Biology subjects

Adair, K.

Publications and source records attributed to Adair, K..

3 recordsLinked to original sources

bioRxiv2026

MicroAge Mission: Effects of Microgravity and Heat Shock Protein 10 Overexpression on the Proteome of Human Tissue-Engineered Muscle Constructs - Implications for Skeletal Muscle Ageing

Age-related loss of skeletal muscle mass and function, or sarcopenia, presents a growing clinical challenge, mirroring the accelerated muscle atrophy seen in microgravity. This study, part of the UK Space Agencys MicroAge Mission, aimed to investigate microgravity-induced proteomic changes in 3D human skeletal muscle constructs and assess whether mitochondrial Heat Shock Protein 10 (HSP10) overexpression could modulate these responses. Constructs derived from control human AB1167 myoblasts and AB1167 myoblasts that were transduced to overexpress HSP10, were flown to the International Space Station (ISS), with a ground reference experiment (GRE) conducted post-flight. Proteomic analysis using mass spectrometry and bioinformatics revealed significant alterations in metabolic, structural, and mitochondrial protein profiles after microgravity exposure. Microgravity caused downregulation of key proteins involved in energy metabolism, stress responses and structural integrity, while upregulating catabolic and apoptotic enzymes. Many of these modifications parallel previously reported changes in protein composition of muscle with ageing on earth. Overexpression of HSP10 attenuated the effects of microgravity, with fewer proteins showing significant changes and reduced disruption to mitochondrial and cytoskeletal components. Pathway analysis indicated that HSP10 overexpression preserved mitochondrial protein expression, particularly in the matrix, and promoted mitochondrial gene expression and translation under microgravity conditions. Notably, 284 proteins altered by microgravity in unmodified muscle constructs remained stable in HSP10-overexpressing constructs, suggesting a protective effect. MitoCarta 3.0 analysis confirmed that HSP10 expression modulated protein responses at the mitochondrial level, mitigating declines in bioenergetic proteins that are typically associated with microgravity. Collectively, the findings demonstrate that microgravity induces extensive proteomic remodelling in human muscle, which is partially offset by HSP10 overexpression. These results offer insights into muscle atrophy in spaceflight and suggest that targeting mitochondrial stress pathways via chaperone modulation may be a viable strategy to combat sarcopenia and disuse-induced muscle loss on Earth and in space.

physiology↗

bioRxiv2025

Drivers of Variation of the Zebrafish Egg Microbiome

Microbiomes are integral to the fitness of many animals, yet little is known about early-life microbiome assembly. What is known largely comes from studies in non-model organisms, where it is difficult to distinguish host genetics from the environment as drivers of microbiome assembly. Here, we used a popular vertebrate model, zebrafish (Danio rerio), to address the major drivers of environmental assembly in 124 individuals. We surveyed the egg microbiome from fertilization to hatching using 16S rRNA gene sequencing and investigated development stage and parentage as potential drivers of microbiome variation. Phylogenetic diversity of the egg microbiome decreased during development, suggesting that environmental filtering may be a major driver of community assembly. Parentage also had an influence on microbiome assembly; eggs derived from the same clutch were often more similar in microbiome composition compared to eggs derived from different clutches. The effect of parentage on microbiome similarity decreased over development, suggesting that parents may be an initial source of egg microbiome members. The egg microbiome undergoes dramatic compositional shifts during development. Understanding the drivers of this variation is important to consider, especially given the role of the microbiome in health and development, and that early exposure to microbes may shape later animal development. Our findings suggest that parents may serve as an important source of microbial symbionts to their offspring, even in an animal that does not provide parental care, such as laboratory zebrafish, and that the developing egg may play an increasingly important role in driving microbiome variation across individuals. ImportanceEarly-life microbiome composition is integral for establishing the normal functioning of multiple host systems, including the nervous system, gastro-intestinal tract, and immune system. However, the drivers of variation in early-life microbiome composition are underexplored, especially in Danio rerio (zebrafish), an important model organism that has allowed extensive exploration of the role of the microbiome in host health and development. Here, we characterize the microbiome of individual zebrafish eggs and determine the effects of parental identity and developmental time on shaping the egg microbiome prior to hatching. Both parentage and age influence microbiome composition and diversity. We found evidence that species-sorting (i.e. selection of microbes by the egg) is an important driver of microbiome assembly during egg development. Furthermore, the effect of parentage on the microbiome, while significant throughout embryonic development, decays over time. Despite the lack of parental care in laboratory reared zebrafish, these findings suggest that the parents are significant source of microbes to their offspring.

microbiology↗

bioRxiv2024

Relationship Between Circulating FGF21 and Physiological and Lifestyle Characteristics, an Exploratory Study

Fibroblast growth factor 21 (FGF21) is a biomarker that has been linked to metabolic health. This study was conducted to examine the relationship between FGF21 and its purported upstream regulators and downstream targets in healthy humans. Male and female participants completed three study visits. During visit 1 anthropometrics were measured and a VO2peak test was conducted on a stationary bike. During visits 2 and 3 resting metabolic rate, heart rate, and blood pressure were recorded and a blood sample was taken. Results from visits 2 and 3 were averaged before statistical analysis. Additionally, participants completed a food frequency questionnaire to detail typical diet over the previous month and had three days of measured physical activity and sleep. Moderate correlations between FGF21 and measured sleep (r = 0.34, p = 0.05), saturated fat intake (r = -0.37, p = 0.04), and blood urea nitrogen levels (r = -0.47, p = 0.01) were observed. Additionally, greater intensities of daily physical activity were associated with lower FGF21 levels. Serum FGF21 levels may be influenced by lifestyle variables such as sleep and physical activity, diet, and other circulating biomarkers. Highlights- FGF21 is positively correlated with sleep in healthy humans. - Sugar intake is positively correlated with FGF21 concentrations in humans. - Blood urea nitrogen concentrations are negatively correlated with FGF21 in humans.

physiology↗