Biology subjects

Peters, C.

Publications and source records attributed to Peters, C..

22 records · Page 2Linked to original sources

bioRxiv2020

Functional spreading of hyperexcitability induced by human and synthetic intracellular Aβ oligomers

BackgroundIntracellular amyloid-beta oligomers (iA{beta}o) accumulation and neuronal hyperexcitability are two crucial events at early stages of Alzheimers disease (AD). However, to date, no mechanism linking them has been reported. MethodsHere, the effects of human AD brain-derived (h-iA{beta}o) and synthetic (iA{beta}o) peptides on synaptic currents and action potential (AP) firing were investigated in hippocampal neurons in vitro, ex vivo and in vivo. ResultsStarting from 500 pM, iA{beta}o rapidly increased the frequency of synaptic currents and higher concentrations potentiated the AMPA receptor-mediated current. Both effects were PKC-dependent. Parallel recordings of synaptic currents and nitric oxide (NO)-related fluorescence changes indicated that the increased frequency, related to pre-synaptic release, was dependent on a NO-mediated retrograde signaling. Moreover, increased synchronization in NO production was also observed in neurons neighboring those dialyzed with iA{beta}o, indicating that iA{beta}o can increase network excitability at a distance. Current-clamp recordings suggested that iA{beta}o increased neuronal excitability via AMPA-driven synaptic activity without altering membrane intrinsic properties. ConclusionThese results strongly indicate that iA{beta}o causes functional spreading of hyperexcitability through a synaptic-driven mechanism and offer an important neuropathological significance to intracellular species in the initial stages of AD, which include brain hyperexcitability and seizures.

neuroscience↗

bioRxiv2020

Measuring Metacognition of Direct and Indirect Parameters of Voluntary Movement

We can make exquisitely precise movements without the apparent need for conscious monitoring. But can we monitor the low-level movement parameters when prompted? And what are the mechanisms that allow us to monitor our movements? To answer these questions, we designed a semi-virtual ball throwing task. On each trial, participants first threw a virtual ball by moving their arm (with or without visual feedback, or replayed from a previous trial) and then made a two-alternative forced choice on the resulting ball trajectory. They then rated their confidence in their decision. We measured metacognitive efficiency using meta-d/d and compared it between different informational domains of the first-order task (motor, visuomotor or visual information alone), as well as between two different versions of the task based on different parameters of the movement: proximal (position of the arm) or distal (resulting trajectory of the ball thrown). We found that participants were able to monitor their performance based on distal motor information as well as when proximal information was available. Their metacognitive efficiency was also equally high in conditions with different sources of information available. The analysis of correlations across participants revealed an unexpected result: while metacognitive efficiency correlated between informational domains (which would indicate domain-generality of metacognition), it did not correlate across the different parameters of movement. We discuss possible sources of this discrepancy and argue that specific first-order task demands may play a crucial role in our metacognitive ability and should be considered when making inferences about domain-generality based on correlations.

neuroscience↗

bioRxiv2019

quasitools: A Collection of Tools for Viral Quasispecies Analysis

Summaryquasitools is a collection of newly-developed, open-source tools for analyzing viral quasispcies data. The application suite includes tools with the ability to create consensus sequences, call nucleotide, codon, and amino acid variants, calculate the complexity of a quasispecies, and measure the genetic distance between two similar quasispecies. These tools may be run independently or in user-created workflows.\n\nAvailabilityThe quasitools suite is a freely available application licensed under the Apache License, Version 2.0. The source code, documentation, and file specifications are available at: https://phac-nml.github.io/quasitools/\n\nContactgary.vandomselaar@canada.ca

bioinformatics↗

bioRxiv2017

Phenotypic consequences of RNA polymerase dysregulation in Escherichia coli

Many bacterial adaptive responses to changes in growth conditions due to biotic and abiotic factors involve reprogramming of gene expression at the transcription level. The bacterial RNA polymerase (RNAP), which catalyzes transcription, can thus be considered as the major mediator of cellular adaptive strategies. But how do bacteria respond if a stress factor directly compromises the activity of the RNAP? We used a phage-derived small protein to specifically perturb bacterial RNAP activity in exponentially growing Escherichia coli. Using cytological profiling, tracking RNAP behavior at single-molecule level and transcriptome analysis, we reveal that adaptation to conditions that directly perturb bacterial RNAP performance can result in a biphasic growth behavior and thereby confer the adapted bacterial cells an enhanced ability to tolerate diverse antibacterial stresses. The results imply that while synthetic transcriptional rewiring may confer bacteria with the intended desirable properties, such approaches may also collaterally allow them to acquire undesirable traits.

microbiology↗