Biology subjects

Essig, M.

Publications and source records attributed to Essig, M..

4 recordsLinked to original sources

bioRxiv2020

Whole-brain dynamics in aging: disruptions in functional connectivity and the role of the rich club

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state fMRI studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent (BOLD) signals to analyze resting-state fMRI data from 620 subjects divided into two groups ( middle-age group (n=310); age range, 50-65 years vs. older group (n=310); age range, 66-91 years). Applying the Intrinsic-Ignition Framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

neuroscience↗

bioRxiv2019

Brain BOLD MRI O2 and CO2 stress testing: Implications for perioperative neurocognitive disorder following surgery

Respiratory end-tidal (ET) gas control is fundamental to anaesthetic management. The range of ET O2 and CO2 during the conduct of anaesthesia can significantly deviate from values in the awake state. Recent work shows ET CO2 influences the incidence of perioperative neurocognitive disorder (POND). We examine the effects of controlled alterations in both ET O2 and CO2 on cerebral blood flow (CBF) in awake adults using BOLD MRI. Twelve healthy adults had BOLD and CBF responses measured to alterations in ET CO2 and O2 in various combinations commonly observed under anaesthesia. Dynamic alterations in regional BOLD and CBF were seen in all subjects with expected and inverse responses to both stimuli. These effects were incremental and rapid (within seconds). The most dramatic effects were seen with combined hyperoxia and hypocapnia. Inverse responses increased with age. Here we show that human brain CBF responds dramatically to alterations in ET respiratory gas tensions commonly seen during anaesthesia. Such alterations may impact the observed incidence of POND following surgery and intensive care, and is an important area for further investigation.

neuroscience↗

bioRxiv2019

Strategies based on sum of peak intensities may better reflect protein expression than peak area integration in iTRAQ protein expression measurement by LC-MS/MS using a TripleTOF 5600+ platform

In the field of quantitative proteomics, the Isobaric Tags for Relative & Absolute Quantitation (iTRAQ) technology has demonstrated efficacy for proteome monitoring despite its lack of a consensus for data handling. In this study, after peptide and protein identification, we compared the widespread quantitation method based on the calculation of MS/MS reporter ion peaks areas ratios (ProteinPilot) to the alternative method based on the calculation of ratios of the sum of peak intensities (jTRAQx (Quant)) and we processed output data with the in-house Customizable iTRAQ Ratios Calculator (CiR-C) algorithm. Quantitation based on peak area ratios displayed no significant linear correlation with Western blot quantitation. In contrast, quantitation based on the sum of peak intensities displayed a significant linear association with Western blot quantitation (non-zero slope; Pearson correlation coefficient test, r = 0.2962, p = 0.0099 **) with an average bias of 0.08747 {+/-} 0.5004 and 95% Limits of Agreement from - 0.8932 to 1.068. We proposed the Mascot-jTRAQx-CiR-C strategy as a simple yet powerful data processing adjunct to the iTRAQ technology.

cell biology↗

bioRxiv2018

Cyclosporine A inhibits MRTF-SRF signalling through Na+/K+ ATPase inhibition & Actin remodelling

Calcineurin Inhibitors (CNI) are the pillars of immunosuppression in transplantation. However, they display a potent nephrotoxicity whose mechanisms remained widely unsolved. We used an untargeted quantitative proteomic approach (iTRAQ technology) to highlight new targets of CNI in renal proximal tubular cells (RPTCs). CNI-treated RPTCs proteome displayed an over-representation of Actin-binding proteins with a CNI-specific expression profile. Cyclosporine A (CsA) induced F-Actin remodelling and depolymerisation, decreased F-Actin-stabilizing, polymerization-promoting Cofilin (CFL) oligomers and inhibited the G-Actin-regulated serum responsive factor (SRF) pathway. Inhibition of CFL canonical phosphorylation pathway reproduced CsA effects; however, Ser3, an analogue of the phosphorylation site of CFL prevented the effects of CsA which suggests that CsA acted independently from the canonical CFL regulation. CFL is known to be regulated by the Na+/K+-ATPase. Molecular docking calculations evidenced 2 inhibiting sites of CsA on Na+/K+-ATPase and a 23% decrease in Na+/K+-ATPase activity of RPTCs was observed with CsA. Ouabain, a specific inhibitor of Na+/K+-ATPase also reproduced CsA effects on Actin organization and SRF activity. Altogether, these results described a new original pathway explaining CsA nephrotoxicity.

cell biology↗