Biology subjects

Meyer, A.

Publications and source records attributed to Meyer, A..

45 records · Page 3Linked to original sources

bioRxiv2020

Autophagy in T cells from aged donors is maintained by spermidine, and correlates with function and vaccine responses

Older adults are at high risk for infectious diseases such as the recent COVID-19 and vaccination seems to be the only long-term solution to the pandemic. While most vaccines are less efficacious in older adults, little is known about the molecular mechanisms that underpin this. Autophagy, a major degradation pathway and one of the few processes known to prevent aging, is critical for the maintenance of immune memory in mice. Here, we show induction of autophagy is specifically induced in human vaccine-induced antigen-specific T cells in vivo. Reduced IFN{gamma} secretion by vaccine-induced T cells in older vaccinees correlates with low autophagy. We demonstrate in human cohorts that levels of the endogenous autophagy-inducing metabolite spermidine, fall with age and supplementing it in vitro recovers autophagy and T cell function. Finally, our data show that endogenous spermidine maintains autophagy via the translation factor eIF5A and transcription factor TFEB. With these findings we have uncovered novel targets and biomarkers for the development of anti-aging drugs for human T cells, providing evidence for the use of spermidine in improving vaccine immunogenicity in the aged human population.

physiology↗

bioRxiv2020

Towards complete and error-free genome assemblies of all vertebrate species

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are only available for a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling the most accurate and complete reference genomes to date. Here we summarize these developments, introduce a set of quality standards, and present lessons learned from sequencing and assembling 16 species representing major vertebrate lineages (mammals, birds, reptiles, amphibians, teleost fishes and cartilaginous fishes). We confirm that long-read sequencing technologies are essential for maximizing genome quality and that unresolved complex repeats and haplotype heterozygosity are major sources of error in assemblies. Our new assemblies identify and correct substantial errors in some of the best historical reference genomes. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an effort to generate high-quality, complete reference genomes for all ~70,000 extant vertebrate species and help enable a new era of discovery across the life sciences.

genomics↗

bioRxiv2019

Parallel and non-parallel changes of the gut microbiota during trophic diversification in repeated young adaptive radiations of sympatric cichlid fish

Recent increases in understanding the ecological and evolutionary roles of microbial communities has underscored their importance for their hosts biology. Yet, little is known about gut microbiota dynamics during early stages of ecological diversification and speciation. We studied the gut microbiota of extremely young adaptive radiations of Nicaraguan crater lake cichlid fish (Amphilophus cf. citrinellus) to test the hypothesis that parallel evolution in trophic ecology is associated with parallel changes of the gut microbiota. Bacterial communities of the water (eDNA) and guts were highly distinct, indicating that the gut microbiota is shaped by host-specific factors. Across individuals of the same crater lake, differentiation in trophic ecology was associated with gut microbiota differentiation, suggesting that diet affects the gut microbiota. However, differences in trophic ecology were much more pronounced across than within species whereas little evidence was found for similar patterns in taxonomic and functional changes of the gut microbiota. Across the two crater lakes, we could not detect evidence for parallel changes of the gut microbiota associated with trophic ecology. Similar cases of non-parallelism have been observed in other recently diverged fish species and might be explained by a lack of clearly differentiated niches during early stages of ecological diversification.

evolutionary biology↗

bioRxiv2019

Speaking in the brain: The interaction between words and syntax in producing sentences

This neuroimaging study investigated the neural infrastructure of sentence-level language production. We compared brain activation patterns, as measured with BOLD-fMRI, during production of sentences which differed in verb argument structures (intransitives, transitives, ditransitives) and the lexical status of the verb (known verbs or pseudo-verbs). An example for the type of sentence to be produced started a mini-block of six sentences with the same structure. For each trial, participants were first given the (pseudo-)verb followed by three geometric shapes to serve as verb arguments in the sentences. Production of sentences with known verbs yielded greater activation compared to those with pseudo-verbs in the core language network of left inferior frontal gyrus, the left posterior middle temporal gyrus, and a more posterior middle temporal region extending into the angular gyrus (LpMTG/AG), analogous to effects observed in language comprehension. Increasing the number of verb arguments led to greater activation in an overlapping left pMTG/AG area, particularly for known verbs, as well as in the bilateral precuneus. Thus, producing sentences with more complex structures using existing verbs lead to increased activation in the language network, suggesting some reliance on memory retrieval of stored lexical-syntactic information during sentence production. This study thus provides evidence from sentence-level language production in line with functional models of the language network that have so far been mainly based on single word production, comprehension and processing in aphasia.

neuroscience↗

bioRxiv2019

Learning lexical-syntactic biases: An fMRI study on how we connect words and syntactic information

Language processing often involves learning new words and how they relate to each other. These relations are realized through syntactic information connected to a word, e.g. a word can be verb or a noun, or both, like the word run. In a behavioral and an fMRI task we showed that words and their syntactic properties, i.e. lexical items which were either syntactically ambiguous or unambiguous, can be learned through the probabilities of co-occurrence in an exposure session and subsequently used in a production task. Novel words were processed within regions of the language network (left inferior frontal and posterior middle temporal gyrus) and more syntactic options led to higher activations herein, even when the words were shown in isolation, suggesting combined lexical-syntactic representation. When words were shown in untrained grammatical contexts, activation in left inferior frontal cortex increased. This might reflect competition between the newly learned representation and the presented information. The results elucidate the lexical nature of the neural representations of lexical-syntactic information within the language network and the specific role of the left inferior frontal cortex in unification of the novel words with the surrounding context.

neuroscience↗

bioRxiv2019

Disruption of large-scale electrophysiological networks in stroke patients with visuospatial neglect

Stroke frequently produces attentional dysfunctions including symptoms of hemispatial neglect, which is characterized by a breakdown of awareness for the contralesional hemispace. Recent studies with functional MRI (fMRI) suggest that hemineglect patients display abnormal intra-and inter-hemispheric functional connectivity. However, since stroke is a vascular disorder and fMRI signals remain sensitive to non-neuronal (i.e. vascular) coupling, more direct demonstrations of neural network dysfunction in hemispatial neglect are warranted. Here, we utilize electroencephalogram (EEG) source imaging to uncover differences in resting-state network organization between patients with right-hemispheric stroke (N = 15) and age-matched, healthy controls (N = 27), and determine the relationship between hemineglect symptoms and brain network organization. We estimated intra-and inter-regional differences in cortical communication, by calculating the spectral power and amplitude envelope correlations (AEC) of narrow-band EEG oscillations. We firstly observed focal frequency-slowing within the right posterior cortical regions, reflected in relative delta/theta power increases and alpha/beta/gamma decreases. Secondly, nodes within the right temporal and parietal cortex consistently displayed anomalous intra- and inter- hemispheric coupling, stronger in delta and gamma bands, and weaker in theta, alpha, and beta bands. Finally, a significant association was observed between the severity of left-hemispace search deficits (e.g. cancellation test omissions) and reduced functional connectivity within the alpha and beta bands. In sum, our novel results validate the hypothesis of large-scale cortical network disruption following stroke, and reinforce the proposal that abnormal brain oscillations may be intimately involved in the pathophysiology of visuospatial neglect.

neuroscience↗

bioRxiv2017

Neural entrainment determines the words we hear

Low-frequency neural entrainment to rhythmic input has been hypothesized as a canonical mechanism that shapes sensory perception in time. Neural entrainment is deemed particularly relevant for speech analysis, as it would contribute to the extraction of discrete linguistic elements from continuous acoustic signals. Yet, its causal influence in speech perception has been difficult to establish. Here, we provide evidence that oscillations build temporal predictions about the duration of speech tokens that directly influence perception. Using magnetoencephalography (MEG), we studied neural dynamics during listening to sentences that changed in speech rate. We observed neural entrainment to preceding speech rhythms persisting for several cycles after the change in rate. The sustained entrainment was associated with changes in the perceived duration of the last words vowel, resulting in the perception of words with radically different meanings. These findings support oscillatory models of speech processing, suggesting that neural oscillations actively shape speech perception.

neuroscience↗

bioRxiv2017

ATP sensing in living plant cells reveals tissue gradients and stress dynamics of energy physiology

Growth and development of plants is ultimately driven by light energy captured through photosynthesis. ATP acts as universal cellular energy cofactor fuelling all life processes, including gene expression, metabolism, and transport. Despite a mechanistic understanding of ATP biochemistry, ATP dynamics in the living plant have been largely elusive. Here we establish live MgATP2- assessment in plants using the fluorescent protein biosensor ATeam1.03-nD/nA. We generate Arabidopsis sensor lines and investigate the sensor in vitro under conditions appropriate for the plant cytosol. We establish an assay for ATP fluxes in isolated mitochondria, and demonstrate that the sensor responds rapidly and reliably to MgATP2- changes in planta. A MgATP2- map of the Arabidopsis seedling highlights different MgATP2- concentrations between tissues and in individual cell types, such as root hairs. Progression of hypoxia reveals substantial plasticity of ATP homeostasis in seedlings, demonstrating that ATP dynamics can be monitored in the living plant.\n\nOne-sentence SummarySensing of MgATP2- by fluorimetry and microscopy allows dissection of ATP fluxes of isolated organelles, and dynamics of cytosolic MgATP2- in vivo.\n\nFunding AgenciesThis work was supported by the Deutsche Forschungsgemeinschaft (DFG) through the Emmy-Noether programme (SCHW1719/1-1; M.S. and GR4251/1-1; C.G.), the Research Training Group GRK 2064 (M.S.; A.J.M.), the Priority Program SPP1710 (A.J.M.) and a grant (SCHW1719/5-1; M.S.) as part of the package PAK918. The Seed Fund grant CoSens from the Bioeconomy Science Center, NRW (A.J.M.; M.S.) is gratefully acknowledged. The scientific activities of the Bioeconomy Science Center were financially supported by the Ministry of Innovation, Science and Research within the framework of the NRW Strategieprojekt BioSC (No. 313/323-400-002 13). A.Co. received funding by the Ministero dellIstruzione, dellUniversita e della Ricerca through the FIRB 2010 programme (RBFR10S1LJ_001) and Piano di Sviluppo di Ateneo 2015 (Universita degli Studi di Milano). M.Z. received funding by the Ministero dellIstruzione, dellUniversita e della Ricerca (Italy) through the PRIN 2010 programme (PRIN2010CSJX4F). S.W. and T.N. received travel support by the Deutscher Akademischer Austauschdienst (DAAD). V.D.C. was supported by the European Social Fund, Operational Programme 2007/2013, and an Erasmus+ Traineeship grant. M.D.F was supported by The Human Frontier Science Program (RPG0053/2012), and the Leverhulme Foundation (RPG-2015-437). I.M.M. was supported by a grant from the Danish Council for Independent Research - Natural Sciences. V.C.P. was supported by the Innovation and Technology Fund (Funding Support to Partner State Key Laboratories in Hong Kong) of the HKSAR.\n\nAbbreviationsAAC - ADP/ATP carrier; AK - adenylate kinase; cAT - carboxyatractyloside; CCCP - carbonyl cyanide m-chlorophenyl hydrazone; CFP - cyan fluorescent protein; CLSM - confocal laser scanning microscopy; ETC - electron transport chain; FRET - Forster Resonance Energy Transfer; LSFM - light sheet fluorescence microscopy.

plant biology↗

bioRxiv2017

A Possible Role Of Microglia In Zika Virus Infection Of The Fetal Human Brain

Maternal Zika virus (ZIKV) infection during pregnancy is increasingly recognized as the cause of an epidemic of microcephaly and other neurological anomalies in human fetuses. However, it remains unclear how ZIKV gains access to the highly vulnerable population of neural progenitors of the fetal central nervous system (CNS), and which cell types of the CNS may serve as viral reservoirs. To model viral interaction with cells of the fetal CNS in vitro, we investigated the tropism of ZIKV for different iPS-derived human cells, with a particular focus on microglia-like cells derived from human pluripotent stem cells. We show that ZIKV infected isogenic neural progenitors, astrocytes and microglia-like cells, but was only cytotoxic to neural progenitors. Infected glial cells propagated the virus and maintained viral load over time, leading to viral spread to susceptible cells. ZIKV-infected microglia, when co-cultured with pre-established neural spheroids, invaded the tissue and initiated neural infection. Since microglia derive from primitive macrophages originating in anatomical proximity to the maternal vasculature of the placenta, we propose that they may act in vivo as a viral reservoir for ZIKV and, owing to their natural ability to traverse the embryo, can establish infection of the fetal brain. Infection of immature neural stem cells by invading microglia may occur in the early stages of pregnancy, before vascular circulation is established. Our data are also consistent with the virus affecting the integrity of the blood-brain barrier (BBB), which may allow infection of the brain at later stages.

neuroscience↗