reagents were kindly provided by CAVD: X2988, ZM106.9, and 3817. We thank S. Tabruyn and F. Arbogast for their assistance with in vivo studies. We thank the SickKids-University Health Network Flow Cytometry Facility. This work wassupported by Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant 6280100058 (J.-P.J.) and by Operating Grant PJ4- 169662 from the Canadian Institutes of Health Research (CIHR; B.T. and J.-P.J.). This research was also supported by the European Union’s Horizon 2020 research and innovation program under Marie Sklodowska-Curie Grant 790012 (E.R.), a Hospital for Sick Children Restracomp Postdoctoral Fellowship (C.B.A.), an NSERC postgraduate doctoral scholarship (T.Z.), a predoctoral fel- lowship from the Basque Government (PRE_2019_2_0046) (S.I.), the Canadian Institute for Advanced Research (CIFAR) Azrieli Global Scholar program (J.-P.J.), the Ontario Early Researcher Awards program (J.-P.J.), and the CanadaResearch Chairs program (B.T. and J.-P.J.). This work was supported, in part, by NSERC Discovery Grant RGPIN-2019-06442 and CIHR Project Grant–Priority Announcement PJH-175379 to C.G., and a CIHR Canada Graduate Scholarship (CGS-M) to J.B. Further support was obtained from the Spanish Ministry of Sci- ence, Innovation and Universities (MCIU) with the support of the Spanish Research Agency/The European Regional Development Fund (AEI/FEDER) (RTI2018-095624-B-C21) (J.L.N.) and the Basque Government (IT1196-19) (J.L.N.). Biophysical data were collected at the Structural & Biophysical Core facility supported by the Canada Foundation for Innovation and Ontario Research Fun

    The Incorporation of Host Proteins into the External HIV-1 Envelope

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    The incorporation of biologically active host proteins into HIV-1 is a well-established phenomenon, particularly due to the budding mechanism of viral egress in which viruses acquire their external lipid membrane directly from the host cell. While this mechanism might seemingly imply that host protein incorporation is a passive uptake of all cellular antigens associated with the plasma membrane at the site of budding, this is not the case. Herein, we review the evidence indicating that host protein incorporation can be a selective and conserved process. We discuss how HIV-1 virions displaying host proteins on their surface can exhibit a myriad of altered phenotypes, with notable impacts on infectivity, homing, neutralization, and pathogenesis. This review describes the canonical and emerging methods to detect host protein incorporation, highlights the well-established host proteins that have been identified on HIV-1 virions, and reflects on the role of these incorporated proteins in viral pathogenesis and therapeutic targeting. Despite many advances in HIV treatment and prevention, there remains a global effort to develop increasingly effective anti-HIV therapies. Given the broad range of biologically active host proteins acquired on the surface of HIV-1, additional studies on the mechanisms and impacts of these incorporated host proteins may inform the development of novel treatments and vaccine designs

    Quantifying the hip-ankle synergy in short-term maximal cycling

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    Simulation studies have demonstrated that the hip and ankle joints form a task-specific synergy during the downstroke in maximal cycling to enable the power produced by the hip extensor muscles to be transferred to the crank. The existence of the hip-ankle synergy has not been investigated experimentally. Therefore, we sought to apply a modified vector coding technique to quantify the strength of the hip-ankle moment synergy in the downstroke during short-term maximal cycling at a pedalling rate of 135 rpm. Twelve track sprint cyclists performed 3 × 4 s seated sprints at 135 rpm, interspersed with 2 × 4 s seated sprints at 60 rpm on an isokinetic ergometer. Data from the 60 rpm sprints were not analysed in this study. Joint moments were calculated via inverse dynamics, using pedal forces and limb kinematics. The hip-ankle moment synergy was quantified using a modified vector coding method. Results showed, for 28.8% of the downstroke the hip and ankle moments were in-phase, demonstrating the hip and ankle joints tend to work in synergy in the downstroke, providing some support findings from simulation studies of cycling. At a pedalling rate of 135 rpm the hip-phase was most frequent (42.5%) significantly differing from the in- (P = 0.044), anti- (P < 0.001), and ankle-phases (P = 0.004), demonstrating hip-dominant action. We believe this method shows promise to answer research questions on the relative strength of the hip-ankle synergy between different cycling conditions (e.g., power output and pedalling rates)

    Effects of strength training on the biomechanics and coordination of short-term maximal cycling

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    From Crossref journal articles via Jisc Publications RouterHistory: epub 2022-06-28, issued 2022-06-28Publication status: PublishedFunder: The author(s) reported there is no funding associated with the work featured in this articl

    Effects of strength training on the biomechanics and coordination of short-term maximal cycling.

    No full text
    From PubMed via Jisc Publications RouterPublication status: aheadofprintThe aim was to investigate the effects of a gym-based strength training intervention on biomechanics and intermuscular coordination patterns during short-term maximal cycling. Twelve track sprint cyclists performed 3 × 4 s seated sprints at 135 rpm, interspersed with 2 × 4 s seated sprints at 60 rpm on an isokinetic ergometer, repeating the session 11.6 ± 1.4 weeks later following a training programme that included two gym-based strength training sessions per week. Joint moments were calculated via inverse dynamics, using pedal forces and limb kinematics. EMG activity was measured for 9 lower limb muscles. Track cyclists 'leg strength" increased (7.6 ± 11.9 kg, = 0.050 and ES = 0.26) following the strength training intervention. This was accompanied by a significant increase in crank power over a complete revolution for sprints at 135 rpm (26.5 ± 36.2 W, = 0.028 and ES = 0.29). The increase in leg strength and average crank power was associated with a change in biceps femoris muscle activity, indicating that the riders successfully adapted their intermuscular coordination patterns to accommodate the changes in personal constraints to increase crank power

    A UV-LED module that is highly effective at inactivating human coronaviruses and HIV-1

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    Abstract Ultraviolet (UV) light has previously been established as useful method of disinfection, with demonstrated efficacy to inactivate a broad range of microorganisms. The advent of ultraviolet light-emitting diodes provides advantages in ease of disinfection, in that there can be delivery of germicidal UV with the same light unit that delivers standard white light to illuminate a room. Herein we demonstrate the efficacy and feasibility of ultraviolet light-emitting diodes as a means of decontamination by inactivating two distinct virus models, human coronavirus 229E and human immunodeficiency virus. Importantly, the same dose of ultraviolet light that inactivated human viruses also elicited complete inactivation of ultraviolet-resistant bacterial spores (Bacillus pumilus), a gold standard for demonstrating ultraviolet-mediated disinfection. This work demonstrates that seconds of ultraviolet light-emitting diodes (UV-LED) exposure can inactivate viruses and bacteria, highlighting that UV-LED could be a useful and practical tool for broad sanitization of public spaces
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