julilili42/papers huggingface dataset:
Biallelic TANGO1 mutations cause a novel syndromal disease due to hampered cellular collagen secretion
2020-02-26

The transport and Golgi organization 1 (TANGO1) proteins play pivotal roles in the secretory pathway. Full length TANGO1 is a transmembrane protein localised at endoplasmic reticulum (ER) exit sites, where it binds bulky cargo within the ER lumen and recruits membranes from the ER Golgi intermediate compartment to create an exit route for their export. Here we report the first TANGO1-associated syndrome in humans. A synonymous substitution that results in exon eight skipping in most mRNA molecules, ultimately leading to a truncated TANGO1 protein was identified as disease-causing mutation. The four homozygously affected sons of a consanguineous family display severe dentinogenesis imperfecta, short stature, various skeletal abnormalities, insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. Functional studies in HeLa and U2OS cells revealed that the corresponding truncated TANGO1 protein is dispersed in the ER and its expression in cells with intact endogenous TANGO1 impairs cellular collagen I secretion.
How Does Our Voice Change as We Age? A Systematic Review and Meta-Analysis of Acoustic and Perceptual Voice Data From Healthy Adults Over 50 Years of Age
2020-02-26

Purpose Approximately 30% of adults over the age of 50 years present with altered vocal function. Our understanding of how these changes manifest acoustically and perceptually is derived from relatively modest-sized studies using a diversity of tools. Voice changes can arise from the onset of disease or disorder, but also age-related physiological changes, which may not reflect pathology as such. Here, we bring together data on acoustic, perceptual, and instrumental assessments (electroglottography), with the aim of gaining a better understanding of the changes occurring across these measurement domains. We consider these changes in the context of different acoustic features, software programs, and perceptual protocols. Method Studies of voice function in healthy older adults over the age of 50 years were sought. Literature was systematically searched with 746 abstracts reviewed. Forty-seven studies were included in the review. A meta-analysis of included studies compared voice acoustic parameters between sex and age. Sixteen acoustic parameters collected from 1,475 participants were analyzed in the meta-analysis. These included some previously unpublished analyses using data provided by authors of included studies. Results Data from the systematic review suggest that older individuals are perceived to present with higher overall scores of dysphonia and roughness, breathiness, strain, and instability. Acoustically, males have significantly higher scores on measures of perturbation, including noise-to-harmonic ratio and absolute jitter. The meta-analysis outcomes suggest that participants aged 80–89 years produce significantly higher fundamental frequency, jitter percent, shimmer percent, and shimmer in decibels compared to participants aged 60–69 years and a significant increase in relative average perturbation, jitter percent, and shimmer in decibels compared to participants aged 70–79 years. Limited data were available comparing acoustic measures using the same acoustic software. Conclusions Variations in fundamental frequency and frequency and amplitude perturbation increase as healthy adults age. It was difficult to draw definitive conclusions based on existing literature due to variability in hardware used, limited descriptions of study cohorts, or missing data from statistical analysis. Supplemental Material https://doi.org/10.23641/asha.11868663
The 2014 TeV γ-Ray Flare of Mrk 501 Seen with H.E.S.S.: Temporal and Spectral Constraints on Lorentz Invariance Violation
2020-02-26

The blazar Mrk 501 (z = 0.034) was observed at very-high-energy (VHE, E ≳ 100 GeV) gamma-ray wavelengths during a bright flare on the night of 2014 June 23-24 (MJD 56832) with the H.E.S.S. phase-II array of Cherenkov telescopes. Data taken that night by H.E.S.S. at large zenith angle reveal an exceptional number of gamma-ray photons at multi-TeV energies, with rapid flux variability and an energy coverage extending significantly up to 20 TeV. This data set is used to constrain Lorentz invariance violation (LIV) using two independent channels: a temporal approach considers the possibility of an energy dependence in the arrival time of gamma-rays, whereas a spectral approach considers the possibility of modifications to the interaction of VHE gamma-rays with extragalactic background light (EBL) photons. The non-detection of energy-dependent time delays and the non-observation of deviations between the measured spectrum and that of a supposed power-law intrinsic spectrum with standard EBL attenuation are used independently to derive strong constraints on the energy scale of LIV (E QG) in the subluminal scenario for linear and quadratic perturbations in the dispersion relation of photons. For the case of linear perturbations, the 95% confidence level limits obtained are E QG,1 &gt; 3.6 ×1017 GeV using the temporal approach and E QG,1 &gt; 2.6 ×1019 GeV using the spectral approach. For the case of quadratic perturbations, the limits obtained are E QG,2 &gt; 8.5 ×1010 GeV using the temporal approach and E QG,2 &gt; 7.8 ×1011 GeV using the spectral approach.
Majorana representation for mixed states
2020-02-26

We generalize the Majorana stellar representation of spin- pure states to\\nmixed states, and in general to any hermitian operator, defining a bijective\\ncorrespondence between three spaces: the spin density-matrices, a projective\\nspace of homogeneous polynomials of four variables, and a set of equivalence\\nclasses of points (constellations) on spheres of different radii. The\\nrepresentation behaves well under rotations by construction, and also under\\npartial traces where the reduced density matrices inherit their constellation\\nclasses from the original state . We express several concepts and\\noperations related to density matrices in terms of the corresponding\\npolynomials, such as the anticoherence criterion and the tensor representation\\nof spin- states described in [1].\\n
Upper limits on very-high-energy gamma-ray emission from core-collapse supernovae observed with H.E.S.S.
2020-02-26

Young core-collapse supernovae with dense-wind progenitors may be able to accelerate cosmic-ray hadrons beyond the knee of the cosmic-ray spectrum, and this may result in measurable gamma-ray emission. We searched for gamma-ray emission from ten supernovae observed with the High Energy Stereoscopic System (H.E.S.S.) within a year of the supernova event. Nine supernovae were observed serendipitously in the H.E.S.S. data collected between December 2003 and December 2014, with exposure times ranging from 1.4 to 53 h. In addition we observed SN 2016adj as a target of opportunity in February 2016 for 13 h. No significant gamma-ray emission has been detected for any of the objects, and upper limits on the >1 TeV gamma-ray flux of the order of ~10−13 cm−2s−1 are established, corresponding to upper limits on the luminosities in the range ~2 × 1039 to ~1 × 1042 erg s−1. These values are used to place model-dependent constraints on the mass-loss rates of the progenitor stars, implying upper limits between ~2 × 10−5 and ~2 × 10−3 M⊙ yr−1 under reasonable assumptions on the particle acceleration parameters.
Identification and regulation of the xenometabolite derivatives cis- and trans-3,4-methylene-heptanoylcarnitine in plasma and skeletal muscle of exercising humans
2020-02-26

Little is known about xenometabolites in human metabolism, particularly under exercising conditions. Previously, an exercise-modifiable, likely xenometabolite derivative, cis-3,4-methylene-heptanoylcarnitine, was reported in human plasma. Here, we identified trans-3,4-methylene-heptanoylcarnitine, and its cis-isomer, in plasma and skeletal muscle by liquid chromatography-mass spectrometry. We analyzed the regulation by exercise and the arterial-to-venous differences of these cyclopropane ring-containing carnitine esters over the hepatosplanchnic bed and the exercising leg in plasma samples obtained in three separate studies from young, lean and healthy males. Compared with other medium-chain acylcarnitines, the plasma concentrations of the 3,4-methylene-heptanoylcarnitine isomers only marginally increased with exercise. Both isomers showed a more than twofold increase in the skeletal muscle tissue of the exercising leg; this may have been due to the net effect of fatty acid oxidation in the exercising muscle and uptake from blood. The latter idea is supported by a more than twofold increased net uptake in the exercising leg only. Both isomers showed a constant release from the hepatosplanchnic bed, with an increased release of the trans-isomer after exercise. The isomers differ in their plasma concentration, with a four times higher concentration of the cis-isomer regardless of the exercise state. This is the first approach studying kinetics and fluxes of xenolipid isomers from tissues under exercise conditions, supporting the hypothesis that hepatic metabolism of cyclopropane ring-containing fatty acids is one source of these acylcarnitines in plasma. The data also provide clear evidence for an exercise-dependent regulation of xenometabolites, opening perspectives for future studies about the physiological role of this largely unknown class of metabolites.
Prophylactic Antiviral Activity of Sulfated Glycomimetic Oligomers and Polymers
2020-02-27

In this work, we investigate the potential of highly sulfated synthetic glycomimetics to act as inhibitors of viral binding/infection. Our results indicate that both long-chain glycopolymers and short-chain glycooligomers are capable of preventing viral infection. Notably, glycopolymers efficiently inhibit Human Papillomavirus (HPV16) infection in vitro and maintain their antiviral activity in vivo, while the glycooligomers exert their inhibitory function post attachment of viruses to cells. Moreover, when we tested the potential for broader activity against several other human pathogenic viruses, we observed broad-spectrum antiviral activity of these compounds beyond our initial assumptions. While the compounds tested displayed a range of antiviral efficacies, viruses with rather diverse glycan specificities such as Herpes Simplex Virus (HSV), Influenza A Virus (IAV), and Merkel Cell Polyomavirus (MCPyV) could be targeted. This opens new opportunities to develop broadly active glycomimetic inhibitors of viral entry and infection.
On the turbulence driving mode of expanding H ii regions
2020-02-27

Abstract We investigate the turbulence driving mode of ionizing radiation from massive stars on the surrounding interstellar medium. We run hydrodynamical simulations of a turbulent cloud impinged by a plane-parallel ionization front. We find that the ionizing radiation forms pillars of neutral gas reminiscent of those seen in observations. We quantify the driving mode of the turbulence in the neutral gas by calculating the driving parameter b, which is characterized by the relation between the variance of the logarithmic density contrast [where s = ln (ρ/ρ0) with the gas density ρ and its average ρ0], and the turbulent Mach number . Previous works have shown that b ∼ 1/3 indicates solenoidal (divergence-free) driving and b ∼ 1 indicates compressive (curl-free) driving, with b ∼ 1 producing up to ten times higher star formation rates than b ∼ 1/3. The time variation of b in our study allows us to infer that ionizing radiation is inherently a compressive turbulence driving source, with a time-averaged b ∼ 0.76 ± 0.08. We also investigate the value of b of the pillars, where star formation is expected to occur, and find that the pillars are characterized by a natural mixture of both solenoidal and compressive turbulent modes (b ∼ 0.4) when they form, and later evolve into a more compressive turbulent state with b ∼ 0.5–0.6. A virial parameter analysis of the pillar regions supports this conclusion. This indicates that ionizing radiation from massive stars may be able to trigger star formation by producing predominately compressive turbulent gas in the pillars.
Avulsion Injuries of the Pelvis and Hip
2020-02-27

Background Avulsion injuries of the pelvis and hip region are typical injuries in adolescent athletes but can be found in adults as well. Typical sites for avulsion injuries include the origin/insertion of tendons and ligaments. Among adolescents, the not yet ossified apophysis is also frequently involved. The pelvis and hip are especially prone to such injuries due to their complex musculotendinous anatomy. Clinical history and physical examination in combination with the recognition of typical imaging findings are essential for correct diagnosis of these mostly acute, but sometimes also chronic injuries. Methods This review article describes typical avulsion injuries of the pelvis and hip and illustrates common radiological findings. Taking current literature into account, there is a special focus on the trauma mechanism, clinical examination, typical imaging findings and clinical management. Results and Conclusion Detailed knowledge of musculotendinous anatomy and typical injury mechanisms allows a correct diagnosis of avulsion injuries often only based on clinical examination and radiographic findings. Further imaging with ultrasound and MRI may be necessary to evaluate tendon retraction in non-osseous avulsion injuries and extent of soft-tissue damage. Knowledge of potential complications of acute/chronic injuries can help to avoid unnecessary examinations or invasive interventions. Conservative management of avulsion injuries usually leads to functionally good results. However, in the case of competitive athletes, relatively wide bone fragment dislocation or marked tendon retraction, operative re-fixation may be considered in order to expedite the rehabilitation process. Key Points: Citation Format
Prevalence of Psychotropic Drugs in Cases of Severe Adverse Drug Reactions Leading to Unplanned Emergency Visits in General Hospitals
2020-02-27

Abstract Introduction The prevalence of psychotropic drug use in our society is increasing especially in older adults, thereby provoking severe adverse drug reactions (ADR). To identify specific patient risk profiles associated with psychotropic drug use in the situation of polymedication. Methods Cases of ADRs in general emergency departments (ED) collected within the multi-center prospective observational study (ADRED) were analyzed (n=2215). We compared cases with use of psychotropic drugs and without concerning their clinical presentation at the ED. Results A third of patients (n=731, 33%) presenting to the ED with an ADR took at least 1 psychotropic drug. Patients with psychotropic drug use tended to be older, more often female, and took a higher number of drugs (all p&lt;0.001). The frequency of falls was almost 3 times higher than compared to the non-psychotropic drug group (10.5 vs. 3.9%, p&lt;0.001), and similar syncope was also more often seen in the psychotropic drug users (8.8 vs. 5.5%, p=0.004). The use of psychotropic drugs increased the risk for falls by a factor of 2.82 (OR, 95% CI (1.90–4.18)), when adjusting for gender, age, numbers of pre-existing diseases, and drugs, respectively. Discussion The association of psychotropic drug use with fall and syncope in combination with polymedication and older age leads to the suspicion that psychotropic drugs might be potentially harmful in specific risk populations such as older adults. It may lead us to thoroughly weigh the benefit against risk in a patient-oriented way, leading to an integrative personalized therapy approach.
Evidence for modulation of EEG microstate sequence by vigilance level
2020-02-27

Abstract The momentary global functional state of the brain is reflected in its electric field configuration and cluster analytical approaches have consistently shown four configurations, referred to as EEG microstate classes A to D. Changes in microstate parameters are associated with a number of neuropsychiatric disorders, task performance, and mental state establishing their relevance for cognition. However, the common practice to use eye-closed resting state data to assess the temporal dynamics of microstate parameters might induce systematic confounds related to vigilance levels. Here, we studied the dynamics of microstate parameters in two independent data sets and showed that the parameters of microstates are strongly associated with vigilance level assessed both by EEG power analysis and fMRI global signal. We found that the duration and contribution of microstate class C, as well as transition probabilities towards microstate class C were positively associated with vigilance, whereas the sign was reversed for microstate classes A and B. Furthermore, in looking for the origins of the correspondence between microstates and vigilance level, we found Granger-causal effects of vigilance levels on microstate sequence parameters. Collectively, our findings suggest that duration and occurrence of microstates have a different origin and possibly reflect different physiological processes. Finally, our findings indicate the need for taking vigilance levels into consideration in resting-sate EEG investigations.
PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth
2020-02-27

Abstract Background: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Results: We demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/Akt activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/Akt activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells. Conclusions: Altogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology.
Interior-boundary conditions for Schrödinger operators on codimension-1 boundaries
2020-02-27

Interior-boundary conditions (IBCs) are boundary conditions on wave functions\\nfor Schr\\\\"odinger equations that allow that probability can flow into (and thus\\nbe lost at) a boundary of configuration space while getting added in another\\npart of configuration space. IBCs are of particular interest because they allow\\ndefining Hamiltonians involving particle creation and annihilation (as used in\\nquantum field theories) without the need for renormalization or ultraviolet\\ncut-off. For those Hamiltonians, the relevant boundary has codimension 3. In\\nthis paper, we develop (what we conjecture is) the general form of IBCs for the\\nLaplacian operator (or Schr\\\\"odinger operators), but we focus on the simpler\\ncase of boundaries with codimension 1.\\n
Identity-Based Crossmodal Negative Priming: Aftereffects of Ignoring in One Sensory Modality on Responding to Another Sensory Modality
2020-02-27

Abstract Negative Priming (NP) refers to the phenomenon that responses towards previously ignored stimuli, as compared to new stimuli, are impaired. That is, NP is reflected in the performance on the probe display of a prime–probe sequence. NP is established in vision, audition and touch. In the current study, we presented participants with auditory, visual, and tactile manifestations of the same temporal patterns in order to measure NP across the senses. On each trial, the sensory modality shifted from the prime to the probe. Each prime and probe display consisted of a target and a distractor stimulus, presented to the same sensory modality. On some trials, the prime distractor repeated as probe target (ignored-repetition trials), on other trials the probe stimuli had not been involved in the prime display (control trials). We observed NP between audition and touch (Experiment 1) and between vision and audition (Experiment 2). These findings indicate that the processes underpinning NP can operate at an amodal, postperceptual level.
Localized prediction of glutamate from whole-brain functional connectivity of the pregenual anterior cingulate cortex
2020-02-27

Abstract Local measures of neurotransmitters provide crucial insights into neurobiological changes underlying altered functional connectivity in psychiatric disorders. However, non-invasive neuroimaging techniques such as magnetic resonance spectroscopy (MRS) may cover anatomically and functionally distinct areas, such as p32 and p24 of the pregenual anterior cingulate cortex (pgACC). Here, we aimed to overcome this low spatial specificity of MRS by predicting local glutamate and GABA based on functional characteristics and neuroanatomy, using complementary machine learning approaches. Functional connectivity profiles of pgACC area p32 predicted pgACC glutamate better than chance (R 2 = .324) and explained more variance compared to area p24 using both elastic net and partial least squares regression. In contrast, GABA could not be robustly predicted. To summarize, machine learning helps exploit the high resolution of fMRI to improve the interpretation of local neurometabolism. Our augmented multimodal imaging analysis can deliver novel insights into neurobiology by using complementary information.
Rapid evolution in managed grasslands: different land-use regimes are associated with contrasting phenotypes inPlantago lanceolata
2020-02-27

Abstract Land-use intensification is a major driver of biodiversity declines, and it is known to decrease species numbers and alter community composition of managed grasslands. An open question is whether similar impacts occur within species, i.e. whether grassland management affects also the genetic diversity of plant populations and alters their genetic composition, possibly reflecting adaptation to land use. To address these questions, we sampled 61 populations of the common grassland herb Plantago lanceolata that covered a broad range of land use intensities in the German Biodiversity Exploratories, and we grew their offspring in a common environment to quantify variation in plant size, architecture, reproduction, and leaf economy. All measured traits harboured substantial heritable variation, and six out of nine traits showed population differentiation. Interestingly, several traits were significantly correlated with land use intensity, but with opposing trends for mowing versus grazing: Increased mowing intensity was associated with larger plant size and lower specific leaf area (SLA), which may reflect evolutionary responses to increased light competition and a lesser need for resource conservation in highly productive meadows. In contrast, increased grazing intensity tended to be associated with smaller plant size and higher SLA, a phenotype syndrome known from grazing lawns. Moreover, we found that land-use intensification also affected genetic diversity, again with opposing effects for mowing versus grazing: while increased mowing was associated with decreased levels of intrapopulation phenotypic variation, the opposite was true for increased grazing intensity. In summary, land use intensification has not only already caused rapid evolutionary changes in these grassland populations, it also affects their future evolutionary potential.