Biology subjects

Draper, G.

Publications and source records attributed to Draper, G..

3 recordsLinked to original sources

bioRxiv2025

Training and match running distances and perceived exertion at sea-level and altitude in elite North American soccer: A natural longitudinal cross-over case series.

PurposeThere is limited real-world data on differential perceptions of exertion in professional soccer at altitude. In a natural cross-over design, we quantified responses to training and matches at sea level and altitude. MethodsTotal, and high-speed, running distance and differential session ratings of perceived exertion for breathlessness (s-RPE-B) and leg exertion (s-RPE-L) were collected from 19 professional soccer players (age: 27.3 {+/-} 3.4 years, stature: 181.2 {+/-} 5.9cm, mass: 78.7 {+/-} 8.1kg) at sea-level and altitude. Data were collected for matches raining sessions one and two days pre match. ResultsDifferences between altitude conditions were estimated through mixed-linear modeling, with 95% confidence intervals representing values highly compatible with our observed data. In matches, total distance may have been reduced (95% confidence intervals 43 to -833 m, surprisal [s] = 3.74) and s-RPE-B may have increased (-0.6 to 10.7, s = 3.66) at altitude. A clear perceptual shift was observed with s-RPE-B increasing relative to s-RPE-L (-13.4 to -7.17, s >13) at altitude. Training at altitude included higher total (318 to 661 m, s > 13), and high-speed (33.1 to 93 m, s > 13), running distances but s-RPE-L reduced (-14.2 to -1.01, s = 5.39) and s-RPE-B increased relative to s-RPE-L (-15.1 to -3.93, s = 10.3). ConclusionsOur key finding was breathlessness increased relative to leg exertion at altitude.

physiology↗

bioRxiv2019

SEMA4C is a novel target to limit osteosarcoma growth, progression, and metastasis

Semaphorins, specifically type IV, are important regulators of axonal guidance and have been increasingly implicated in poor prognoses in a number of different solid cancers. In conjunction with their cognate PLXNB family receptors, type IV members have been increasingly shown to mediate oncogenic functions necessary for tumor development and malignant spread. In this study, we investigated the role of semaphorin 4C (SEMA4C) in osteosarcoma growth, progression, and metastasis. We investigated the expression and localization of SEMA4C in primary osteosarcoma patient tissues and its tumorigenic functions in these malignancies. We demonstrate that overexpression of SEMA4C promotes properties of cellular transformation, while RNAi knockdown of SEMA4C promotes adhesion and reduces cellular proliferation, colony formation, migration, wound healing, tumor growth, and lung metastasis. These phenotypic changes were accompanied by reductions in activated AKT signaling, G1 cell cycle delay, and decreases in expression of mesenchymal marker genes SNAI1, SNAI2, and TWIST1. Lastly, monoclonal antibody blockade of SEMA4C in vitro mirrored that of the genetic studies. Together, our results indicate a multi-dimensional oncogenic role for SEMA4C in metastatic osteosarcoma and more importantly that SEMA4C has actionable clinical potential.

cancer biology↗

bioRxiv2018

Highly efficient multiplex human T cell engineering without double-strand breaks using Cas9 base editors

Chimeric antigen receptor engineered T cell (CAR-T) immunotherapy has shown efficacy against a subset of hematological malignancies1,2, yet its autologous nature and ineffectiveness against epithelial and solid cancers limit widespread application. To overcome these limitations, targeted nucleases have been used to disrupt checkpoint inhibitors and genes involved in alloreactivity3-6. However, the production of allogeneic, \"off-the-shelf\" T cells with enhanced function requires multiplex genome editing strategies that risk off-target effects, chromosomal rearrangements, and genotoxicity due to simultaneous double-strand break (DSB) induction at multiple loci7-10. Moreover, it has been well documented that DSBs are toxic lesions that can drive genetic instability11,12. Alternatively, CRISPR/Cas9 base editors afford programmable enzymatic nucleotide conversion at targeted loci without induction of DSBs13,14. We reasoned this technology could be used to knockout gene function in human T cells while minimizing safety concerns associated with current nuclease platforms. Through systematic reagent and dose optimization, we demonstrate highly efficient multiplex base editing and consequent protein knockout in primary human T cells at loci relevant to the generation of allogeneic CAR-T cells including the T cell receptor constant (TRAC) locus, {beta}-2 microglobulin (B2M), and programmed cell death 1 (PDCD1). Multiplex base edited T cells equipped with a CD19 CAR killed target cells more efficiently; and importantly, both DSB induction and translocation frequency were greatly reduced compared to cells engineered with Cas9 nuclease. Collectively, our results establish a novel multiplex gene editing platform to enhance both the safety and efficacy of engineered T cell-based immunotherapies.

genetics↗