julilili42/papers huggingface dataset:
Staphylococcus aureus PSM Peptides Modulate Human Monocyte-Derived Dendritic Cells to Prime Regulatory T Cells
2018-11-13

<i>Staphylococcus aureus</i> (Sa), as one of the major human pathogens, has very effective strategies to subvert the human immune system. Virulence of the emerging community-associated methicillin-resistant Sa (CA-MRSA) depends on the secretion of phenol-soluble modulin (PSM) peptide toxins e.g., by binding to and modulation of innate immune cells. Previously, by using mouse bone marrow-derived dendritic cells we demonstrated that PSMs in combination with various Toll-like receptor (TLR) ligands induce a tolerogenic DC phenotype (tDC) characterized by the production of IL-10 and impaired secretion of pro-inflammatory cytokines. Consequently, PSM-induced tDCs favored priming of CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> T<sub>regs</sub> with suppressor function while impairing the Th1 response. However, the relevance of these findings for the human system remained elusive. Here, we analyzed the impact of PSMα3 on the maturation, cytokine production, antigen uptake, and T cell stimulatory capacity of human monocyte-derived DCs (moDCs) treated simultaneously with either LPS (TLR4 ligand) or Sa cell lysate (TLR2 ligand). Herein, we demonstrate that PSMs indeed modulate human moDCs upon treatment with TLR2/4 ligands via multiple mechanisms, such as transient pore formation, impaired DC maturation, inhibited pro- and anti-inflammatory cytokine secretion, as well as reduced antigen uptake. As a result, the adaptive immune response was altered shown by an increased differentiation of naïve and even CD4<sup>+</sup> T cells from patients with Th1/Th17-induced diseases (spondyloarthritis and rheumatoid arthritis) into CD4<sup>+</sup>CD127<sup>-</sup>CD25<sup>hi</sup>CD45RA<sup>-</sup>FoxP3<sup>hi</sup> regulatory T cells (T<sub>regs</sub>) with suppressor function. This T<sub>reg</sub> induction was mediated most predominantly by direct DC-T-cell interaction. Thus, PSMs from highly virulent Sa strains affect DC functions not only in the mouse, but also in the human system, thereby modulating the adaptive immune response and probably increasing the tolerance toward the bacteria. Moreover, PSMα3 might be a novel peptide for tolerogenic DC induction that may be used for DC vaccination strategies.
Justinian’s Men: Careers and Relationships of Byzantine Army Officers, 518–610, by David Alan Parnell
2018-11-13

David Alan Parnell describes the eastern Roman army of the sixth century, especially in the Age of Justinian, as ‘a complex web of social relationships’ (p. 1) and ‘a collection of identities’ (p. 3). Following an introduction, seven chapters elucidate the key structural features of the army. The author’s reflections on the ‘Byzantine Army Structure’ (pp. 13–31) are introductory in nature, serving to inform the reader about the structure and operation of the military forces in the sixth century. Among other subjects, Parnell discusses the role of foederati, who, under Justinian, had largely lost their character as ethnically non-Roman and now appeared ‘somewhat like special forces’ (p. 16). With respect to recruitment, the author favours a rather optimistic view: ‘In summary, it seems plausible to conclude that there are no truly sufficient grounds for claiming that the imperial government faced a significant manpower shortage in its efforts to recruit men into the army’ (pp. 27ff.). This attitude is somewhat surprising in the light of recent intense discussions of the considerable demographic effects of the ‘Justinianic Plague’ and its consequences for the capacity of the Eastern Roman Empire to defend itself. The author does not discuss the related question of financial difficulties (illustrated by repeated complaints about outstanding unpaid wages in the sixth century) until much later (cf. pp. 169ff.). Against this background, Parnell’s conjecture that recruitment was normally voluntary under Justinian by reason of an adequate demographic basis (p. 28) is unconvincing.
A Sampling Approach to Evaluative Conditioning
2018-11-13

&lt;p&gt;In an evaluative conditioning procedure (EC), a conditioned stimulus (CS) is paired with positive or negative unconditioned stimuli (US) and consequently acquires US valence. We introduce a sampling perspective into the EC paradigm by repeatedly giving participants agency over which CSs they want to sample (i.e., for what CSs they want to see conditioning trials). Half of the CSs was paired positively, while the other half was paired negatively. We also introduced a yoked condition, in which participants saw the same information produced by the sampling condition, but did not get to make any decisions. In three experiments, we found that over time a preference for sampling positively paired CSs over negatively paired CSs develops. We replicated standard EC effects and found that a higher number of pairings leads to more positive evaluative shifts, but more so in the sampling than in the yoked condition. This finding shows that evaluative conditioning depends on the learner’s willingness to attend to certain CSs. The results of this set of studies also suggest that agency increases the readiness to process the presented CS-US pairs. This reasoning is supported by memory data that indicate better memory for the number of pairings and paired valence in the sampling condition compared to the yoked condition. Implications for the external validity of the EC paradigm are also discussed.&lt;/p&gt;
A Sampling Approach to Evaluative Conditioning
2018-11-13

&lt;p&gt;In an evaluative conditioning procedure (EC), a conditioned stimulus (CS) is paired with positive or negative unconditioned stimuli (US) and consequently acquires US valence. We introduce a sampling perspective into the EC paradigm by repeatedly giving participants agency over which CSs they want to sample (i.e., for what CSs they want to see conditioning trials). Half of the CSs was paired positively, while the other half was paired negatively. We also introduced a yoked condition, in which participants saw the same information produced by the sampling condition, but did not get to make any decisions. In three experiments, we found that over time a preference for sampling positively paired CSs over negatively paired CSs develops. We replicated standard EC effects and found that a higher number of pairings leads to more positive evaluative shifts, but more so in the sampling than in the yoked condition. This finding shows that evaluative conditioning depends on the learner&rsquo;s willingness to attend to certain CSs. The results of this set of studies also suggest that agency increases the readiness to process the presented CS-US pairs. This reasoning is supported by memory data that indicate better memory for the number of pairings and paired valence in the sampling condition compared to the yoked condition. Implications for the external validity of the EC paradigm are also discussed.&lt;/p&gt;
A Sampling Approach to Evaluative Conditioning
2018-11-13

In an evaluative conditioning procedure (EC), a conditioned stimulus (CS) is paired with positive or negative unconditioned stimuli (US) and consequently acquires US valence. We introduce a sampling perspective into the EC paradigm by repeatedly giving participants agency over which CSs they want to sample (i.e., for what CSs they want to see conditioning trials). Half of the CSs was paired positively, while the other half was paired negatively. We also introduced a yoked condition, in which participants saw the same information produced by the sampling condition, but did not get to make any decisions. In three experiments, we found that over time a preference for sampling positively paired CSs over negatively paired CSs develops. We replicated standard EC effects and found that a higher number of pairings leads to more positive evaluative shifts, but more so in the sampling than in the yoked condition. This finding shows that evaluative conditioning depends on the learner’s willingness to attend to certain CSs. The results of this set of studies also suggest that agency increases the readiness to process the presented CS-US pairs. This reasoning is supported by memory data that indicate better memory for the number of pairings and paired valence in the sampling condition compared to the yoked condition. Implications for the external validity of the EC paradigm are also discussed.
Particle transport within the pulsar wind nebula HESS J1825–137
2018-11-14

Context. We present a detailed view of the pulsar wind nebula (PWN) HESS J1825–137. We aim to constrain the mechanisms dominating the particle transport within the nebula, accounting for its anomalously large size and spectral characteristics. Aims. The nebula was studied using a deep exposure from over 12 years of H.E.S.S. I operation, together with data from H.E.S.S. II that improve the low-energy sensitivity. Enhanced energy-dependent morphological and spatially resolved spectral analyses probe the very high energy (VHE, E &gt; 0.1 TeV) γ -ray properties of the nebula. Methods. The nebula emission is revealed to extend out to 1.5° from the pulsar, ~1.5 times farther than previously seen, making HESS J1825–137, with an intrinsic diameter of ~100 pc, potentially the largest γ -ray PWN currently known. Characterising the strongly energy-dependent morphology of the nebula enables us to constrain the particle transport mechanisms. A dependence of the nebula extent with energy of R ∝ E α with α = −0.29 ± 0.04 stat ± 0.05 sys disfavours a pure diffusion scenario for particle transport within the nebula. The total γ -ray flux of the nebula above 1 TeV is found to be (1.12 ± 0.03 stat ± 0.25 sys ) × 10 −11 cm −2 s −1 , corresponding to ~64% of the flux of the Crab nebula. Results. HESS J1825–137 is a PWN with clearly energy-dependent morphology at VHE γ -ray energies. This source is used as a laboratory to investigate particle transport within intermediate-age PWNe. Based on deep observations of this highly spatially extended PWN, we produce a spectral map of the region that provides insights into the spectral variation within the nebula.
Gene correction of HBB mutations in CD34+ hematopoietic stem cells using Cas9 mRNA and ssODN donors
2018-11-14

Our approach provides guidance on non-viral gene correction in CD34<sup>+</sup> HSCs using Cas9 mRNA and chemically modified ssODN. However, further optimization is needed to increase the homology directed repair (HDR) to attain a real clinical benefit for β-thalassemia.
Confocal Laser Endomicroscopy as a Guidance Tool for Transbronchial Lung Cryobiopsies in Interstitial Lung Disorder
2018-11-14

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Transbronchial cryobiopsy (TBCB) of the lung parenchyma is a minimally invasive alternative for surgical lung biopsy in interstitial lung disease (ILD) patients. Drawbacks are the nondiagnostic rate and complication risk of pneumothorax and bleeding. Fluoroscopy is the current guidance tool for TBCB, which is limited by 2D imaging and a radiation dose for the patient. Confocal laser endomicroscopy (CLE) is a high-resolution imaging technique that provides immediate feedback during bronchoscopy about the elastin fiber network of peripheral lung areas. Both the visceral pleura and fibrotic lung areas consist of elastin fibers and are therefore potentially detectable with CLE. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; To investigate whether CLE is capable of (1) distinguishing fibrotic from normal alveolar areas and (2) identifying the pleura. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In and ex vivo CLE imaging obtained during bronchoscopy was compared with histology of lung biopsies in 14 ILD patients. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; CLE imaging of the alveolar compartment was feasible in all patients without adverse events. Based on CLE imaging, key characteristics that influence both diagnostic yield (dense fibrotic areas) and complication rate (pleura and subpleural space) were visualized. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; CLE seems a promising alternative to fluoroscopy as a guidance tool for TBCB procedures.
Transit analysis of the CoRoT-5, CoRoT-8, CoRoT-12, CoRoT-18, CoRoT-20, and CoRoT-27 systems with combined ground- and space-based photometry
2018-11-14

We have initiated a dedicated project to follow-up with ground-based photometry the transiting planets discovered by CoRoT in order to refine the orbital elements, constrain their physical parameters, and search for additional bodies in the system. From 2012 September to 2016 December we carried out 16 transit observations of six CoRoT planets (CoRoT-5 b, CoRoT-8 b, CoRoT-12 b, CoRoT-18 b, CoRoT-20 b, and CoRoT-27 b) at three observatories located in Germany and Spain. These observations took place between 5 and 9 yr after the planet's discovery, which has allowed us to place stringent constraints on the planetary ephemeris. In five cases we obtained light curves with a deviation of the mid-transit time of up to ∼115 min from the predictions. We refined the ephemeris in all these cases and reduced the uncertainties of the orbital periods by factors between 1.2 and 33. In most cases our determined physical properties for individual systems are in agreement with values reported in previous studies. In one case, CoRoT-27 b, we could not detect any transit event in the predicted transit window.© 2018 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society.
A systems-level analysis highlights microglial activation as a modifying factor in common forms of human epilepsy
2018-11-14

Abstract The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying &gt;2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.
The processing of dialectal variants: Further insight from French
2018-11-14

ABSTRACT In two semantic priming experiments, this study examined how southern French speakers process the standard French [o] variant in closed syllables in comparison to their own variant [ɔ]. In Experiment 1, southern French speakers showed facilitation in the processing of the associated target word VIOLET whether the word prime mauve was pronounced by a standard French speaker ([mov]) or a southern French speaker ([mɔv]). More importantly, Experiment 1 has also revealed that words of type mauve , which are subject to dialectal variation, behave exactly in the same way as words of type gomme , which are pronounced with [ɔ] by both southern and standard French speakers, and for which we also found no modulation in the magnitude of the priming effect as a function of the dialect of the speaker. Experiment 2 replicated the priming effect found with the standard French variant [mov], and failed to show a priming effect with nonwords such as [mœv] that also differ from the southern French variant [mɔv] by only one phonetic feature. Our study thus provides further evidence for efficient processing of dialectal variants during spoken word recognition, even if these variants are not part of the speaker’s own productions.
Intramural haematoma of the ascending aorta – not so malignant after all?
2018-11-14

Intramural haematoma of the ascending aorta – not so malignant after all? Udo Sechtem Udo Sechtem Udo Sechtem, Robert Bosch Krankenhaus Stuttgart, Auerbachstr. 110, D-70376 Stuttgart, Germany. Email: udo.sechtem@rbk.de Search for other works by this author on: Oxford Academic Google Scholar European Heart Journal. Acute Cardiovascular Care, Volume 9, Issue 3_suppl, 1 October 2020, Pages S3–S4, https://doi.org/10.1177/2048872618812397 Published: 01 October 2020
3D gradient echo snapshot CEST MRI with low power saturation for human studies at 3T
2018-11-15

Purpose For clinical implementation, a chemical exchange saturation transfer (CEST) imaging sequence must be fast, with high signal‐to‐noise ratio (SNR), 3D coverage, and produce robust contrast. However, spectrally selective CEST contrast requires dense sampling of the Z‐spectrum, which increases scan duration. This article proposes a compromise: using a 3D snapshot gradient echo (GRE) readout with optimized CEST presaturation, sampling, and postprocessing, highly resolved Z‐spectroscopy at 3T is made possible with 3D coverage at almost no extra time cost. Methods A 3D snapshot CEST sequence was optimized for low‐power CEST MRI at 3T. Pulsed saturation was optimized for saturation power and saturation duration. Spectral sampling and postprocessing (B 0 correction, denoising) was optimized for spectrally selective Lorentzian CEST effect extraction. Reproducibility was demonstrated in 3 healthy volunteers and feasibility was shown in 1 tumor patient. Results Low‐power saturation was achieved by a train of 80 pulses of duration t p = 20 ms (total saturation time t sat = 3.2 seconds at 50% duty cycle) with B 1 = 0.6 μT at 54 irradiation frequency offsets. With the 3D snapshot CEST sequence, a 180 × 220 × 54 mm field of view was acquired in 7 seconds per offset. Spectrally selective CEST effects at +3.5 and –3.5 ppm were quantified using multi‐Lorentzian fitting. Reproducibility was high with an intersubject coefficient of variation below 10% in CEST contrasts. Amide and nuclear overhauser effect CEST effects showed similar correlations in tumor and necrosis as show in previous ultra‐high field work. Conclusion A sophisticated CEST tool ready for clinical application was developed and tested for feasibility.
A single class of ARF GTPase activated by several pathway-specific ARF-GEFs regulates essential membrane traffic in Arabidopsis
2018-11-15

In eukaryotes, GTP-bound ARF GTPases promote intracellular membrane traffic by mediating the recruitment of coat proteins, which in turn sort cargo proteins into the forming membrane vesicles. Mammals employ several classes of ARF GTPases which are activated by different ARF guanine-nucleotide exchange factors (ARF-GEFs). In contrast, flowering plants only encode evolutionarily conserved ARF1 GTPases (class I) but not the other classes II and III known from mammals, as suggested by phylogenetic analysis of ARF family members across the five major clades of eukaryotes. Instead, flowering plants express plant-specific putative ARF GTPases such as ARFA and ARFB, in addition to evolutionarily conserved ARF-LIKE (ARL) proteins. Here we show that all eight ARF-GEFs of Arabidopsis interact with the same ARF1 GTPase, whereas only a subset of post-Golgi ARF-GEFs also interacts with ARFA, as assayed by immunoprecipitation. Both ARF1 and ARFA were detected at the Golgi stacks and the trans-Golgi network (TGN) by both live-imaging with the confocal microscope and nano-gold labeling followed by EM analysis. ARFB representing another plant-specific putative ARF GTPase was detected at both the plasma membrane and the TGN. The activation-impaired form (T31N) of ARF1, but neither ARFA nor ARFB, interfered with development, although ARFA-T31N interfered, like ARF1-T31N, with the GDP-GTP exchange. Mutant plants lacking both ARFA and ARFB transcripts were viable, suggesting that ARF1 is sufficient for all essential trafficking pathways under laboratory conditions. Detailed imaging of molecular markers revealed that ARF1 mediated all known trafficking pathways whereas ARFA was not essential to any major pathway. In contrast, the hydrolysis-impaired form (Q71L) of both ARF1 and ARFA, but not ARFB, had deleterious effects on development and various trafficking pathways. However, the deleterious effects of ARFA-Q71L were abolished by ARFA-T31N inhibiting cognate ARF-GEFs, both in cis (ARFA-T31N,Q71L) and in trans (ARFA-T31N + ARFA-Q71L), suggesting indirect effects of ARFA-Q71L on ARF1-mediated trafficking. The deleterious effects of ARFA-Q71L were also suppressed by strong over-expression of ARF1, which was consistent with a subset of BIG1-4 ARF-GEFs interacting with both ARF1 and ARFA. Indeed, the SEC7 domain of BIG5 activated both ARF1 and ARFA whereas the SEC7 domain of BIG3 only activated ARF1. Furthermore, ARFA-T31N impaired root growth if ARF1-specific BIG3 was knocked out and only ARF1- and ARFA-activating BIG4 was functional. Activated ARF1 recruits different coat proteins to different endomembrane compartments, depending on its activation by different ARF-GEFs. Unlike ARF GTPases, ARF-GEFs not only localize at distinct compartments but also regulate specific trafficking pathways, suggesting that ARF-GEFs might play specific roles in traffic regulation beyond the activation of ARF1 by GDP-GTP exchange.
Early clinical features and risk factors for cesarean scar pregnancy: a retrospective case-control study
2018-11-15

The aim of this study was to investigate early clinical features and risk factors for cesarean scar pregnancy (CSP). Study group of 206 CSP patients out of 6853 women with early pregnancies, diagnosed from 2014 to 2016 was compared with a randomly selected control group of 412 patients. Early clinical features for CSP were vaginal bleeding (OR: 9.65; 95% CI: 5.67-16.41), lower abdominal pain (OR: 3.8; 95% CI: 1.52-9.54) and increased white blood cells (OR: 1.30; 95% CI: 1.12-1.50). Important risk factors for CSP were artificial abortion within the last pregnancy (OR: 4.13; 95% CI: 2.23-7.66), 0 ∼ 1 year and 2 ∼ 3 year interval between present and last pregnancy (OR: 2.27; 95% CI: 1.11-4.67 and OR: 2.15; 95% CI: 1.15-4.03). Pregnancy problems are important issues within the scope of 'Gynecological Endocrinology'. Vaginal bleeding and lower abdominal pain, although unspecific, could be early clinical symptoms of CSP, especially if main risk factors exist such as abortion within the last pregnancy and short interval to the last pregnancy. Knowing this can help for prevention and early diagnosis CSP which can reduce life-threatening complications such as massive hemorrhage and can avoid hysterectomy. Consequence also must be to avoid unwanted pregnancies by using effective contraception, especially in risk patients.