Lymphotoxin-ß-receptor (LTßR) signaling on hepatocytes is required for liver regeneration after partial hepatectomy.

Lymphotoxin-ß-receptor deficient (LTßR-/-) and Tumor Necrosis Factor Receptor p55 deficient (TNFRp55-/-) mice show defects in liver regeneration (LR) after partial hepatectomy (PHx) with significantly increased mortality. LTßR and TNFRp55 belong to the core members of the TNF/TNFR superfamily. Interestingly, combined failure of LTßR and TNFRp55 signaling after PHx leads to a complete defect in LR. Here, we first addressed the question which liver cell population crucially requires LTßR signaling for efficient LR. To this end, mice with a conditionally targeted LTßR allele (LTßRfl/fl) were crossed to AlbuminCre and LysozymeMCre mouse lines to unravel the function of the LTßR on hepatocytes and monocytes/macrophages/Kupffer cells, respectively. Analysis of these mouse lines clearly reveals that LTßR is required on hepatocytes for efficient LR while no deficit in LR was found in LTßRfl/fl × LysMCre mice. Second, the molecular basis for the cooperating role of LTßR and TNFRp55 signaling pathways in LR was investigated by transcriptome analysis of etanercept treated LTßR-/- (LTßR-/-/ET) mice. Bioinformatic analysis and subsequent verification by qRT-PCR identified novel target genes (Cyclin-L2, Fas-Binding factor 1, interferon-related developmental regulator 1, Leucyl-tRNA Synthetase 2, and galectin-4) that are upregulated by LTßR/TNFRp55 signaling after PHx and fail to be upregulated after PHx in LTßR-/-/ET mice.

Processing symbolic and non-symbolic proportions: Domain-specific numerical and domain-general processes in intraparietal cortex.

Previous studies on the processing of fractions and proportions focused mainly on the processing of their overall magnitude information in the intraparietal sulcus (IPS). However, the IPS is also associated with domain-general cognitive functions beyond processing overall magnitude, which may nevertheless be involved in operating on magnitude information of proportions. To pursue this issue, the present study aimed at investigating whether there is a shared neural correlate for proportion processing in the intraparietal cortex beyond overall magnitude processing and how part-whole relations are processed on the neural level. Across four presentation formats (i.e., fractions, decimals, dot patterns, and pie charts) we observed a shared neural substrate in bilateral inferior parietal cortex, slightly anterior and inferior to IPS areas recently found for overall magnitude proportion processing. Nevertheless, when evaluating the neural correlates of part-whole processing (i.e., contrasting fractions, dot patterns, and pie charts vs. decimals), we found wide-spread activation in fronto-parietal brain areas. These results indicate involvement of domain-general cognitive processes in part-whole processing beyond processing the overall magnitude of proportions. The dissociation between proportions involving part-whole relations and decimals was further substantiated by a representational similarity analysis, which revealed common neural processing for fractions, pie charts, and dot patterns, possibly representing their bipartite part-whole structure. In contrast, decimals seemed to be processed differently on the neural level, possibly reflecting missing processes of actual proportion calculation in decimals.

Magnitude processing of symbolic and non-symbolic proportions: an fMRI study.

BACKGROUND: Recent research indicates that processing proportion magnitude is associated with activation in the intraparietal sulcus. Thus, brain areas associated with the processing of numbers (i.e., absolute magnitude) were activated during processing symbolic fractions as well as non-symbolic proportions. Here, we investigated systematically the cognitive processing of symbolic (e.g., fractions and decimals) and non-symbolic proportions (e.g., dot patterns and pie charts) in a two-stage procedure. First, we investigated relative magnitude-related activations of proportion processing. Second, we evaluated whether symbolic and non-symbolic proportions share common neural substrates. METHODS: We conducted an fMRI study using magnitude comparison tasks with symbolic and non-symbolic proportions, respectively. As an indicator for magnitude-related processing of proportions, the distance effect was evaluated. RESULTS: A conjunction analysis indicated joint activation of specific occipito-parietal areas including right intraparietal sulcus (IPS) during proportion magnitude processing. More specifically, results indicate that the IPS, which is commonly associated with absolute magnitude processing, is involved in processing relative magnitude information as well, irrespective of symbolic or non-symbolic presentation format. However, we also found distinct activation patterns for the magnitude processing of the different presentation formats. CONCLUSION: Our findings suggest that processing for the separate presentation formats is not only associated with magnitude manipulations in the IPS, but also increasing demands on executive functions and strategy use associated with frontal brain regions as well as visual attention and encoding in occipital regions. Thus, the magnitude processing of proportions may not exclusively reflect processing of number magnitude information but also rather domain-general processes.

Impact of associative word learning on phonotactic processing in 6-month-old infants: A combined EEG and fNIRS study.

During early language development native phonotactics are acquired in a 'bottom-up' fashion, relying on exquisite auditory differentiation skills operational from birth. Since basic lexico-semantic abilities have been demonstrated from 6 months onwards, 'top-down' influences on phonotactic learning may complement the extraction of transitional probabilities in phonotactic learning. Such a bidirectional acquisition strategy predicts, that familiarization with (proto)words should affect processing of untrained word-forms of similar phonological structure. We investigated 6-month-old infants undergoing an associative training to establish a pseudoword-pseudoobject link. Comparison between pre- and post-training responses to trained and untrained items allowed investigating training effects. Additionally phonotactic status (50% legal, 50% illegal with regard to German) allowed investigating influences of previous language experience. EEG and functional near-infrared spectroscopy (fNIRS) provided measures of electrophysiological and hemodynamic responses. We find evidence for a robust effect of associative training on pseudoword processing when presented in isolation. This transferred to untrained items. Previous linguistic experience showed a much weaker effect. Taken together the results suggest that sensitivity to phonotactic contrasts is present at 6 months, but that acceptance as lexical candidates is rapidly modulated when word forms following non-native phonotactics become potentially meaningful due to repeated exposure in a semantic context.

Treadmill walking during vocabulary encoding improves verbal long-term memory.

Moderate physical activity improves various cognitive functions, particularly when it is applied simultaneously to the cognitive task. In two psychoneuroendocrinological within-subject experiments, we investigated whether very low-intensity motor activity, i.e. walking, during foreign-language vocabulary encoding improves subsequent recall compared to encoding during physical rest. Furthermore, we examined the kinetics of brain-derived neurotrophic factor (BDNF) in serum and salivary cortisol. Previous research has associated both substances with memory performance.In both experiments, subjects performed better when they were motorically active during encoding compared to being sedentary. BDNF in serum was unrelated to memory performance. In contrast we found a positive correlation between salivary cortisol concentration and the number of correctly recalled items. In summary, even very light physical activity during encoding is beneficial for subsequent recall.