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Biology subjects

Sims, M.

Publications and source records attributed to Sims, M..

3 recordsLinked to original sources

Paired exposure to blue light and nutrient alters subsequent photo-avoidance in Physarum polycephalum

Whilst forms of non-associative learning such as habituation are widely reported in single-celled organisms, whether associative learning is possible in systems without a nervous system is contested. In this study, we implemented a conditioning paradigm in the acellular slime mould Physarum polycephalum through repeated pairings of nutrients with an aversive blue light stimulus. We first established that blue light is aversive under our conditioning protocol, slowing migration and producing broader, less directed growth, confirming its well documented effect on behaviour. Subjects were then trained in up to four training sessions by placing an oat stimulus inside a region with blue light before testing with the light presented alone. Trained subjects were more likely to reach the blue light region compared to untrained controls, with shorter latency, suggesting that Physarum weakens its avoidance of blue light after the region has repeatedly coincided with a nutrient. However, engagement did not strengthen with additional pairings, a pattern that admits multiple competing explanations in which associative and non-associative processes plausibly contribute to more transient associative-like effects. We conclude that a history of co-presentation is sufficient to relax an aversive response in Physarum but cannot, within the present study, attribute that change to associative learning.

animal behavior and cognition↗

CYP4F2 is a human-specific determinant of circulating N-acyl amino acid levels

N-acyl amino acids are a large family of circulating lipid metabolites that modulate energy expenditure and fat mass in rodents. However, little is known about the regulation and potential cardiometabolic functions of N-acyl amino acids in humans. Here, we analyze the cardiometabolic phenotype associations and genetic regulation of four plasma N-fatty acyl amino acids (N-oleoyl-leucine, N-oleoyl-phenylalanine, N-oleoyl-serine, and N-oleoyl-glycine) in 2,351 individuals from the Jackson Heart Study. N-oleoyl-leucine and N-oleoyl-phenylalanine were positively associated with traits related to energy balance, including body mass index, waist circumference, and subcutaneous adipose tissue. In addition, we identify the CYP4F2 locus as a human-specific genetic determinant of plasma N-oleoyl-leucine and N-oleoyl-phenylalanine levels. In vitro, CYP4F2-mediated hydroxylation of N-oleoyl-leucine and N-oleoyl-phenylalanine results in metabolic diversification and production of many previously unknown lipid metabolites with varying characteristics of the fatty acid tail group, including several that structurally resemble fatty acid hydroxy fatty acids (FAHFAs). By contrast, FAAH-regulated N-oleoyl-glycine and N-oleoyl-serine were inversely associated with traits related to glucose and lipid homeostasis. These data uncover a human-specific enzymatic node for the metabolism of a subset of N-fatty acyl amino acids and establish a framework for understanding the cardiometabolic roles of individual N-fatty acyl amino acids in humans.

biochemistry↗

Increased levels of circulating neurotoxic metabolites in patients with mild Covid19

SARS-CoV-2 corona virus causes a multi-faceted and poorly defined clinical and pathological phenotype involving hyperinflammation, cytokine release, and long-term cognitive deficits, with an undefined neuropathological mechanism. Inflammation increases the activity of the kynurenine pathway, which is linked to neurodegenerative and psychiatric disorders. We sought to determine whether the kynurenine pathway is impacted in patients with mild COVID-19, leading to elevated neurotoxic metabolites in blood, and whether such changes are associated with pro-inflammatory cytokines. Serum samples were taken from 150 patients and analyzed by ELISA and ultra-high performance liquid chromatography (UHPLC). The data were analyzed using multiple linear regression models adjusted for age and sex. We found increased levels of kynurenine, quinolinic acid and 3-hydroxykynurenine in serum from patients with mild COVID-19, together with increased levels of IL-6, ICAM-1, VCAM-1 and neopterin. The levels of neurotoxic metabolites were significantly associated with key inflammatory cytokines including IL-6 and TNF. The COVID-19 risk-factor hypertension was associated with the highest levels of neurotoxic metabolites in plasma. These neuroactive metabolites could be part of the pathological mechanisms underlying cognitive impairment during and post-COVID and should be explored as potential biomarkers for long-COVID symptoms.

neuroscience↗