Biology subjects

Maier, M.

Publications and source records attributed to Maier, M..

8 recordsLinked to original sources

bioRxiv2026

Expectation Shapes Neural Preparation for AI-generated and Real Image Processing: Evidence from EEG

AbstractAI-generated images, videos, and news have become an inseparable part of daily life, leading to increasing skepticism toward online information. Understanding how expectations about the presence of AI-generated content influence perception is crucial for elucidating the underlying neural mechanisms and facilitating the generation of naturalistic avatars. In this study, we analyzed an existing EEG dataset (N = 29) in which participants viewed emotional facial photographs of only real individuals while being informed that upcoming faces were either real ("REAL") or AI-generated ("FAKE"). We examined pre-stimulus oscillatory activities in the one-second EEG interval before stimulus onset and found significantly lower alpha power when participants expected "FAKE" compared to "REAL" faces. This effect was region-specific, particularly in right occipito-parietal and temporo-parietal regions, as identified by both sensor- and source- level analyses. In addition, the modulation effect between pre-stimulus alpha activity and post-stimulus event-related potentials (ERPs) was measured. A significant correlation between changes in late positive potential (LPP) amplitudes and pre-stimulus alpha power was observed exclusively for "FAKE" smiling faces, consistent with our previous findings. These results suggest that AI-related expectations modulate neural preparatory states, with lower alpha activity presumably reflecting increased attentional demands for stimuli believed to be artificially generated. This study demonstrates that top-down beliefs systematically shape both pre- and post-stimulus neural dynamics, providing new insights into how cognitive expectations bias perceptual processing, with implications for understanding human-AI interaction and improving the design and evaluation of AI- generated content in real-world contexts.

neuroscience↗

bioRxiv2026

In vivo gene disruption and homology-directed repair in muscles and muscle stem cells using CRISPR/Cas9

Programmable endonucleases such as CRISPR/Cas9 provide powerful tools to edit mammalian genomes by engaging cellular mechanisms of DNA double-strand break (DSB) repair. CRISPR-catalysed homology-directed repair (CRISPR-HDR), though generally less efficient than other modes of DNA repair, holds particular promise to enable precise sequence replacement by targeted insertion of a homologous DNA template1,2. While recent studies have reported appreciable levels of HDR in cardiomyocytes in vivo3, skeletal muscle myofibres have historically been considered refractory to HDR-mediated genome editing4. Furthermore, how repair outcomes differ across tissues after systemic delivery of CRISPR/Cas9 editors, whether precise HDR editing can be achieved in regenerative tissue stem cells, and how developmental timing influences accessibility to CRISPR-induced repair remain unclear. Here, we use an adeno-associated virus (AAV)-delivered in vivo GFP-to-BFP colour-switching reporter system (AAV-GFP-to-BFP) to examine in vivo CRISPR-HDR with cellular- and tissue-level resolution. We find that postnatal cardiac muscle, skeletal muscle, and muscle stem cells undergo templated HDR at different rates across discrete developmental stages in mice. While HDR-edited muscle stem cells and myofibres were readily detectable after in vivo editing in juvenile mice, editing in neonatal mice yielded more efficient HDR in cardiac tissue. Based on these results, we adapted the CRISPR-HDR approach to rescue the therapeutically relevant Dmd mutation in mdx mice, demonstrating recoding to the wild-type protein sequence in both skeletal and cardiac muscles. These results provide a framework for advancing donor-templated DNA repair in living postnatal animals, and reveal unexpected cellular, developmental, and disease-related constraints on precise, therapeutic in vivo gene correction.

cell biology↗

bioRxiv2026

In vivo base editing via single myotrophic adeno-associated viruses in dystrophic mouse muscle and satellite cells

Duchenne muscular dystrophy (DMD) is the most common, lethal X-linked neuromuscular disorder of childhood and is caused by mutations in the Dmd gene that disrupt dystrophin expression. Although adeno-associated virus-mediated gene therapies hold tremendous promise for DMD treatment, their clinical applications have been limited by dose-dependent vector and genome-level toxicities. Here, we developed and tested a single-vector adenine base editing strategy as a potentially safer genome editing approach to recode the pathogenic nonsense mutation into a benign missense mutation in mdx4cvDMD mouse model. Delivered using a muscle-tropic adeno-associated virus (MyoAAV) at a clinically-feasible dose (4E13 VG/kg), this strategy enabled detectable molecular recoding of the mdx4cv mutation in mice ranging in age from 3 days to 6 months. Yet, the overall efficiency and therapeutic impact of in vivo base editing with this system was highest in mice treated at the juvenile stage, with animals administered MyoAAV vectors at 3 weeks of age showing robust recovery of dystrophin expression and significant improvement in muscle contractile properties only one month later. Notably, introduction of adenine base editors either earlier in development, in neonatal mice, or later, in adulthood, yielded substantially lower editing efficiencies, particularly in muscle satellite cells whose editing is essential to ensure durable rescue of dystrophin expression in growing and regenerating muscle. Taken together, these results demonstrate the therapeutic potential of single-vector adenine base editing for DMD and underscore the importance of recipient age and disease stage in achieving optimal treatment outcomes for this and other genetic muscle disorders.

cell biology↗

bioRxiv2024

Characterization of the three-dimensional synaptic and mitochondrial nanoarchitecture within glutamatergic synaptic complexes in postmortem human brain via focused ion beam-scanning electron microscopy

Synaptic function is directly reflected in quantifiable ultrastructural features using electron microscopy (EM) approaches. This coupling of synaptic function and ultrastructure suggests that in vivo synaptic function can be inferred from EM analysis of ex vivo human brain tissue. To investigate this, we employed focused ion beam-scanning electron microscopy (FIB-SEM), a volume EM (VEM) approach, to generate ultrafine-resolution, three-dimensional (3D) micrographic datasets of postmortem human dorsolateral prefrontal cortex (DLPFC), a region with cytoarchitectonic characteristics distinct to human brain. Synaptic, sub-synaptic, and organelle measures were highly consistent with findings from experimental models that are free from antemortem or postmortem effects. Further, 3D neuropil reconstruction revealed a unique, ultrastructurally-complex, spiny dendritic shaft that exhibited features characteristic of heightened synaptic communication, integration, and plasticity. Altogether, our findings provide critical proof-of-concept data demonstrating that ex vivo VEM analysis is an effective approach to infer in vivo synaptic functioning in human brain.

neuroscience↗

bioRxiv2023

Genetic reprogramming by brief inhibition of the renin-angiotensin system in spontaneously hypertensive rats leads to persistently reduced kidney renin and low blood pressure.

BACKGROUNDPrevention of human hypertension is an important challenge and has been achieved in experimental models. Brief treatment with renin-angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this reprogramming, but relevant genetic changes are unknown. METHODSIn SHR, we studied the effect of treatment between 10 and 14 weeks of age with the angiotensin receptor blocker, losartan, or the angiotensin-converting enzyme (ACE) inhibitor, perindopril (with controls for non-specific effects of lowering BP) on differential RNA expression, DNA methylation and renin immunolabelling in the kidney at 20 weeks of age. RESULTSRNA sequencing revealed a 6-fold increase in renin gene (Ren) expression during losartan treatment (P < 0.0001). At 20 weeks, six weeks after treatment cessation, mean arterial pressure remained lower in the treated SHR (P = 0.006), kidney Ren expression was reduced by 23% (P = 0.03) and DNA methylation within the Ren promoter region was increased (P = 0.04). Experiments with the ACE inhibitor perindopril confirmed a long-term reduction in kidney Ren expression of 43% (P = 1.4 x 10-6). Renin immunolabelling was also lower after losartan or perindopril treatment (P = 0.002). RNA sequencing identified differential expression of 13 candidate genes (Grhl1, Ammecr1l, Hs6st1, Nfil3, Fam221a, Lmo4, Adamts1, Cish, Hif3a, Bcl6, Rad54l2, Adap1, Dok4) and the miRNA miR-145-3p. We found correlations between expression of mRNAs, miRNAs and lncRNAs that we believe represent genetic networks underpinning the decreased Ren expression and lower BP. Gene ontogeny analyses revealed that these networks were enriched with genes relevant to BP, RAS and the kidneys. CONCLUSIONSEarly RAS inhibition in SHR reprograms genetic pathways and networks resulting in a legacy of reduced Ren expression and the persistent reduction in BP.

genetics↗

bioRxiv2020

Time course and shared neurocognitive mechanisms of mental imagery and visual perception

When we imagine an object and when we actually see that object, similar brain regions become active. Yet, the time course and mechanisms with which imagery engages perceptual networks remain to be better understood. An emerging view holds that imagery and perception follow distinct dynamics during early visual processing with similarities arising only during later, high-level visual processing. However, confounds of visual stimulation and paradigms favoring observation of high-level processes associated with subjective imagery strength may have precluded evidence of earlier shared mechanisms. We therefore manipulated prior knowledge that informs early-stage top-down predictions and tracked electrophysiological brain responses while fully controlling visual stimulation. Participants saw and imagined objects associated with varying amounts of semantic knowledge. Imagery and perception were equally influenced by knowledge at an early stage (P1 component), revealing shared mechanisms that support low-level visual processing. This finding complements previous research by showing that imagery is not merely perception in reverse. Instead, in line with the predictive processing framework, both, perception and imagery are active and constructive processes that share top-down mechanisms already in early phases of processing.

neuroscience↗

bioRxiv2018

Revealing an extended critical window of recovery post-stroke

The impact of rehabilitation on post-stroke motor recovery and its dependency on the patients chronicity remain unclear. The existence and regularity of a, so called, proportional recovery rule across a range of functional deficits and therapies supports the notion that functional interventions have little or no impact beyond spontaneous recovery rates in a critical window of recovery which lasts from 3 to 6 months post-stroke. In this meta-analysis, we apply a bootstrap analysis method to assess the overall impact of a specific VR-based rehabilitation protocol for the upper extremities on a homogeneous sample of 219 individuals with hemiparesis at various stages post stroke. Our analysis uncovers a precise gradient of sensitivity to treatment that expands more than one year beyond the limits of the so-called critical window of recovery. These findings redefine the limits of the so-called critical window of recovery and suggest that stroke-derived plasticity mechanisms do facilitate functional recovery even at the chronic and late chronic stage.

neuroscience↗

bioRxiv2018

Budding yeast complete DNA replication after chromosome segregation begins

To faithfully transmit genetic information, cells must replicate their entire genome before division. This is thought to be ensured by the temporal separation of replication and chromosome segregation. Here we show that in a substantial fraction of unperturbed yeast cells, DNA replication finishes during anaphase, late in mitosis. High cyclin-Cdk activity inhibits replication in metaphase, and the decrease in cyclin-Cdk activity during mitotic exit allows DNA replication to finish at difficult-to-replicate regions. Replication during late mitosis correlates with elevated mutation rates, including copy number variation. Thus, yeast cells temporally overlap replication and chromosome segregation during normal growth, possibly allowing cells to maximize population-level growth rate while simultaneously exploring greater genetic space.\n\nOne Sentence SummaryCompletion of DNA replication is coupled to downregulation of Cyclin-Dependent Kinase during mitotic exit.

cell biology↗