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Koller, B.

Publications and source records attributed to Koller, B..

2 recordsLinked to original sources

Mental development is associated with cortical connectivity of the ventral and nonspecific thalamus of preterm newborns

The thalamus is a key hub for regulating cortical connectivity. Dysmaturation of thalamocortical networks that accompany white matter injury have been hypothesized as neuroanatomical correlate of late life neurocognitive impairment following preterm birth. Our objective was to find a link between thalamocortical connectivity measures at term equivalent age and two year neurodevelopmental outcome in preterm infants. Diffusion tensor MRI of 58 infants (postmenstrual age at birth, mean (SD), 29.71 (1.47) weeks) was used to trace connections between the cortex and thalami. We found strong correlation between mental developmental index and two complementary measures of thalamocortical networks: connectivity strength projected to a cortical skeleton and pathway length emerging from thalamic voxels (partial correlation, R=0.552 and R=0.535, respectively, threshold-free cluster enhancement, corrected p-value<0.05), while psychomotor development was not associated with thalamocortical connectivity. Post hoc stepwise linear regression analysis revealed that parental socioeconomic scale, postmenstrual age and the duration of mechanical ventilation at the intensive care unit contribute to the variability of outcome. Our findings independently validated previous observations in preterm infants, providing additional evidence injury or dysmaturation of tracts emerging from ventral specific and various non-specific thalamus projecting to late-maturing cortical regions are predictive of mental, but not psychomotor developmental outcomes.

neuroscience↗

Live-cell imaging of circadian clock protein dynamics in CRISPR-generated knock-in cells

The current model of the mammalian circadian oscillator is predominantly based on data from genetics and biochemistry experiments, while the cell biology of circadian clocks is still in its infancy. Here, we describe a new strategy for the efficient generation of knock-in reporter cell lines using CRISPR technology that is particularly useful for lowly or transiently expressed genes, such as those coding for circadian clock proteins. We generated single and double knock-in cells with endogenously expressed PER2 and CRY1 fused to fluorescent proteins, which allowed to simultaneously monitor the dynamics of CRY1 and PER2 proteins in live single cells. Both proteins are highly rhythmic in the nucleus of human cells with PER2 showing a much higher amplitude than CRY1. Surprisingly, CRY1 protein is nuclear at all circadian times indicating the absence of circadian gating of nuclear import. Furthermore, in the nucleus of individual cells CRY1 abundance rhythms are phase-delayed ([~]5 hours), and CRY1 levels are much higher (>6 times) compared to PER2 questioning the current model of the circadian oscillator. Our knock-in strategy will allow the generation of additional single, double or triple knock-in cells for circadian clock proteins, which should greatly advance our understanding about the cell biology of circadian clocks.

cell biology↗