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Mutations are the ultimate basis of evolution, yet their occurrence rate is known only for few species. We directly estimated the spontaneous mutation rate and the mutational spectrum in the non-biting midge C. riparius with a new approach. Individuals from ten mutation accumulation lines over five generations were deep genome sequenced to count de novo mutations (DNMs) that were not present in a pool of F1 individuals, representing parental genotypes. We identified 51 new single site mutations of which 25 were insertions or deletions and 26 single point mutations. This shift in the mutational spectrum compared to other organisms was explained by the high A/T content of the species. We estimated a haploid mutation rate of 2.1 x 10−9 (95% confidence interval: 1.4 x 10−9 – 3.1 x 10−9) which is in the range of recent estimates for other insects and supports the drift barrier hypothesis. We show that accurate mutation rate estimation from a high number of observed mutations is feasible with moderate effort even for non-model species.
Models of perceptual decision making have historically been designed to maximally explain behaviour and brain activity independently of their ability to actually perform tasks. More recently, performance-optimized models have been shown to correlate with brain responses to images and thus present a complementary approach to understand perceptual processes. In the present study, we compare how these approaches comparatively account for the spatio-temporal organization of neural responses elicited by ambiguous visual stimuli. Forty-six healthy human subjects performed perceptual decisions on briefly flashed stimuli constructed from ambiguous characters. The stimuli were designed to have 7 orthogonal properties, ranging from low-sensory levels (e.g. spatial location of the stimulus) to conceptual (whether stimulus is a letter or a digit) and task levels (i.e. required hand movement). Magneto-encephalography source and decoding analyses revealed that these 7 levels of representations are sequentially encoded by the cortical hierarchy, and actively maintained until the subject responds. This hierarchy appeared poorly correlated to normative, drift-diffusion, and 5-layer convolutional neural networks (CNN) optimized to accurately categorize alpha-numeric characters, but partially matched the sequence of activations of 3/6 state-of-the-art CNNs trained for natural image labeling (VGG-16, VGG-19, MobileNet). Additionally, we identify several systematic discrepancies between these CNNs and brain activity, revealing the importance of single-trial learning and recurrent processing. Overall, our results strengthen the notion that performance-optimized algorithms can converge towards the computational solution implemented by the human visual system, and open possible avenues to improve artificial perceptual decision making.
A novel approach to identify the geometrical (anti)clusters formed by the Polyakov loops of the same sign and to study their properties in the lattice SU(2) gluodynamics is developed. The (anti)cluster size distributions are analyzed for the lattice coupling constant β ∈ 2 [2:3115; 3]. The found distributions are similar to the ones existing in 2- and 3-dimensional Ising systems. Using the suggested approach, we explain the phase transition in SU(2) gluodynamics at β = 2.52 as a transition between two liquids during which one of the liquid droplets (the largest cluster of a certain Polyakov loop sign) experiences a condensation, while another droplet (the next to the largest cluster of opposite Polyakov loop sign) evaporates. The clusters of smaller sizes form two accompanying gases, which behave oppositely to their liquids. The liquid drop formula is used to analyze the distributions of the gas (anti)clusters and to determine their bulk, surface and topological parts of free energy. Surprisingly, even the monomer multiplicities are reproduced with high quality within such an approach. The behavior of surface tension of gaseous (anti)clusters is studied. It is shown that this quantity can serve as an order parameter of the deconfinement phase transition in SU(2) gluodynamics. Moreover, the critical exponent β of surface tension coefficient of gaseous clusters is found in the upper vicinity of critical temperature. Its value coincides with the one found for 3-dimensional Ising model within error bars. The Fisher topological exponent τ of (anti)clusters is found to have the same value 1:806±0:008, which agrees with an exactly solvable model of the nuclear liquid-gas phase transition and disagrees with the Fisher droplet model, which may evidence for the fact that the SU(2) gluodynamics and the model are in the same universality class.
We cannot imagine a political system without opposition. Despite this crucial position in politics, political science has largely neglected to study oppositions. Attempting to fill this gap, this article analyses the institutional opportunities of parliamentary oppositions. It offers a parsimonious framework by distinguishing two dimensions of opposition influence: Some institutions enable oppositions to control governments, while others offer opportunities to present alternatives. A comparison of oppositions’ opportunities in 21 democracies shows that countries fall into four groups along these dimensions: In majoritarian democracies, weak control mechanisms are countered by excellent opportunities to publicize alternatives. Consociational democracies are characterized by strong control mechanisms, but provide only weak opportunities to present alternatives. Moreover, in Southern Europe, control mechanisms and opportunities to present alternatives are weak, while both are pronounced in Nordic Europe. The results are summarized in three indices that can easily be applied in future research examining oppositions and their power.
Compared to sequence analyses, phylogenetic reconstruction from transposable elements (TEs) offers an additional perspective to study evolutionary processes. However, detecting phylogenetically informative TE insertions requires tedious experimental work, limiting the power of phylogenetic inference. Here, we analyzed the genomes of seven bear species using high throughput sequencing data to detect thousands of TE insertions. The newly developed pipeline for TE detection called TeddyPi (TE detection and discovery for Phylogenetic Inference) obtained 150,513 high-quality TE insertions in the genomes of ursine and tremarctine bears. By integrating different TE insertion callers and using a stringent filtering approach, the TeddyPi pipeline produced highly reliable TE insertion calls, which were confirmed by extensive in vitro validation experiments. Screening for single nucleotide substitutions in the flanking regions of the TEs show that these substitutions correlate with the phylogenetic signal from the TE insertions. Our phylogenomic analyses show that TEs are a major driver of genomic variation in bears and enabled phylogenetic reconstruction of a well-resolved species tree, even with strong signals for incomplete lineage sorting and introgression. The analyses show that the Asiatic black, sun and sloth bear form a monophyletic clade. TeddyPi is open source and can be adapted to various TE and structural variation callers. The pipeline makes it easy to confidently extract thousands of TE insertions even from low coverage genomes of non-model organisms, opening new possibilities for biologists to study phylogenies, evolutionary processes as well as rates and patterns of (retro-)transposition and structural variation.
Synaptic release sites are characterized by exocytosis-competent synaptic vesicles tightly anchored to the presynaptic active zone (PAZ) whose proteome orchestrates the fast signaling events involved in synaptic vesicle cycle and plasticity. Allocation of the amyloid precursor protein (APP) to the PAZ proteome implicated a functional impact of APP in neuronal communication. In this study, we combined state-of-the-art proteomics, electrophysiology and bioinformatics to address protein abundance and functional changes at the native hippocampal PAZ in young and old APP-KO mice. We evaluated if APP deletion has an impact on the metabolic activity of presynaptic mitochondria. Furthermore, we quantified differences in the phosphorylation status after long-term-potentiation (LTP) induction at the purified native PAZ. We observed an increase in the phosphorylation of the signaling enzyme calmodulin-dependent kinase II (CaMKII) only in old APP-KO mice. During aging APP deletion is accompanied by a severe decrease in metabolic activity and hyperphosphorylation of CaMKII. This attributes an essential functional role to APP at hippocampal PAZ and putative molecular mechanisms underlying the age-dependent impairments in learning and memory in APP-KO mice.
The amyloid precursor protein (APP) was discovered in the 1980s as the precursor protein of the amyloid A4 peptide. The amyloid A4 peptide, also known as A-beta (Aβ), is the main constituent of senile plaques implicated in Alzheimer’s disease (AD). In association with the amyloid deposits, increasing impairments in learning and memory as well as the degeneration of neurons especially in the hippocampus formation are hallmarks of the pathogenesis of AD. Within the last decades much effort has been expended into understanding the pathogenesis of AD. However, little is known about the physiological role of APP within the central nervous system (CNS). Allocating APP to the proteome of the highly dynamic presynaptic active zone (PAZ) identified APP as a novel player within this neuronal communication and signaling network. The analysis of the hippocampal PAZ proteome derived from APP-mutant mice demonstrates that APP is tightly embedded in the underlying protein network. Strikingly, APP deletion accounts for major dysregulation within the PAZ proteome network. Ca2+-homeostasis, neurotransmitter release and mitochondrial function are affected and resemble the outcome during the pathogenesis of AD. The observed changes in protein abundance that occur in the absence of APP as well as in AD suggest that APP is a structural and functional regulator within the hippocampal PAZ proteome. Within this review article, we intend to introduce APP as an important player within the hippocampal PAZ proteome and to outline the impact of APP deletion on individual PAZ proteome subcommunities.
Transcranial electrical stimulation has widespread clinical and research applications, yet its effect on ongoing neural activity in humans is not well established. Previous reports argue that transcranial alternating current stimulation (tACS) can entrain and enhance neural rhythms related to memory, but the evidence from non-invasive recordings has remained inconclusive. Here, we measure endogenous spindle and theta activity intracranially in humans during low-frequency tACS and find no stable entrainment of spindle power during non-REM sleep, nor of theta power during resting wakefulness. As positive controls, we find robust entrainment of spindle activity to endogenous slow-wave activity in 66% of electrodes as well as entrainment to rhythmic noise-burst acoustic stimulation in 14% of electrodes. We conclude that low-frequency tACS at common stimulation intensities neither acutely modulates spindle activity during sleep nor theta activity during waking rest, likely because of the attenuated electrical fields reaching the cortical surface.
Das Clearing von Euro-OTC-Derivaten post Brexit – eine Analyse der vorliegenden Kostenschätzungen
(2017)
Im Zusammenhang mit dem Brexit wird über die Kosten einer Relokation des Clearing des Euro-OTC-Derivate-Geschäftes auf ein EU-CCP diskutiert. Das vorliegende Papier zeigt, dass die bislang vorliegenden Kostenschätzungen, die von Kosten in Höhe von bis zu USD 100 Mrd. für einen Zeitraum von fünf Jahren ausgehen, viel zu hoch sind. Die erwarteten Kosten einer Relokation liegen vielmehr bei ca. USD 0,6 Mrd. p.a. bzw. ca. USD 3,2 Mrd. für eine Übergangsphase von fünf Jahren. Angesichts der hohen Bedeutung von systemrelevanten CCPs für die Stabilität der Eurozone sollten diese Kosten nicht entscheidungsrelevant für eine Relokation sein.
In the context of the upcoming Brexit, a relocation of the clearing of euro-OTC derivatives for EU-based firms is the subject of controversial discussion. The opponents of a relocation argue that a relocation would cause additional costs for market participants of up to USD 100 bn over a period of 5 years. This paper shows that this cost estimate is fairly unrealistic and that relocation costs would amount to approximately USD 0.6 bn p.a., which translates to cumulative costs of around USD 3.2 bn for a transition period of 5 years. In light of the strategic importance of systemically relevant CCPs for the financial stability of the eurozone, the potential relocation costs should not be a decision criterion.