A novel hydrogen peroxide evolved CHO host can improve the expression of difficult to express bispecific antibodies.

The manufacture of bispecific antibodies by Chinese hamster ovary (CHO) cells is often hindered by lower product yields compared to monoclonal antibodies. Recently, reactive oxygen species have been shown to negatively impact antibody production. By contrast, strategies to boost cellular antioxidant capacity appear to be beneficial for recombinant protein expression. With this in mind, we generated a novel hydrogen peroxide evolved host using directed host cell evolution. Here we demonstrate that this host has heritable resistance to hydrogen peroxide over many generations, displays enhanced antioxidant capacity through the upregulation of several, diverse antioxidant defense genes such as those involved in glutathione synthesis and turnover, and has improved glutathione content. Additionally, we show that this host has significantly improved transfection recovery times, improved growth and viability properties in a fed-batch production process, and elevated expression of two industrially relevant difficult to express bispecific antibodies compared to unevolved CHO control host cells. These findings demonstrate that host cell evolution represents a powerful methodology for improving specific host cell characteristics that can positively impact the expression of difficult to express biotherapeutics.

Qualitative changes in children's physical activity and sedentary behaviours throughout the COVID-19 pandemic: The HomeSPACE project.

Opportunities for children to be physically active during the COVID-19 pandemic were limited, resulting in a decrease in overall physical activity and an increase in sedentary behaviour during the lockdown restrictions of the pandemic. This study further explored these changes across various stages of the restrictions, starting during the first UK-wide lockdown in March 2020 through to the "new normal" in December 2021. Nine families, consisting of eleven children (36% girls, 64% boys; aged 13.38 years ± 1.14), eight mothers and one father were tracked throughout this time, using semi-structured interviews to explore the fluctuations in physical activity and sedentary behaviour in the home environment in the context of self-determination theory. Findings indicate that as restrictions eased, physical activity within the home decreased, as children were exposed to more opportunities at school and in the community; these opportunities seemingly increased children's motivation to be physically active through increasing levels of their basic psychological needs of autonomy, competence, and relatedness. Some children's physical activity levels have returned to pre-COVID-19 levels, with a newfound enjoyment for being physically active. Whilst others now prefer to pursue more sedentary behaviours that became habitual during the lockdown restrictions. Accessible opportunities now need to be promoted to drive up children's motivations to be physically active following the years of uncertainty around the COVID-19 pandemic.

Motor Competence between Children with and without Additional Learning Needs: A Cross-Sectional Population-Level Study.

The aim of this study was to examine associations in motor competence between children with additional learning needs (ALN) and typically developing children. This cross-sectional study involved a nationally representative cohort of 4555 children (48.98% boys; 11.35 ± 0.65 years) from sixty-five schools across Wales (UK). Demographic data were collected from schools, and children were assessed using the Dragon Challenge assessment of motor competence, which consists of nine tasks completed in a timed circuit. A multi-nominal multi-level model with random intercept was fitted to explore the proficiency between children with ALN and those without. In all nine motor competence tasks, typically developing children demonstrated higher levels of proficiency than their peers with ALN, with these associations evident after accounting for age, sex, ethnicity, and socioeconomic status. This study highlights motor competence inequalities at a population level and emphasises the need for policymakers, practitioners, and researchers to prioritise motor competence development, particularly for children with ALN.