Biology subjects

Kohler, K.

Publications and source records attributed to Kohler, K..

4 recordsLinked to original sources

bioRxiv2025

Dim light at night impacts circadian rhythms and Alzheimer's disease-like neuroinflammation and neuropathology in humanized APP SAA knock-in mice

Artificial light at night (light pollution) is widespread but understudied in the context of Alzheimers disease (AD). Sleep and circadian disruption have been linked to amyloid-{beta} (A{beta}) accumulation and neuroinflammation, but whether dim light at night (dLAN) modifies these processes remains unclear. We tested whether chronic dLAN exposure (8 lux during the dark phase, 8 weeks) alters circadian rhythms, amyloid pathology, and neuroinflammation in 12-13 month-old humanized APP knock-in (KI) mice. hAPPSAA KI mice, which develop plaques, were compared with hAPPWT KI controls carrying only a humanized APP sequence. dLAN reduced circadian rhythm amplitude and stability while increasing fragmentation in both genotypes within two weeks. In hAPPSAA KI mice, dLAN modestly increased hippocampal plaque burden and soluble neocortical A{beta}. Astrocyte reactivity was elevated by genotype but not altered by nighttime light exposure. In contrast, microglial markers (CD45, MHCII) were increased with dLAN with CD45+ area elevated in hippocampus, and MHCII+ cell counts greater in the cortex and hippocampus of hAPPSAA KI mice. There were also distinct spatial responses between the microglia markers suggesting that dLAN primes microglia toward an antigen-presenting phenotype (MHCII) in the presence of A{beta}. Yet, the microglia/macrophage priming was not associated with amplified cytokine or chemokine levels at the 8-week dLAN exposure timepoint in the brain. These findings add to growing evidence that nighttime light exposure can disrupt circadian and immune regulation, and suggest that environmental light pollution should be further explored as a modifiable factor contributing to Alzheimers disease progression. Statement of SignificanceLight at night is a common feature of modern life, yet its influence on Alzheimers disease remains poorly understood. We show that dim light at night disrupts circadian rhythms, modestly increases amyloid pathology, and shifts microglia toward an antigen-presenting state in an amyloid-prone model. These findings identify light at night as a modifiable factor that may worsen risk or progression of neurodegenerative disease. A critical gap is whether circadian and immune changes resolve after darkness at night is restored. If they persist, early exposure could leave lasting imprints on brain aging. Addressing this question is essential for guiding strategies to mitigate the impact of light pollution.

neuroscience↗

bioRxiv2024

Evolution of polyamine resistance in Staphylococcus aureus through modulation of potassium transport

Microbes must adapt to diverse biotic and abiotic factors encountered in host environments. Polyamines are an abundant class of aliphatic molecules that play essential roles in fundamental cellular processes across the tree of life. Surprisingly, the bacterial pathogen Staphylococcus aureus is highly sensitive to polyamines encountered during infection, and acquisition of a polyamine resistance locus has been implicated in spread of the prominent USA300 methicillin-resistant S. aureus lineage. At present, alternative pathways of polyamine resistance in staphylococci are largely unknown. Here we applied experimental evolution to identify novel mechanisms and consequences of S. aureus adaption when exposed to increasing concentrations of the polyamine spermine. Evolved populations of S. aureus exhibited striking evidence of parallel adaptation, accumulating independent mutations in the potassium transporter genes ktrA and ktrD. Mutations in either ktrA or ktrD are sufficient to confer polyamine resistance and function in an additive manner. Moreover, we find that ktr mutations provide increased resistance to multiple classes of unrelated cationic antibiotics, suggesting a common mechanism of resistance. Consistent with this hypothesis, ktr mutants exhibit alterations in cell surface charge indicative of reduced affinity and uptake of cationic molecules. Finally, we observe that laboratory-evolved ktr mutations are also present in diverse natural S. aureus isolates, suggesting these mutations may contribute to antimicrobial resistance during human infections. Collectively this study identifies a new role for potassium transport in S. aureus polyamine resistance with consequences for susceptibility to both host-derived and clinically-used antimicrobials.

microbiology↗

bioRxiv2022

Interdisciplinary analyses of Bronze Age communities from Western Hungary reveal complex population histories

In this study we report 21 ancient shotgun genomes from present-day Western Hungary, from previously understudied Late Copper Age Baden, and Bronze Age Somogyvar-Vinkovci, Kisapostag, and Encrusted Pottery archaeological cultures (3530 - 1620 cal BCE). Our results indicate the presence of high steppe ancestry in the Somogyvar-Vinkovci culture. They were then replaced by the Kisapostag group, who exhibit an outstandingly high (up to [~]47%) Mesolithic hunter-gatherer ancestry, despite this component being thought to be highly diluted by the time of the Early Bronze Age. The Kisapostag population contributed the genetic basis for the succeeding community of the Encrusted pottery culture. We also found an elevated hunter-gatherer component in a local Baden culture associated individual, but no connections were proven to the Bronze Age individuals. The hunter-gatherer ancestry in Kisapostag is likely derived from two main sources, one from a Funnelbeaker or Globular Amphora culture related population and one from a previously unrecognised source in Eastern Europe. We show that this ancestry not only appeared in various groups in Bronze Age Central Europe, but also made contributions to Baltic populations. The social structure of Kisapostag and Encrusted pottery cultures is patrilocal, similarly to most contemporaneous groups. Furthermore, we developed new methods and method standards for computational analyses of ancient DNA, implemented to our newly developed and freely available bioinformatic package. By analysing clinical traits, we found carriers of aneuploidy and inheritable genetic diseases. Finally, based on genetic and anthropological data, we present here the first female facial reconstruction from the Bronze Age Carpathian Basin.

genomics↗

bioRxiv2017

Parallel ancient genomic transects reveal complex population history of early European farmers

Ancient DNA studies have established that European Neolithic populations were descended from Anatolian migrants who received a limited amount of admixture from resident hunter-gatherers. Many open questions remain, however, about the spatial and temporal dynamics of population interactions and admixture during the Neolithic period. Using the highest-resolution genome-wide ancient DNA data set assembled to date--a total of 177 samples, 127 newly reported here, from the Neolithic and Chalcolithic of Hungary (6000-2900 BCE, n = 98), Germany (5500-3000 BCE, n = 42), and Spain (5500-2200 BCE, n = 37)--we investigate the population dynamics of Neolithization across Europe. We find that genetic diversity was shaped predominantly by local processes, with varied sources and proportions of hunter-gatherer ances try among the three regions and through time. Admixture between groups with different ancestry profiles was pervasive and resulted in observable population transformation across almost all cultural transitions. Our results shed new light on the ways that gene flow reshaped European populations throughout the Neolithic period and demonstrate the potential of time-series-based sampling and modeling approaches to elucidate multiple dimensions of historical population interactions.

genetics↗