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RNA is one of the key components in the central dogma of biology. The protein-coding mRNAs are synthesised in the nucleus, processed to form the mature mRNA molecule, exported to the cytosol where they are translated into the functional protein, and eventually degraded. Gene expression can be regulated by adjusting, for example, mRNA synthesis or degradation rates. These mRNA metabolic rates are measured with RNA metabolic labelling experiments: Newly synthesised RNAs are tagged with modified nucleosides and can thereby be distinguished from pre-existing RNA transcripts. Yet, the analysis of metabolic labelling data is statistically challenging. The tagging of newly synthesised RNA transcripts is incomplete as only a fraction of the native nucleosides is replaced by the modified nucleoside. Also, to our knowledge, no currently available analysis tool provides a framework to investigate mRNA export. To address these challenges, I developed a dynamic model of mRNA metabolism. The model distinguishes between the nuclear and cytosolic compartment (two-compartment model) and thereby allows to analyse nuclear export in addition to cytosolic degradation. The data pre-processing steps are specifically tailored to metabolic labelling data and include the estimation of RNA labelling efficiencies in a time-dependent manner. We performed a metabolic labelling experiment on HeLa-S3 cells combined with cellular fractionation to measure nuclear and cytosolic RNA separately. We then applied my model to estimate nuclear and cytosolic RNA half lives. We find that nuclear half lives are much higher than cytosolic half lives, which leads to the conclusion that mRNA export is slower than mRNA degradation. Consequently, mRNA transcripts spend most of their lifetime in the nucleus and are more abundant in the nucleus than in the cytosol. We discover a group of outstanding genes, called ‘Supernova’ genes, which show an exceptionally fast mRNA export, arguing for a novel and distinct export

Gesture processing deficits constitute a key symptom of apraxia, a disorder of motor cognition frequently observed after left-hemispheric stroke. The clinical relevance of apraxia stands in stark contrast to the paucity of therapeutic options available. Transcranial direct current stimulation (tDCS) is a promising tool for modulating disturbed network function after stroke. Here, we investigate the effect of parietal tDCS on gesture processing in healthy human subjects. Neuropsychological and imaging studies suggest that the imitation and matching of hand gestures involve the left inferior parietal lobe (IPL). Using neuronavigation based on cytoarchitectonically defined anatomical probability maps, tDCS was applied over left IPL-areas PF, PFm, or PG in healthy participants (n = 26). Before and after tDCS, subjects performed a gesture matching task and a person discrimination task for control. Changes in error rates and reaction times were analyzed for the effects of anodal and cathodal tDCS (compared with sham tDCS). Matching of hand gestures was specifically facilitated by anodal tDCS applied over the cytoarchitectonically defined IPL-area PFm, whereas tDCS over IPL-areas PF and PG did not elucidate significant effects. Taking into account tDCS electrode size and the central position of area PFm within IPL, it can be assumed that the observed effect is rather the result of a combined stimulation of the supramarginal and angular gyrus than an isolated PFm stimulation. Our data confirm the pivotal role of the left IPL in gesture processing. Furthermore, anatomically guided tDCS of the left IPL may constitute a promising approach to neurorehabilitation of apraxic patients with gesture processing deficits.

The right intraparietal sulcus (rIPS) is a key region for the endogenous control of selective visual attention in the human brain. Previous studies suggest that the rIPS is especially involved in top-down control and spatial distribution of attention across both visual hemifields. We further explored these attentional functions using transcranial direct current stimulation (tDCS) of the rIPS to modulate behavioral performance in a partial report task. Performance was analyzed according to the theory of visual attention (TVA) (Bundesen, 1990), which provides a computational framework to investigate different parameters of visuo-attentional processing such as top-down control, attentional weighting, capacity of visual short term memory, and processing speed. We investigated the effects of different tDCS current strengths (1 mA and 2 mA) in two experiments: 1 mA tDCS (anodal, cathodal, sham) did not affect any of the TVA parameters, but cathodal 2 mA stimulation significantly enhanced top-down control as evidenced by a reduction of the alpha parameter of TVA, regardless of hemifield. This differential impact on the top-down control component of attentional processing suggests that the horizontal rIPS is mainly involved in attentional selection as none of the spatial or resource variables of TVA were altered. Furthermore, the data add evidence to previous work highlighting (1) the importance of using appropriate current strength in stimulation protocols, and (2) that the often reported inhibitory effect of cathodal stimulation in e. g., motor tasks might not extend to cognitive paradigms.