Search bioRxiv⌕ Search

Biology subjects

Gross, G.

Publications and source records attributed to Gross, G..

2 recordsLinked to original sources

Exhaled breath profiling for non-invasive monitoring of cognitive functioning in children

IntroductionChildhood is a critical period for the development of executive functioning skills, including selective attention and inhibitory control, which are essential for cognitive development. Optimal brain development during this time requires appropriate levels of macronutrient intake. Metabolomics can offer valuable insights into which metabolites cognitive functioning and the underlying gut-brain interactions. ObjectivesThis study aimed to explore to use of breathomics to investigate associations between exhaled metabolites and executive functioning in children. MethodsChildren (8-10 years; N = 31) were recruited via flyers at schools and after-school care. The assessment of executive functioning was done using Eriksen flanker task. Breath samples were collected in Tedlar(R) bags and analyzed with proton transfer reaction-mass spectrometry (PTR-MS). On-breath peaks were selected and subjected to partial least squares (PLS) regression. Significance multivariate correlation (sMC) was used afterwards to select metabolites bearing predictive power towards executive functioning. ResultsGut microbiome-related metabolites (methane, ethanol, and butyric acid) present in exhaled breath were associated with an improved executive functioning, whereas isoprene was linked to reduced executive functioning. Additionally, increased levels of inflammatory markers, ethylene and acetaldehyde, were associated with a higher compatibility effect in error rates, suggesting diminished cognitive control. These VOCs were putatively linked with specific gut microbial taxa; for instance, reduced Bacteroidetes abundance (associated with methane production) is associated with decreased inhibitory control, while Enterobacteriaceae were linked to lipopolysaccharide-induced inflammation which is also a process that causes increased ethylene production. ConclusionThis proof-of-concept study demonstrates that VOCs in exhaled breath could serve as a promising non-invasive tool for assessing gut-brain interactions related to executive functioning in children.

biochemistry↗

Improved CAR-T cell activity associated with increased mitochondrial function primed by galactose

CD19 CAR-T cells have led to durable remissions in patients with refractory B-cell malignancies; nevertheless, most patients eventually relapse in the long term. Many interventions aimed at improving current products have been reported, with a subset of them focusing on a direct or indirect link to the metabolic state of the CAR-T cells. We assessed clinical products from an ongoing clinical trial utilizing CD19-28z CAR-T cells from patients with acute lymphoblastic leukemia. CAR-T clinical products leading to a complete response had significantly higher mitochondrial function (by oxygen consumption rate) irrespective of mitochondrial content. Next, we replaced the carbon source of the media from glucose to galactose to impact cellular metabolism. Galactose-containing media increased mitochondrial activity in CAR-T cells, and improved in vitro efficacy, without any consistent phenotypic change in memory profile. Finally, CAR-T cells produced in galactose-based glucose-free media resulted in increased mitochondrial activity. Using an in vivo model of Nalm6 injected mice, galactose-primed CAR-T cells significantly improved leukemia-free survival compared to standard glucose-cultured CAR-T cells. Our results prove the significance of mitochondrial metabolism on CAR-T cell efficacy and suggest a translational pathway to improve clinical products.

immunology↗