Biology subjects

Roux, L.

Publications and source records attributed to Roux, L..

3 recordsLinked to original sources

bioRxiv2024

Link between respiratory pauses and vigilance states in freely moving mice

Brain activity and breathing rate influence each other but it remains unclear how fine respiratory features vary across vigilance states. Using simultaneous nasal pressure and hippocampal local field potential recordings in freely-moving mice, we show that the position of respiratory pauses within breathing cycles distinguish Wake, Rapid Eye Movement (REM) and non-REM (NREM) sleep states. Model-based predictions of vigilance states based on respiratory features perform well even on animals outside of the training set, suggesting the rules are generalized. Respiratory features underwent specific changes at state transitions, such as progressive elimination of pauses after inhalation foreshadowing REM. During NREM, respiratory changes predicted moment-to moment sigma power variations beyond movement-defined packets delineated by micro-arousals, as pauses after inhalation fragmented NREM sleep into [~]30s windows of high sigma power. Overall, our findings reveal that respiratory features structure the macro- and micro-architecture of sleep, opening new windows into brain states through respiration.

neuroscience↗

bioRxiv2023

Skin microbiome attributes associate with biophysical skin aging

Two major arms of skin aging are changes in the skins biophysical conditions and alterations in the skin microbiome. This work partitioned both arms to study their interaction in detail. Leveraging the resolution provided by shotgun metagenomics, we explored how skin microbial species, strains, and gene content interact with the biophysical traits of the skin during aging. With a dataset well-controlled for confounding factors, we found that skin biophysical traits, especially the collagen diffusion coefficient, are associated with the composition and the functional potential of the skin microbiome, including the abundance of bacterial strains found in nosocomial infections and the abundance of antibiotic resistance genes. Our findings reveal important associations between skin biophysical features and aging-related changes in the skin microbiome and generate testable hypotheses for the mechanisms of such associations.

genomics↗

bioRxiv2018

Hydrophobicity drives the systemic distribution of lipid-conjugated siRNAs via lipid transport pathways

Efficient delivery of therapeutic RNA is the fundamental obstacle preventing its clinical utility. Lipid conjugation improves plasma half-life, tissue accumulation, and cellular uptake of small interfering RNAs (siRNAs). However, the impact of conjugate structure and hydrophobicity on siRNA pharmacokinetics is unclear, impeding the design of clinically relevant lipid-siRNAs. Using a panel of biologically-occurring lipids, we show that lipid conjugation modulates siRNA hydrophobicity and governs spontaneous partitioning into distinct plasma lipoprotein classes in vivo. Lipoprotein binding influences siRNA distribution by delaying renal excretion and promoting uptake into lipoprotein receptor-enriched tissues. Lipid-siRNAs elicit mRNA silencing without causing toxicity in a tissue-specific manner. Lipid-siRNA internalization occurs independently of lipoprotein endocytosis, and is mediated by siRNA phosphorothioate modifications. Although biomimetic lipoprotein nanoparticles have been considered for the enhancement of siRNA delivery, our findings suggest that hydrophobic modifications can be leveraged to incorporate therapeutic siRNA into endogenous lipid transport pathways without the requirement for synthetic formulation.

pharmacology and toxicology↗