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Klimes, P.

Publications and source records attributed to Klimes, P..

9 recordsLinked to original sources

Sleep spindles stabilize human thalamocortical networks, inhibiting pathological disruptions

The thalamus coordinates sleep-dependent brain function including memory consolidation, sensory gating, and network stability through spindle oscillations. Thalamocortical circuits are also affected in many neurological and neuropsychiatric disorders. Yet how human thalamocortical circuits respond to pathological disruptions remain poorly understood. Here, we leveraged interictal epileptiform discharges (IEDs) as spontaneous perturbations to probe spindle-generating circuits and thalamocortical dynamics in vivo. Using multi-night intracranial recordings spanning multiple thalamic nuclei and cortical regions in 55 individuals with epilepsy, we investigated interactions between sleep spindles and epileptic activity across timescales from milliseconds to days. Sleep spindles were associated with IED suppression, whereas IEDs increased subsequent spindle probability, revealing bidirectional interactions between physiological and pathological activity. Nights with lower IEDs corresponded to increased spindle occurrence, longer duration, and faster frequency, reflecting a more stable thalamocortical state. These findings propose sleep spindles as potential regulators of thalamocortical networks that actively respond to and regulate pathological activity.

neuroscience↗

A hyperbolic topological atlas reveals polyamine steering of a shared developmental manifold in Arabidopsis

High-throughput plant phenotyping captures development at scale, yet image-rich screens are still often reduced to static trait summaries. We tested whether nutrient availability, polyamine priming, concentration, and their transport reshape Arabidopsis rosette development by generating distinct morphologies or by changing residence along a common trajectory. We analyzed 138,223 time-resolved rosette images from Col-0 and five mutants involved in polyamine transport (put1-5) primed to putrescine, spermidine, spermine, dose, and nutrient regimes using a self-supervised vision backbone, Poincare embedding, hyperbolic Mapper, and manifold straightening. The data form a single connected developmental manifold with 410 nodes and 746 edges, organized from an early, low-nutrient-biased hub through high-betweenness transition corridors to two late, nutrient-enriched terminal regions. Polyamine identity stratifies this manifold by developmental phase: putrescine enriches early states, spermidine occupies transition corridors, and spermine marks late compact rosettes. Nutrient richness and dose change distal occupancy, whereas put genotypes alter dwell time within shared regions rather than producing separate topologies. Manifold straightening resolves these effects into a short early lateral deflection followed by convergence, yielding two scalar readouts, early transverse offset and distal occupancy, that summarize treatment action on a common morphodynamic scale. The framework converts large image screens into interpretable developmental geometry for image-based phenomics.

bioinformatics↗

LOCOPOTS: a low-cost high-throughput screening platform for in vitro potato phenotyping under abiotic stress

Potato crop is highly vulnerable to abiotic stresses like salinity and low nutrient availability. Rapid identification of stress-resilient genotypes is therefore essential for breeding, yet conventional phenotyping is often slow, space-demanding and expensive. We present LOCOPOTS -- a LOw-COst high-throughput screening platform for in vitro POTatoes under abiotic Stress -- which combines individual in vitro plant culture, low-cost RGB imaging and machine-learning-based automatic segmentation using a trained model of a convolutional neural network, based on U-Net architecture. LOCOPOTS enabled the automated extraction of growth, colour, and vegetation-index traits and demonstrated robust performance across independent phenotyping rounds. We screened 30 potato varieties under control, low-nutrient and saltinity conditions, identifying contrasting growth and physiological responses. Integrated traits such as final area and height, Area_AUC and height_AUC, together with GLI, Chol, cive and chlorophyll fluorescence parameters, discriminated genotype performance under stress. Metabolic profiling further revealed genotype-specific reprogramming in carbon and nitrogen metabolism under low nutrition and salt stress, including changes in fructose, myo-inositol, {beta}-aminobutyric acid, {gamma}-aminobutyric acid, proline, and certain polyamines, identifying them as specific chemical biomarkers of plant stress responses. LOCOPOTS provides a scalable, affordable and space-efficient platform for early screening of potato genetic diversity and identification of candidate traits associated with stress resilience.

plant biology↗

Patient-Derived PSEN1 Cerebral Organoids Revealed Parallel Development of Amyloid-β Accumulation and Network Dysfunction

Alzheimers disease (AD) is a neurodegenerative disorder characterised by progressive dementia, brain atrophy, and ultimately death. Using cerebral organoids derived from human induced pluripotent stem cells (hiPSCs) carrying the familial PSEN1 A246E variant, we investigated the temporal relationship between amyloid-{beta} (A{beta}) dysregulation and spontaneous neuronal activity. Multielectrode array recordings from the differentiation day 60 (DD60) to at least DD130 revealed that AD organoids exhibited transient hyperexcitability and hypersynchrony compared with wild-type (WT) controls, followed by a gradual decline in activity. During the enhanced excitability stage, both elevated A{beta}42/40 and A{beta} aggregate size showed positive correlations with the percentage of active electrodes and the global synchrony index (GSI) in AD organoids. These findings indicate that A{beta} dysregulation might contribute to transient network hyperexcitability in early AD. The results also suggest that patient-derived cerebral organoids may serve as a translational model to examine early network dysfunction and inform future investigations of potential A{beta}-induced changes in excitability during the preclinical stages of AD.

neuroscience↗

Thalamic Interictal Epileptic and Non-Epileptic Events during NREM Sleep in Patients with Focal Epilepsy: a Stereo-EEG Study

BackgroundThalamic recordings are increasingly incorporated into stereo-electroencephalography (SEEG) evaluations of drug-resistant focal epilepsy to guide neuromodulation targeting. Human thalamic electrophysiology, however, is poorly defined, limiting the distinction between pathological and physiological activity. Here, we characterized interictal epileptic and non-epileptic events during non-rapid eye movement (NREM) sleep across multiple thalamic nuclei and examined their relationship to seizure outcomes. MethodsWe analyzed NREM sleep SEEG recordings from 64 patients with drug-resistant focal epilepsy. Electrodes sampled four thalamic nuclei: centromedian (CM), pulvinar (Pu), ventral lateral (VL), and ventral posterolateral (VPL). Patients were classified into three outcome groups: favorable, unfavorable, and surgically non-remediable. Rates of thalamic spikes, high-frequency oscillations (HFOs), spike-fast activity, and sleep spindles were analyzed and compared across nuclei and outcomes. FindingsRecordings of the thalamus revealed both pathological and physiological interictal events. Interictal epileptic events were infrequent. Only [~]0.2% of seizure-onset zone spikes propagated to the thalamus. Thalamic spike-fast activity was indicative of unfavorable surgical outcomes (CM: p = 0.047, d = 0.46) or surgically non-remediable epilepsy (VL: p = 0.002, d = 0.84). In contrast, thalamic sleep spindles were ubiquitous but reduced in surgically non-remediable patients (CM: p = 0.031, d = -0.58; VL: p = 0.005, d = -0.79). Finally, unique thalamic SEEG patterns were identified, including spikes concomitant with spindles, isolated spikes, and physiological fast ripples. InterpretationThis study provides a comprehensive characterization of thalamic interictal events during NREM sleep, enriching our understanding of thalamic pathophysiology and highlighting the value of thalamic recordings in presurgical evaluation.

neuroscience↗

Sleep fragmentation drives local, network-specific epileptic activity in human epilepsy

Sleep has complex links with epileptic activity, yet the causal role of sleep instability in driving and modulating pathological discharges in the human brain remains incompletely understood. Here we directly examine this by characterising the fine-scale temporal coupling between experimentally induced sleep arousals and interictal epileptiform discharges (IEDs), using combined stereo-electroencephalography and polysomnography recordings in patients with epilepsy. Sleep arousals triggered rapid IED increases, with effects gated by anatomical region and sleep stage. Increases were confined to neocortical regions and occurred during both non-rapid eye movement stage 2 (N2) and stage 3 (N3) sleep, with a larger effect observed in N2. IED increases did not differ between the seizure-onset zone and surrounding regions. Despite elevating IED counts, arousals did not alter IED spatial propagation, indicating state-dependent enhancement of local cortical excitability without recruitment of broader epileptic networks. These findings establish a causal role for sleep instability in actively driving pathological activity on fine-grained spatiotemporal scales, and highlight sleep stabilisation as a promising therapeutic strategy to reduce epileptic burden and preserve cortical network function.

neuroscience↗

Decrypting the complex phenotyping traits of plants by machine learning

Phenotypes, defining an organisms behaviour and physical attributes, arise from the complex, dynamic interplay of genetics, development, and environment, whose interactions make it enormously challenging to forecast future phenotypic traits of a plant at a given moment. This work reports AMULET, a modular approach that uses imaging-based high-throughput phenotyping and machine learning to predict morphological and physiological plant traits hours to days before they are visible. AMULET streamlines the phenotyping process by integrating plant detection, prediction, segmentation, and data analysis, enhancing workflow efficiency and reducing time. The machine learning models used data from over 30,000 plants, using the Arabidopsis thaliana-Pseudomonas syringae pathosystem. AMULET also demonstrated its adaptability by accurately detecting and predicting phenotypes of in vitro potato plants after minimal fine-tuning with a small dataset. The general approach implemented through AMULET streamlines phenotyping and will improve breeding programs and agricultural management by enabling pre-emptive interventions optimising plant health and productivity.

plant biology↗

Disturbance increases functional diversity but decreases phylogenetic diversity of an arboreal tropical ant community

O_LITropical rainforest canopies host a highly diverse arthropod fauna, which contribute to ecosystem function through their functional (FD) and phylogenetic diversity (PD). While a lot of previous research has documented the severe negative impacts of disturbance on the FD and PD of ground invertebrate communities, our understanding of arboreal counterparts is limited. C_LIO_LIHere, we studied the effects of forest disturbance on an ecologically important invertebrate group, the ants, in a lowland rainforest in New Guinea. We exhaustively sampled 4000 m2 area of a primary and a secondary forest for canopy ants. We report > 2800 occurrences of 128 ant species in 852 trees, one of the most comprehensive arboreal collections to date. C_LIO_LITo test how ant PD and FD differ between the two forests, we constructed the ant species-level community phylogeny and measured 10 functional traits. Furthermore, we assessed by data exclusion the influence of species which were not nesting in individual trees (visitors) or only nesting (nesters), and of non-native species on FD and PD values. We expected that disturbance would decrease FD and PD in tree dwelling ants. We hypothesized that traits in primary forests would be more overdispersed due to the greater availability of ecological niches, while secondary forests would have stronger trait clustering due to a a stronger habitat filtering caused by more extreme microclimate. C_LIO_LIPrimary forests had higher species richness and PD than secondary forest. Surprisingly, we found higher FD in secondary forest. This pattern was robust even if we decoupled functional and phylogenetic signals or if non-native ant species were excluded from the data. Visitors did not contribute strongly to FD, but they increased PD. Community trait means further corroborate the functional distinctiveness of arboreal ants among secondary and primary forest, with almost all traits being impacted by disturbance and forest succession. C_LIO_LIWe conclude that the most plausible explanation is increased competition among closely related ant species in the secondary forest, which drives trait divergence. In the primary forest, abiotic habitat filters leads to more similar morphology and thus lower FD of phylogenetically more diverse ant assemblages. C_LI

ecology↗

The cortical wiring scheme of hierarchical information processing

AO_SCPLOWBSTRACTC_SCPLOWThe vast net of fibres within and underneath the cortex is optimised to support the convergence of different levels of brain organisation. Here we propose a novel coordinate system of the human cortex based on an advanced model of its connectivity. Our approach is inspired by seminal, but so far largely neglected models of cortico-cortical wiring established by post mortem anatomical studies and capitalizes on cutting-edge neuroimaging and machine learning. The new model expands the currently prevailing diffusion MRI tractography approach by incorporation of additional features of cortical microstructure and cortico-cortical proximity. Studying several datasets, we could show that our coordinate system robustly recapitulates established sensory-limbic and anterior-posterior dimensions of brain organisation. A series of validation experiments showed that the new wiring space reflects cortical microcircuit features (including pyramidal neuron depth and glial expression) and allowed for competitive simulations of functional connectivity and dynamics across a broad range contexts (based on resting-state fMRI, task-based fMRI, and human intracranial EEG coherence). Our results advance our understanding of how cell-specific neurobiological gradients produce a hierarchical cortical wiring scheme that is concordant with increasing functional sophistication of human brain organisation. Our evaluations demonstrate the cortical wiring space bridges across scales of neural organisation and can be easily translated to single individuals. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/899583v4_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1b1c601org.highwire.dtl.DTLVardef@3e76c7org.highwire.dtl.DTLVardef@e828e5org.highwire.dtl.DTLVardef@1d4f8ce_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗