Biology subjects

Kaufmann, P.

Publications and source records attributed to Kaufmann, P..

4 recordsLinked to original sources

bioRxiv2026

Peptidylglycine α-amidating monooxygenase restores brain microvascular blood flow and improves recovery following ischemic stroke

IntroductionReduced or absent capillary blood flow (termed no-reflow) even after arterial recanalization is associated with poorer neurological outcomes following ischemic stroke. The aim of the current study was to test whether acute administration of peptidylglycine -amidating monooxygenase (PAM) can increase capillary blood flow and improve brain recovery after ischemic stroke. MethodsA 60-minute ischemic stroke was induced using middle cerebral artery occlusion (MCAO) in rats. A modified, long-acting PAM enzyme was administered 30 minutes after induction of ischemia and rats were recovered for either 24 hours or 7 days. In all animals, real-time cerebral blood flow was assessed before, during and after MCAO using trasncranial contrast enhanced ultrasound (tCEU). For rats in the 7-day protocol, a modified neuroscore test was used to assess neurological deficit following MCAO. At the end of each experiment, a transcardiac perfusion was used to generate a fluorescent vascular cast and histology was used to examine capillary diameters and determine infarct volume. ResultsFollowing MCAO and arterial recanalization, untreated rats had reduced cerebral blood flow across brain regions affected by ischemia, indicative of no-reflow. PAM administration led to enhanced cerebral blood flow in affected regions, and this was associated with increased capillary diameters 24 hours after ischemic stroke. Although there was no difference in infarct volume at 24 hours, by day 7, infarct volume was markedly reduced in the PAM group and these animals exhibited improved neurological function compared to the untreated group. ConclusionAdministration of PAM improves capillary blood flow after ischemic stroke leading to enhanced neurological and brain recovery. This work highlights PAM as a novel theraputic approach to improve brain blood flow and recovery after ischemic stroke. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/732201v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@3095ddorg.highwire.dtl.DTLVardef@1bf159borg.highwire.dtl.DTLVardef@239afdorg.highwire.dtl.DTLVardef@19476e3_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2026

From constraint to opportunity: Relaxing sexual antagonism reveals adaptive potential maintained by balancing selection

Despite ongoing selection, genetic variation in fitness-related traits often persists. Balancing selection can maintain polymorphisms through genetic trade-offs, including those between the sexes. Sexually antagonistic (SA) selection is challenging to detect at the genomic level and its broader evolutionary importance, especially for complex traits, remains unclear. To investigate this, we conducted an evolve-and-resequence experiment in Callosobruchus maculatus, manipulating the strength of SA trade-offs over body size and tracking genome-wide responses. When selection simultaneously favored larger females and smaller males, allele frequency changes were constrained and genome-wide divergence remained limited. In contrast, relaxing SA trade-offs by selecting on only one sex led to large, repeatable allele frequency shifts. These loci also showed signatures of long-term balancing selection in the ancestral population. Together, our results demonstrate that SA trade-offs can act both as a constraint, limiting sex-specific responses under antagonistic selection pressures, but also as a source of adaptive potential once antagonism is relaxed.

evolutionary biology↗

bioRxiv2023

Trial-to-trial similarity and distinctness of muscle synergy activation coefficients increases during learning and with a higher level of movement proficiency

Muscle synergy analyses are used to increase our understanding of motor control. Spatially fixed synergy vectors coordinate multiple co-active muscles through activation commands, known as activation coefficients. To better understand motor learning, it is crucial to know how synergy recruitment varies during a learning task and different levels of movement proficiency. Within one session participants walked on a line, a beam, and learned to walk on a tightrope - tasks that represent different levels of proficiency. Muscle synergies were extracted over all conditions and the number of synergies was determined through the knee-point of the total variance accounted for (tVAF) curve. We found that the tVAF of one synergy decreased with task proficiency (line < beam < tightrope). Additionally, trial-to-trial similarity and distinctness of synergy activation coefficients increased with proficiency and after a learning process. We conclude that precise adjustment and refinement of synergy activation coefficients play a crucial role in motor learning.

neuroscience↗

bioRxiv2023

Y-linked copy number polymorphism of target of rapamycin(TOR) is associated with sexual size dimorphism in seed beetles

The Y chromosome is theorized to facilitate evolution of sexual dimorphism by accumulating sexually antagonistic loci, but empirical support is scarce. Due to the lack of recombination Y chromosomes are prone to degenerative processes, which poses a constraint on their adaptive potential. Yet, in the seed beetle Callosobruchus maculatus segregating Y linked variation affects male body size and thereby sexual size dimorphism (SSD). Here we assemble C. maculatus sex chromosome sequences and identify molecular differences associated with Y-linked SSD variation. The assembled Y chromosome is largely euchromatic and contains over 400 genes, many of which are ampliconic with a mixed autosomal and X chromosome ancestry. Functional annotation suggests that the Y chromosome plays important roles in males beyond primary reproductive functions. Crucially, we find that, besides an autosomal copy of the gene target of rapamycin (TOR), males carry an additional TOR copy on the Y chromosome. TOR is a conserved regulator of growth across taxa, and our results suggest that a Y-linked TOR provides a male specific opportunity to alter body size. A comparison of Y haplotypes associated with male size difference uncovers a copy number variation for TOR, where the haplotype associated with decreased male size, and thereby increased sexual dimorphism, has two additional TOR copies. This suggests that sexual conflict over growth has been mitigated by autosome to Y translocation of TOR followed by gene duplications. Our results reveal that despite of suppressed recombination, the Y chromosome can harbour adaptive potential as a male-limited supergene.

evolutionary biology↗