gebhart/patrepeval huggingface dataset:
The Respiratory Burst Oxidase (1992)

Sbarra and Karnovsky were the first to present evidence suggesting the presence in phagocytes of a special enzyme designed to generate reactive oxidants for purposes of host defense. In the years since their report appeared, a great deal has been learned about this enzyme, now known as the respiratory burst oxidase. It has been found to be a plasma membrane-bound heme- and flavin-containing enzyme, dormant in resting cells, that catalyzes the one-electron reduction of oxygen to O2- at the expense of NADPH: O2 + NADPH----O2- + NADP+ + H+ Its behavior in whole cells and its response to various activating stimuli have been described in detail, although important insights continue to emerge, as for example a very interesting new series of observations on differences in oxidase activation patterns between suspended and adherent cells. The enzyme has been shown by biochemical and genetic studies to consist of at least six components. In the resting cell, three of these components are in the cytosol and three in the plasma membrane, but when the cell passes from its resting to its activated state the cytosolic components are all transferred to the plasma membrane, presumably assembling the oxidase. Of the components initially bound to the membrane, two constitute cytochrome b558, a heme protein characteristic of the respiratory burst oxidase, and the third may represent an oxidase flavoprotein. With regard to the cytosolic components, one is a phosphoprotein and another is the NADPH-binding component, possibly a second oxidase flavoprotein. The nature of the third (p67phox) is a puzzle. Four of the six oxidase components have now been cloned and sequenced. These findings only scratch the surface, however, and many questions remain. How many oxidase components, for example, remain to be discovered, and how do they fit together to form the active enzyme? How is the route of activation of the oxidase integrated into the general signal transduction systems of the cell? How did the oxidase come to be? Could there be a widespread system that generates small amounts of O2- as an intercellular signaling molecule, as recent work is beginning to suggest, and did the ever-destructive respiratory burst oxidase arise from that innocuous system as the creation of some evolutionary Frankenstein--an oxidase from hell? Finally, will it be possible to develop drugs that specifically block the respiratory burst oxidase, and will such drugs prove to be clinically useful as anti-inflammatory agents?(ABSTRACT TRUNCATED AT 400 WORDS)
Identification of the Cytolinker Plectin as a Major Early In Vivo Substrate for Caspase 8 during CD95- and Tumor Necrosis Factor Receptor-Mediated Apoptosis (2000)

Caspase 8 plays an essential role in the execution of death receptor-mediated apoptosis. To determine the localization of endogenous caspase 8, we used a panel of subunit-specific anti-caspase 8 monoclonal antibodies in confocal immunofluorescence microscopy. In the human breast carcinoma cell line MCF7, caspase 8 predominantly colocalized with and bound to mitochondria. After induction of apoptosis through CD95 or tumor necrosis factor receptor I, active caspase 8 translocated to plectin, a major cross-linking protein of the three main cytoplasmic filament systems, whereas the caspase 8 prodomain remained bound to mitochondria. Plectin was quantitatively cleaved by caspase 8 at Asp 2395 in the center of the molecule in all cells tested. Cleavage of plectin clearly preceded that of other caspase substrates such as poly(ADP-ribose) polymerase, gelsolin, cytokeratins, or lamin B. In primary fibroblasts from plectin-deficient mice, apoptosis-induced reorganization of the actin cytoskeleton, as seen in wild-type cells, was severely impaired, suggesting that during apoptosis, plectin is required for the reorganization of the microfilament system.
Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4 + T Cells (2005)

In untreated human immunodeficiency virus type 1 (HIV-1) infection, most viral genomes in resting CD4(+) T cells are not integrated into host chromosomes. This unintegrated virus provides an inducible latent reservoir because cellular activation permits integration, virus gene expression, and virus production. It remains controversial whether HIV-1 is stable in this preintegration state. Here, we monitored the fate of HIV-1 in resting CD4(+) cells by using a green fluorescent protein (GFP) reporter virus carrying an X4 envelope. After virus entry into resting CD4(+) T cells, both rescuable virus gene expression, visualized with GFP, and rescuable virion production, assessed by p24 release, decayed with a half-life of 2 days. In these cells, reverse transcription goes to completion over 2 to 3 days, and 50% of the viruses that have entered undergo functional decay before reverse transcription is complete. We distinguished two distinct but closely related factors contributing to loss of rescuable virus. First, some host cells undergo virus-induced apoptosis upon viral entry, thereby reducing the amount of rescuable virus. Second, decay processes directly affecting the virus both before and after the completion of reverse transcription contribute to the loss of rescuable virus. The functional half-life of full-length, integration-competent reverse transcripts is only 1 day. We propose that rapid intracellular decay processes compete with early steps in viral replication in infected CD4(+) T cells. Decay processes dominate in resting CD4(+) T cells as a result of the slow kinetics of reverse transcription and blocks at subsequent steps. Therefore, the reservoir of unintegrated HIV-1 in recently infected resting CD4(+) T cells is highly labile.
A lysine substitution in the ATP-binding site of eucaryotic initiation factor 4A abrogates nucleotide-binding activity. (1989)

Eucaryotic initiation factor 4A (eIF-4A) is a member of a family of proteins believed to be involved in the ATP-dependent melting of RNA secondary structure. These proteins contain a derivative of the consensus ATP-binding site AXXGXGKT. To assess the importance of the consensus amino acid sequence in eIF-4A for ATP binding, we mutated the consensus amino-proximal glycine and lysine to isoleucine and asparagine, respectively. The effect of the mutations was examined by UV-induced cross-linking of [alpha-32P]dATP to eIF-4A. Mutation of the lysine residue (but not of the glycine residue) resulted in the loss of [alpha-32P]dATP cross-linking to eIF-4A, suggesting that the lysine is an important determinant in ATP binding to eIF-4A.
Anti-CNS Antibodies in Childhood Neurologic Diseases (1989)

To study the incidence of circulating anti-CNS antibodies in childhood neurologic diseases, a population study was undertaken. Serum samples were obtained from a total of 348 children and stored at -80 degrees C until being studied. The samples were collected when routine blood tests were being performed. In all cases informed consent was obtained. This study was approved by hospital ethics review committees. One hundred and ninety-nine of the samples were from children with no known neurologic illnesses and served as the control group. One hundred and twenty-one of the samples were from children with epilepsy and the remaining 28 from a number of different neurologic conditions. The serum samples were screened against normal, adult, autopsy-derived cerebellar and frontal cortex tissue sections and Western blots. Serum immunoreactivity was revealed using HRP-conjugated anti-human IgG. Significant findings included: (1) patients with epilepsy had an increased incidence of anti-CNS reactivity as revealed on frontal cortex immunoblots (p less than 0.05) but not on cerebellar immunoblots; (2) there was an increase in the incidence of immunoblot reactivity with age in the controls and the neurology cases; (3) there was an increased incidence of immunoblot reactivity in those cases with a presumed inflammatory central or peripheral neurologic disease; (4) in six additional cases with opsoclonus-myoclonus there was cerebellar-specific immunoreactivity with identified antigenic molecular weights of 27 and 35, and 62 kDaltons; (5) in 31 additional cases of systemic lupus erythematosus there was significant immunoblot reactivity (p less than 0.001) when compared to a subset of age-matched controls. There was no difference in immunoreactivity between males and females. There was no significant increase in immunoreactivity in those children with cognitive disturbances including developmental delay and mental retardation.
Recombinant Measles Viruses Expressing Altered Hemagglutinin (H) Genes: Functional Separation of Mutations Determining H Antibody Escape from Neurovirulence (2001)

Measles virus (MV) strain CAM/RB, which was adapted to growth in the brain of newborn rodents, is highly neurovirulent. It has been reported earlier that experimentally selected virus variants escaping from the monoclonal antibodies (MAbs) Nc32 and L77 to hemagglutinin (H) preserved their neurovirulence, whereas mutants escaping MAbs K71 and K29 were found to be strongly attenuated (U. G. Liebert et al., J. Virol. 68:1486-1493, 1994). To investigate the molecular basis of these findings, we have generated a panel of recombinant MVs expressing the H protein from CAM/RB and introduced the amino acid substitutions thought to be responsible for antibody escape and/or neurovirulence. Using these recombinant viruses, we identified the amino acid changes conferring escape from the MAbs L77 (377R-->Q and 378M-->K), Nc32 (388G-->S), K71 (492E-->K and 550S-->P), and K29 (535E-->G). When the corresponding recombinant viruses were tested in brains of newborn rodents, we found that the mutations mediating antibody escape did not confer differential neurovirulence. In contrast, however, replacement of two different amino acids, at positions 195G-->R and 200S-->N, which had been described for the escape mutant set, caused the change in neurovirulence. Thus, antibody escape and neurovirulence appear not to be associated with the same structural alterations of the MV H protein.
Expression of the Duffy antigen in K562 cells. Evidence that it is the human erythrocyte chemokine receptor. (1994)

The human malarial parasite Plasmodium vivax invades erythrocytes by binding to a cell surface protein identified as the Duffy blood group antigen. The molecular properties of the Duffy antigen, which was recently cloned, are very similar to those of a chemokine binding protein known as the human erythrocyte chemokine receptor. This has led to the suggestion that these two molecules are the same protein. To further investigate the suspected double identity of the Duffy antigen we have transfected it into a human erythroleukemic cell line, K562. Cells stably expressing the Duffy antigen were isolated and used to characterize the protein. K562 cells transfected with the Duffy antigen displayed specific 125I-melanoma growth-stimulating activity (MGSA) binding while mock transfected cells did not. Comparison of 125I-MGSA binding to the Duffy antigen and the human erythrocyte chemokine receptor showed that the specific 125I-MGSA binding to both proteins was displaced by excess unlabeled MGSA, interleukin-8, RANTES, monocyte chemotactic peptide-1, and platelet factor 4, but not by macrophage inflammatory protein-1 alpha or -1 beta. Scatchard analysis of competition binding studies with these unlabeled chemokines revealed high affinity binding to the Duffy antigen with KD binding values of 24 +/- 4.9, 20 +/- 4.7, 41.9 +/- 12.8, and 33.9 +/- 7 nM for MGSA, interleukin-8, RANTES, and monocyte chemotactic peptide-1, respectively. A monoclonal antibody, Fy6, to the Duffy antigen inhibited 125I-MGSA binding to K562 cells expressing the Duffy antigen. Cell membranes from K562 cells permanently expressing the Duffy antigen were chemically cross-linked with 125I-MGSA. SDS-polyacrylamide gel electrophoresis analysis of the cross-linked products showed covalent incorporation of radiolabeled MGSA into a protein of molecular mass 47 kDa, and cross-linking was inhibited in the presence of unlabeled MGSA. These studies provide evidence that the Duffy blood group antigen is the same protein as the human erythrocyte chemokine receptor.
Genomic Approaches to Deconstruct Pluripotency (2011)

Embryonic stem cells (ESCs) first derived from the inner cell mass of blastocyst-stage embryos have the unique capacity of indefinite self-renewal and potential to differentiate into all somatic cell types. Similar developmental potency can be achieved by reprogramming differentiated somatic cells into induced pluripotent stem cells (iPSCs). Both types of pluripotent stem cells provide great potential for fundamental studies of tissue differentiation, and hold promise for disease modeling, drug development, and regenerative medicine. Although much has been learned about the molecular mechanisms that underlie pluripotency in such cells, our understanding remains incomplete. A comprehensive understanding of ESCs and iPSCs requires the deconstruction of complex transcription regulatory networks, epigenetic mechanisms, and biochemical interactions critical for the maintenance of self-renewal and pluripotency. In this review, we will discuss recent advances gleaned from application of global "omics" techniques to dissect the molecular mechanisms that define the pluripotent state.
A Visuo-haptic Sensor for the Exploration of Deformable Objects (2014)

Abstract—We present a linear tactile sensor for grasping applications, which is based on a passive rubber foam material mounted on the fingers of a gripper and a low-cost camera pointed towards the actuator. This concept allows to visually measure local deformation, geometry and forces, without the need for costly dedicated sensors in the actuator. In an experiment, the geometry and deformation behavior of a deformable object (plastic bottle) is explored with the proposed sensor. 1) Introduction: Autonomous grasping of partially unknown, de-formable objects in human environments is a complex problem. In general it requires an object model, a grasp planner as well as visual and haptic feedback. The latter is needed during the grasping process to obtain the current state and provided by a dedicated laminar
Early Lesions of Proliferative Enteritis in Pigs and Hamsters (1989)

Gnotobiotic pigs and conventional hamsters were given suspensions of intestinal mucosa from a pig with proliferative hemorrhagic enteropathy and killed 10 or 21 days later. Affected animals had evidence of marked proliferation of immature enterocytes in the intestinal crypts. Numerous Campylobacter-like organisms were in the cytoplasm of enterocytes, and in some instances, bacteria were closely associated with enterocytes. Some intracellular bacteria lying below the microvillous border were within membrane-bound structures. Immunofluorescence and electron immunogold staining with specific antibodies indicated that these organisms were antigenically different from curved bacteria in the crypt lumen of early lesions. This study indicates that the life cycle of the intracellular organisms may involve entry into crypt enterocytes from the intestinal lumen with subsequent intracellular multiplication.
Fibronectin-fragment-induced cartilage chondrolysis is associated with release of catabolic cytokines (1997)

Fibronectin fragments have both catabolic and anabolic activities toward articular cartilage explants in vitro. Whereas a 1 nM concentration of an N-terminal 29 kDa fibronectin fragment (Fn-f) increases the proteoglycan (PG) content of cartilage without induction of matrix metalloproteinases (MMPs), 0.1-1 microM Fn-f temporarily suppresses PG synthesis and enhances MMP release. The higher concentrations cause an initially rapid PG depletion during the first week of culture, followed by much slower PG loss and gradually increasing rates of PG synthesis. To test for the involvement of mediators, human articular cartilage was cultured with Fn-f, and conditioned media were assayed for selected cytokines and factors. With 1 nM Fn-f, the release of the anabolic factors, insulin growth factor-I and transforming growth factor beta1, from cultured cartilage was enhanced by 50-100% during the entire 28-day culture period and this was associated with both supernormal rates of PG synthesis and PG content. However, the higher concentrations of Fn-f additionally enhanced release, by at least 10-fold, of the cytokines, tumour necrosis factor alpha, interleukin-1alpha, interleukin-1beta and interleukin-6 while causing depletion of cartilage PG. Release of tumour necrosis factor alpha, interleukin 1beta and interleukin 1alpha peaked at days 2, 3 and 9 during or slightly after the period of maximal PG depletion and decreased to control levels by days 7, 7 and 21 respectively, whereas release of interleukin 6 was enhanced throughout the culture period. Neutralizing antibodies to the catabolic cytokines reduced Fn-f-mediated MMP-3 release and suppression of PG synthesis. The temporal aspects of this interplay between catabolic and anabolic factors are consistent with the kinetics of Fn-f-mediated cartilage damage and attempted repair and may be relevant to cartilage damage and repair in vivo.
Electric-Field-Assisted Convective Assembly of Colloidal Crystal Coatings (2010)

A new technique that combines evaporative convective deposition of colloidal crystal coatings with an electric field to achieve more rapid assembly and reduce the defects in the crystal structure is reported. When an ac voltage is applied across the particle suspension and the substrate in the convective assembly process, a longer film spreads from the meniscus by the electrowetting-on-dielectric (EWOD) effect. The data suggest that the EWOD-increased liquid surface area results in increased evaporation-driven particle flux and crystal assembly that is up to five times more rapid. The extended drying film also provides more time for particle rearrangement before the structure becomes fixed, resulting in formation of crystal domains an order of magnitude larger than those deposited by convective assembly alone. The results demonstrate that EWOD is a facile tool for controlling particle assembly processes in wetting films. The technique could be used in improved large-scale colloidal crystal coating processes.
Probing the synthetic capabilities of a center of biochemical catalysis (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProbing the synthetic capabilities of a center of biochemical catalysisSidney M. HechtCite this: Acc. Chem. Res. 1992, 25, 12, 545–552Publication Date (Print):December 1, 1992Publication History Published online1 May 2002Published inissue 1 December 1992https://pubs.acs.org/doi/10.1021/ar00024a001https://doi.org/10.1021/ar00024a001research-articleACS PublicationsRequest reuse permissionsArticle Views175Altmetric-Citations60LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Knots in Rings (2006)

The aim of this work was to elucidate the oxidative folding mechanism of the macrocyclic cystine knot protein MCoTI-II. We aimed to investigate how the six-cysteine residues distributed on the circular backbone of the reduced unfolded peptide recognize their correct partner and join up to form a complex cystine-knotted topology. To answer this question, we studied the oxidative folding of the naturally occurring peptide using a range of spectroscopic methods. For both oxidative folding and reductive unfolding, the same disulfide intermediate species was prevalent and was characterized to be a native-like two-disulfide intermediate in which the Cys1-Cys18 disulfide bond was absent. Overall, the folding pathway of this head-to-tail cyclized protein was found to be similar to that of linear cystine knot proteins from the squash family of trypsin inhibitors. However, the pathway differs in an important way from that of the cyclotide kalata B1, in that the equivalent two-disulfide intermediate in that case is not a direct precursor of the native protein. The size of the embedded ring within the cystine knot motif appears to play a crucial role in the folding pathway. Larger rings contribute to the independence of disulfides and favor an on-pathway native-like intermediate that has a smaller energy barrier to cross to form the native fold. The fact that macrocyclic proteins are readily able to fold to a complex knotted structure in vitro in the absence of chaperones makes them suitable as protein engineering scaffolds that have remarkable stability.
Studies on the constituents of Xanthoceras sorbifolia Bunge. II. Major sapogenol and a prosapogenin from the fruits of Xanthoceras sorbifolia Bunge. (1984)

The main sapogenol and a prosapogenin from the fruits of Xanthoceras sorbifolia BUNGE (Sapindaceae) were examined. On the basis of chemical and spectral analyses, the structure of the new sapogenol obtained by acid hydrolysis of crude saponin fraction was established to be 21β, 22α-diangeloyloxy-3β, 15α, 16α, 28-tetrahydroxyolean-12-ene (=21, 22-di-O-angeloyl-R1-bar-rigenol) (1). The structure of the prosapogenin was identified as 21β-(3, 4-di-O-angeloyl-β-D-fucopyranosyl) oxy-3β, 16α, 22α, 24, 28-pentahydroxyolean-12-ene (napoleogenin B) (6) on the basis of spectral and X-ray crystal diffraction analyses.
Synthesis and Characterization of Stereoregular Ethylene-Vinyl Alcohol Copolymers Made by Ring-Opening Metathesis Polymerization (2005)

The syntheses of regioregular as well as stereoregular ethylene-vinyl alcohol (EVOH) copolymers by ring-opening metathesis polymerization (ROMP) with ruthenium catalysts are reported. Symmetric cyclooctenediol monomers were protected as acetates, carbonates, or acetonides to temporarily increase ring strain as well as impart solubility to the monomer. Polymer molecular weights could be easily controlled by either varying the monomer-to-catalyst ratio or by the addition of a chain transfer agent. Hydrogenation and subsequent deprotection of the ROMP polymers afforded the EVOH materials in high yields, and the structures were confirmed by 1H NMR and 13C NMR spectroscopies. Thermal properties of the corresponding EVOH copolymers are reported and suggest that differences in diol stereochemistry significantly affect the polymer morphology.