julilili42/papers huggingface dataset:
NLRP3/IL1β inflammasome associated with the aging bladder triggers bladder dysfunction in female rats
2019-01-31

Bladder dysfunction is associated with fibrosis‐-mediated aging, but the corresponding mechanism remains to be elucidated. Activation of the NACHT, LRR and PYD domains‐containing protein 3 (NLRP3) inflammasome is related to chronic diseases associated with aging, including organ fibrosis. The present study aimed to explore the role of NLRP3/interleukin 1β in aging‐associated bladder dysfunction. Female Sprague‐Dawley rats were divided into the following two groups (n=10 rats/group): 2‐month‐old group (young group) and 24‐month‐old group (old group). Urodynamics were performed to assess the bladder function of the rats. The histological alterations were identified using Masson's trichrome staining. The protein expression of the NLRP3 inflammasome and NAD‐dependent protein deacetylase sirtuin‐3, mitochondrial (SIRT3) were detected by western blot analysis, and immunohistochemistry was used to examine a senescence marker (p21) and the NLRP3 inflammasome in the bladder. The localization of the key molecule Caspase1 was determined using immunofluorescence. The voiding time was longer in the old group compared with the young group. The expression levels of SIRT3 were reduced in the bladders of the old group, while those of the NLRP3 inflammasome and the senescence marker were significantly higher in the bladders of the old group compared with the young group. Increased collagen deposition leads to chronic bladder fibrosis with increased NLRP3. In the histological examination, the bladders of the old group displayed increased collagen deposition, urothelial thinning and detrusor shrinkage compared with the young group. Tissue fibrosis and urothelial alterations are the principal causes of bladder dysfunction during aging. Downregulated SIRT3 and upregulated expression of the NLRP3 inflammasome are involved in the degradation of aging bladders. Inflamm‐aging is a novel mechanism underlying bladder dysfunction.
The network underlying human higher-order motor control: Insights from machine learning-based lesion-behaviour mapping in apraxia
2019-01-31

Abstract Neurological patients with apraxia of pantomime provide us with a unique opportunity to study the neural correlates of higher-order motor function. Previous studies using lesion-behaviour mapping methods led to inconsistent anatomical results, reporting various lesion locations to induce this symptom. We hypothesised that the inconsistencies might arise from limitations of mass-univariate lesion-behaviour mapping approaches if our ability to pantomime the use of objects is organised in a brain network. Thus, we investigated apraxia of pantomime by using multivariate lesion behaviour mapping based both on support vector regression and sparse canonical correlations in a sample of 130 left-hemisphere stroke patients. Both multivariate methods identified multiple areas to underlie high-order motor control, including inferior parietal lobule, precentral gyrus, posterior parts of middle temporal cortex, and insula. Further, long association fibres were affected, such as the superior longitudinal fascicle, inferior occipito-frontal fascicle, uncinated fascicle, and superior occipito-frontal fascicle. The findings thus not only underline the benefits of multivariate lesion-behaviour mapping in brain networks, but they also uncovered that higher-order motor control indeed is based on a common anatomical network.
Self-Sensing Enzyme-Powered Micromotors Equipped with pH-Responsive DNA Nanoswitches
2019-02-01

Biocatalytic micro- and nanomotors have emerged as a new class of active matter self-propelled through enzymatic reactions. The incorporation of functional nanotools could enable the rational design of multifunctional micromotors for simultaneous real-time monitoring of their environment and activity. Herein, we report the combination of DNA nanotechnology and urease-powered micromotors as multifunctional tools able to swim, simultaneously sense the pH of their surrounding environment, and monitor their intrinsic activity. With this purpose, a FRET-labeled triplex DNA nanoswitch for pH sensing was immobilized onto the surface of mesoporous silica-based micromotors. During self-propulsion, urea decomposition and the subsequent release of ammonia led to a fast pH increase, which was detected by real-time monitoring of the FRET efficiency through confocal laser scanning microscopy at different time points (i.e., 30 s, 2 and 10 min). Furthermore, the analysis of speed, enzymatic activity, and propulsive force displayed a similar exponential decay, matching the trend observed for the FRET efficiency. These results illustrate the potential of using specific DNA nanoswitches not only for sensing the micromotors' surrounding microenvironment but also as an indicator of the micromotor activity status, which may aid to the understanding of their performance in different media and in different applications.
Cyanobacterial antimetabolite 7-deoxy-sedoheptulose blocks the shikimate pathway to inhibit the growth of prototrophic organisms
2019-02-01

Abstract Antimetabolites are small molecules that inhibit enzymes by mimicking physiological substrates. We report the discovery and structural elucidation of the antimetabolite 7-deoxy-sedoheptulose (7dSh). This unusual sugar inhibits the growth of various prototrophic organisms, including species of cyanobacteria, Saccharomyces , and Arabidopsis . We isolate bioactive 7dSh from culture supernatants of the cyanobacterium Synechococcus elongatus . A chemoenzymatic synthesis of 7dSh using S. elongatus transketolase as catalyst and 5-deoxy- d -ribose as substrate allows antimicrobial and herbicidal bioprofiling. Organisms treated with 7dSh accumulate 3-deoxy- d - arabino -heptulosonate 7-phosphate, which indicates that the molecular target is 3-dehydroquinate synthase, a key enzyme of the shikimate pathway, which is absent in humans and animals. The herbicidal activity of 7dSh is in the low micromolar range. No cytotoxic effects on mammalian cells have been observed. We propose that the in vivo inhibition of the shikimate pathway makes 7dSh a natural antimicrobial and herbicidal agent.
S2k Guidelines for Cutaneous Basal Cell Carcinoma – Part 2: Treatment, Prevention and Follow‐up
2019-02-01

Summary Basal cell carcinoma (BCC) is the most common malignant tumor among fair‐skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow‐up of patients with basal cell carcinoma.
Crystallographic preferred orientations of ice deformed in direct-shear experiments at low temperatures
2019-02-01

Abstract. Synthetic polycrystalline ice was sheared at temperatures of −5, −20 and −30 ∘C, to different shear strains, up to γ=2.6, equivalent to a maximum stretch of 2.94 (final line length is 2.94 times the original length). Cryo-electron backscatter diffraction (EBSD) analysis shows that basal intracrystalline slip planes become preferentially oriented parallel to the shear plane in all experiments, with a primary cluster of crystal c axes (the c axis is perpendicular to the basal plane) perpendicular to the shear plane. In all except the two highest-strain experiments at −30 ∘C, a secondary cluster of c axes is observed, at an angle to the primary cluster. With increasing strain, the primary c-axis cluster strengthens. With increasing temperature, both clusters strengthen. In the −5 ∘C experiments, the angle between the two clusters reduces with strain. The c-axis clusters are elongated perpendicular to the shear direction. This elongation increases with increasing shear strain and with decreasing temperature. Highly curved grain boundaries are more prevalent in samples sheared at higher temperatures. At each temperature, the proportion of curved boundaries decreases with increasing shear strain. Subgrains are observed in all samples. Microstructural interpretations and comparisons of the data from experimentally sheared samples with numerical models suggest that the observed crystallographic orientation patterns result from a balance of the rates of lattice rotation (during dislocation creep) and growth of grains by strain-induced grain boundary migration (GBM). GBM is faster at higher temperatures and becomes less important as shear strain increases. These observations and interpretations provide a hypothesis to be tested in further experiments and using numerical models, with the ultimate goal of aiding the interpretation of crystallographic preferred orientations in naturally deformed ice.
Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria
2019-02-01

Abstract Biogenic amines synthesis in phenylketonuria (PKU) patients with high phenylalanine (Phe) concentration is thought to be impaired due to inhibition of tyrosine and tryptophan hydroxylases and competition with amino acids at the blood‐brain barrier. Dopamine and serotonin deficits might explain brain damage and progressive neuropsychiatric impairment in adult PKU patients. Ten early treated adult PKU patients (mean age 38.2 years) and 15 age‐matched controls entered the study. Plasma and cerebrospinal fluid (CSF) Phe, 5‐hydroxyindoleacetic acid (5‐HIAA), 5‐hydroxytryptophan (5‐HTP), 3,4‐dihydroxy‐ l ‐phenylalanine ( l ‐DOPA) and homovanillic acid (HVA) were analyzed. Voxel‐based morphometry statistical nonparametric mapping was used to test the age‐corrected correlation between gray matter atrophy and CSF biogenic amines levels. 5‐HIAA and 5‐HTP were significantly reduced in PKU patients compared to controls. Significant negative correlations were found between CSF 5‐HIAA, HVA, and 5‐HTP and Phe levels. A decrease in 5‐HIAA and 5‐HTP concentrations correlated with precuneus and frontal atrophy, respectively. Lower HVA levels correlated with occipital atrophy. Biogenic amines deficits correlate with specific brain atrophy patterns in adult PKU patients, in line with serotonin and dopamine projections. These findings may support a more rigorous Phe control in adult PKU to prevent neurotransmitter depletion and accelerated brain damage due to aging.
Phenolic Bis-styrylbenzo[c]-1,2,5-thiadiazoles as Probes for Fluorescence Microscopy Mapping of Aβ Plaque Heterogeneity
2019-02-01

A fluorescent bis-styryl-benzothiadiazole (BTD) with carboxylic acid functional groups (X-34/Congo red analogue) showed lower binding affinity toward Aβ1-42 and Aβ1-40 fibrils than its neutral analogue. Hence, variable patterns of neutral OH-substituted bis-styryl-BTDs were generated. All bis-styryl-BTDs showed higher binding affinity to Aβ1-42 fibrils than to Aβ1-40 fibrils. The para-OH on the phenyl rings was beneficial for binding affinity while a meta-OH decreased the affinity. Differential staining of transgenic mouse Aβ amyloid plaque cores compared to peripheral coronas using neutral compared to anionic bis-styryl ligands indicate differential recognition of amyloid polymorphs. Hyperspectral imaging of transgenic mouse Aβ plaque stained with uncharged para-hydroxyl substituted bis-styryl-BTD implicated differences in binding site polarity of polymorphic amyloid plaque. Most properties of the corresponding bis-styryl-BTD were retained with a rigid alkyne linker rendering a probe insensitive to cis-trans isomerization. These new BTD-based ligands are promising probes for spectral imaging of different Aβ fibril polymorphs.
Subcortical Shape Alterations in Major Depressive Disorder: Findings from the ENIGMA Major Depressive Disorder Working Group
2019-02-01

Abstract Alterations in regional subcortical brain volumes have been widely investigated as part of the efforts of an international consortium, ENIGMA, to determine reliable structural brain signatures for Major Depressive Disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work to precisely map localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with MDD had lower surface area in the subiculum of the hippocampus, the basolateral amygdala, and the nucleus accumbens shell. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum of the hippocampus and the basolateral amygdala. Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala. Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.
Moment of inertia–mass universal relations for neutron stars in scalar-tensor theory with self-interacting massive scalar field
2019-02-01

\\n We are investigating universal relations between different normalisations of the moment of inertia and the compactness of neutron stars in slow rotation approximation. We study the relations in particular class of massive scalar-sensor theories with self-interaction, for which significant deviations from General Relativity are allowed for values of the parameters that are in agreement with the observations. Moment of inertia-compactness relations are examined for different normalisation of the moment of inertia. It is shown that for all studied cases the deviations from EOS universality are small for the examined equations of state. On the other hand the scalarization can lead to large deviations from the general relativistic universal relations for values of the parameters that are in agreement with the current observations that can be potentially used to set further test the scalar-tensor theories.\\n
Reductive Elimination and Oxidative Addition of Hydrogen at Organostannylium and Organogermylium Cations
2019-02-01

Abstract Bulkily substituted organodihydrogermylium and ‐stannylium cations [Ar*EH 2 ] + (E=Ge, Sn; Ar*=2,6‐Trip 2 C 6 H 3 , Trip=2,4,6‐triisopropylphenyl) were characterized as salts of the weakly coordinating perfluorinated alkoxyaluminate anion [Al{OC(CF 3 ) 3 } 4 ] − . At room temperature, the stannylium cation liberates hydrogen to generate the low valent organotin cation [Ar*Sn] + . In contrast, the dihydrogermylium cation transfers the hydrogen atoms to an aryl moiety of the terphenyl ligand and oxidatively adds either hydrogen under an atmosphere of hydrogen or a sp 2 CH unit of the 1,2‐difluorobenzene solvent.
Harnessing anaerobic digestion for combined cooling, heat, and power on dairy farms: An environmental life cycle and techno-economic assessment of added cooling pathways
2019-02-01

Anaerobic digestion coupled with combined heat and power production on dairy farms is environmentally advantageous; however, high capital and operating costs have limited its adoption, especially in the United States, where renewable electricity and heat production are under-incentivized. Biogas is also at a disadvantage because it has to compete with very low natural gas prices. The objective of this study was to evaluate the feasibility of integrating absorption refrigeration technology for combined cooling, heat, and power (CCHP) on the farm to help bridge this economic hurdle. A combined environmental life cycle and techno-economic assessment was used to compare 2 cooling pathways with and without co-digestion. We considered using CCHP to (1) displace electricity-driven refrigeration processes (e.g., milk chilling/refrigeration, biogas inlet cooling) or (2) mitigate heat stress in dairy cattle via conductive cow cooling. All cooling scenarios reduced environmental emissions compared with combined heat and power only, with an appreciable reduction in land use impacts when employing conductive cow cooling. However, none of the cooling scenarios achieved economically viability. When using cooling power to displace electricity-driven refrigeration processes, economic viability was constrained by low electricity prices and a lack of incentives in the United States. When used for conductive cow cooling, economic viability was constrained by (1) low waste heat-to-cooling conversion efficiency; (2) limited conductive cow cooling effectiveness (i.e., heat-stress mitigation); and (3) low heat stress frequency and limited severity. However, we predict that with minor improvements in conductive cow cooling effectiveness and in hotter climates, CCHP for conductive cow cooling would be economically viable even in current US energy markets.
The contrast sensitivity function of a small cryptobenthic marine fish
2019-02-01

Spatial resolution is a key property of eyes when it comes to understanding how animals' visual signals are perceived. This property can be robustly estimated by measuring the contrast sensitivity as a function of different spatial frequencies, defined as the number of achromatic vertical bright and dark stripe pairs within one degree of visual angle. This contrast sensitivity function (CSF) has been estimated for different animal groups, but data on fish are limited to two free-swimming, freshwater species (i.e., goldfish and bluegill sunfish). In this study, we describe the CSF of a small marine cryptobenthic fish (Tripterygion delaisi) using an optokinetic reflex approach. Tripterygion delaisi features a contrast sensitivity that is as excellent as other fish species, up to 125 (reciprocal of Michelson contrast) at the optimal spatial frequency of 0.375 c/°. The maximum spatial resolution is instead relatively coarse, around 2.125 c/°. By comparing our results with acuity values derived from anatomical estimates of ganglion cells' density, we conclude that the optokinetic reflex seems to be adapted to process low spatial frequency information from stimuli in the peripheral visual field and show that small marine fish can feature excellent contrast sensitivity at optimal spatial frequency.
Markerless Racket Pose Detection and Stroke Classification Based on Stereo Vision for Table Tennis Robots
2019-02-01

For table tennis robots, it is a significant challenge to understand the opponent's movements and return the ball accordingly with high performance. One has to cope with various ball speeds and spins resulting from different stroke types. In this paper, we propose a real-time 3D racket pose detection method and classify racket movements into five stroke categories with a neural network. By using two monocular cameras, we can extract the racket's contours and choose some special points as feature points in image coordinates. With the 3D geometrical information of a racket, a wide baseline stereo matching method is proposed to find the corresponding feature points and compute the 3D position and orientation of the racket by triangulation and plane fitting. Then, a Kalman filter is adopted to track the racket pose, and a neural network with two hidden layers is used to classify the pose movements. We conduct two experiments to evaluate the accuracy of racket pose detection and classification, in which the average error in position and orientation is around 7.8 mm and 7.2° by comparing with the ground truth from a KUKA robot. The classification accuracy is 98%, the same as the human pose estimation method with Convolutional Pose Machines (CPMs).
Release of Immunomodulatory Ebola Virus Glycoprotein-Containing Microvesicles Is Suppressed by Tetherin in a Species-Specific Manner
2019-02-01

The Ebola virus glycoprotein (EBOV-GP) forms GP-containing microvesicles, so-called virosomes, which are secreted from GP-expressing cells. However, determinants of GP-virosome release and their functionality are poorly understood. We characterized GP-mediated virosome formation and delineated the role of the antiviral factor tetherin (BST2, CD317) in this process. Residues in the EBOV-GP receptor-binding domain (RBD) promote GP-virosome secretion, while tetherin suppresses GP-virosomes by interactions involving the GP-transmembrane domain. Tetherin from multiple species interfered with GP-virosome release, and tetherin from the natural fruit bat reservoir showed the highest inhibitory activity. Moreover, analyses of GP from various ebolavirus strains, including the EBOV responsible for the West African epidemic, revealed the most efficient GP-virosome formation by highly pathogenic ebolaviruses. Finally, EBOV-GP-virosomes were immunomodulatory and acted as decoys for EBOV-neutralizing antibodies. Our results indicate that GP-virosome formation might be a determinant of EBOV immune evasion and pathogenicity, which is suppressed by tetherin.
Augmented contractility of murine femoral arteries in a streptozotocin diabetes model is related to increased phosphorylation of MYPT1
2019-02-01

Diabetes mellitus (DM) is a metabolic disorder with high prevalence, and a major risk factor for macro- and microvascular abnormalities. This study was undertaken to explore the mechanisms of hypercontractility of murine femoral arteries (FA) obtained from mice with streptozotocin (STZ)-induced diabetes and its relation to the phosphorylation profile of the myosin phosphatase target subunit 1, MYPT1. The immunoreactivity of MYPT1 toward phospho-MYPT1-T696, MYPT1-T853, or MYPT1-S695, used as a read out for MYPT1 phosphorylation, has been studied by Western Blotting. Contractile activity of FA from control and STZ mice has been studied by wire myography. At basal conditions (no treatment), the immunoreactivity of MYPT1-T696/T853 was ~2-fold higher in the STZ arteries compared with controls. No changes in MYPT1-T696/853 phosphorylation were observed after stimulation with the Thromboxan-A<sub>2</sub> analog, U46619. Neither basal nor U46619-stimulated phosphorylation of MYPT1 at S695 was affected by STZ treatment. Mechanical distensibility and basal tone of FA obtained from STZ animals were similar to controls. Maximal force after treatment of FA with the contractile agonists phenylephrine (10 μmol/L) or U46619 (1 μmol/L) was augmented in the arteries of STZ mice by ~2- and ~1.5-fold, respectively. In summary, our study suggests that development of a hypercontractile phenotype in murine FA in STZ diabetes is at least partially related to an increase in phosphorylation of MLCP at MYPT1-T696/853. Interestingly, the phosphorylation at S695 site was not altered in STZ-induced diabetes, supporting the view that S695 may serve as a sensor for mechanical activity which is not directly involved in tone regulation.