Biology subjects

Koster, R.

Publications and source records attributed to Koster, R..

5 recordsLinked to original sources

bioRxiv2026

The pan-cancer whole-genome landscape of Adolescent and Young Adult solid cancers

Cancer incidence in adolescents and young adults (AYAs; 18-39 years) is rising, but how their tumors differ genomically from those of older adults (OAs) is unclear. We analyzed paired tumor-normal whole-genomes from 698 AYAs and 5,220 OAs, with subcohorts matched by cancer group to disentangle age from tumor type. AYA tumors carried fewer somatic variants yet largely shared the same genetic drivers; many apparent age differences reflected age-dependent cancer subtypes, such as IDH-mutant glioma and HPV-positive cervical cancer. Colibactin, APOBEC and homologous recombination deficiency-associated signatures were more prevalent in AYA colorectal, gynecological and breast cancers, respectively, but were not more mutagenic when present, suggesting earlier-life activity rather than AYA-specific mutagenesis. Tumor type-concordant pathogenic germline variants were enriched in AYAs (10.9% overall versus 6.6% in matched OAs; p=0.006), often with a somatic second hit. Age thus shaped AYA cancer genomes through mutational processes, subtype composition and germline predisposition, supporting comprehensive tumor-normal profiling beyond driver-focused testing.

cancer biology↗

bioRxiv2026

Cortico-muscular control of postural balance in older adults - effects of training on functional connectivity

BackgroundBalance training in older adults can lead to reduced centre of mass accelerations and reduced angular momenta after perturbations of unipedal stance, reflecting an enhanced ability to recover balance. It has been suggested that the co-occurring changes in muscle synergies indicated strategy-specific adaptations in feedback control. MethodsWe investigated the cortical involvement in such adaptations by focusing on the interaction between muscle synergies and cortical activity after perturbations. Twenty older adults (>65 years) underwent short-term and three-week long-term balance training, and we assessed their recovery from unpredictable mediolateral perturbations during unipedal stance. We measured high-density EEG and activation of leg and trunk muscles. The representations of the balance-related muscle synergies were localised in the cortex using coherence-based beamformers in the {beta}-frequency band. ResultsBalance performance was accompanied by task-specific {beta}-band activation in the somatotopic representation of the lower extremities in the primary motor cortex. The {beta}-power significantly dropped during the response to perturbations, while the coherence with the activation of muscle synergies significantly increased, especially for synergies active in the early stage of balance recovery. The task-related changes in cortico-synergy coherence, especially during the later phase of balance recovery, were significantly affected by short-term training. ConclusionRefinements of feedback control seem to underlie balance improvements in older adults. The significant changes in the cortico-synergy interaction after balance training suggest cortical involvement in these refinements.

neuroscience↗

bioRxiv2021

Rapid Directed Molecular Evolution of Fluorescent Proteins in Mammalian Cells

In vivo imaging of model organisms is heavily reliant on fluorescent proteins with high intracellular brightness. Here we describe a practical method for rapid optimization of fluorescent proteins via directed molecular evolution in cultured mammalian cells. Using this method, we were able to perform screening of large gene libraries containing up to 2{middle dot}107 independent random genes of fluorescent proteins expressed in HEK cells completing one iteration directed evolution in a course of [~]8 days. We employed this approach to develop a set of green and near-infrared fluorescent proteins with enhanced intracellular brightness. The developed near-infrared fluorescent proteins demonstrated high performance for fluorescent labeling of neurons in culture and in vivo in model organisms such as C.elegans, Drosophila, zebrafish, and mice. Spectral properties of the optimized near-infrared fluorescent proteins enabled crosstalk-free multicolor imaging in combination with common green and red fluorescent proteins, as well as dual-color near-infrared fluorescence imaging. The described method has a great potential to be adopted by protein engineers due to its simplicity and practicality. We also believe that the new enhanced fluorescent proteins will find wide application for in vivo multicolor imaging of small model organisms.

molecular biology↗

bioRxiv2020

The underlying mechanisms of improved balance aftershort- and long-term training in older adults

Training improves balance control in older adults, but the time course and neural mechanisms underlying these improvements are unclear. We studied balance robustness and performance, H-reflex gains, paired reflex depression, and co-contraction duration in ankle muscles after one and ten training sessions in 22 older adults (+65yrs). Mediolateral balance robustness, time to balance loss in unipedal standing on a platform with decreasing rotational stiffness, improved (33%) after one session, with no further improvement after ten sessions. Balance performance, absolute mediolateral center of mass velocity, improved (18.75%) after one session in perturbed unipedal standing and (18.18%) after ten sessions in unperturbed unipedal standing. Co-contraction duration of soleus/tibialis anterior increased (16%) after ten sessions. H-reflex gain and paired reflex depression excitability did not change. H-reflex gains were lower, and soleus/tibialis anterior co-contraction duration was higher in participants with more robust balance after ten sessions, and co-contraction duration was higher in participants with better balance performance at several time-points. Changes in robustness and performance were uncorrelated with changes in co-contraction duration, H-reflex gain, or paired reflex depression. In older adults, balance robustness improved over a single session, while performance improved gradually over multiple sessions. Changes in co-contraction and excitability of ankle muscles were not exclusive causes of improved balance. HighlightsO_LIBalance robustness and balance performance in perturbed unipedal standing was improved after one balance training session, with no further improvement after ten sessions. C_LIO_LIBalance performance in unperturbed unipedal standing was improved after ten sessions C_LIO_LIH-reflex and paired reflex depression did not change after training in unipedal or bipedal standing. C_LIO_LICo-contraction duration of antagonistic ankle muscles increased after ten sessions in perturbed and unperturbed unipedal standing. C_LIO_LIChanges in co-contraction duration and excitability of ankle muscles were not exclusive causes of improved balance. C_LI

neuroscience↗

bioRxiv2018

Human hippocampal theta oscillations reflect sequential dependencies during spatial planning.

Movement-related theta oscillations in rodent hippocampus coordinate forward sweeps of location-specific neural activity that could be used to evaluate spatial trajectories online. This raises the possibility that increases in human hippocampal theta power accompany the evaluation of upcoming spatial choices. To test this hypothesis, we measured neural oscillations during a spatial planning task that closely resembles a perceptual decision-making paradigm. In this task, participants searched visually for the shortest path between a start and goal location in novel mazes that contained multiple choice points, and were subsequently asked to make a spatial decision at one of those choice points. We observed ~4-8 Hz hippocampal/medial temporal lobe theta power increases specific to sequential planning that were negatively correlated with subsequent decision speed, where decision speed was inversely correlated with choice accuracy. These results implicate the hippocampal theta rhythm in decision tree search during planning in novel environments.

neuroscience↗