bioRxiv Science⌕ Search

Biology subjects

Cooke, D.

Publications and source records attributed to Cooke, D..

3 recordsLinked to original sources

Motor Evoked Potentials in Preclinical Models of Spinal Cord Injury and Stroke in Rodents: A Systematic Review.

Motor Evoked Potentials (MEPs) serve as an invaluable tool for assessing corticospinal tract (CST) integrity and motor pathway function in preclinical models of spinal cord injury (SCI) and stroke. Despite their diagnostic and prognostic utility, substantial methodological variability persists across studies, complicating interpretation and cross-study comparisons. This systematic review synthesizes MEP acquisition and interpretation protocols from 83 rodent SCI and stroke studies published since 2015, aiming to outline common practices, identify sources of variability, and highlight methodological gaps. Our analysis reveals a predominance of SCI models and a focus on hindlimb MEPs, employing diverse stimulation protocols including transcranial electrical stimulation (TES), direct cortical stimulation (DCoS), and transcranial magnetic stimulation (TMS). Anesthetic approaches are notably heterogeneous, representing a potentially large source of variability in MEP acquisition. Amplitude and latency, often measured jointly, emerged as the most frequently reported MEP parameters. Critically, MEPs bridge cellular and molecular changes to observable behaviour by reflecting the integrated functionality of neural cell populations and their circuits. However, a lack of standardization in reporting, particularly for secondary electrophysiological features and stimulation intensity, hinders reproducibility. We emphasize the necessity for standardized protocols for stimulation, electrode positioning, and data analysis, particularly the use of comprehensive recruitment curves. Adopting these best practices will enhance the transparency, comparability, and translational potential of MEP methodology in advancing our understanding and treatment strategies for neurological disorders.

neuroscience↗

Cysteine Restriction-Specific Effects of Sulfur Amino Acid Restriction on Lipid Metabolism

Decreasing dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), i.e., sulfur amino acid restriction (SAAR). Contrarily, human diets used in clinical studies did not eliminate cysteine and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not with methionine, suggesting that CR, but not MR, is responsible for the antiadiposity effects of SAAR in rodents. Whether this is true, and if so, the underlying mechanisms are unknown. Using multiple diets with variable concentrations of methionine and cysteine, we demonstrate that the anti-adiposity effects of SAAR are due to CR. CR increased serinogenesis (serine biosynthesis from non-glucose substrates) by diverting substrates from glyceroneogenesis, essential for fatty acid/triglyceride cycling. Molecular data suggest that the CR results in glutathione depletion, which induces Nrf2 and downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck-M. Using multiple mouse models, we show that the magnitude of SAAR-induced changes in molecular markers depends on dietary fat concentration (60 fat>10% fat), gender (males>females), and age-at-onset (young>adult). Our findings are translationally relevant as we found a negative correlation of plasma serine with triglycerides and metabolic syndrome criteria in a cross-sectional epidemiological study. SAAR-like diets with high polyunsaturated fatty acids increased plasma serine in a short-term human feeding study. Serinogenesis might be a potential target to correct hypertriglyceridemia.

biochemistry↗

Heat efficiently inactivates coronaviruses inside vehicles

Heat is an established method to inactivate coronaviruses, and there is utility in using heat to reduce viral load on common touch points in vehicles exposed to a person shedding SARS-CoV-2. As SARS-CoV-2 is a Biosafety level (BSL)-3 pathogen, real world testing of heat as a sanitation method for public and private vehicles becomes a challenge, requiring a surrogate coronavirus that can be handled safely outside of a BSL-3 facility. In this study, we used Bovine Coronavirus (BCoV) as a surrogate for SARS-CoV-2 to test the efficacy of heat-based betacoronavirus inactivation. In vitro, a 30-minute exposure to 56{degrees}C completely inactivated BCoV in solution, and a 15-minute exposure reduced recovery of BCoV >1000-fold. When heated to 56{degrees}C for 15 minutes, the infectivity of BCoV spotted and dried on typical porous and non-porous automobile interior materials was reduced by 99 - 99.99%. When BCoV was spotted and dried on hard plastic (seat) material placed inside an out of service transit bus, 56{degrees}C heat for 30 minutes reduced BCoV infectivity 85 - 99.5%. Thus, 56{degrees}C is an accessible, rapid, and effective method to inactivate coronaviruses inside motor vehicles.

microbiology↗