julilili42/papers huggingface dataset:
Molybdenum Cofactor Catabolism Unravels the Physiological Role of the Drug Metabolizing Enzyme Thiopurine S‐Methyltransferase
2022-05-11

Therapy of molybdenum cofactor (Moco) deficiency has received US Food and Drug Administration (FDA) approval in 2021. Whereas urothione, the urinary excreted catabolite of Moco, is used as diagnostic biomarker for Moco‐deficiency, its catabolic pathway remains unknown. Here, we identified the urothione‐synthesizing methyltransferase using mouse liver tissue by anion exchange/size exclusion chromatography and peptide mass fingerprinting. We show that the catabolic Moco S‐methylating enzyme corresponds to thiopurine S‐methyltransferase (TPMT), a highly polymorphic drug‐metabolizing enzyme associated with drug‐related hematotoxicity but unknown physiological role. Urothione synthesis was investigated in vitro using recombinantly expressed human TPMT protein, liver lysates from Tpmt wild‐type and knock‐out ( Tpmt −/− ) mice as well as human liver cytosol. Urothione levels were quantified by liquid‐chromatography tandem mass spectrometry in the kidneys and urine of mice. TPMT‐genotype/phenotype and excretion levels of urothione were investigated in human samples and validated in an independent population‐based study. As Moco provides a physiological substrate (thiopterin) of TPMT, thiopterin‐methylating activity was associated with TPMT activity determined with its drug substrate (6‐thioguanin) in mice and humans. Urothione concentration was extremely low in the kidneys and urine of Tpmt −/− mice. Urinary urothione concentration in TPMT‐deficient patients depends on common TPMT polymorphisms, with extremely low levels in homozygous variant carriers ( TPMT*3A/*3A ) but normal levels in compound heterozygous carriers ( TPMT*3A/*3C ) as validated in the population‐based study. Our work newly identified an endogenous substrate for TPMT and shows an unprecedented link between Moco catabolism and drug metabolism. Moreover, the TPMT example indicates that phenotypic consequences of genetic polymorphisms may differ between drug‐ and endogenous substrates.
Evaluation of mathematical models for predicting particle size distribution using digital soil mapping in semiarid agricultural lands
2022-05-11

Soil Particle Size Distribution (PSD) is a fundamental physical property that can affect soil hydraulic properties, soil structure characterization, and available water. Many models have been applied to define the PSD curve, but predicting the spatial distribution information of PSD has been rarely investigated. Therefore, the main objective of the current study was to predict soil texture fractions using the most accurate PSD models. First, the performance of 16 mathematical PSD models was evaluated. Then, Random Forest (RF) was used to determine the relationship between covariates (i.e., remote sensing and the digital elevation model) and georeferenced measurements of the best PSD models' parameters. Results indicated that a PSD model may be acceptable for some particle diameters or even whole particles, but not necessarily be suitable for other particles. For example, in the estimation of sand content, the best model was Simple Lognormal, while the Fred-4p was the best model in the estimation of the clay fraction. Importantly, the Jaky model with only one parameter of P did a great job in predicting soil particle fractions. Further, the spatial distribution of clay, silt, and sand contents was accurately derived from the predicted map of P (R2 for Sand = 0.86). Consequently, the current research indicated that the combination of PSD models and digital soil mapping techniques can be used to quantify the spatial distribution of the PSD curve in other similar agroclimatological regions.
The unique laurel-leaf points of Volgu document long-distance transport of raw materials in the Solutrean
2022-05-11

Abstract The Upper Palaeolithic Solutrean culture that coincided with the last glacial maximum has become famous for documenting an increasing investment of time and effort in the production of tools. However, Solutrean lithic assemblages predominantly document local procurement of flint and only in rare cases, stones were transported over distances above 100 km. The perhaps most remarkable Solutrean artefacts are the large bifacial laurel-leaf points of Volgu. Some studies on the points suggested long-distance transport, proposing multiple raw material locations in the &gt; 170 km distant Paris Basin. These findings were not based on physical or chemical measurements but rather on evaluations of macro- and microscopically visible features at the surface of the flint. In this study, we aim to verify previously made propositions on the Volgu points’ origin with an archaeometric technique. For this, we apply reflectance infrared spectroscopy, a method that relies on identifying differences in the crystallographic properties of flint. We compare eight of the Volgu laurel-leaf points with five regions of Upper Cretaceous flint deposits in France and Belgium. We found that the Volgu points’ flint is most similar to flint from the south-eastern Paris Basin in terms of its crystallography (identifying a region between 170 and 250 km from Volgu). Our findings provide a reproducible line of evidence for the long-distance procurement of flint to produce exceptional artefacts in the Solutrean. Our study is the first application of this method to flint sourcing in a European context. It has therefore also implications for future provenance studies on other archaeological sites in France.
Towards robust smart data-driven soil erodibility index prediction under different scenarios
2022-05-11

Soil erosion is a major cause of damage to agricultural lands in many parts of the world and is of particular concern in semiarid parts of Iran. We use five machine learning techniques-Random Forest (RF), M5P, Reduced Error Pruning Tree (REPTree), Gaussian Processes (GP), and Pace Regression (PR)-under two scenarios to predict soil erodibility in the Dehgolan region, Kurdistan Province, Iran. Our models are based on a variety of soil properties, including soil texture, structure, permeability, bulk density, aggregates, organic matter, and chemical constituents. We checked the validity of the models with statistical metrics, including the coefficient of determination (R-2), mean absolute error (MAE), root mean squared error (RMSE), T-tests, Taylor diagrams, and box plots. All five algorithms show a positive correlation between the soil erodibility factor (K) and silt, sand, fine sand, bulk density, and infiltration. The GP model has the highest prediction accuracy (R-2 = 0.843, MAE = 0.0044, RMSE = 0.0050). It outperformed the RF (R-2 = 0.812, MAE = 0.0050, RMSE = 0.0061), PR, (R-2 = 0.794, MAE = 0.0037, RMSE = 0.0052), M5P (R-2 = 0.781, MAE = 0.0043, RMSE = 0.0053), and REPTree (R-2 = 0.752, MAE = 0.0045, RMSE = 0.0056) algorithms and thus is a useful complement to studies aimed at predicting soil erodibility in areas with similar climate and soil characteristics.
Interactive analysis of biosurfactants in fruit-waste fermentation samples using BioSurfDB and MEGAN
2022-05-11

Abstract Agroindustrial waste, such as fruit residues, are a renewable, abundant, low-cost, commonly-used carbon source. Biosurfactants are molecules of increasing interest due to their multifunctional properties, biodegradable nature and low toxicity, in comparison to synthetic surfactants. A better understanding of the associated microbial communities will aid prospecting for biosurfactant-producing microorganisms. In this study, six samples of fruit waste, from oranges, mangoes and mixed fruits, were subjected to autochthonous fermentation, so as to promote the growth of their associated microbiota, followed by short-read metagenomic sequencing. Using the DIAMOND+MEGAN analysis pipeline, taxonomic analysis shows that all six samples are dominated by Proteobacteria, in particular, a common core consisting of the genera Klebsiella , Enterobacter , Stenotrophomonas , Acinetobacter and Escherichia . Functional analysis indicates high similarity among samples and a significant number of reads map to genes that are involved in the biosynthesis of lipopeptide-class biosurfactants. Gene-centric analysis reveals Klebsiella as the main assignment for genes related to putisolvins biosynthesis. To simplify the interactive visualization and exploration of the surfactant-related genes in such samples, we have integrated the BiosurfDB classification into MEGAN and make this available. These results indicate that microbiota obtained from autochthonous fermentation have the genetic potential for biosynthesis of biosurfactants, suggesting that fruit wastes may provide a source of biosurfactant-producing microorganisms, with applications in the agricultural, chemical, food and pharmaceutical industries.
Connecting Exploration, Generalization, and Planning in Correlated Trees
2022-05-11

Human reinforcement learning (RL) is characterized by different challenges. Exploration has been studied extensively in multi-armed bandits, while planning has been investigated in multi-step decision tasks. More recent work has added structured rewards to study generalization. However, past studies have often focused on a single one of these aspects, making it hard to compare results. We propose a generative model for constructing correlated trees to provide a unified and scalable method for studying exploration, planning, and generalization in a single task. In an online experiment, we find that people use structure (when provided) to generalize and perform uncertainty-directed exploration, with structure helping more in larger environments. In environments without structure, exploration becomes more random and more planning is needed. All behavioral effects are captured in a single model with recoverable parameters. In conclusion, our results connect past research on human RL in one framework using correlated trees.
A phospho-switch provided by LRR receptor-like kinase, ALK1/QSK1/KIN7, prioritizes ABCG36/PEN3/PDR8 transport toward defense
2022-05-11

Abstract Based on its proposed substrate preferences, the ABC transporter, ABCG36/PDR8/PEN3, from the model plant Arabidopsis stands at the cross-road between growth and defence. Recently, ABCG36 was shown to export a few indolic compounds, including the auxin precursor, indole-3-butyric acid (IBA), and to be implicated in the export of the major phytoalexin of Arabidopsis, camalexin, although clear-cut proof of camalexin transport activity is still lacking. Here we provide strong evidence that ABCG36 catalyses the direct, ATP-dependent export of camalexin over the plasma membrane, however, most likely in functional interplay with non-camalexin transporting ABCG isoforms. We identify the leucin-rich repeat receptor-like kinase, Auxin-induced LRR Kinase1 (ALK1/KIN7/QSK1), as a functional kinase to physically interact with and phosphorylate ABCG36. ABCG36 phosphorylation by ALK1 represses unilaterally IBA but not camalexin export leading to a prioritization of ABCG transport toward defense. As a consequence, phospho-dead mutants of ABCG36, like alk1 and abcg36 alleles, are hypersensitive toward infection with the root pathogen, F. oxysporum , caused by elevated fungal progression. Our findings indicate a novel, direct regulatory circuit between a receptor kinase and an ABC transporter determining transporter substrate specificity. It appears that growth and defense balance decisions in plants are performed on the transporter level by means of a reversible phospho-switch.
Convexity estimates for hypersurfaces moving by concave curvature functions
2022-05-11

We study fully nonlinear geometric flows that deform strictly k-convex hypersurfaces in Euclidean space with pointwise normal speed given by a concave function of the principal curvatures. Specifically, the speeds we consider are obtained by performing a nonlinear interpolation between the mean and the k-harmonic mean of the principal curvatures. Our main result is a convexity estimate showing that, on compact solutions, regions of high curvature are approximately convex. In contrast to the mean curvature flow, the fully nonlinear flows considered here preserve k-convexity in a Riemannian background, and we show that the convexity estimate carries over to this setting as long as the ambient curvature satisfies a natural pinching condition.
Supplementary material to &quot;The patchwork loess of Central Asia: Implications for interpreting aeolian dynamics and past climate circulation in piedmont regions&quot;
2022-05-11

Optically Stimulated Luminescence (OSL) dating 1.1.Sample preparation All the samples were processed and measured under subdued red-light conditions at the Institute of Geosciences, Johannes Gutenberg University and the Max Planck Institute for Chemistry (MPIC) in Mainz, Germany.Different grain size fractions were extracted by wetsieving.However due to the lack of sufficient coarse grains (>45 μm), fine grain (4-11 μm) samples were prepared for OSL analysis using established protocols (Frechen et al., 1996).For the preparation of fine grain (4-11 μm) fraction -the <63 μm sediment was treated with 10% HCl followed by 10% H2O2 to remove carbonates and organics respectively.The sediment was then treated with 0.1N sodium oxalate to remove clays.The 4-11 μm polymineral fraction was obtained from the bulk fraction (<63 μm) by settling using Stokes Law.This polymineral fine grain fraction was treated with 37% Hexafluorosilicic acid (H2SiF6) for 7 days to remove feldspar and washed with 10% HCl to remove fluoride precipitates to obtain fine grained (4-11 μm) quartz rich fraction (Jackson et al, 1976).All aliquots were prepared by depositing a suspension of 4-11 μm quartz fraction using acetone on 9.7 mm stainless steel discs.The purity of the quartz extracts for all samples was verified by the near background signal observed on IR stimulation of the sample after a given dose (c.19 Gy) for all the samples (Duller, 2003). Luminescence MeasurementsAll luminescence measurements were made using an automated Risø TL-DA-20 reader equipped with a 90 Sr/ 90 Y beta sources (Thomsen et al., 2006) calibrated to a dose rate of 0.095 ± 0.02 Gy/s.The sample was stimulated using IR LED (870 ± 30 nm, 300 mW/cm 2 ) and blue LED (470±30 nm, 80 mW/cm 2 ) and the emitted luminescence signal was detected by by EMI 9235QA photomultiplier tube fitted with a 7.5 mm Hoya U-340 and a combination of Schott BG-39 and BG-3 filters to detect quartz and feldspar emissions respectively.
ATM - Quinoline-based inhibitors with urea moeities - Part I
2022-05-11

The files include raw trajectory files (2500 ns each) of the Desmond MD simulations of different ATM inhibitors within the ATM's ATP binding active site. System numbering goes as follow: 701- HsATM FM618 (AZD0156)<br> 702- HsATM FM883<br> 703- HsATM CA002<br> 705- HsATM FM638<br> 706- HsATM CA053 741- HsATM with FM975_trans charged Where the last number represents the number of the replica (1-5). Simulation details and system generation are provided in the respective publication
Severe acute hepatitis and acute liver failure of unknown origin in children: a questionnaire-based study within 34 paediatric liver centres in 22 European countries and Israel, April 2022
2022-05-12

To detect potential concern about severe acute hepatitis in children, we conducted a survey among 50 ERN RARE-LIVER centres. By 26 April 2022, 34 centres, including 25 transplant centres, reported an estimated median of 3–5, 0–2 and 3–5 cases in 2021, 2020 and 2019 and a mean of 2 (range: 0–8) cases between January and April 2022 (mean in 10 large liver transplant centres: 3). Twelve centres reported suspicion of an increase, but no rise.
Palaeoecological signals for Mesolithic land use in a Central European landscape?
2022-05-12

ABSTRACT During the Early Holocene, climate was the major factor causing fires, but whether during the Mesolithic (~11.5–7.4 cal ka BP) people co‐shaped their environment by means of fire remains of debate. Few studies have tackled this question by linking high‐resolution multi‐proxy palaeoecological studies from near Mesolithic occupation sites. An Early Holocene sediment record from the Ammer Valley palaeo‐wetland in south‐west Germany was studied using pollen, micro‐ and macrocharcoal, and plant macroremains. Archaeological evidence from Early and Late Mesolithic sites of Rottenburg‐Siebenlinden allowed us to link this palaeoecological record with Mesolithic land use in the same catchment. Between 11.6 and 10.6 cal ka bp, intensive wildfires reinforced the persistence of open and pioneer vegetation. A transition from a river‐dominated landscape towards a wetland with open stagnant waters at 10.6–9.5 cal ka bp made the region attractive to hunter‐gatherers, providing various plant resources (incl. hazel). From 10.1 cal ka bp onwards, Mesolithic communities may have shaped their environment by using fire as a tool to expand open areas, which were important for the implementation of their subsistence strategies. After 9.5 cal ka bp , human control over fires cannot be excluded as Mesolithic occupation phases chronologically coincide with frequent low‐intensity fires and vegetation disturbance.
A Study on Decisive Early Stages in White Etching Crack Formation Induced by Lubrication
2022-05-12

The reliability of rolling bearings is affected by white etching crack (WEC) or white structure flaking (WSF) failures, causing tremendous commercial burdens for bearing manufacturers and operators. The research for the underlying failure mechanism has attracted interest from a large scientific community over decades. Despite the significant amount of efforts, a root cause of white etching cracking is still missing. Amongst other factors, lubricant chemistry is considered to be essential in WEC formation. The authors aim to elucidate this key parameter by provoking white etching crack formation on a FE8 bearing test rig using a well-described set of chemicals in high- and low-reference lubricants. Scanning electron microscopy and energy dispersive X-ray analysis prove the presence of a patchy tribofilm on the surface of bearing washers, leading most likely to a higher frictional torque at the early stages of operation when the low reference oil is used. Secondary neutral mass spectrometry (SNMS) shows a hydrogen containing tribofilm in the shallow subsurface of about 30 nm depth, suggesting that hydrogen proliferating into bearing material may subsequently facilitate crack propagation via dislocation pileups, leading to premature bearing failure.
Genetic and Epigenetic Differentiation Across Intertidal Gradients in the Foundation Plant Spartina alterniflora
2022-05-12

Ecological genomics approaches have informed us about the structure of genetic diversity in natural populations that might underlie patterns in trait variation. However, we still know surprisingly little about the mechanisms that permit organisms to adapt to variable environmental conditions. The salt marsh foundation plant Spartina alterniflora exhibits a dramatic range in phenotype that is associated with a pronounced intertidal environmental gradient across a narrow spatial scale. Both genetic and non-genetic molecular mechanisms might underlie this phenotypic variation. To investigate both, we used epigenotyping-by-sequencing (epiGBS) to evaluate the make-up of natural populations across the intertidal environmental gradient. Based on recent findings, we expected that both DNA sequence and DNA methylation diversity would be explained by source population and habitat within populations. However, we predicted that epigenetic variation might be more strongly associated with habitat since similar epigenetic modifications could be rapidly elicited across different genetic backgrounds by similar environmental conditions. Overall, with PERMANOVA we found that population of origin explained a significant amount of the genetic (8.6%) and epigenetic (3.2%) variance. In addition, we found that a small but significant amount of genetic and epigenetic variance (&amp;lt;1%) was explained by habitat within populations. The interaction of population and habitat explained an additional 2.9% of the genetic variance and 1.4% of the epigenetic variance. By examining genetic and epigenetic variation within the same fragments (variation in close-cis), we found that population explained epigenetic variation in 9.2% of 8,960 tested loci, even after accounting for differences in the DNA sequence of the fragment. Habitat alone explained very little (&amp;lt;0.1%) of the variation in these close-cis comparisons, but the interaction of population and habitat explained 2.1% of the epigenetic variation in these loci. Using multiple matrix regression with randomization (MMRR) we found that phenotypic differences in natural populations were correlated with epigenetic and environmental differences even when accounting for genetic differences. Our results support the contention that sequence variation explains most of the variation in DNA methylation, but we have provided evidence that DNA methylation distinctly contributes to plant responses in natural populations.
Finger-Based Numerical Training Increases Sensorimotor Activation for Arithmetic in Children—An fNIRS Study
2022-05-12

Most children use their fingers when learning to count and calculate. These sensorimotor experiences were argued to underlie reported behavioral associations of finger gnosis and counting with mathematical skills. On the neural level, associations were assumed to originate from overlapping neural representations of fingers and numbers. This study explored whether finger-based training in children would lead to specific neural activation in the sensorimotor cortex, associated with finger movements, as well as the parietal cortex, associated with number processing, during mental arithmetic. Following finger-based training during the first year of school, trained children showed finger-related arithmetic effects accompanied by activation in the sensorimotor cortex potentially associated with implicit finger movements. This indicates embodied finger-based numerical representations after training. Results for differences in neural activation between trained children and a control group in the IPS were less conclusive. This study provides the first evidence for training-induced sensorimotor plasticity in brain development potentially driven by the explicit use of fingers for initial arithmetic, supporting an embodied perspective on the representation of numbers.
Near-Complete Remission of Glioblastoma in a Patient Treated with an Allogenic Dendritic Cell-Based Vaccine: The Role of Tumor-Specific CD4+T-Cell Cytokine Secretion Pattern in Predicting Response and Recurrence
2022-05-12

Immunotherapy has brought hope to the fight against glioblastoma, but its efficacy remains unclear. We present the case of CST, a 25-year-old female patient with a large right-hemisphere glioblastoma treated with a dendritic–tumor cell fusion vaccine. CST showed a near-complete tumor response, with a marked improvement in her functional status and simultaneous increases in tumor-specific CD8+ and CD4+ T cells. Two months before recurrence, the frequency of tumor-specific T cells decreased, while that of IL-17 and CD4+ T cells increased. CST passed away 15 months after enrollment. In this illustrative case, the tumor-specific CD4+ T-cell numbers and phenotype behaved as treatment efficacy biomarkers, highlighting the key role of the latter in glioblastoma immunotherapy.