Biology subjects

Meyer, B.

Publications and source records attributed to Meyer, B..

30 records · Page 2Linked to original sources

bioRxiv2023

Ecological genomics in the Northern krill uncovers loci for local adaptation across ocean basins

Krill is a vital food source for many marine animals but also strongly impacted by climate change. Genetic adaptation could support populations, but remains uncharacterized. We assembled the 19 Gb Northern krill genome and compared genome-scale variation among 74 specimens from the colder Atlantic Ocean and warmer Mediterranean Sea. The genome is dominated by methylated transposable elements and contains many duplicated genes implied in molting and vision. Analysis of 760 million SNPs indicates extensive homogenizing gene-flow among populations. Nevertheless, we detect extreme divergence across hundreds of genes, governing ecophysiological functions like photoreception, circadian regulation, reproduction and thermal tolerance. Such standing variation may be essential for resilience in zooplankton, necessitating insight into adaptive variation to forecast their roles in future marine ecosystems and support ocean conservation. One-Sentence SummaryGenome-scans of Northern krill link genes for photoreception, reproduction and thermal tolerance to ecological adaptation.

evolutionary biology↗

bioRxiv2022

Arousal defines the conditions for facilitation by L-DOPA of extinction consolidation and associated prefrontal activity

Even after successful extinction, conditioned fear can return. Strengthening the consolidation of the fear-inhibitory safety memory formed during extinction is one way to counteract return of fear. In this preregistered direct replication study in male participants, we confirm that spontaneous post-extinction reactivations of a neural activation pattern evoked in the ventromedial prefrontal cortex (vmPFC) during extinction predict extinction memory retrieval 24 h later. We do not confirm that L-DOPA administration after extinction enhances retrieval and that this is mediated by enhancement of the number of vmPFC reactivations. However, additional non-preregistered analyses reveal a beneficial effect of L-DOPA on extinction retrieval when controlling for the trait-like stable baseline levels of salivary alpha-amylase enzymatic activity (trait sAA) levels that participants show on the three experimental days. Further, trait sAA negatively predicts retrieval, and this effect is rescued by L-DOPA treatment. Our results suggest that individuals with high basal levels of sympathetic nervous system (SNS) activity may have poor extinction and that L-DOPA may be selectively beneficial for these individuals, which holds potential for clinical applications.

neuroscience↗

bioRxiv2022

Human acute microelectrode array recordings with broad cortical access, single-unit resolution and parallel behavioral monitoring

Human single-unit studies currently rely on neurosurgical procedures that provide only limited brain coverage and on recording devices that do not integrate easily into established surgical routines. Here, we report reliable and robust acute multi-channel recordings with broad cortical access using planar microelectrode arrays (MEA) implanted intracortically in awake brain surgery. We provide a comprehensive characterization of extracellular neuronal activity acquired intraoperatively in tumor patients with large open craniotomies. MEA implantation was fast, safe and yielded high-quality signals at the microcircuit, local field potential level, and at the cellular, single-unit level. Recording from parietal association cortex, a region previously unexplored in human single-unit studies, we demonstrate applications on these complementary spatial scales and describe travelling waves of oscillatory activity as well as single-neuron and neuronal population responses during numerical cognition including operations with uniquely human number symbols. Intraoperative MEA recordings are practicable and can be scaled up to explore cellular and microcircuit mechanisms of a wide range of human brain functions.

neuroscience↗

bioRxiv2021

The most comprehensive annotation of the Krill transcriptome provides new insights for the study of physiological processes and environmental adaptation

The krill species Euphausia superba plays a critical role in the food chain of the Antarctic ecosystem, as the abundance of its biomass affects trophic levels both below it and above. Major changes in climate conditions observed in the Antarctic Peninsula region in the last decades have already altered the distribution of the krill population and its reproductive dynamics. A deeper understanding of the adaptation capabilities of this species, and of the molecular mechanisms behind it are urgently needed. The availability of a large body of RNA-seq assays gave us the opportunity to extend the current knowledge of the krill transcriptome, considerably reducing errors and redundancies. Our study covered the entire developmental process, from larval stages to adult individuals, providing information of central relevance for ecological studies. Here we describe the KrillDB2 database, a resource combining the latest annotation of the krill transcriptome with a series of analyses specifically targeting genes and molecular processes relevant to krill physiology. KrillDB2 provides in a single resource the most complete collection of experimental data and bioinformatic annotations: it includes an extended catalog of krill genes; an atlas of their expression profiles over all RNA-seq datasets publicly available; a study of differential expression across multiple conditions such as developmental stages, geographical regions, seasons, and sexes. Finally, it provides initial indications about non-coding RNAs, a class of molecules whose contribute to krill physiology has never been reported before.

ecology↗

bioRxiv2021

Enhanced fitness of SARS-CoV-2 variant of concern B.1.1.7, but not B.1.351, in animal models

Emerging variants of concern (VOCs) drive the SARS-CoV-2 pandemic. We assessed VOC B.1.1.7, now prevalent in several countries, and VOC B.1.351, representing the greatest threat to populations with immunity to the early SARS-CoV-2 progenitors. B.1.1.7 showed a clear fitness advantage over the progenitor variant (wt-S614G) in ferrets and two mouse models, where the substitutions in the spike glycoprotein were major drivers for fitness advantage. In the "superspreader" hamster model, B.1.1.7 and wt-S614G had comparable fitness, whereas B.1.351 was outcompeted. The VOCs had similar replication kinetics as compared to wt-S614G in human airway epithelial cultures. Our study highlights the importance of using multiple models for complete fitness characterization of VOCs and demonstrates adaptation of B.1.1.7 towards increased upper respiratory tract replication and enhanced transmission in vivo. Summary sentenceB.1.1.7 VOC outcompetes progenitor SARS-CoV-2 in upper respiratory tract replication competition in vivo.

microbiology↗

bioRxiv2021

Don't Stress, It's Under Control: Neural Correlates of Stressor Controllability in Humans

Animal research has repeatedly shown that experience of control over an aversive event can protect against the negative consequences of later uncontrollable stress. Neurobiologically, this effect is assumed to correspond to persistent changes in the pathway linking the ventromedial prefrontal cortex (vmPFC) and the dorsal raphe nucleus. However, it remains unclear to what extent these findings translate to humans. During functional magnetic resonance imaging, we subjected participants to controllable and uncontrollable aversive but non-painful electric stimuli, as well as to a control condition without aversive stimulation. In each trial, a symbol signalled whether participants could terminate the stressor through correct performance in a button-matching task or whether the stressor would be randomly terminated, i.e., uncontrollable. Along with neural responses, we assessed participants accuracy, reaction times, and heart rate. To relate neural activations and subjective experience, we asked participants to rate perceived control, helplessness, and stress. Results were largely in line with our hypotheses. The vmPFC was generally deactivated by stress, but this effect was attenuated when participants could terminate the stressor compared to when their responses had no effect. Furthermore, activation in stress-responsive regions, including the bilateral insula, was reduced during controllable trials. Under uncontrollable stress, greater vmPFC recruitment was linked to reduced feelings of helplessness. An investigation of condition-dependent differences in vmPFC connectivity yielded no significant results. Our findings further corroborate animal research and emphasise the role of the vmPFC in controllability-dependent regulation of stress responses. Based on the results, we discuss future directions in the context of resilience research and mental health promotion.

neuroscience↗

bioRxiv2021

SARS-CoV-2 RBD in vitro evolution follows contagious mutation spread, yet generates an able infection inhibitor

SARS-CoV-2 is continually evolving, with more contagious mutations spreading rapidly. Using in vitro evolution to affinity maturate the receptor-binding domain (RBD) of the spike protein towards ACE2 resulted in the more contagious mutations, S477N, E484K, and N501Y, to be among the first selected, explaining the convergent evolution of the "European" (20E-EU1), "British" (501.V1),"South African" (501.V2), and Brazilian" variants (501.V3). Plotting the binding affinity to ACE2 of all RBD mutations against their incidence in the population shows a strong correlation between the two. Further in vitro evolution enhancing binding by 600-fold provides guidelines towards potentially new evolving mutations with even higher infectivity. For example, Q498R epistatic to N501Y. Nevertheless, the high-affinity RBD is also an efficient drug, inhibiting SARS-CoV-2 infection. The 2.9[A] Cryo-EM structure of the high-affinity complex, including all rapidly spreading mutations, provides a structural basis for future drug and vaccine development and for in silico evaluation of known antibodies.

biochemistry↗

bioRxiv2020

Characterisation of protease activity during SARS-CoV-2 infection identifies novel viral cleavage sites and cellular targets for drug repurposing

SARS-CoV-2 is the causative agent behind the COVID-19 pandemic, and responsible for over 170 million infections, and over 3.7 million deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved understanding of the basic biology of SARS-CoV-2. Both viral and cellular proteases play a crucial role in SARS-CoV-2 replication, and inhibitors targeting proteases have already shown success at inhibiting SARS-CoV-2 in cell culture models. Here, we study proteolytic cleavage of viral and cellular proteins in two cell line models of SARS-CoV-2 replication using mass spectrometry to identify protein neo-N-termini generated through protease activity. We identify previously unknown cleavage sites in multiple viral proteins, including major antigenic proteins S and N, which are the main targets for vaccine and antibody testing efforts. We discovered significant increases in cellular cleavage events consistent with cleavage by SARS-CoV-2 main protease, and identify 14 potential high-confidence substrates of the main and papain-like proteases, validating a subset with in vitro assays. We showed that siRNA depletion of these cellular proteins inhibits SARS-CoV-2 replication, and that drugs targeting two of these proteins: the tyrosine kinase SRC and Ser/Thr kinase MYLK, showed a dose-dependent reduction in SARS-CoV-2 titres. Overall, our study provides a powerful resource to understand proteolysis in the context of viral infection, and to inform the development of targeted strategies to inhibit SARS-CoV-2 and treat COVID-19.

microbiology↗

bioRxiv2019

Architecture and modular assembly of the Sulfolobus S-layers revealed by electron cryo-tomography

Surface protein layers (S-layers) often form the only structural component of the archaeal cell wall and are therefore important for cell survival. S-layers have a plethora of cellular functions including maintenance of cell shape, osmotic and mechanical stability, the formation of a semi-permeable protective barrier around the cell, cell-cell interaction, as well as surface adhesion. Despite the central importance of the S-layer for archaeal life, their three-dimensional architecture is still poorly understood. Here we present the first detailed 3D electron cryo-microscopy maps of archaeal S-layers from three different Sulfolobus strains. We were able to pinpoint the positions and determine the structure of the two subunits SlaA and SlaB. We also present a model describing the assembly of the mature S-layer.

microbiology↗

bioRxiv2019

Community driven dynamics of oscillatory network responses to threat

Physiological responses to threat stimuli involve neural synchronized oscillations in cerebral networks with distinct organization properties. Community architecture within these networks and its dynamic adaptation could play a critical role in achieving optimal physiological responses.\n\nHere we applied dynamic network analyses to address the early phases of threat processing at the millisecond level, describing multi-frequency (theta and alpha) integration and basic reorganization properties (flexibility and clustering) that drive physiological responses. We quantified cortical and subcortical network interactions and captured illustrative reconfigurations using community allegiance as essential fingerprints of large-scale adaptation.\n\nA theta band driven community reorganization of key anatomical regions forming the threat network (TN) along with transitions of nodes from the dorsal attention (DAN) and salience (SN) circuits predict the optimal physiological response to threat. We show that increase flexibility of the community network architecture drives the physiological responses during instructed threat processing. Nodal switches modulate the directionality of information flows in the involved circuits.\n\nThese results provide a captivating perspective of flexible network responses to threat and shed new light on basic physiological principles relevant for the development of stress- and threat-related mental disorders.

neuroscience↗

bioRxiv2018

A computational model of task allocation in social insects: ecology and interactions alone can drive specialisation

Social insect colonies are capable of allocating their workforce in a decentralised fashion; addressing a variety of tasks and responding effectively to changes in the environment. This process is fundamental to their ecological success, but the mechanisms behind it remain poorly understood. While most models focus on internal and individual factors, empirical evidence highlights the importance of ecology and social interactions. To address this gap we propose a game theoretical model of task allocation. Individuals are characterised by a trait that determines how they split their energy between two prototypical tasks: foraging and regulation. To be viable, a colony needs to learn to adequately allocate its workforce between these two tasks. We study two different processes: individuals can learn relying exclusively on their own experience, or by using the experiences of others via social learning. We find that social organisation can be determined by the ecology alone, irrespective of interaction details. Weakly specialised colonies in which all individuals tend to both tasks emerge when foraging is cheap; harsher environments, on the other hand, lead to strongly specialised colonies in which each individual fully engages in a single task. We compare the outcomes of self-organised task allocation with optimal group performance. Counter to intuition, strongly specialised colonies perform suboptimally, whereas the group performance of weakly specialised colonies is closer to optimal. Social interactions lead to important differences when the colony deals with dynamic environments. Colonies whose individuals rely on their own experience are more exible when dealing with change. Our computational model is aligned with mathematical predictions in tractable limits. This different kind of model is useful in framing relevant and important empirical questions, where ecology and interactions are key elements of hypotheses and predictions.

ecology↗

bioRxiv2018

Excitability regulation in the dorsomedial prefrontal cortex during sustained instructed fear responses: a TMS-EEG study

BackgroundThreat detection is essential for protecting individuals from precarious situations. Early studies suggested a network of amygdala, limbic regions and dorsomedial prefrontal cortex (dmPFC) involved in fear processing. Excitability regulation in the dmPFC might be crucial for physiological fear processing, while an abnormal excitability pattern could lead to mental illness. Non-invasive paradigms to measure excitability regulation during fear processing in humans are missing.\n\nMethodsWe adapted an experimental approach of excitability characterization using electroencephalography (EEG) recordings and transcranial magnetic stimulation (TMS) over the dmPFC during an instructed fear paradigm to dynamically dissect its role in fear processing. Event-related (ERP) and TMS-evoked potentials (TEP) were analyzed to trace dmPFC excitability in healthy young volunteers (n = 40, age = 27.6 {+/-} 5.7 years, 22 females). Moreover, we linked the excitability regulation patterns to individual structural MRI-derived properties of gray matter microstructural integrity of the fear network.\n\nResultsAn increased cortical excitability was demonstrated in the threat (T) condition in comparison to no-threat (NT) as showed by increased amplitude of evoked potentials. Furthermore, TMS over the dmPFC induced markedly increased evoked responses during T condition in relation to NT. Moreover, we found that the structural integrity of the dmPFC and the amygdala predict excitability regulation patterns as measured by ERP and TEP during fear processing.\n\nConclusionsWe describe the dynamic range of excitability regulation in dmPFC during fear processing. The applied paradigm can be used to non-invasively track response abnormalities to threat stimuli in healthy subjects or patients with mental disorders.

neuroscience↗