Biology subjects

Wirtz, J.

Publications and source records attributed to Wirtz, J..

6 recordsLinked to original sources

bioRxiv2026

Repeated Neuromuscular Electrical Stimulation Protocol Disrupts Muscle-to-Brain Signaling in Rats

Objective. Neuromuscular electrical stimulation (NMES) is increasingly used to preserve or restore muscle function in patients unable to exercise, and acute NMES improves cognitive performance and increases hippocampal mature brain-derived neurotrophic factor (BDNF). However, the consequences of repeated sessions for muscle-to-brain signaling remain poorly understood. We examined whether seven consecutive days of quadriceps NMES would reproduce this acute response. Methods. Male Wistar rats received daily 30-min quadriceps NMES or SHAM sessions under isoflurane for seven consecutive days. Blood was collected immediately after the final session and 24 h later, when muscle and hippocampal tissues were also collected. An independent cohort underwent behavioral testing. Results. Repeated NMES increased serum creatine kinase activity and quadriceps fibrillar collagen deposition without altering muscle mass, myofiber size, or degeneration-regeneration markers. These changes were accompanied by low-grade systemic inflammation and corticosterone elevation persisting 24 h after the final session. In the hippocampus, NMES increased inflammatory cytokine expression, astrocytic and microglial markers, and glucocorticoid receptor phosphorylation. Mature BDNF, TrkB phosphorylation and ERK1/2 signaling decreased, whereas proBDNF, p75NTR and JNK signaling increased; Akt and mTOR phosphorylation were unchanged. Synaptophysin, GAP43 and PSD95 also decreased. NMES increased marble burying and forced-swim immobility, without detectable changes in locomotion, recognition memory, or neuronal profile density. Conclusions. Repeated daily NMES engaged a distinct, maladaptive mode of muscle-to-brain signaling rather than reproducing the benefits reported after acute stimulation. Stimulation parameters and recovery intervals that avoid this response need to be defined before repeated NMES can be recommended as an exercise substitute.

physiology↗

bioRxiv2026

Impacts of genome architecture on the repeatability of polygenic adaptation

A central but poorly resolved question regards how genome architecture shapes the selection response and repeatability of polygenic adaptation. We addressed this question using Evolve-and-Resequence experiments under rapid salinity decline in two sibling species (clades) of the invasive copepod Eurytemora affinis complex that differ strikingly in chromosome number (15 versus 4). The 4-chromosome genome arose from chromosomal fusions of the ancestral 15-chromosome genome, bringing together coadapted alleles at fusion sites. Across 10-20 generations of selection, both clades adapted to low salinity but followed divergent evolutionary trajectories. The selection lines of the 15-chromosome clade exhibited highly parallel genomic responses, whereas the 4-chromosome clade lines showed delayed and less repeatable responses. Forward genetic simulations revealed that strong synergistic epistasis among beneficial alleles best explained elevated parallelism in the 15-chromosome clade. Additional simulations varying chromosome number and epistasis revealed that strong positive epistasis, combined with high chromosome numbers, enhances parallelism by enabling recombination to assemble coadapted allelic combinations. In contrast, the high starting frequency of beneficial alleles in the 4-chromosome clade lines indicated selection on standing variation, likely acting on alternative linked haplotypes. These findings demonstrate that genome architecture and gene-gene interactions jointly determine the dynamics and predictability of polygenic adaptation.

evolutionary biology↗

bioRxiv2024

Muller's Ratchet and Gene Duplication

Copy number of genes in gene families can be highly variable among individuals and may continue to change across generations. Here, we study a model of duplication-selection interaction, which is related to Haighs mutation-selection model of Mullers ratchet. New gene copies are generated by duplication but fitness of individuals decreases as copy number increases. Our model comes in two flavours: duplicates are copied either from a single template or from any existing copy. A duplication-selection equilibrium exists in both cases for infinite size populations and is given by a shifted Poisson or a negative binomial distribution. Unless counteracted by synergistic epistasis, finite populations suffer from loss of low copy-number haplotypes by drift, forcing them into a regime called run-away evolution in which new copies accumulate without bound nor equilibrium. We discuss a few empirical examples and interpret them in the light of our models. Generally, large gene families appear too over-dispersed to fit the single template model suggesting a dynamic, and potentially accelerating, duplication process.

evolutionary biology↗

bioRxiv2024

Modeling the velocity of evolving lineages and predicting dispersal patterns

Accurate estimation of the dispersal velocity or speed of evolving organisms is no mean feat. In fact, existing probabilistic models in phylogeography or spatial population genetics generally do not provide an adequate framework to define velocity in a relevant manner. For instance, the very concept of instantaneous speed simply does not exist under one of the most popular approaches that models the evolution of spatial coordinates as Brownian trajectories running along a phylogeny (Lemey et al., 2010). Here, we introduce a new family of models - the so-called "Phylogenetic Integrated Velocity" (PIV) models - that use Gaussian processes to explicitly model the velocity of evolving lineages instead of focusing on the fluctuation of spatial coordinates over time. We describe the properties of these models and show an increased accuracy of velocity estimates compared to previous approaches. Analyses of West Nile virus data in the U.S.A. indicate that PIV models provide sensible predictions of the dispersal of evolving pathogens at a one-year time horizon. These results demonstrate the feasibility and relevance of predictive phylogeography in monitoring epidemics in time and space.

evolutionary biology↗

bioRxiv2018

Interdependence of linkage disequilibrium, chromatin architecture and compositional genome organization of mammals

Recent investigation established a link between DNA sequences and chromatin architecture and explained the evolutionary conservation of TADs (Topologically Associated Domains) and LADs (Lamina Associated Domains) in mammals. This prompted us to analyse the relationship between chromatin architecture and recombination landscapes of human and mouse. The results revealed that: (1) Blocks of elevated linkage disequilibrium tend to coincide with TADs and isochores, indicating co-evolving regulatory elements and genes in insulated neighbourhood; (2) double strand break (DSB) and recombination frequencies increase in GC-rich TADs, whereas recombination cold spots are typical of LADs; (3) binding and loading of proteins which are critical for DSB and meiotic recombination (Spo11, DMC1, H3K4me3 and PRMD9) are higher in GC-rich TADs. One explanation for these observations is that the occurrence of DSB and recombination in meiotic cells are associated to compositional and epigenetic features (genomic code) that are similar to those guiding the architecture of chromosomes in the interphase nucleus of pre-leptotene spermatocytes.

genomics↗

bioRxiv2018

Topological linkage disequilibrium calculated from coalescent genealogies

We revisit the classical concept of two-locus linkage disequilibrium (LD) and introduce a novel way of looking at haplotypes. In contrast to defining haplotypes as allele combinations at two marker loci, we concentrate on the clustering of sampled chromosomes induced by their coalescent genealogy. The root of a binary coalescent trees defines two clusters of chromosomes. At two different loci this assignment may be different as a result of recombination. We show that the amount of shared chromosomes among clusters at two different loci, measured by the squared correlation, constitutes a natural measure of LD. We call this topological LD (tLD) since it is induced by the topology of the coalescent tree. We find that its rate of decay decreases more slowly with distance between loci than that of conventional LD. Furthermore, tLD has a smaller coefficient of variation, which should render it more accurate for any kind of mapping purposes than conventional LD. We conclude with a practical application to the LCT region in human populations.

evolutionary biology↗