julilili42/papers huggingface dataset:
Early silcrete heat treatment in Central Australia: Puritjarra and Kulpi Mara
2020-07-24

Abstract Heat treatment of stone for tool making has important implications for our understanding of the early human history of the Australian continent. New data on the antiquity of Australian heat treatment and its evolution through time in different regions have posed questions about the origin and temporal stability of technical practices. In this paper, we present the first evolutionary sequence of the use of heat treatment in Central Australia, with a trend to lower levels of heat treatment over time. Different trends are found in other regions across Australia: on the eastern seaboard, heat treatment became more prevalent over time, while in the inland, semi-arid Willandra lakes region heat treatment gradually disappeared over time. In central Australia, the long-term trend is towards fewer heat-affected specimens over time, but this happens in a single transition from stable high levels in the Pleistocene to stable moderate levels in the Mid- to Late Holocene. These evolutionary trends are consistent with regional diversification, reflecting adaptations to local conditions, and are not consistent with technological uniformity across the continent.
Crystal structure and molecular dynamics of human POLDIP2, a multifaceted adaptor protein in metabolism and genome stability
2020-07-24

Abstract Polymerase δ-interacting protein 2 (POLDIP2, PDIP38) is a multifaceted, ‘moonlighting’ protein, involved in binding protein partners from many different cellular processes, including mitochondrial metabolism, DNA replication and repair, and reactive oxygen species generation. POLDIP2 is found in multiple cellular compartments, potentially shuttled depending on its role. How POLDIP2 binds to and coordinates many different proteins is currently unknown. Towards this goal, we present the crystal structure of the ‘mitochondrial’ fragment of POLDIP2 to 2.8 Å. POLDIP2 exhibited a compact two-domain β-strand-rich globular structure, confirmed by circular dichroism and small angle X-ray scattering approaches. POLDIP2 comprised canonical DUF525 (ApaG) and YccV-like domains, but with the conserved domain linker packed tightly, resulting in an ‘extended’ YccV module. A central channel through POLDIP2 was observed which we hypothesise could influence structural changes potentially mediated by redox conditions, following observation of a modified cysteine residue in the channel. Unstructured regions were rebuilt by ab initio modelling to generate a model of full length POLDIP2. Molecular dynamics simulations revealed a highly dynamic N-terminal region tethered to the YccV-domain by an extended linker, potentially facilitating interactions with distal binding partners. Finally we build models of POLDIP2 interacting in complex with two of its partners in genome stability, PrimPol and PCNA. These indicate that dynamic flexibility of the POLDIP2 N-terminal and loop regions are critical to mediate protein-protein interactions.
3D-Printed Facet Optics: Novel Adjustable Technical Optics Inspired by Compound Eyes
2020-07-24

Bio-inspired by compound eyes in insects, the authors identify advantages of such an optical system and propose a novel optics that combines basic principles from compound eyes with an additional technical zooming feature. The 3D-printed, bio-inspired fiber optic set-up is based on ommatidia, the small single components of compound eyes. The advantageous aspects that are transferred from the inspiring organisms are that no focusing on objects is needed and a maximum depth of focus is always achieved. Two adjustable technical features are an adjustable field of view per pixel and a zooming possibility, not found in animals. Prototypes were produced as a proof of concept. One of them was manufactured using a stereolithography 3D printer. They were positively tested with regard to the implemented features. Optional further functionalities and developments are discussed. Possible applications of the 3D-printed, bio-inspired designs are optical devices that benefit from adjusting the field of view per pixel to zooming. Suggested are novel microscopes and screens with built-in cameras enabling online eye-to-eye communication without having to concentrate on the location of a camera.
Students’ Digital Media Self-Efficacy and Its Importance for Higher Education Institutions: Development and Validation of a Survey Instrument
2020-07-25

Abstract Although digital media are in general very common, their role in academic settings and their relevance for academic achievement are not satisfactorily explored. A research gap that is particularly apparent during the corona crisis in 2020 when university processes in many countries are suddenly almost completely digitalised. Research suggests a link between students’ diversity, in particular, their socio-economic background, academic self-efficacy expectations, study-related attitudes, and academic achievement. However, previous empirical studies on digital media at universities predominantly describe different types of media usage patterns but little is revealed about the students’ study-related attitudes and performance. The present study aims at developing a survey instrument to explore the relationship of individual, contextual as well as social background factors concerning academic achievement, with a special focus on academic and digital media self-efficacy expectations (DMSE). For this purpose, a new scale for DMSE has been constructed, based on existing psychological research. After pre-testing the instrument in 2017, data was collected at four German universities in summer 2018 (n = 2039). Validity and reliability are shown and the instrument appears suitable for further research in order to explore the interplay of student learning and digital media use in higher education, integrating the institutional and social context.
Memory Engrams in the Neocortex
2020-07-25

While in the past much of our knowledge about memory representations in the brain has relied on loss-of-function studies in which whole brain regions were temporarily inactivated or permanently lesioned, the recent development of new methods has ushered in a new era of downright “engram excitement.” Animal research is now able to specifically label, track, and manipulate engram cells in the brain. While early studies have mostly focused on single brain regions like the hippocampus, recently more and more evidence for brain-wide distributed engram networks is emerging. Memory research in humans has also picked up pace, fueled by promising magnetic resonance imaging (MRI)-based methods like diffusion-weighted MRI (DW-MRI) and brain decoding. In this review, we will outline recent advancements in engram research, with a focus on human data and neocortical representations. We will illustrate the available noninvasive methods for the detection of engrams in different neocortical regions like the medial prefrontal cortex and the posterior parietal cortex and discuss evidence for systems consolidation and parallel memory encoding. Finally, we will explore how reactivation and prior knowledge can lead to and enhance engram formation in the neocortex.
Labour market policy under the new European economic governance: France in the focus of the new European labour market policy
2020-07-25

The article examined the influence of the European crisis politics on French labour market regulation. The European crisis management has resulted in institutionalised interventionism, that restraint the European Union member states’ ability to regulate her national labour markets. France was less affected by the crisis but it was also in the focus of the European interventionism. On the basis of the labour market reforms ‘Loi Macron’ and ‘Loi El Khomri’, the article investigates what role the European institutions play and how big was the influence of the European Union in the national negotiation process.
Pseudo-hyperscanning shows common neural activity during face-to-face communication of affect to be associated with shared affective feelings but not with mere emotion recognition
2020-07-25

Current theories in cognitive neuroscience assume that internal simulation, i.e., the reproduction of brain activity underlying another person's inner state and behaviour in the perceiver's brain, plays an important role in understanding others. Here we test the prediction that common neural activity during facial communication of affect leads to interpersonal understanding. Six female senders and 30 male observers (six of which were the senders romantic partners and 24 unknown others) underwent pseudo-hyperscanning fMRI (functional magnetic resonance imaging). Senders were asked to submerge themselves into emotional situations and to facially express their emotional feelings as they arose to the observer. Observers were uninformed about the sender's task and were asked to watch and feel with the sender. Using between-brain spatial correlation analysis we found that mere emotion recognition was not closely related to the degree to which an observer reproduced the sender's spatial pattern of neural activity in his own brain. However, in runs in which the observer had correctly identified the communicated emotion, between-brain similarity of spatial patterns of neural activity predicted the degree to which the observer experienced a similar emotional feeling as the sender. This effect remained significant when differences between romantic partners and unknown others and sender effects were removed. These findings are in line with previous studies that suggest that facial emotion recognition, at least at a coarse level, might be supported by neural processes that do not rely on internal simulation. Shared affective experiences, on the other hand, might arise from common neural activity between the sender's and the observer's brain, leading to a "shared space of affect" which might be critical for the flow of more subtle affective information between brains.
Regulation of trehalase activity by multi-site phosphorylation and 14-3-3 interaction
2020-07-25

Abstract Protein phosphorylation enables a rapid adjustment of cellular activities to diverse intracellular and environmental stimuli. Many phosphoproteins are targeted on more than one site, which allows the integration of multiple signals and the implementation of complex responses. However, the hierarchy and interplay between multiple phospho-sites are often unknown. Here, we study multi-site phosphorylation using the yeast trehalase Nth1 and its activator, the 14-3-3 protein Bmh1, as a model. Nth1 is known to be phosphorylated by the metabolic kinase PKA on four serine residues and by the cell cycle kinase CDK on one residue. However, how these five phospho-sites adjust Nth1 activity remains unclear. Using a novel reporter construct, we investigated the contribution of the individual sites for the regulation of the trehalase and its 14-3-3 interactor. In contrast to the constitutively phosphorylated S20 and S83, the weaker sites S21 and S60 are only phosphorylated by increased PKA activity. For binding Bmh1, S83 functions as the high-affinity “gatekeeper” site, but successful binding of the Bmh1 dimer and thus Nth1 activation requires S60 as a secondary site. Under nutrient-poor conditions with low PKA activity, S60 is not efficiently phosphorylated and the cell cycle dependent phosphorylation of S66 by Cdk1 contributes to Nth1 activity, likely by providing an alternative Bmh1 binding site. Additionally, the PKA sites S20 and S21 modulate the dephosphorylation of Nth1 on downstream Bmh1 sites. In summary, our results expand our molecular understanding of Nth1 regulation and provide a new aspect of the interaction of 14-3-3 proteins with their targets.
Comparison of solitary and collective foraging strategies of Caenorhabditis elegans in patchy food distributions
2020-07-26

Collective foraging has been shown to benefit organisms in environments where food is patchily distributed, but whether this is true in the case where organisms do not rely on long-range communications to coordinate their collective behaviour has been understudied. To address this question, we use the tractable laboratory model organism Caenorhabditis elegans , where a social strain ( npr-1 mutant) and a solitary strain (N2) are available for direct comparison of foraging strategies. We first developed an on-lattice minimal model for comparing collective and solitary foraging strategies, finding that social agents benefit from feeding faster and more efficiently simply owing to group formation. Our laboratory foraging experiments with npr-1 and N2 worm populations, however, show an advantage for solitary N2 in all food distribution environments that we tested. We incorporated additional strain-specific behavioural parameters of npr-1 and N2 worms into our model and computationally identified N2's higher feeding rate to be the key factor underlying its advantage, without which it is possible to recapitulate the advantage of collective foraging in patchy environments. Our work highlights the theoretical advantage of collective foraging owing to group formation alone without long-range interactions and the valuable role of modelling to guide experiments. This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems'.
Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity
2020-07-26

Abstract Background Multiple sclerosis (MS) disease risk is associated with reduced sun exposure. This study assessed the relationship between measures of sun-exposure (vitamin D (vitD), latitude) and MS disease severity, the mechanisms of action, and effect-modification by medication and sun-sensitivity associated MC1R variants. Methods Two multi-center cohort studies (n NationMS =946, n BIONAT =991). Outcomes were the multiple sclerosis severity score (MSSS) and the number of Gd-enhancing lesion (GELs). RNAseq of four immune cell populations before and after UV-phototherapy of five MS patients. Results High serum vitD was associated with reduced MSSS ( P NationMS =0.021; P BIONAT =0.007) and reduced risk for disease aggravation ( P NationMS =0.032). Low latitude was associated with higher vitD, lower MSSS ( P NationMS =0.018), fewer GELs ( P NationMS =0.030) and reduced risk for aggravation ( P NationMS =0.044). The influence of latitude on disability seemed to be lacking in the subgroup of interferon-β treated patients (interaction- P BIONAT =0.042, interaction- P NationMS =0.053). In genetic analyses, for carriers of MC1R :rs1805008(T), who reported increased sensitivity towards sunlight ( P NationMS =0.038), the relationship between latitude und the number of GELs was inversed ( P NationMS =0.001). Phototherapy induced a vitD and type I interferon signature that was most apparent in the transcriptome of monocytes ( P =1×10 −6 ). Conclusion VitD is associated with reduced MS severity and disease aggravation. This is likely driven by sun-exposure, as latitude also correlated with disability and serum vitD. However, sun-exposure might be detrimental for sun-sensitive patients. A direct induction of type I interferons through sun-exposure could explain a reduced effect of latitude in interferon-β treated patients. This could also explain opposite effects of sun-exposure in MS and the type I interferon and sun-sensitivity-associated disease Lupus.
Specific changes in sleep oscillations after blocking human metabotropic glutamate receptor 5 in the absence of altered memory function
2020-07-26

Abstract Background Sleep consolidates declarative memory by repeated replay linked to the cardinal oscillations of NonREM sleep. However, there is so far little evidence of classical glutamatergic plasticity induced by this replay. Rather, we have previously reported that blocking NMDA or AMPA receptors does not affect sleep-dependent consolidation of declarative memory. Aims Investigate the role of metabotropic glutamate receptor 5 (mGluR5) on memory processing during sleep. Methods In two placebo-controlled within-subject cross-over experiments with 20 healthy humans each, we used fenobam to block mGluR5 during sleep. In Experiment I, participants learned word-pairs (declarative task) and a finger sequence (procedural task) in the evening, then received the drug and recall was tested in the next morning. To cover possible effects on synaptic renormalization processes during sleep, in Experiment II, participants learned new word-pairs in the morning after sleep. Results/Outcomes Surprisingly, fenobam neither reduced retention of memory across sleep nor new learning after sleep, although it severely altered sleep architecture and memoryrelevant EEG oscillations. In NonREM sleep, fenobam suppressed 12-15 Hz spindles but augmented 2-4 Hz delta waves, whereas in REM sleep it suppressed 4-8 Hz theta and 16-22 Hz beta waves. Notably, under Fenobam NonREM spindles became more consistently phase-coupled to the slow oscillation. Conclusions/Interpretations Our findings indicate that mGluR5-related plasticity is not essential for memory processing during sleep, even though mGlurR5 are strongly implicated in the regulation of the cardinal sleep oscillations. Declaration of interest/Funding The authors have nothing to disclose and funders had no influence on the research presented here.
Direct medium-chain carboxylic-acid oil separation from a bioreactor by an electrodialysis/phase separation cell
2020-07-26

Abstract Medium-chain carboxylic acids (MCCAs) are valuable platform chemicals with numerous industrial-scale applications. These MCCAs can be produced from waste biomass sources or syngas fermentation effluent through an anaerobic fermentation process called chain elongation. We have previously demonstrated successful approaches to separate &gt;90%-purity oil with several MCCAs by integrating the anaerobic bioprocess with membrane-based liquid-liquid extraction (pertraction) and membrane electrolysis. However, membrane electrolysis without pertraction was not able to separate MCCA oil. Therefore, we developed an electrodialysis/phase separation cell (ED/PS) and evaluated whether it can function as a stand-alone extraction and separation unit. First, we tested an ED/PS cell, which, when evaluated in series with pertraction, achieved a maximum MCCA-oil flux of 1,665 g d -1 per projected area (m 2 ) (19.3 mL oil d -1 ) and a MCCA-oil transfer efficiency [100%*moles MCCA-oil moles electrons -1 ] of 74% at 15 A m -2 . This extraction system demonstrated a ∼10 times lower electric-power consumption of 1.05 kWh kg -1 MCCA oil when compared to membrane electrolysis in series with pertration (11.1 kWh kg -1 MCCA oil) at 15 A m -2 . Second, we evaluated our ED/PS as a stand-alone unit when integrated with the anaerobic bioprocess (without pertraction), and demonstrated that we can selectively extract and separate MCCA oil directly from chain-elongating bioreactor broth with just an abiotic electrochemical cell. We assumed that such a stand-alone unit would reduce capital and operating costs, but electric-power consumption increased considerably due to the lower MCCA concentrations in the bioreactor broth compared to the pertraction broth. Only a full techno-economic analysis will be able to determine whether the use of the ED/PS cell should be as a stand-alone unit or after pertraction.
Transcriptome Profiling Identifies TIGIT as a Marker of T‐Cell Exhaustion in Liver Cancer
2020-07-27

BACKGROUND AND AIMS Programmed death 1 (PD‐1) checkpoint inhibition has shown promising results in patients with hepatocellular carcinoma, inducing objective responses in approximately 20% of treated patients. The roles of other coinhibitory molecules and their individual contributions to T‐cell dysfunction in liver cancer, however, remain largely elusive. APPROACH AND RESULTS We performed a comprehensive mRNA profiling of cluster of differentiation 8 (CD8) T cells in a murine model of autochthonous liver cancer by comparing the transcriptome of naive, functional effector, and exhausted, tumor‐specific CD8 T cells. Subsequently, we functionally validated the role of identified genes in T‐cell exhaustion. Our results reveal a unique transcriptome signature of exhausted T cells and demonstrate that up‐regulation of the inhibitory immune receptor T‐cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine‐based inhibitor motif domains (TIGIT) represents a hallmark in the process of T‐cell exhaustion in liver cancer. Compared to PD‐1, expression of TIGIT more reliably identified exhausted CD8 T cells at different stages of their differentiation. In combination with PD‐1 inhibition, targeting of TIGIT with antagonistic antibodies resulted in synergistic inhibition of liver cancer growth in immunocompetent mice. Finally, we demonstrate expression of TIGIT on tumor‐infiltrating CD8 T cells in tissue samples of patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma and identify two subsets of patients based on differential expression of TIGIT on tumor‐specific T cells. CONCLUSIONS Our transcriptome analysis provides a valuable resource for the identification of key pathways involved in T‐cell exhaustion in patients with liver cancer and identifies TIGIT as a potential target in checkpoint combination therapies.
Electron Hopping Enables Rapid Electron Transfer between Quinone-/Hydroquinone-Containing Organic Molecules in Microbial Iron(III) Mineral Reduction
2020-07-27

The mechanism of long-distance electron transfer via redox-active particulate natural organic matter (NOM) is still unclear, especially considering its aggregated nature and the resulting low diffusivity of its quinone- and hydroquinone-containing molecules. Here we conducted microbial iron(III) mineral reduction experiments in which anthraquinone-2,6-disulfonate (AQDS, a widely used analogue for quinone- and hydroquinone-containing molecules in NOM) was immobilized in agar to achieve a spatial separation between the iron-reducing bacteria and ferrihydrite mineral. Immobilizing AQDS in agar also limited its diffusion, which resembled electron-transfer behavior of quinone- and hydroquinone-containing molecules in particulate NOM. We found that, although the diffusion coefficient of the immobilized AQDS/AH<sub>2</sub>QDS was 10 times lower in agar than in water, the iron(III) mineral reduction rate (1.60 ± 0.28 mmol L<sup>-</sup>1 Fe(II) d<sup>-1</sup>) was still comparable in both media, indicating the existence of another mechanism that accelerated the electron transfer under low diffusive conditions. We found the correlation between the heterogeneous electron-transfer rate constant (10<sup>-3</sup> cm s<sup>-1</sup>) and the diffusion coefficient (10<sup>-7</sup> cm<sup>2</sup> s<sup>-1</sup>) fitting well with the "diffusion-electron hopping" model, suggesting that electron transfer via the immobilized AQDS/AH<sub>2</sub>QDS couple was accomplished through a combination of diffusion and electron hopping. Electron hopping increased the diffusion concentration gradient up to 10<sup>6</sup>-fold, which largely promoted the overall electron-transfer rate during microbial iron(III) mineral reduction. Our results are helpful to explain the electron-transfer mechanisms in particulate NOM.