julilili42/papers huggingface dataset:
Moved by Emotions: Affective Concepts Representing Personal Life Events Induce Freely Performed Steps in Line With Combined Sagittal and Lateral Space-Valence Associations
2019-12-11

Embodiment approaches to cognition and emotion have put forth the idea that the way we think and talk about affective events often recruits spatial information that stems, to some extent, from our bodily experiences. For example, metaphorical expressions such as "being someone's right hand" or "leaving something bad behind" convey affectivity associated with the lateral and sagittal dimensions of space. Action tendencies associated with affect such as the directional fluency of hand movements (dominant right hand-side - positive; non-dominant left hand-side - negative) and approach-avoidance behaviors (forward - positive; backwards - negative) might be mechanisms supporting such associations. Against this background, experimental research has investigated whether positive and negative words are freely allocated into space (e.g., close or far from one's body) or resonate with congruent (vs. incongruent) predefined manual actions usually performed by joysticks or button presses (e.g., positive - right; negative - left, or vice versa). However, to date, it is unclear how the processing of affective concepts resonate with directional actions of the whole body, the more if such actions are performed freely within a context enabling both, lateral and sagittal movements. Accordingly, 67 right-handed participants were to freely step on an 8-response pad (front, back, right, left, front-right, front-left, back-right, or back-left) after being presented in front of them valence-laden personal life-events submitted before the task (e.g., words or sentences such as "graduation" or "birth of a child"). The most revealing finding of this study indicates that approach-avoidance behaviors and space-valence associations across laterality are interwoven during whole body step actions: Positive events induced steps highly biased to front-right whereas negative events induced steps highly biased to back-left.
Genome Sequence of the Yeast Saprochaete ingens CBS 517.90
2019-12-11

Chromosome-scale genome assembly of the yeast Saprochaete ingens CBS 517.90 was determined by a combination of technologies producing short (HiSeq X; Illumina) and long (MinION; Oxford Nanopore Technologies) reads. The 21.2-Mbp genome sequence has a GC content of 36.9% and codes for 6,475 predicted proteins.
Assessment of Cognitive-Driven Performance-Based Activities of Daily Living Dysfunction in Parkinson’s Disease
2019-12-11

Abstract Objectives: Parkinson’s disease (PD) patients with mild cognitive impairment (PD-MCI) have an increased risk of developing dementia (PDD). As activities of daily living (ADL) impairment is mandatory for the diagnosis of PDD, assessing early signs of instrumental ADL (iADL) dysfunction, especially in PD-MCI, is essential. In PD, self- and caregiver-reported iADL performance is often confounded by motor dysfunction and mood. Objective and time-efficient performance-based measurements are needed to screen for cognitive-related iADL dysfunction. We evaluated the Erlangen Test of Activities of Daily Living in Mild Dementia and Mild Cognitive Impairment (ETAM) in PD and determined its value for characterizing a subgroup of PD-MCI patients with mild performance-based iADL impairment. Methods: Twenty-one cognitively normal PD patients (PD-NC), 24 PD-MCI patients, and 18 healthy controls (HC) were analyzed. Assessments included the ETAM, a comprehensive neuropsychological test battery, iADL, mood, and motor measurements. Results: PD-MCI patients scored significantly lower on the ETAM total score compared to PD-NC patients ( p = .002), whereas HC and PD-NC patients did not statistically differ. No HC scored lower than 27 points (diagnostic cutoff for mild iADL impairment); only PD-MCI patients scored below this cutoff (29.2%) suggesting the ETAM is able to characterize a PD-MCI subgroup with early iADL impairment. PD-MCI patients below the cutoff were more impaired in the attention domain ( p = .04). Conclusions: The ETAM is a potentially valuable clinical assessment, able to detect first signs of iADL dysfunction in PD-MCI. Further studies in larger cohorts are needed to evaluate the prognostic ability for predicting PDD.
Tuning the in vitro sensing and signaling properties of cyanobacterial PII protein by mutation of key residues
2019-12-12

Abstract PII proteins comprise an ancient superfamily of signal transduction proteins, widely distributed among all domains of life. In general, PII proteins measure and integrate the current carbon/nitrogen/energy status of the cell through interdependent binding of ATP, ADP and 2-oxogluterate. In response to effector molecule binding, PII proteins interact with various PII-receptors to tune central carbon- and nitrogen metabolism. In cyanobacteria, PII regulates, among others, the key enzyme for nitrogen-storage, N-acetyl-glutamate kinase (NAGK), and the co-activator of the global nitrogen-trascription factor NtcA, the PII-interacting protein-X (PipX). One of the remarkable PII variants from Synechococcus elongatus PCC 7942 that yielded mechanistic insights in PII-NAGK interaction, is the NAGK-superactivating variant I86N. Here we studied its interaction with PipX. Another critical residue is Lys58, forming a salt-bridge with 2-oxoglutarate in a PII-ATP-2-oxoglutarate complex. Here, we show that Lys58 of PII protein is a key residue for mediating PII interactions. The K58N mutation not only causes the loss of 2-oxogluterate binding but also strongly impairs binding of ADP, NAGK and PipX. Remarkably, the exchange of the nearby Leu56 to Lys in the K58N variant partially compensates for the loss of K58. This study demonstrates the potential of creating custom tailored PII variants to modulate metabolism.
AtDAT1 Is a Key Enzyme of D-Amino Acid Stimulated Ethylene Production in Arabidopsis thaliana
2019-12-12

D-Enantiomers of proteinogenic amino acids (D-AAs) are found ubiquitously, but the knowledge about their metabolism and functions in plants is scarce. A long forgotten phenomenon in this regard is the D-AA-stimulated ethylene production in plants. As a starting point to investigate this effect, the <i>Arabidopsis</i> accession Landsberg <i>erecta</i> (L<i>er</i>) got into focus as it was found defective in metabolizing D-AAs. Combining genetics and molecular biology of T-DNA insertion lines and natural variants together with biochemical and physiological approaches, we could identify AtDAT1 as a major D-AA transaminase in <i>Arabidopsis</i>. <i>Atdat1</i> loss-of-function mutants and <i>Arabidopsis</i> accessions with defective <i>AtDAT1</i> alleles were unable to produce the metabolites of D-Met, D-Ala, D-Glu, and L-Met. This result corroborates the biochemical characterization, which showed highest activity of AtDAT1 using D-Met as a substrate. Germination of seedlings in light and dark led to enhanced growth inhibition of <i>atdat1</i> mutants on D-Met. Ethylene measurements revealed an increased D-AA stimulated ethylene production in these mutants. According to initial working models of this phenomenon, D-Met is preferentially malonylated instead of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC). This decrease of ACC degradation should then lead to the increase of ethylene production. We could observe a reciprocal relation of malonylated methionine and ACC upon D-Met application and significantly more malonyl-methionine in <i>atdat1</i> mutants. Unexpectedly, the malonyl-ACC levels did not differ between mutants and wild type. With AtDAT1, the first central enzyme of plant D-AA metabolism was characterized biochemically and physiologically. The specific effects of D-Met on ACC metabolism, ethylene production, and plant development of <i>dat1</i> mutants unraveled the impact of AtDAT1 on these processes; however, they are not in full accordance to previous working models. Instead, our results imply the influence of additional factors or processes on D-AA-stimulated ethylene production, which await to be uncovered.
Gut microbiome signatures of risk and prodromal markers of Parkinson’s disease
2019-12-12

Abstract Objectives Alterations of the gut microbiome in Parkinson’s disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they may be related to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. Methods Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and taxonomic composition in stool samples of 666 elderly TREND study participants. Results Among risk and prodromal markers, physical inactivity, constipation and age showed associations with α- and β-diversity, and for both measures subthreshold parkinsonism and physical inactivity showed interaction effects. Moreover, male sex, possible REM-sleep behavior disorder (RBD), smoking as well as body-mass-index, antidiabetic and urate-lowering medication were associated with β-diversity. Physical inactivity and constipation severity were increased in individuals with the Firmicutes -enriched enterotype. Subthreshold parkinsonism was least frequently observed in individuals with the Prevotella -enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history and the overall prodromal PD probability showed no significant microbiome associations. Interpretation Several risk and prodromal markers of PD are associated with changes in gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases.
Analysis of brain atrophy and local gene expression in genetic frontotemporal dementia
2019-12-12

Abstract Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder characterized by neuronal loss in the frontal and temporal lobes. Despite progress in understanding which genes are associated with the aetiology of FTD, the biological basis of how mutations in these genes lead to cell loss in specific cortical regions remains unclear. In this work we combined gene expression data for 16,772 genes from the Allen Institute for Brain Science atlas with brain maps of gray matter atrophy in symptomatic C9orf72 , GRN and MAPT mutation carriers obtained from the Genetic FTD Initiative study. No significant association was seen between ( C9orf2 , GRN and MAPT expression and the atrophy patterns in the respective genetic groups. Between 1,000 and 5,000 genes showed a negative or positive correlation with the atrophy pattern within each individual genetic group, with the most significantly associated genes being TREM2 , SSBP3 and GPR158 (negative association in C9orf72 , GRN and MAPT respectively) and RELN, MXRA8 and LPA (positive association in C9orf72 , GRN and MAPT respectively). An overrepresentation analysis identified a negative correlation with genes involved in mitochondrial function, and a positive correlation with genes involved in vascular and glial cell function in each of the genetic groups. After adjusting for spatial autocorrelation, a set of 423 and 700 genes showed significant positive and negative correlation, respectively, with atrophy patterns in all three maps. The gene set with increased expression in spared cortical regions was enriched for neuronal and microglial genes, while the gene set with increased expression in atrophied regions was enriched for astrocyte and endothelial cell genes. Our analysis suggests that these cell types may play a more active role in the onset of neurodegeneration in FTD than previously assumed, and in the case of the positively-associated cell marker genes, potentially through emergence of neurotoxic astrocytes and alteration in the blood-brain barrier respectively. Abbreviated summary Altmann et al. investigated the concordance between spatial cortical gene expression in healthy subjects and atrophy patterns in genetic frontotemporal dementia. They found that elevated gene expression of endothelial cell and astrocyte-related genes in regions with atrophy, suggesting a role of these cell types in the aetiology of frontotemporal dementia.
Glacial cycle ice-sheet evolution controlled by oceanbed properties
2019-12-12

Improving constraints on the basal ice/bed properties is essential for accurate prediction of ice-sheet grounding-line positions and stability. Furthermore, the history of grounding-line positions since the Last Glacial Maximum has proven challenging to understand due to uncertainties in bed conditions. Here we use a 3D full-Stokes ice-sheet model to investigate the effect of differing ocean bed properties on ice-sheet advance and retreat over a glacial cycle. We do this for the Ekström Ice Shelf catchment, East Antarctica. We find that predicted ice volumes differ by >50%, resulting in two entirely different catchment geometries triggered exclusively by variable ocean bed properties. Grounding-line positions between simulations differ by >100% (49 km), show significant hysteresis, and migrate non-steadily with long quiescent phases disrupted by leaps of rapid migration. These results highlight that constraints for both bathymetry and substrate geologic properties are urgently needed for predicting ice-sheet evolution and sea-level change.
The role of operational expenditures and misalignments in fundraising for international humanitarian aid
2019-12-13

Abstract Funding for international humanitarian aid falls far behind demand for disaster response, hampering the operations of international humanitarian organizations (IHOs). One remedy to close this gap is to increase the effectiveness of fundraising activities for IHOs. This remedy means spending as little as possible in fundraising activities but, at the same time, still receiving sufficient donations to implement disaster response programs in response to the needs that arise when disasters occur. We contribute to the literature by theoretically developing and estimating a conceptual framework that links donation behavior to the operations that IHOs aim to pursue; the framework incorporates operational costs communicated in appeals, fundraising efforts, and media attention. We argue that effects are not homogenous across disasters but that IHOs can leverage public attention and disaster and appeal characteristics, such as operational costs, to increase donations. We test the framework on a unique data set for disaster response programs operated by the International Federation of Red Cross and Red Crescent Societies (IFRC), covering 174 disasters to which the IFRC responded between 2010 and 2017.
H.E.S.S. and Fermi-LAT observations of PSR B1259–63/LS 2883 during its 2014 and 2017 periastron passages
2019-12-13

Context. PSR B1259–63/LS 2883 is a gamma-ray binary system consisting of a pulsar in an eccentric orbit around a bright Oe stellar-type companion star that features a dense circumstellar disc. The bright broad-band emission observed at phases close to periastron offers a unique opportunity to study particle acceleration and radiation processes in binary systems. Observations at gamma-ray energies constrain these processes through variability and spectral characterisation studies. Aims. The high- and very-high-energy (HE, VHE) gamma-ray emission from PSR B1259–63/LS 2883 around the times of its periastron passage are characterised, in particular, at the time of the HE gamma-ray flares reported to have occurred in 2011, 2014, and 2017. Short-term and average emission characteristics of PSR B1259–63/LS 2883 are determined. Super-orbital variability is searched for in order to investigate possible cycle-to-cycle VHE flux changes due to different properties of the companion star’s circumstellar disc and/or the conditions under which the HE gamma-ray flares develop. Methods. Spectra and light curves were derived from observations conducted with the H.E.S.S-II array in 2014 and 2017. Phase-folded light curves are compared with the results obtained in 2004, 2007, and 2011. Fermi -LAT observations from 2010/11, 2014, and 2017 are analysed. Results. A local double-peak profile with asymmetric peaks in the VHE light curve is measured, with a flux minimum at the time of periastron t p and two peaks coinciding with the times at which the neutron star crosses the companion’s circumstellar disc (~ t p ± 16 d). A high VHE gamma-ray flux is also observed at the times of the HE gamma-ray flares (~ t p + 30 d) and at phases before the first disc crossing (~ t p − 35 d). The spectral energy range now extends to below 200 GeV and up to ~45 TeV. Conclusions. PSR B1259–63/LS 2883 displays periodic flux variability at VHE gamma-rays without clear signatures of super-orbital modulation in the time span covered by the monitoring of the source with the H.E.S.S. telescopes. This flux variability is most probably caused by the changing environmental conditions, particularly at times close to periastron passage at which the neutron star is thought to cross the circumstellar disc of the companion star twice. In contrast, the photon index remains unchanged within uncertainties for about 200 d around periastron. At HE gamma-rays, PSR B1259–63/LS 2883 has now been detected also before and after periastron, close to the disc crossing times. Repetitive flares with distinct variability patterns are detected in this energy range. Such outbursts are not observed at VHEs, although a relatively high emission level is measured. The spectra obtained in both energy regimes displays a similar slope, although a common physical origin either in terms of a related particle population, emission mechanism, or emitter location is ruled out.
Clinically Relevant OATP2B1 Inhibitors in Marketed Drug Space
2019-12-13

OATP2B1 is an intestinal and hepatic drug uptake transporter. Intestinal OATP2B1 has been elucidated as the mechanism of unexpected clinical drug-drug interactions (DDIs), where drug exposure was unexpectedly decreased with unchanged half-life. Hepatic OATP2B1 may be an understudied clinical DDI mechanism. The aim of the present work was to understand the prevalence of clinically relevant intestinal and hepatic OATP2B1 inhibitors in marketed drug space. HEK293 cells stably overexpressing human OATP2B1 or vector control were generated and cultured for 72 h in a 96-well format. OATP2B1-mediated uptake of dibromofluorescein (DBF) was found to be optimal at 10 μM concentration and 30 min incubation time. A total of 294 drugs (top 300 marketed drugs, excluding biologics and restricted drugs, supplemented with ∼100 small-molecule drugs) were screened for OATP2B1 inhibition at 10 μM. Drugs demonstrating ≥50% inhibition in this screen were advanced for IC<sub>50</sub> determination, which was extrapolated to clinical intestinal and hepatic OATP2B1 inhibition as per 2017 FDA DDI guidance. Of the 294 drugs screened, 67 elicited ≥50% inhibition of OATP2B1-mediated DBF uptake at 10 μM screening concentration. For the 67 drugs flagged in the single-concentration inhibition screen, upon evaluation of a full concentration range, IC<sub>50</sub> values could be determined for 58 drugs. OATP2B1 IC<sub>50</sub> values established for these 58 drugs were extrapolated as potentially clinically relevant at the intestinal level for 38 orally administered drugs (<i>I</i><sub>gut</sub>/IC<sub>50</sub> ≥ 10), and 17 were flagged as potential clinical inhibitors of hepatic OATP2B1 uptake (1 + <i>I</i><sub>in,max,u</sub>/IC<sub>50</sub> ≥ 1.1). This analysis of 294 drugs demonstrated prevalence of clinically relevant intestinal and hepatic OATP2B1 inhibitors to be 13 and 6%, respectively. As OATP2B1-inhibitor drugs are not exceedingly rare, these results suggest that clinical OATP2B1 DDIs have been rarely observed because OATP2B1 is uncommonly the predominant determinant of drug disposition.
Structure or Exchange? On the Feasibility of Chemical Exchange Detection with Balanced Steady‐State Free Precession in Tissue – An In Vitro Study
2019-12-13

Balanced steady‐state free precession imaging has recently been suggested for chemical exchange detection (bSSFPX). The objective of this work is to investigate the contributions of microstructural, chemical shift and chemical exchange effects to the asymmetry of the bSSFP profile at field strengths of 3 T and 9.4 T. To this end, in vitro bSSFPX experiments are performed for a range of repetition times and flip angles in glucose water solutions with different MnCl 2 concentrations and tissue homogenates obtained from the brainstem of pig brains. The experimental results are compared to multi‐pool Bloch‐McConnell simulations. Additionally, the influence of white matter tract geometry is analyzed ex vivo in pig brain hemispheres measured at two different angles with respect to B 0 . The detectable bSSFP profile asymmetry in glucose solutions with tissue‐like relaxation times and white matter homogenates was consistent with Bloch‐McConnell simulations but relatively small. In intact white matter tracts, the asymmetry was dominated by structural effects with a strong dependency on tract orientation relative to B 0 . In tracts perpendicular to B 0 , the asymmetry was ≈ 3‐4 times higher than in the homogenates, thus barely affected by chemical exchange effects. In conclusion, chemical exchange‐related bSSFP profile asymmetries are detectable in tissue homogenates, however, the observed asymmetry level is generally low and prone to confounding structural effects rendering in vivo chemical exchange detection with bSSFP challenging in the brain.
FePc and FePcF16 on Rutile TiO2(110) and (100): Influence of the Substrate Preparation on the Interaction Strength
2019-12-13

Interface properties of iron phthalocyanine (FePc) and perfluorinated iron phthalocyanine (FePcF16) on rutile TiO2(100) and TiO2(110) surfaces were studied using X-ray photoemission spectroscopy (XPS), X-ray absorption spectroscopy (XAS), and low-energy electron diffraction (LEED). It is demonstrated that the interaction strength at the interfaces is considerably affected by the detailed preparation procedure. Weak interactions were observed for all studied interfaces between FePc or FePcF16 and rutile, as long as the substrate was exposed to oxygen during the annealing steps of the preparation procedure. The absence of oxygen in the last annealing step only had almost no influence on interface properties. In contrast, repeated substrate cleaning cycles performed in the absence of oxygen resulted in a more reactive, defect-rich substrate surface. On such reactive surfaces, stronger interactions were observed, including the cleavage of some C–F bonds of FePcF16.