julilili42/papers huggingface dataset:
Are you laughing at me? Neural correlates of social intent attribution to auditory and visual laughter
2019-10-22

Abstract Laughter is a multifaceted signal, which can convey social acceptance facilitating social bonding as well as social rejection inflicting social pain. In the current study, we addressed the neural correlates of social intent attribution to auditory or visual laughter within an fMRI study to identify brain areas showing linear increases of activation with social intent ratings. Negative social intent attributions were associated with activation increases within the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC). Interestingly, negative social intent attributions of auditory laughter were represented more rostral than visual laughter within this area. Our findings corroborate the role of the mPFC/ACC as key node for processing “social pain” with distinct modality‐specific subregions. Other brain areas that showed an increase of activation included bilateral inferior frontal gyrus and right superior/middle temporal gyrus (STG/MTG) for visually presented laughter and bilateral STG for auditory presented laughter with no overlap across modalities. Similarly, positive social intent attributions were linked to hemodynamic responses within the right inferior parietal lobe and right middle frontal gyrus, but there was no overlap of activity for visual and auditory laughter. Our findings demonstrate that social intent attribution to auditory and visual laughter is located in neighboring, but spatially distinct neural structures.
Multiple layers of phospho-regulation coordinate metabolism and the cell cycle in budding yeast
2019-10-22

Abstract The coordination of metabolism and growth with cell division is crucial for proliferation. While it has long been known that cell metabolism regulates the cell division cycle, it is becoming increasingly clear that the cell division cycle also regulates metabolism. In budding yeast, we previously showed that over half of all measured metabolites change concentration through the cell cycle indicating that metabolic fluxes are extensively regulated during cell cycle progression. However, how this regulation is achieved still remains poorly understood. Since both the cell cycle and metabolism are regulated to a large extent by protein phosphorylation, we here decided to measure the phosphoproteome through the budding yeast cell cycle. Specifically, we chose a cell cycle synchronisation strategy that avoids stress and nutrient-related perturbations of metabolism, and we grew the yeast on ethanol minimal medium to force cells to utilize their full biosynthetic repertoire. Using a tandem-mass-tagging approach, we found over 200 sites on metabolic enzymes and transporters to be phospho-regulated. These sites were distributed among many pathways including carbohydrate catabolism, lipid metabolism and amino acid synthesis and therefore likely contribute to changing metabolic fluxes through the cell cycle. Among all one thousand sites whose phosphorylation increases through the cell cycle, the CDK consensus motif and an arginine-directed motif were highly enriched. This arginine-directed R-R-x-S motif is associated with protein-kinase A, which regulates metabolism and promotes growth. Finally, we also found over one thousand sites that are dephosphorylated through the G1/S transition. We speculate that the phosphatase Glc7/ PP1, known to regulate both the cell cycle and carbon metabolism, may play an important role because its regulatory subunits are phospho-regulated in our data. In summary, our results identify extensive cell cycle dependent phosphorylation and dephosphorylation of metabolic enzymes and suggest multiple mechanisms through which the cell division cycle regulates metabolic signalling pathways to temporally coordinate biosynthesis with distinct phases of the cell division cycle.
PINK1 Regulates Dopamine and Lipids at Mitochondria to Maintain Synapses and Neuronal Function
2019-10-22

Abstract Mitochondrial dysfunction contributes to the pathogenesis of Parkinson’s disease but it is not clear why inherent mitochondrial defects lead specifically to the death of dopaminergic neurons of the mid brain. PINK1 is mitochondrial kinase and PINK1 mutations cause early onset Parkinson’s disease. We found that in neuronal progenitors, PINK1 regulates mitochondrial morphology, mitochondrial contact to the endoplasmic reticulum (ER) and the phosphorylation of Miro1. A compensatory metabolic shift towards lipid synthesis provides mitochondria with the components needed for membrane renewal and oxidative phosphorylation, maintaining the mitochondrial network once mature. Cholesterol is increased by loss of PINK1, promoting overall membrane rigidity. This alters the distribution of phosphorylated DAT at synapses and impairs dopamine uptake. PINK1 is required for the phosphorylation of tyrosine hydroxylase at Ser19, dopamine and calcium homeostasis and dopaminergic pacemaking. We suggest a novel mechanism for PINK1 pathogenicity in Parkinson’s disease in addition to but not exclusive of mitophagy. We also provide a basis for potential therapeutics by showing that low doses of the cholesterol depleting drug ß-cyclodextrin reverse PINK1-specific phenotypes.
Genetic modifiers of risk and age at onset in GBA associated Parkinson’s disease and Lewy body dementia
2019-10-23

Abstract Parkinson’s disease is a genetically complex disorder. Multiple genes have been shown to contribute to the risk of Parkinson’s disease, and currently 90 independent risk variants have been identified by genome-wide association studies. Thus far, a number of genes (including SNCA, LRRK2, and GBA) have been shown to contain variability across a spectrum of frequency and effect, from rare, highly penetrant variants to common risk alleles with small effect sizes. Variants in GBA, encoding the enzyme glucocerebrosidase, are associated with Lewy body diseases such as Parkinson’s disease and Lewy body dementia. These variants, which reduce or abolish enzymatic activity, confer a spectrum of disease risk, from 1.4- to &amp;gt;10-fold. An outstanding question in the field is what other genetic factors that influence GBA-associated risk for disease, and whether these overlap with known Parkinson’s disease risk variants. Using multiple, large case-control datasets, totalling 217 165 individuals (22 757 Parkinson’s disease cases, 13 431 Parkinson’s disease proxy cases, 622 Lewy body dementia cases and 180 355 controls), we identified 1691 Parkinson’s disease cases, 81 Lewy body dementia cases, 711 proxy cases and 7624 controls with a GBA variant (p.E326K, p.T369M or p.N370S). We performed a genome-wide association study and analysed the most recent Parkinson’s disease-associated genetic risk score to detect genetic influences on GBA risk and age at onset. We attempted to replicate our findings in two independent datasets, including the personal genetics company 23andMe, Inc. and whole-genome sequencing data. Our analysis showed that the overall Parkinson’s disease genetic risk score modifies risk for disease and decreases age at onset in carriers of GBA variants. Notably, this effect was consistent across all tested GBA risk variants. Dissecting this signal demonstrated that variants in close proximity to SNCA and CTSB (encoding cathepsin B) are the most significant contributors. Risk variants in the CTSB locus were identified to decrease mRNA expression of CTSB. Additional analyses suggest a possible genetic interaction between GBA and CTSB and GBA p.N370S induced pluripotent cell-derived neurons were shown to have decreased cathepsin B expression compared to controls. These data provide a genetic basis for modification of GBA-associated Parkinson’s disease risk and age at onset, although the total contribution of common genetics variants is not large. We further demonstrate that common variability at genes implicated in lysosomal function exerts the largest effect on GBA associated risk for disease. Further, these results have implications for selection of GBA carriers for therapeutic interventions.
The dynamics of Early Celtic consumption practices: A case study of the pottery from the Heuneburg
2019-10-23

The Early Celtic site of the Heuneburg (Baden-Wuerttemberg, Germany) has long been understood as a hallmark of early urbanization in Central Europe. The rich collection of Mediterranean imports recovered from the settlement, the elite burials in its surroundings and the Mediterranean-inspired mudbrick fortification wall further point to the importance of intercultural connections with the Mediterranean as a crucial factor in the transformation of Early Iron Age societies. We describe a new facet of this process by studying the transformation of consumption practices, especially drinking habits, brought about by intercultural encounters from the late 7th to the 5th century BC through the analysis of organic remains in 133 ceramic vessels found at the Heuneburg using Organic Residue Analysis (ORA). During the Ha D1 phase, fermented beverages, including Mediterranean grape wine, were identified in and appear to have been consumed from local handmade ceramics. The latter were recovered from different status-related contexts within the Heuneburg, suggesting an early and well-established trade/exchange system of this Mediterranean product. This contrasts with the results obtained for the drinking and serving vessels from the Ha D3 phase that were studied. The consumption of fermented beverages (wine and especially bacteriofermented products) appears to have been concentrated on the plateau. The ORA analyses presented here seem to indicate that during this time, grape wine was consumed primarily from imported vessels, and more rarely from local prestigious fine wheel-made vessels. In addition to imported wine, we demonstrate the consumption of a wide variety of foodstuffs, such as animal fats (especially dairy products), millet, plant oils and waxy plants, fruit and beehive products as well as one or several other fermented beverage(s) that were probably locally produced. Through this diachronic study of vessel function from different intra-site contexts, we inform on changing and status-related practices of food processing and consumption.
Cognitive Correlates of Computational Thinking
2019-10-23

Coding as a practical skill and computational thinking (CT) as a cognitive ability have become an important topic in education and research. It has been suggested that CT, as an early predictor of academic success, should be introduced and fostered early in education. However, there is no consensus on the underlying cognitive correlates of CT in young elementary school children. Therefore, the present work aimed at (i) assessing CT and investigating its associations to established cognitive abilities, and (ii) evaluating a newly developed CT course for elementary school children.
Angular X-ray Cross-Correlation Analysis (AXCCA): Basic Concepts and Recent Applications to Soft Matter and Nanomaterials
2019-10-23

Angular X-ray cross-correlation analysis (AXCCA) is a technique which allows quantitative measurement of the angular anisotropy of X-ray diffraction patterns and provides insights into the orientational order in the system under investigation. This method is based on the evaluation of the angular cross-correlation function of the scattered intensity distribution on a two-dimensional (2D) detector and further averaging over many diffraction patterns for enhancement of the anisotropic signal. Over the last decade, AXCCA was successfully used to study the anisotropy in various soft matter systems, such as solutions of anisotropic particles, liquid crystals, colloidal crystals, superlattices composed by nanoparticles, etc. This review provides an introduction to the technique and gives a survey of the recent experimental work in which AXCCA in combination with micro- or nanofocused X-ray microscopy was used to study the orientational order in various soft matter systems.
Solute Transport and Transformation in an Intermittent, Headwater Mountain Stream with Diurnal Discharge Fluctuations
2019-10-23

Time-variable discharge is known to control both transport and transformation of solutes in the river corridor. Still, few studies consider the interactions of transport and transformation together. Here, we consider how diurnal discharge fluctuations in an intermittent, headwater stream control reach-scale solute transport and transformation as measured with conservative and reactive tracers during a period of no precipitation. One common conceptual model is that extended contact times with hyporheic zones during low discharge conditions allows for increased transformation of reactive solutes. Instead, we found tracer timescales within the reach were related to discharge, described by a single discharge-variable StorAge Selection function. We found that Resazurin to Resorufin (Raz-to-Rru) transformation is static in time, and apparent differences in reactive tracer were due to interactions with different ages of storage, not with time-variable reactivity. Overall we found reactivity was highest in youngest storage locations, with minimal Raz-to-Rru conversion in waters older than about 20 h of storage in our study reach. Therefore, not all storage in the study reach has the same potential biogeochemical function and increasing residence time of solute storage does not necessarily increase reaction potential of that solute, contrary to prevailing expectations.
High-Affinity DARPin Allows Targeting of MeV to Glioblastoma Multiforme in Combination with Protease Targeting without Loss of Potency
2019-10-23

Measles virus (MeV) is naturally cytolytic by extensive cell-to-cell fusion. Vaccine-derived MeV is toxic for cancer cells and is clinically tested as oncolytic virus. To combine the potential of MeV with enhanced safety, different targeting strategies have been described. We generated a receptor-targeted MeV by using receptor-blind viral attachment protein genetically fused to designed ankyrin repeat protein (DARPin) binding domains specific for the epidermal growth factor receptor (EGFR). To reduce on-target toxicity for EGFR<sup>+</sup> healthy cells, we used an engineered viral fusion protein activatable by tumor-associated matrix metalloproteases (MMPs) for additional protease targeting. The dual-targeted virus replicated exclusively on EGFR<sup>+</sup>/MMP<sup>+</sup> tumor cells but was safe on healthy EGFR<sup>+</sup> target cells, primary human keratinocytes. Nevertheless, glioblastoma and other tumor cells were efficiently killed by all targeted viruses, although replication and oncolysis were slower for protease-targeted MeV. <i>In vivo</i>, efficacy of EGFR-targeted MeV was virtually unimpaired, whereas also dual-targeted MeV showed significant intra-tumoral spread and efficacy and could be armed with a prodrug convertase. The use of DARPin-domains resulted in potent EGFR-targeted MeV and for the first time effective dual retargeting of an oncolytic virus, further enhancing tumor selectivity. Together with powerful cell-toxic genes, the application as highly tumor-specific platform is promising.
Development of a Questionnaire on Self-concept, Motivational Beliefs, and Attitude Towards Programming
2019-10-23

Academic self-concept, motivational beliefs, and attitudes towards a school subject are relevant for learning and educational achievement. A positive self-concept in science and mathematics is argued to motivate students to persist and advance in studying these subjects. In particular, self-concept, motivational beliefs, and attitudes towards STEM domains were found to be predictive of educational achievement. Recently, programming was suggested to be a key competence in education.
Establishing an infrastructure for collaboration in primate cognition research
2019-10-24

Inferring the evolutionary history of cognitive abilities requires large and diverse samples. However, such samples are often beyond the reach of individual researchers or institutions, and studies are often limited to small numbers of species. Consequently, methodological and site-specific-differences across studies can limit comparisons between species. Here we introduce the ManyPrimates project, which addresses these challenges by providing a large-scale collaborative framework for comparative studies in primate cognition. To demonstrate the viability of the project we conducted a case study of short-term memory. In this initial study, we were able to include 176 individuals from 12 primate species housed at 11 sites across Africa, Asia, North America and Europe. All subjects were tested in a delayed-response task using consistent methodology across sites. Individuals could access food rewards by remembering the position of the hidden reward after a 0, 15, or 30-second delay. Overall, individuals performed better with shorter delays, as predicted by previous studies. Phylogenetic analysis revealed a strong phylogenetic signal for short-term memory. Although, with only 12 species, the validity of this analysis is limited, our initial results demonstrate the feasibility of a large, collaborative open-science project. We present the ManyPrimates project as an exciting opportunity to address open questions in primate cognition and behaviour with large, diverse datasets.
A Retrospective Study to Compare the Recurrence Rate After Treatment of Pterygium by Conjunctival Autograft, Primary Closure, and Amniotic Membrane Transplantation
2019-10-24

BACKGROUND This study aimed to investigate the effectiveness of conjunctival autograft compared with primary closure and amniotic membrane transplantation for primary pterygium excision. MATERIAL AND METHODS Data were retrospectively studied from all primary pterygium excisions from January 2002 to December 2017 from the electronic database at the University Eye Hospital, Tübingen. RESULTS From 521 primary pterygium excisions, 284 (54.5%) were primary closures, 203 (39.0%) were conjunctival autografts, and 34 (6.5%) were amniotic membrane transplants. The mean number of primary pterygium excisions was 33 per year (range, 14-56 per year). The mean patient age was 58±15 years. Younger age was associated with a significantly increased recurrence rate (P=0.002). The mean pterygium recurrence rate in the three study groups at 12 months after surgery was 11.3% (range, 6.4-14.7%). Recurrence occurred 13 patients (6.4%) in the conjunctival autograft group, 41 patients (14.4%) in the primary closure group, and five patients (14.7%) in the amniotic membrane transplantation group. Conjunctival autograft was associated with a significantly lower recurrence rate (P=0.005). CONCLUSIONS A retrospective study at a single center to compare conjunctival autograft with primary closure and amniotic membrane transplantation for primary pterygium excision showed a significantly lower recurrence rate after surgery using a conjunctival autograft.
Associations between cognitive performance and sigma power during sleep in children with attention-deficit/hyperactivity disorder, healthy children, and healthy adults
2019-10-24

Sigma power during sleep is associated with cognitive abilities in healthy humans. We examined the relationship between sigma power in sleep EEG and intelligence and alertness in schoolchildren with ADHD (n = 17) in comparison to mentally healthy children (n = 16) and adults (n = 23). We observed a positive correlation between sigma power in sleep stage 2 and IQ in healthy adults but a negative correlation in children with ADHD. Furthermore, children with ADHD showed slower reaction times in alertness testing than both control groups. In contrast, only healthy children displayed a positive correlation between sigma power and reaction times. These data suggest that the associations between sigma power and cognitive performance underlie distinct developmental processes. A negative association between IQ and sigma power indicates a disturbed function of sleep in cognitive functions in ADHD, whereas the function of sleep appears to be matured early in case of motor-related alertness performance.
Synthesis, Structure, and Electronic Properties of Sn9O5Cl4(CN2)2
2019-10-24

The formation of the new compound Sn<sub>9</sub>O<sub>5</sub>Cl<sub>4</sub>(CN<sub>2</sub>)<sub>2</sub> is reported and placed in the context of several other recently discovered tin carbodiimide compounds (Sn(CN<sub>2</sub>), Sn<sub>2</sub>O(CN<sub>2</sub>), and Sn<sub>4</sub>Cl<sub>2</sub>(CN<sub>2</sub>)<sub>3</sub>), all of which contain divalent tin. The crystal structure of Sn<sub>9</sub>O<sub>5</sub>Cl<sub>4</sub>(CN<sub>2</sub>)<sub>2</sub>, as determined by X-ray powder diffraction, includes an unusual [Sn<sub>8</sub>O<sub>3</sub>] cluster, in which tin atoms form the motif of a hexagonal bipyramid. An additional tin atom and two oxygen atoms connect these clusters into chains. Mössbauer spectroscopy shows tin to predominantly adopt the +2 oxidation state, and electronic structure calculations predict Sn<sub>9</sub>O<sub>5</sub>Cl<sub>4</sub>(CN<sub>2</sub>)<sub>2</sub> to be a semiconductor.
Highly Oriented Hexacene Molecules Grown in Thin Films on Cu(110)–(2 × 1)O
2019-10-24

Larger acenes, such as hexacene, are increasingly considered as promising materials for applications in optoelectronic devices. We studied electronic interface properties and the molecular orientation of hexacene on Cu(110)–(2 × 1)O using X-ray absorption spectroscopy (XAS) and photoelectron spectroscopy. Interactions between hexacene and the substrate are weak. The detailed investigation of the orientation greatly benefits from a combination of polarization-dependent XAS and angle-resolved photoemission. The angular dependence of valence band features indicates that the molecules grow highly oriented with their long axes parallel to the oxygen rows of the Cu(110)–(2 × 1)O substrate, whereas XAS reveals that the short axis of the molecule is distinctly tilted with respect to the substrate surface. This orientation is maintained up to a film thickness of at least 16 nm, indicating that Cu(110)–(2 × 1)O acts as a template for the hexacene film growth.
Assessing direct and indirect effects of pediatric influenza vaccination in Germany by individual-based simulations
2019-10-24

Children have a high burden of influenza and play a central role in spreading influenza. Routinely vaccinating children against influenza may, thus, not only reduce their disease burden, but also that of the general population, including the elderly who frequently suffer severe complications. Using the published individual-based tool 4Flu, we simulated how pediatric vaccination would change infection incidence in Germany. Transmission of four influenza strains was simulated in 100,000 individuals with German demography and contact structure. After initialization with the recorded trivalent influenza vaccination coverage for 20 years (1997-2016), all vaccinations were switched to quadrivalent influenza vaccine (QIV). Scenarios where vaccination coverage of children (0.5-17-year-old) was increased from the current value (4.3%) to a maximum of 10-60% were compared to baseline with unchanged coverage, averaging results of 1,000 pairs of simulations over a 20-year evaluation period (2017-2036). Pediatric vaccination coverage of 10-60% annually prevented 218-1,732 (6.3-50.5%) infections in children, 204-1,961 (2.9-28.2%) in young adults and 95-868 (3.1-28.9%) in the elderly in a population of 100,000 inhabitants; overall, 34.1% of infections in the total population (3.7 million infections per year in Germany) can be prevented if 60% of all children are vaccinated annually. 4.4-4.6 vaccinations were needed to prevent one infection among children; 1.7-1.8 were needed to prevent one in the population. Enhanced pediatric vaccination prevents many infections in children and even more in young adults and the elderly.