Constitutive expression of Yes-associated protein (Yap) in adult skeletal muscle fibres induces muscle atrophy and myopathy

Peer reviewedPublisher PD

Skeletal Muscle Fiber Adaptations Following Resistance Training Using Repetition Maximums or Relative Intensity

The purpose of the study was to compare the physiological responses of skeletal muscle to a resistance training (RT) program using repetition maximum (RM) or relative intensity (RISR). Fifteen well-trained males underwent RT 3 d·wk−1 for 10 weeks in either an RM group (n = 8) or RISR group (n = 7). The RM group achieved a relative maximum each day, while the RISR group trained based on percentages. The RM group exercised until muscular failure on each exercise, while the RISR group did not reach muscular failure throughout the intervention. Percutaneous needle biopsies of the vastus lateralis were obtained pre-post the training intervention, along with ultrasonography measures. Dependent variables were: Fiber type-specific cross-sectional area (CSA); anatomical CSA (ACSA); muscle thickness (MT); mammalian target of rapamycin (mTOR); adenosine monophosphate protein kinase (AMPK); and myosin heavy chains (MHC) specific for type I (MHC1), type IIA (MHC2A), and type IIX (MHC2X). Mixed-design analysis of variance and effect size using Hedge’s g were used to assess within- and between-group alterations. RISR statistically increased type I CSA (p = 0.018, g = 0.56), type II CSA (p = 0.012, g = 0.81), ACSA (p = 0.002, g = 0.53), and MT (p \u3c 0.001, g = 1.47). RISR also yielded a significant mTOR reduction (p = 0.031, g = −1.40). Conversely, RM statistically increased only MT (p = 0.003, g = 0.80). Between-group effect sizes supported RISR for type I CSA (g = 0.48), type II CSA (g = 0.50), ACSA (g = 1.03), MT (g = 0.72), MHC2X (g = 0.31), MHC2A (g = 0.87), and MHC1 (g = 0.59); with all other effects being of trivial magnitude (g \u3c 0.20). Our results demonstrated greater adaptations in fiber size, whole-muscle size, and several key contractile proteins when using RISR compared to RM loading paradigm

Skeletal Muscle Fiber Adaptations Following Resistance Training Using Repetition Maximums or Relative Intensity

The purpose of the study was to compare the physiological responses of skeletal muscle to a resistance training (RT) program using repetition maximum (RM) or relative intensity (RISR). Fifteen well-trained males underwent RT 3 d·wk−1 for 10 weeks in either an RM group (n = 8) or RISR group (n = 7). The RM group achieved a relative maximum each day, while the RISR group trained based on percentages. The RM group exercised until muscular failure on each exercise, while the RISR group did not reach muscular failure throughout the intervention. Percutaneous needle biopsies of the vastus lateralis were obtained pre-post the training intervention, along with ultrasonography measures. Dependent variables were: Fiber type-specific cross-sectional area (CSA); anatomical CSA (ACSA); muscle thickness (MT); mammalian target of rapamycin (mTOR); adenosine monophosphate protein kinase (AMPK); and myosin heavy chains (MHC) specific for type I (MHC1), type IIA (MHC2A), and type IIX (MHC2X). Mixed-design analysis of variance and effect size using Hedge’s g were used to assess within- and between-group alterations. RISR statistically increased type I CSA (p = 0.018, g = 0.56), type II CSA (p = 0.012, g = 0.81), ACSA (p = 0.002, g = 0.53), and MT (p \u3c 0.001, g = 1.47). RISR also yielded a significant mTOR reduction (p = 0.031, g = −1.40). Conversely, RM statistically increased only MT (p = 0.003, g = 0.80). Between-group effect sizes supported RISR for type I CSA (g = 0.48), type II CSA (g = 0.50), ACSA (g = 1.03), MT (g = 0.72), MHC2X (g = 0.31), MHC2A (g = 0.87), and MHC1 (g = 0.59); with all other effects being of trivial magnitude (g \u3c 0.20). Our results demonstrated greater adaptations in fiber size, whole-muscle size, and several key contractile proteins when using RISR compared to RM loading paradigms

Elucidation of the Cellular Interactome of Ebola Virus Nucleoprotein and Identification of Therapeutic Targets

Ebola virus (EBOV) infection results in severe disease and in some cases lethal haemorrhagic fever. The infection is directed by seven viral genes that encode nine viral proteins. By definition viruses are obligate intracellular parasites and require aspects of host cell biology in order to replicate their genetic material, assemble new virus particles and subvert host cell anti-viral responses. Currently licenced antivirals are targeted against viral proteins to inhibit their function. However, experience with treating HIV and influenza virus demonstrates that resistant viruses are soon selected. An emerging area in virology is to transiently target host cell proteins that play critical proviral roles in virus biology, especially for acute infections. This has the advantage that the protein being targeted is evolutionary removed from the genome of the virus. Proteomics can aid in discovery biology and identify cellular proteins that may be utilised by the virus to facilitate infection. This work focused on defining the interactome of the EBOV nucleoprotein and identified that cellular chaperones, including HSP70, associate with this protein to promote stability. Utilisation of a mini-genome replication system based on a recent Makona isolate demonstrated that disrupting the stability of NP had an adverse effect on viral RNA synthesis

Comparison of the Relationship between Lying and Standing Ultrasonography Measures of Muscle Morphology with Isometric and Dynamic Force Production Capabilities

The purpose of the current study was (1) to examine the differences between standing and lying measures of vastus lateralis (VL), muscle thickness (MT), pennation angle (PA), and cross-sectional area (CSA) using ultrasonography; and (2) to explore the relationships between lying and standing measures with isometric and dynamic assessments of force production—specifically peak force, rate of force development (RFD), impulse, and one-repetition maximum back squat. Fourteen resistance-trained subjects (age = 26.8 ± 4.0 years, height = 181.4 ± 6.0 cm, body mass = 89.8 ± 10.7 kg, back squat to body mass ratio = 1.84 ± 0.34) agreed to participate. Lying and standing ultrasonography images of the right VL were collected following 48 hours of rest. Isometric squat assessments followed ultrasonography, and were performed on force platforms with data used to determine isometric peak force (IPF), as well as RFD and impulse at various time points. Forty-eight hours later, one-repetition maximum back squats were performed by each subject. Paired-samples t-tests revealed statistically significant differences between standing and lying measurements of MT (p \u3c 0.001), PA (p \u3c 0.001), and CSA (p ≤ 0.05), with standing values larger in all cases. Further, standing measures were correlated more strongly and abundantly to isometric and dynamic performance. These results suggest that if practitioners intend to gain insight into strength-power potential based on ultrasonography measurements, performing the measurement collection with the athlete in a standing posture may be preferred

Comparison of the Relationship between Lying and Standing Ultrasonography Measures of Muscle Morphology with Isometric and Dynamic Force Production Capabilities

The purpose of the current study was (1) to examine the differences between standing and lying measures of vastus lateralis (VL), muscle thickness (MT), pennation angle (PA), and cross-sectional area (CSA) using ultrasonography; and (2) to explore the relationships between lying and standing measures with isometric and dynamic assessments of force production—specifically peak force, rate of force development (RFD), impulse, and one-repetition maximum back squat. Fourteen resistance-trained subjects (age = 26.8 ± 4.0 years, height = 181.4 ± 6.0 cm, body mass = 89.8 ± 10.7 kg, back squat to body mass ratio = 1.84 ± 0.34) agreed to participate. Lying and standing ultrasonography images of the right VL were collected following 48 hours of rest. Isometric squat assessments followed ultrasonography, and were performed on force platforms with data used to determine isometric peak force (IPF), as well as RFD and impulse at various time points. Forty-eight hours later, one-repetition maximum back squats were performed by each subject. Paired-samples t-tests revealed statistically significant differences between standing and lying measurements of MT (p \u3c 0.001), PA (p \u3c 0.001), and CSA (p ≤ 0.05), with standing values larger in all cases. Further, standing measures were correlated more strongly and abundantly to isometric and dynamic performance. These results suggest that if practitioners intend to gain insight into strength-power potential based on ultrasonography measurements, performing the measurement collection with the athlete in a standing posture may be preferred

Repetition-to-Repetition Differences Using Cluster and Accentuated Eccentric Loading in the Back Squat

The current investigation was an examination of the repetition-to-repetition magnitudes and changes in kinetic and kinematic characteristics of the back squat using accentuated eccentric loading (AEL) and cluster sets. Trained male subjects (age = 26.1 ± 4.1 years, height = 183.5 ± 4.3 cm, body mass = 92.5 ± 10.5 kg, back squat to body mass ratio = 1.8 ± 0.3) completed four load condition sessions, each consisting of three sets of five repetitions of either traditionally loaded straight sets (TL), traditionally loaded cluster sets (TLC), AEL cluster sets (AEC), and AEL straight sets where only the initial repetition had eccentric overload (AEL1). Eccentric overload was applied using weight releasers, creating a total eccentric load equivalent to 105% of concentric one repetition maximum (1RM). Concentric load was 80% 1RM for all load conditions. Using straight sets (TL and AEL1) tended to decrease peak power (PP) (d = −1.90 to −0.76), concentric rate of force development (RFDCON) (d = −1.59 to −0.27), and average velocity (MV) (d = −3.91 to −1.29), with moderate decreases in MV using cluster sets (d= −0.81 to −0.62). Greater magnitude eccentric rate of force development (RFDECC) was observed using AEC at repetition three (R3) and five (R5) compared to all load conditions (d = 0.21–0.65). Large within-condition changes in RFDECC from repetition one to repetition three (∆REP1–3) were present using AEL1 (d = 1.51), demonstrating that RFDECC remained elevated for at least three repetitions despite overload only present on the initial repetition. Overall, cluster sets appear to permit higher magnitude and improved maintenance of concentric outputs throughout a set. Eccentric overload with the loading protocol used in the current study does not appear to potentiate concentric output regardless of set configuration but may cause greater RFDECCcompared to traditional loadin

Quality control for multiple breath washout tests in multicentre bronchiectasis studies:Experiences from the BRONCH-UK clinimetrics study

Multiple Breath Washout (MBW) to measure Lung Clearance Index (LCI) is increasingly being used as a secondary endpoint in multicentre bronchiectasis studies. LCI data quality control or “over-reading” is resource intensive and the impact is unclear. Objectives: To assess the proportion of MBW tests deemed unacceptable with over-reading, and to assess the change in LCI (number of turnovers), LCI coefficient of variation (CV%) and tidal volume (VT) CV% results after over-reading. Methods: Data were analysed from 250 MBW tests (from 98 adult bronchiectasis patients) collected as part of the Bronch-UK Clinimetrics study in 5 UK centres. Each MBW test was over-read centrally using pre-defined criteria. MBW tests with <2 technically valid and repeatable trials were deemed unacceptable to include in analysis. In accepted tests, values for LCI, LCI CV% and VT CV% before and after over-reading, were compared. Results: Insufficient data was collected in 10/250 tests. With over-reading, 30/240 (12%) were deemed unacceptable to include in analysis. In those accepted tests, overall the change in LCI, LCI CV% and VT CV% with over-reading was not statistically significant. When MBW new sites were compared to MBW expert sites, the change in LCI with over-reading was significantly greater in MBW new sites (p = 0.047). Data suggests that over-reading could be important up to at least 12 months post initiation of MBW activity. Conclusion: MBW over-reading was important in this study as 12% of tests were considered unacceptable. Over-reading improved test result accuracy in sites new to MBW

Constraint propagation equations of the 3+1 decomposition of f(R) gravity

Theories of gravity other than general relativity (GR) can explain the observed cosmic acceleration without a cosmological constant. One such class of theories of gravity is f(R). Metric f(R) theories have been proven to be equivalent to Brans-Dicke (BD) scalar-tensor gravity without a kinetic term. Using this equivalence and a 3+1 decomposition of the theory it has been shown that metric f(R) gravity admits a well-posed initial value problem. However, it has not been proven that the 3+1 evolution equations of metric f(R) gravity preserve the (hamiltonian and momentum) constraints. In this paper we show that this is indeed the case. In addition, we show that the mathematical form of the constraint propagation equations in BD-equilavent f(R) gravity and in f(R) gravity in both the Jordan and Einstein frames, is exactly the same as in the standard ADM 3+1 decomposition of GR. Finally, we point out that current numerical relativity codes can incorporate the 3+1 evolution equations of metric f(R) gravity by modifying the stress-energy tensor and adding an additional scalar field evolution equation. We hope that this work will serve as a starting point for relativists to develop fully dynamical codes for valid f(R) models.Comment: 25 pages, matches published version in CQG, references update

Stakeholder views regarding ethical issues in the design and conduct of pragmatic trials : study protocol

This work is supported by the Canadian Institutes of Health Research through the Project Grant competition (competitive, peer reviewed), award number PJT-153045. Jeremy Grimshaw holds a Canada Research Chair in Health Knowledge Transfer and Uptake and a CIHR Foundation Grant (FDN-143269). Charles Weijer holds a Canada Research Chair in Bioethics. Joanne McKenzie is supported by an Australian National Health and Medical Research Council Career Development Fellowship (1143429). Vipul Jairath hold a personal Endowed Chair at Western University (John and Susan McDonald Endowed Chair). Marion Campbell is based with the Health Services Research Unit which is core-funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. Ian Graham is a CIHR Foundation Grant recipient (FDN# 143237).Peer reviewedPublisher PD