Biology subjects

Fink, G. R.

Publications and source records attributed to Fink, G. R..

23 records · Page 2Linked to original sources

bioRxiv2020

Dynamic graph analysis reveals aging effects on motor network communication

Cognitive performance slows down with increasing age. This includes cognitive processes that are essential for the performance of a motor act, such as the slowing down in response to an external stimulus. The objective of this study was to identify aging-associated functional changes in the brain networks that are involved in the transformation of external stimuli into motor action. To investigate this topic, we employed dynamic graphs based on phase-locking of Electroencephalography signals recorded from healthy younger and older subjects while performing a simple visually-cued finger-tapping task. The network analysis yielded specific age-related network structures varying in time in the low frequencies (2-7 Hz), which are closely connected to stimulus processing, movement initiation and execution in both age groups. The networks in older subjects, however, contained several additional, particularly interhemispheric, connections and showed an overall increased coupling density. Cluster analyses revealed reduced variability of the subnetworks in older subjects, particularly during movement preparation. In younger subjects, occipital, parietal, sensorimotor and central regions were - temporally arranged in this order - heavily involved in hub nodes. Whereas in older subjects, a hub in frontal regions preceded the noticeably delayed occurrence of sensorimotor hubs, indicating different neural information processing in older subjects. All observed changes in brain network organization, which are based on neural synchronization in the low frequencies, provide a possible neural mechanism underlying previous fMRI data, which report an overactivation, especially in the prefrontal and pre-motor areas, associated with a loss of hemispheric lateralization in older subjects.

neuroscience↗

bioRxiv2020

Cortical network fingerprint and prediction of stimulation induced speech impairment in essential tremor

ObjectiveTo gain insights into structural networks associated with stimulation-induced dysarthria (SID) and to predict stimulation-induced worsening of intelligibility in essential tremor patients with bilateral thalamic deep brain stimulation (DBS). MethodsMonopolar reviews were conducted in 14 essential tremor patients. Testing included determination of SID thresholds, intelligibility ratings and a fast syllable repetition task. Volumes of tissue activated (VTAs) were calculated to identify discriminative fibers for stimulation-induced worsening of intelligibility in a structural connectome. The resulting fiber-based atlas structure was than validated in a leave-one-out design. ResultsFibers determined as discriminative for stimulation-induced worsening of intelligibility were mainly connected to the ipsilateral precentral gyrus as well as to both cerebellar hemispheres and the ipsilateral brainstem. In the thalamic area, they ran laterally to the thalamus and postero-medially to the subthalamic nucleus, in close proximity, mainly antero-laterally, to fibers beneficial for tremor control as published by Al-Fatly et al. (2019). The overlap of the respective clinical stimulation settings VTAs with these fibers explained 62.4% (p<0.001) of the variance of stimulation-induced change in intelligibility in a leave-one out analysis. InterpretationThis study demonstrates that SID in essential tremor patients is associated with both, motor cortex and cerebellar connectivity. Furthermore, the identified fiber-based atlas structure might contribute to future postoperative programming strategies to achieve optimal tremor control without speech impairment in ET patients with thalamic DBS.

neuroscience↗

bioRxiv2019

Xrn1p Acts at Multiple Steps in the Budding-Yeast RNAi Pathway to Enhance the Efficiency of Silencing

RNA interference (RNAi) is a gene-silencing pathway that can play roles in viral defense, transposon silencing, heterochromatin formation, and post-transcriptional gene silencing. Although absent from Saccharomyces cerevisiae, RNAi is present in other budding-yeast species, including Naumovozyma castellii, which have an unusual Dicer and a conventional Argonaute that are both required for gene silencing. To identify other factors that act in the budding-yeast pathway, we performed an unbiased genetic selection. This selection identified Xrn1p, the cytoplasmic 5'-to-3' exoribonuclease, as a cofactor of RNAi in budding yeast. Deletion of XRN1 impaired gene silencing in N. castellii, and this impaired silencing was attributable to multiple functions of Xrn1p, including affecting the composition of siRNA species in the cell, influencing the efficiency of siRNA loading into Argonaute, degradation of cleaved passenger strand, and degradation of sliced target RNA.

molecular biology↗

bioRxiv2019

Attentional reorientation along the meridians of the visual field: are there different neural mechanisms at play?

Hemispatial neglect, after unilateral lesions to parietal brain areas, is characterized by an inability to respond to unexpected stimuli in contralesional space. As the visual fields horizontal meridian is most severely affected, the brain networks controlling visuospatial processes might be tuned explicitly to this axis. We investigated such a potential directional tuning in the dorsal and ventral frontoparietal attention networks, with a particular focus on attentional reorientation. We used an orientation-discrimination task where a spatial pre-cue indicated the target position with 80% validity. Healthy participants (n = 29) performed this task in two runs and were required to (re-)orient attention either only along the horizontal or the vertical meridian, while fMRI and behavioral measures were recorded. By using a General Linear Model for behavioral and fMRI data, Dynamic Causal Modeling for effective connectivity, and other predictive approaches, we found strong statistical evidence for a reorientation effect for horizontal and vertical runs. However, neither neural nor behavioral measures differed between vertical and horizontal reorienting. Moreover, models from one run successfully predicted the cueing condition in the respective other run. Our results suggest that activations in the dorsal and ventral attention networks represent higher-order cognitive processes related to spatial attentional (re-)orientating that are independent of directional tuning.

neuroscience↗

bioRxiv2018

Excised linear introns regulate growth in yeast

Spliceosomal introns are ubiquitous non-coding RNAs typically destined for rapid debranching and degradation. Here, we describe 34 excised Saccharomyces cerevisiae introns that, although rapidly degraded in log-phase growth, accumulate as linear RNAs under either saturated-growth conditions or other stresses that cause prolonged inhibition of TORC1, a key integrator of growth signaling. Introns that become stabilized remain associated with components of the spliceosome and differ from the other spliceosomal introns in having a short distance between their lariat branch point and 3' splice site, which is necessary and sufficient for their stabilization. Deletion of these unusual introns is disadvantageous in saturated conditions and causes aberrantly high growth rates of yeast chronically challenged with the TORC1 inhibitor rapamycin. Reintroduction of native or engineered stable introns suppresses this aberrant rapamycin response. Thus, excised introns function within the TOR growth-signaling network of S. cerevisiae, and more generally, excised spliceosomal introns can have biological functions.

molecular biology↗