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While the underlying mechanisms of Parkinson’s disease (PD) are still insufficiently studied, a complex interaction between genetic and environmental factors is emphasized. Nevertheless, the role of the essential trace element zinc (Zn) in this regard remains controversial. In this study we altered Zn balance within PD models of the versatile model organism Caenorhabditis elegans (C. elegans) in order to examine whether a genetic predisposition in selected genes with relevance for PD affects Zn homeostasis. Protein-bound and labile Zn species act in various areas, such as enzymatic catalysis, protein stabilization pathways and cell signaling. Therefore, total Zn and labile Zn were quantitatively determined in living nematodes as individual biomarkers of Zn uptake and bioavailability with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) or a multi-well method using the fluorescent probe ZinPyr-1. Young and middle-aged deletion mutants of catp-6 and pdr-1, which are orthologues of mammalian ATP13A2 (PARK9) and parkin (PARK2), showed altered Zn homeostasis following Zn exposure compared to wildtype worms. Furthermore, age-specific differences in Zn uptake were observed in wildtype worms for total as well as labile Zn species. These data emphasize the importance of differentiation between Zn species as meaningful biomarkers of Zn uptake as well as the need for further studies investigating the role of dysregulated Zn homeostasis in the etiology of PD.
Sentence comprehension requires the assignment of thematic relations between the verb and its noun arguments in order to determine who is doing what to whom. In some languages, such as English, word order is the primary syntactic cue. In other languages, such as German, case-marking is additionally used to assign thematic roles. During development children have to acquire the thematic relevance of these syntactic cues and weigh them against semantic cues. Here we investigated the processing of syntactic cues and semantic cues in 2- and 3-year-old children by analyzing their behavioral and neurophysiological responses. Case-marked subject-first and object-first sentences (syntactic cue) including animate and inanimate nouns (semantic cue) were presented auditorily. The semantic animacy cue either conflicted with or supported the thematic roles assigned by syntactic case-marking. In contrast to adults, for whom semantics did not interfere with case-marking, children attended to both syntactic and to semantic cues with a stronger reliance on semantic cues in early development. Children’s event-related brain potentials indicated sensitivity to syntactic information but increased processing costs when case-marking and animacy assigned conflicting thematic roles. These results demonstrate an early developmental sensitivity and ongoing shift towards the use of syntactic cues during sentence comprehension.
From early on in life, children are able to use information from their environment to form predictions about events. For instance, they can use statistical information about a population to predict the sample drawn from that population and infer an agent’s preferences from systematic violations of random sampling. We investigated whether and how young children infer an agent’s sampling biases. Moreover, we examined whether pupil data of toddlers follow the predictions of a computational model based on the causal Bayesian network formalization of predictive processing. We formalized three hypotheses about how different explanatory variables (i.e., prior probabilities, current observations, and agent characteristics) are used to predict others’ actions. We measured pupillary responses as a behavioral marker of ‘prediction errors’ (i.e., the perceived mismatch between what one’s model of an agent predicts and what the agent actually does). Pupillary responses of 24-month-olds, but not 18-month-olds, showed that young children integrated information about current observations, priors and agents to make predictions about agents and their actions. These findings shed light on the mechanisms behind toddlers’ inferences about agent-caused events. To our knowledge, this is the first study in which young children's pupillary responses are used as markers of prediction errors, which were qualitatively compared to the predictions by a computational model based on the causal Bayesian network formalization of predictive processing.
Workload-Driven Fragment Allocation for Partially Replicated Databases Using Linear Programming
(2019)
In replication schemes, replica nodes can process read-only queries on snapshots of the master node without violating transactional consistency. By analyzing the workload, we can identify query access patterns and replicate data depending to its access frequency. In this paper, we define a linear programming (LP) model to calculate the set of partial replicas with the lowest overall memory capacity while evenly balancing the query load. Furthermore, we propose a scalable decomposition heuristic to calculate solutions for larger problem sizes. While guaranteeing the same performance as state-of-the-art heuristics, our decomposition approach calculates allocations with up to 23% lower memory footprint for the TPC-H benchmark.
Working memory (WM), which underlies the temporary storage and manipulation of information, is critical for multiple aspects of cognition and everyday life. Nevertheless, research examining WM specifically in older adults remains limited, despite the global rapid increase in human life expectancy. We examined WM in a large sample (N=754) of healthy older adults (aged 58-89) in a non-Western population (Chinese speakers) in Taiwan, on a digit n-back task. We tested not only the influence of age itself and of load (1-back vs. 2-back) but also the effects of both sex and education, which have been shown to modulate WM abilities. Mixed-effects regression revealed that, within older adulthood, age negatively impacted WM abilities (with linear, not nonlinear, effects), as did load (worse performance at 2-back). In contrast, education level was positively associated with WM. Moreover, both age and education interacted with sex. With increasing age, males showed a steeper WM decline than females; with increasing education, females showed greater WM gains than males. Together with other findings, the evidence suggests that age, sex, and education all impact WM in older adults, but interact in particular ways. The results have both basic research and translational implications and are consistent with particular benefits from increased education for women.
Words as social tools
(2019)
Successful communication often involves comprehension of both spoken language and observed actions with and without objects. Even very young infants can learn associations between actions and objects as well as between words and objects. However, in daily life, children are usually confronted with both kinds of input simultaneously. Choosing the critical information to attend to in such situations might help children structure the input, and thereby, allow for successful learning. In the current study, we therefore, investigated the developmental time course of children’s and adults’ word and action learning when given the opportunity to learn both word-object and action-object associations for the same object. All participants went through a learning phase and a test phase. In the learning phase, they were presented with two novel objects which were associated with a distinct novel name (e.g., “Look, a Tanu”) and a distinct novel action (e.g., moving up and down while tilting sideways). In the test phase, participants were presented with both objects on screen in a baseline phase, then either heard one of the two labels or saw one of the two actions in a prime phase, and then saw the two objects again on screen in a recognition phase. Throughout the trial, participants’ target looking was recorded to investigate whether participants looked at the target object upon hearing its label or seeing its action, and thus, would show learning of the word-object and action-object associations. Growth curve analyses revealed that 12-month-olds showed modest learning of action-object associations, 36-month-olds learned word-object associations, and adults learned word-object and action-object associations. These results highlight how children attend to the different information types from the two modalities through which communication is addressed to them. Over time, with increased exposure to systematic word-object mappings, children attend less to action-object mappings, with the latter potentially being mediated by word-object learning even in adulthood. Thus, choosing between different kinds of input that may be more relevant in their rich environment encompassing different modalities might help learning at different points in development.
Genetic divergence is impacted by many factors, including phylogenetic history, gene flow, genetic drift, and divergent selection. Rotifers are an important component of aquatic ecosystems, and genetic variation is essential to their ongoing adaptive diversification and local adaptation. In addition to coding sequence divergence, variation in gene expression may relate to variable heat tolerance, and can impose ecological barriers within species. Temperature plays a significant role in aquatic ecosystems by affecting species abundance, spatio-temporal distribution, and habitat colonization. Recently described (formerly cryptic) species of the Brachionus calyciflorus complex exhibit different temperature tolerance both in natural and in laboratory studies, and show that B. calyciflorus sensu stricto (s.s.) is a thermotolerant species. Even within B. calyciflorus s.s., there is a tendency for further temperature specializations. Comparison of expressed genes allows us to assess the impact of stressors on both expression and sequence divergence among disparate populations within a single species. Here, we have used RNA-seq to explore expressed genetic diversity in B. calyciflorus s.s. in two mitochondrial DNA lineages with different phylogenetic histories and differences in thermotolerance. We identify a suite of candidate genes that may underlie local adaptation, with a particular focus on the response to sustained high or low temperatures. We do not find adaptive divergence in established candidate genes for thermal adaptation. Rather, we detect divergent selection among our two lineages in genes related to metabolism (lipid metabolism, metabolism of xenobiotics).