gebhart/patrepeval huggingface dataset:
Correction: A20 (Tnfaip3) Deficiency in Myeloid Cells Protects against Influenza A Virus Infection (2012)

The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. Influenza A virus (IAV) produces double-stranded RNA as an intermediate during the replication life cycle, which activates the intracellular pathogen recognition receptor RIG-I and induces the production of proinflammatory cytokines and antiviral interferon. Understanding the mechanisms that regulate innate immune responses to IAV and other viruses is of key importance to develop novel therapeutic strategies. Here we used myeloid cell specific A20 knockout mice to examine the role of the ubiquitin-editing protein A20 in the response of myeloid cells to IAV infection. A20 deficient macrophages were hyperresponsive to double stranded RNA and IAV infection, as illustrated by enhanced NF-kB and IRF3 activation, concomitant with increased production of proinflammatory cytokines, chemokines and type I interferon. In vivo this was associated with an increased number of alveolar macrophages and neutrophils in the lungs of IAV infected mice. Surprisingly, myeloid cell specific A20 knockout mice are protected against lethal IAV infection. These results challenge the general belief that an excessive host proinflammatory response is associated with IAV-induced lethality, and suggest that under certain conditions inhibition of A20 might be of interest in the management of IAV infections.
Epidermal growth factor: the receptor and its function. (1989)

Epidermal growth factor (EGF) is a small polypeptide hormone with mitogenic properties in vivo and in vitro. EGF elicits biologic responses by binding to a cell surface receptor which is a transmembrane glycoprotein containing a cytoplasmic protein tyrosine kinase. EGF responses are mediated by ligand binding and activation of this intrinsic protein kinase. The receptor can be phosphorylated by other protein kinases, and this may regulate receptor function. Stimulation of the receptor tyrosine kinase activity by ligand binding must regulate the activity of an as yet undefined molecule(s) responsible for transmitting a mitogenic signal to the nucleus.
Figure S7 from Breast Cancer Targeting through Inhibition of the Endoplasmic Reticulum-Based Apoptosis Regulator Nrh/BCL2L10 (2023)

&lt;p&gt;(A) Detection of the Nrh/IP3R1 complex. (B) Effect of UV light on TAT-NDP diffusion into the cytoplasm.&lt;/p&gt;
Long-term Surface Temperature (LoST) Database as a Complement for Transient and Control Preindustrial Simulations (2021)

&amp;lt;div&amp;gt;Estimates of climate sensitivity from Atmosphere-Ocean Coupled General Circulation Model (GCM) simulations present a large spread despite the continued improvements in climate modeling since the 1970s. This variability is partially caused by the dependence of several long-term feedback mechanisms on the reference climate state. However, it is difficult to provide a reference to assess the climatology of preindustrial control simulations as there are no long-term preindustrial observations.&amp;lt;br&amp;gt;In the ground, recent changes in ground surface temperature are observed at shallow depths as perturbations to the quasi-steady state geothermal regime. However, if undisturbed by recent surface temperature changes, the deep ground temperatures vary linearly as a function of depth, and the extrapolation of this linear behavior to the surface can be interpreted as the past long-term surface temperature climatology.&amp;lt;/div&amp;gt;&amp;lt;div&amp;gt;We assemble a new gridded database of past long-term ground surface temperatures (LoST database) obtained from 514 borehole temperature profiles measured across North America, and we explore its use as a potential reference for the evaluation of GCM preindustrial control simulations and past millennium simulations. All temperature profiles are truncated at 300 m depth, allowing to estimate the ground surface climatology for the period 1300-1700 of the common era. We compare the LoST database with observations from the CRU database, as well as with five past millennium simulations and five preindustrial control simulations from the third phase of the Paleoclimate Modelling Intercomparison Project (PMIP3) and the fifth phase of the Coupled Model Intercomparison Project (CMIP5) archives. Our results suggest that LoST temperatures could be employed as a reference to narrow down the spread of surface temperature climatologies on GCM preindustrial control and past millennium simulations.&amp;lt;/div&amp;gt;
Extracorporeal Perfusion for Salvage of Major Amputates (2019)

Taeger, Christian D. MD; Lamby, Philipp MD; Dolderer, Jürgen MD; Philipp, Alois; Kehrer, Andreas MD; Horch, Raymund E. MD; Präbst, Konstantin PhD; Prantl, Lukas MD Author Information
Autoimmune epitopes in messenger RNA (2002)

Patients with systemic autoimmune disorders produce autoantibodies against sequence-specific conformational RNA epitopes on U1 snRNA, 28S rRNA, and transfer RNAs. The molecular basis for immunological reactivity with these highly abundant and stable RNAs is not understood. Here, we report the existence of discrete RNA epitopes in messenger RNAs that are generally less abundant and less stable than snRNAs and tRNAs. An iterative selection and amplification procedure using pooled autoimmune patient sera identified immunoreactive mRNA species. Following deconvolution of the pools to identify the reactive sera, several mRNAs recognized by these autoantibodies were cloned and sequenced. Detailed analysis using one particular serum indicated reactivity against the messages encoding alternative splicing factor (ASF/SF2) and calmodulin. Deletion and site-directed mutagenesis determined that an epitope recognized by this serum is located in a 17-base stem-loop structure common to both messages. This serum was then used to immunoprecipitate native mRNAs encoding ASF/SF2 and calmodulin from total HeLa cell RNA. Our results demonstrate that despite its low abundance and instability, messenger RNA is capable of reacting with autoantibodies generated during an autoimmune response. These data are consistent with direct presentation as a model to explain the generation of RNA conformation-specific autoantibodies.
After-Ripening Induced Transcriptional Changes of Hormonal Genes in Wheat Seeds: The Cases of Brassinosteroids, Ethylene, Cytokinin and Salicylic Acid (2014)

Maintenance and release of seed dormancy is regulated by plant hormones; their levels and seed sensitivity being the critical factors. This study reports transcriptional regulation of brassinosteroids (BR), ethylene (ET), cytokinin (CK) and salicylic acid (SA) related wheat genes by after-ripening, a period of dry storage that decays dormancy. Changes in the expression of hormonal genes due to seed after-ripening did not occur in the anhydrobiotic state but rather in the hydrated state. After-ripening induced dormancy decay appears to be associated with imbibition mediated increase in the synthesis and signalling of BR, via transcriptional activation of de-etiolated2, dwarf4 and brassinosteroid signaling kinase, and repression of brassinosteroid insensitive 2. Our analysis is also suggestive of the significance of increased ET production, as reflected by enhanced transcription of 1-aminocyclopropane-1-carboxylic acid oxidase in after-ripened seeds, and tight regulation of seed response to ET in regulating dormancy decay. Differential transcriptions of lonely guy, zeatin O-glucosyltransferases and cytokinin oxidases, and pseudo-response regulator between dormant and after-ripened seeds implicate CK in the regulation of seed dormancy in wheat. Our analysis also reflects the association of dormancy decay in wheat with seed SA level and NPR independent SA signaling that appear to be regulated transcriptionally by phenylalanine ammonia lyase, and whirly and suppressor of npr1 inducible1 genes, respectively. Co-expression clustering of the hormonal genes implies the significance of synergistic and antagonistic interaction between the different plant hormones in regulating wheat seed dormancy. These results contribute to further our understanding of the molecular features controlling seed dormancy in wheat.
Quercetin Reduces Tumor Necrosis Factor Alpha-Induced Muscle Atrophy by Upregulation of Heme Oxygenase-1 (2018)

The inflammatory cytokine tumor necrosis factor α (TNFα), upregulated in the obese condition, promotes protein degradation and is implicated in obesity-related skeletal muscle atrophy and age-related sarcopenia. Quercetin, a flavonoid, elicits antioxidative and anti-inflammatory activities. In this study, we investigated the effect of quercetin on TNFα-induced skeletal muscle atrophy as well as its potential mechanism of action. In this study, we observed that quercetin suppressed expression of TNFα-induced atrophic factors such as MAFbx/atrogin-1 and MuRF1 in myotubes, and it enhanced heme oxygenase-1 (HO-1) protein level accompanied by increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in myotubes. The HO-1 inhibitor ZnPP suppressed the inhibitory actions of quercetin on TNFα-induced atrophic responses and degradation of IκB-α in myotubes. Moreover, quercetin supplementation to high-fat diet-fed obese mice inhibited obesity-induced atrophic responses in skeletal muscle, accompanied by upregulation of HO-1 and inactivation of nuclear factor-kappa B (NF-κB), and the quercetin actions were attenuated in Nrf2-deficient mice. These findings suggest that quercetin protects against TNFα-induced muscle atrophy under obese conditions through Nrf2-mediated HO-1 induction accompanied by inactivation of NF-κB. Quercetin may be used as a dietary supplement to protect against obesity-induced skeletal muscle atrophy.
Aging Changes in Voltage-Gated Calcium Currents in Hippocampal CA1 Neurons (1996)

Previous current-clamp studies in rat hippocampal slice CA1 neurons have found aging-related increases in long-lasting calcium (Ca)-dependent and Ca-mediated potentials. These changes could reflect an increase in Ca influx through voltage-gated Ca channels but also could reflect a change in potassium currents. Moreover, if altered Ca influx is involved, it is nuclear whether it arises from generally increased Ca channel activity, lower threshold, or reduced inactivation. To analyze the basis for altered Ca potentials, whole-cell voltage-clamp studies of CA1 hippocampal neurons were performed in nondissociated hippocampal slices of adult (3- to 5-month-old) and aged (25- to 26-month-old) rats. An aging-related increase was found in high-threshold Ca and barium (Ba) currents, particularly in the less variable, slowly inactivating (late) current at the end of a depolarization step. Input resistance of neurons did not differ between age groups. In steady-state inactivation and repetitive-pulse protocols, inactivation of Ca and Ba currents was not reduced and, in some cases, was slightly greater in aged neurons, apparently because of larger inward current. The current blocked by nimodipine was greater in aged neurons, indicating that some of the aging increase was in L-type currents. These results indicate that whole-cell Ca currents are increased with aging in CA1 neurons, apparently attributable to greater channel activity rather than to reduced inactivation. The elevated Ca influx seems likely to play a role in impaired function and enhanced susceptibility to neurotoxic influences.
Arsenic trioxide and tetraarsenic oxide induce cytotoxicity and have a synergistic effect with cisplatin in paclitaxel-resistant ovarian cancer cells (2019)

<b>Background:</b> Arsenic compounds (As<sub>2</sub>O<sub>3</sub> and As<sub>4</sub>O<sub>6</sub>) have demonstrated anticancer effects in various malignancies. In this study, the cytotoxicity of arsenic compounds on ovarian cancer cell lines and the anticancer activity of the combination of arsenic compounds and cisplatin IN chemoresistant ovarian cancer cells were investigated.<b>Methods:</b> We investigated the cytotoxicity of As<sub>2</sub>O<sub>3</sub> and As<sub>4</sub>O<sub>6</sub> and their combinations with cisplatin in the paclitaxel-sensitive ovarian cancer cell lines SKOV3ip1 and HeyA8 and paclitaxel-resistant ovarian cancer cell lines SKOV3TRip2 and HeyA8-MDR. Growth and apoptosis were evaluated by MTT assay and annexin V assay using flow cytometry, respectively. For detection of apoptotic cells, immunofluorescence was performed using a cleaved caspase-3 antibody. Cell-cycle distribution was determined by propidium iodide staining and flow cytometry.<b>Results:</b> Treatment of each cell line with As<sub>2</sub>O<sub>3</sub> or As<sub>4</sub>O<sub>6</sub> led to a marked dose-dependent inhibition of cell growth. As<sub>2</sub>O<sub>3</sub> and As<sub>4</sub>O<sub>6</sub> treatment induced caspase-3-dependent apoptosis in all cell lines compared to the respective control groups (<i>p</i> < .05). As<sub>2</sub>O<sub>3</sub> and As<sub>4</sub>O<sub>6</sub> induced apoptosis of paclitaxel-sensitive and -resistant cancer cell lines following G2/M cell cycle arrest (<i>p</i> < .05). A synergistic effect was achieved by combining cisplatin with As<sub>2</sub>O<sub>3</sub> or As<sub>4</sub>O<sub>6</sub> in the paclitaxel-resistant ovarian cancer cell lines.<b>Conclusions:</b> As<sub>2</sub>O<sub>3</sub> and As<sub>4</sub>O<sub>6</sub> can inhibit cell growth and induce apoptosis in paclitaxel-sensitive and -resistant ovarian cancer cell lines. Their combination with cisplatin resulted in a synergistic effect in paclitaxel-resistant cancer cell lines. These results suggest that arsenic compounds may be given in monotherapy or combination therapy with cisplatin for treating paclitaxel-resistant ovarian cancer.
Stem cell factor is a chemotactic factor for human mast cells. (1994)

The mast cell is one of the major effector cells in inflammatory reactions and can be found in most tissues throughout the body. During inflammation, an increase in the number of mast cells can be seen, e.g., in the intraepithelial cell layer after a provoked allergic reaction. Such accumulation probably requires directed migration of mature mast cells or their precursors. To study the migration of human mast cells we used as a model the human mast cell line, HMC-1, and stem cell factor-dependent (also referred to as mast cell growth factor or Kit ligand) cord blood-derived mast cells. The results show that stem cell factor is a potent chemotactic factor for human mast cells in vitro. The chemotactic response to SCF was found to be dose dependent, reaching a maximum at 50 ng/ml. The activity of SCF could be blocked by anti-SCF Abs. We also tested the effect of different intercrines, i.e., IL-8, MIP-1 alpha, MIP-1 beta, RANTES, and MCAF (also referred to as monocyte chemotactic protein 1), on human mast cell migration. Only RANTES was chemotactic for in vitro-developed mast cells. None of the tested intercrines induced migration of HMC-1 cells. For migration, the mast cells were dependent on binding to an extracellular matrix protein. Thus, coating of the filters with fibronectin was required, whereas collagen or laminin did not promote migration. Adhesion of HMC-1 cells to fibronectin could also be shown in an adhesion assay. In addition, expression of receptors for fibronectin could be detected on the surface of the mast cells. These results show that SCF is not only a growth and differentiation factor for human mast cells in vitro but also a potent chemoattractant for such cells.
Broad Spectrum Anticancer Activity of Pistagremic Acid (2013)

Background: Pistagremic acid; 3-methyl-7-(4,4,10,13,14-pentamethyl-3-2,3,4,5,6,7,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthr-en-17-yl)-oct-3-enoic acid was isolated from the chloroform fraction of Pistacia integerrima. Cytotoxic evaluation against NCI-60 DTP human tumor cell line was performed.
Methods: The anticancer assays for this compound were performed in accordance with the protocol of the Drug Evaluation Branch, by the National Cancer Institute (NCI) Developmental Therapeutic Program (www.dtp.nci.nih.gov) to be screened for their anticancer activity in vitro.
Results: It showed broad spectrum antiproliferative activity with an average GI50, and TGI, values 0.103 μM and 0.259 μM, respectively. It also showed significant LC50 value at the average 0.634 μM against all cell lines excluding K-562, RPMI-8226, NCI-H226, and NCI-H460 cell-lines.
Conclusions: Pistagremic acid showed cytotoxicity for all tested cancer cell line, thus it may serve as a potential structure lead for the development of new anticancer drugs.
A Critical Assessment of Exosomes in the Pathogenesis and Stratification of Parkinson’s Disease (2017)

Extracellular vesicles including exosomes are released by a variety of cell types including neurons and exhibit molecular profiles that reflect normal and disease states. As their content represents a snapshot of the intracellular milieu, they could be exploited as biomarkers of the otherwise inaccessible brain microenvironment. In addition they may contribute to the progression of neurodegenerative disorders by facilitating the spread of misfolded proteins at distant sites or activating immune cells. This review summarizes recent advances in the study of exosomes in Parkinson's disease pathophysiology and their potential as disease biomarkers.
IC‐P‐183: Reproducibility of intracranial and hippocampal volume quantification at 1.5T and 3T MRI: Application to ADNI I (2013)

Hippocampal volume (HCV) measured based on high-resolution T1 (3DT1) has been proposed as a key biomarker in Alzheimer's Disease (AD) studies, both for improved subject selection and monitoring treatment efficacy. Intracranial volume (ICV) has also been used as a covariate for standardization of volumetric endpoints. In multicenter clinical trials, MRI data are usually acquired with different scanner types, models and field strengths (1.5T & 3T). The robustness of HCV and ICV segmentation algorithms in such multicenter contexts is therefore of major importance for the overall quality of volumetric assessments. The purpose of this work was to evaluate the reproducibility of two previously reported BioClinica Multi-Atlas Segmentation algorithms BMAS-ICV & BMAS-HCV at 1.5T & 3T using ADNI I subjects. Baseline 3DT1 sequences of 153 Normal Controls, MCI and AD subjects from ADNI I (http://adni.loni.ucla.edu) with two back-to-back 1.5T and two back-to-back 3T acquisitions were used (subjects did not leave the scanners for back-to-back acquisitions). In total, 612 native (uncorrected) 3DT1 sequences were analyzed. ICV and HCV were automatically quantified using BMAS-ICV & BMAS-HCV. ICV and HCV reproducibility was assessed by comparing 1.5T back-to-back volumes, 3T back-to-back volumes as well as 1.5T versus 3T volumes using Pearson's correlation between volumes and the corresponding relative volume error (RVE). Correlation results for back-to-back acquisitions at the same (1.5T and 3T) and between (1.5T vs. 3T) field strengths are reported in Table 1. For back-to-back scans, the mean value of both measurements was used when comparing the two field strengths. The ICV and HCV quantification algorithms were highly reproducible for back-to-back (correlation coefficients higher than 0.99) and for 1.5T vs. 3T (correlations close to 0.98) acquisitions. The proposed ICV and HCV quantification methods based on BMAS-ICV & BMAS-HCV respectively were highly reproducible at various field strengths and with different scanner types. This reproducibility (robustness) is a key requirement for the use of such volumetric assessments in the context of multicenter clinical trials where 1.5 and 3T scanners can be used. The 1.5T vs. 3T comparison also provided an opportunity to evaluate the impact of patient repositioning (test-retest) on ICV and HCV measurements. Reproducibility of ICV (a) and HCV (b) at 1.5T and 3T MRI and corresponding boxplots for ICV (c) and HCV (d).
Design of a compact patch antenna backed by a multi-layer EBG structure using multi-conductor transmission line modeling (2012)

In this paper, multi-conductor transmission-line (MTL) theory is applied to modeling and analysis of shielded two-layer mushroom-type electromagnetic bandgap (EBG) structures. The slow-wave mode predicted by this method is used to design a compact patch antenna. To further reduce the size of the patch antenna, it is shorted at its center resulting in one of the most compact patch antenna design reported in literature with a dimension of 0.1λ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> by 0.18λ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> with a maximum gain of 2.9dB.
Stent Hypersensitivity and Infection in Sinus Cavities (2013)

Persistent mucosal inflammation, granulation tissue formation, hypersensitivity, and multifactorial infection are newly described complications of retained drug-eluting stents from endoscopic sinus surgery for refractory rhinosinusitis. In an important report published in Allergy and Rhinology, a 45-year-old male patient suffering from recalcitrant chronic rhinosinusitis underwent functional endoscopic sinus surgery and was found, for the first time, to have steroid-eluting catheters that were inadvertently left in the ethmoid and frontal sinuses. The retained catheters had caused persistent mucosal inflammation and formation of granulation tissue denoting hypersensitivity reaction. These consequences had induced perpetuation of symptoms of chronic rhinosinusitis. Meticulous removal of the retained stents with the nitinol wings from inflamed tissues of the frontal, ethmoidal, and sphenoethmoidal recesses in which they were completely imbedded was successfully performed without polypoid regrowth. Cultures of specimens taken from both left and right stents showed heavy growth of Stenotrophomonas maltophilia and moderate growth of Klebsiella oxytoca, coagulase negative Staphylococcus, and beta-hemolytic Streptococcus anginosus. Fungal infection was not detected. The current knowledge and experience regarding stent hypersensitivity and infection in relation with the use of stents in sinus cavities is reviewed.
Stimulation of the natural immune system in normal mice by polysaccharide from maitake mushroom (2003)

Maitake D-Fraction is a polysaccharide extracted from the maitake mushroom (Grifola frondosa S.F. Gray). It is a β-glucan with a β-1,6 main chain with β-1,3 branches. Using normal C3H/Hej mice, its effects on the natural immune system, including macrophages, dendritic cells, and natural killer (NK) cells, were investigated. NK cells attack cells infected with pathogens such as bacteria and virus and produce cytokines, such as interferon-gamma (IFN-γ), that can modulate natural and specific immune responses. DFraction was administered to the mice intraperitoneally for 3 consecutive days; spleen cells containing macrophages and dendritic cells were then cultured and the culture supernatants were analyzed for IL-12. At the same time, IFN-γ expression in splenic NK cells was investigated. The levels of these cytokines were increased by D-Fraction. To elucidate NK cell activation by D-Fraction, CD69 expression on the surface of activated NK cells was examined, resulting in an increase in CD69-positive ratio for splenic NK cells. These results indicate that D-Fraction stimulates the natural immunity related to the activation of NK cells indirectly through IL-12 produced by macrophages and dendritic cells. Therefore, administration of D-Fraction to healthy individuals may serve to prevent infection.
ChemInform Abstract: A Dipolar Cycloaddition Approach to Pyrrolo(1,2‐a)indoles Using N‐((Trimethylsilyl)methyl)‐Substituted Indoles. (1989)

Abstract 1,3‐Dipolar cycloaddition of the N‐trimethylsilylmethyl‐substituted indole (V), obtained from gramine (I) as shown in the reaction scheme, with N‐phenylmaleimide (VI) in the presence of equimolar amounts of silver fluoride leads to the formation of the fused dione (VII).