gebhart/patrepeval huggingface dataset:
Decreased Reverse Cholesterol Transport from Tangier Disease Fibroblasts (1997)

Tangier disease is characterized by HDL hypercatabolism and increased deposition of cholesterol in tissues. Tangier disease skin fibroblasts have decreased apoA-I-mediated cholesterol and phospholipid efflux, which may lead to the excess accumulation of cellular cholesterol. The mechanism of apolipoprotein-mediated cholesterol efflux and the apolipoprotein acceptor specificity for cholesterol efflux from normal and Tangier disease fibroblasts was investigated. Normal cells readily effluxed cholesterol and phospholipid to apoA-I and to all of the other apolipoproteins tested (apoA-II, AIV, C-I, C-II, C-III). In contrast, Tangier cells were almost completely defective in cholesterol efflux to apoA-I and to all of the other apolipoproteins tested. HDL was also less effective, by approximately 50%, in stimulating cholesterol efflux from Tangier cells compared with normal cells. In addition, Tangier cells also showed significantly reduced phospholipid efflux to both apolipoproteins and HDL. A similar rate of cholesterol efflux, however, was observed from normal and Tangier cells when phospholipid vesicles or cyclodextrin were used as acceptors. In contrast to normal cells, only phospholipid vesicles and cyclodextrin and not apoA-I or HDL depleted intracellular cholesteryl esters from Tangier cells. Brefeldin, an inhibitor of intracellular vesicular trafficking, decreased HDL-mediated cholesterol efflux by approximately 40% but almost completely blocked both cholesterol and phospholipid efflux to apoA-I from normal cells. Brefeldin also inhibited cholesteryl ester depletion by apoA-I and HDL from normal cells. Brefeldin, however, had no significant effect on cholesterol efflux from Tangier cells to HDL. In summary, Tangier cells were found to be defective in both cholesterol and phospholipid efflux to HDL and apoA-I. The defect in apolipoprotein-mediated lipid efflux was not specific for apoA-I but also occurred for other apolipoproteins, and brefeldin blocked HDL-mediated lipid efflux from normal but not Tangier disease cells. On the basis of these results, a model is proposed whereby decreased cholesterol efflux by apolipoproteins in Tangier cells is the result of a defect in a brefeldin-sensitive pathway of lipid efflux.
Autoantigen-Specific TGFβ-Induced Foxp3+ Regulatory T Cells Prevent Autoimmunity by Inhibiting Dendritic Cells from Activating Autoreactive T Cells (2007)

Several strategies are being designed to test the therapeutic potential of Ag-specific regulatory T cells to prevent or treat autoimmune diseases. In this study, we demonstrate that naive CD4+ Foxp3- T cells specific for a naturally expressed autoantigen (H+/K+ ATPase) can be converted to Foxp3+ T regulatory cells (Tregs) when stimulated in presence of TGFbeta. TGFbeta-induced Tregs (iTregs) have all the characteristics of naturally generated regulatory T cells in vitro, and more importantly, are effective at preventing organ-specific autoimmunity in a murine model of autoimmune gastritis. H+/K+ ATPase specific iTregs were able to inhibit the initial priming and proliferation of autoreactive T cells, and appear to do so by acting on H+/K+ ATPase presenting dendritic cells (DC). DC exposed to iTregs in vivo were reduced in their ability to stimulate proliferation and cytokine production by H+/K+ ATPase specific T cells. iTregs specifically reduced CD80 and CD86 expression on the surface of H+/K+ ATPase presenting DC in vitro. These studies reveal the therapeutic potential of Ag specific iTregs to prevent autoimmunity, and provide a mechanism by which this population of regulatory T cells, and perhaps others, mediate their suppressive effects in vivo.
Control of Metal Nanocrystal Size Reveals Metal-Support Interface Role for Ceria Catalysts (2013)

Interactions between ceria (CeO2) and supported metals greatly enhance rates for a number of important reactions. However, direct relationships between structure and function in these catalysts have been difficult to extract because the samples studied either were heterogeneous or were model systems dissimilar to working catalysts. We report rate measurements on samples in which the length of the ceria-metal interface was tailored by the use of monodisperse nickel, palladium, and platinum nanocrystals. We found that carbon monoxide oxidation in ceria-based catalysts is greatly enhanced at the ceria-metal interface sites for a range of group VIII metal catalysts, clarifying the pivotal role played by the support.
Determination of the human type I interferon receptor binding site on human interferon‐α2 by cross saturation and an NMR‐based model of the complex (2006)

Type I interferons (IFNs) are a family of homologous helical cytokines that exhibit pleiotropic effects on a wide variety of cell types, including antiviral activity and antibacterial, antiprozoal, immunomodulatory, and cell growth regulatory functions. Consequently, IFNs are the human proteins most widely used in the treatment of several kinds of cancer, hepatitis C, and multiple sclerosis. All type I IFNs bind to a cell surface receptor consisting of two subunits, IFNAR1 and IFNAR2, associating upon binding of interferon. The structure of the extracellular domain of IFNAR2 (R2-EC) was solved recently. Here we study the complex and the binding interface of IFNalpha2 with R2-EC using multidimensional NMR techniques. NMR shows that IFNalpha2 does not undergo significant structural changes upon binding to its receptor, suggesting a lock-and-key mechanism for binding. Cross saturation experiments were used to determine the receptor binding site upon IFNalpha2. The NMR data and previously published mutagenesis data were used to derive a docking model of the complex with an RMSD of 1 Angstrom, and its well-defined orientation between IFNalpha2 and R2-EC and the structural quality greatly improve upon previously suggested models. The relative ligand-receptor orientation is believed to be important for interferon signaling and possibly one of the parameters that distinguish the different IFN I subtypes. This structural information provides important insight into interferon signaling processes and may allow improvement in the development of therapeutically used IFNs and IFN-like molecules.
Efficacy of dexmedetomidine for prevention of emergence agitation in patients posted for nasal surgery under desflurane anaesthesia: A prospective double-blinded randomised controlled trial (2018)

Dexmedetomidine significantly reduced the incidence of EA and requirement of desflurane in patients undergoing nasal surgery. However, it was associated with delayed extubation, residual sedation, and prolonged PACU stay.
Characterization of a Germ-Line Deletion, Including the Entire INK4/ARF Locus, in a Melanoma-Neural System Tumor Family: Identification of ANRIL , an Antisense Noncoding RNA Whose Expression Coclusters with ARF (2007)

We have previously detected a large germ-line deletion, which included the entire p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster, in the largest melanoma-neural system tumor (NST) syndrome family known to date by means of heterozygosity mapping based on microsatellite markers. Here, we used gene dose mapping with sequence-tagged site real-time PCR to locate the deletion end points, which were then precisely characterized by means of long-range PCR and nucleotide sequencing. The deletion was exactly 403,231 bp long and included the entire p15/CDKN2B, p16/CDKN2A, and p14/ARF genes. We then developed a simple and rapid assay to detect the junction fragment and to serve as a direct predictive DNA test for this large French family. We identified a new large antisense noncoding RNA (named ANRIL) within the 403-kb germ-line deletion, with a first exon located in the promoter of the p14/ARF gene and overlapping the two exons of p15/CDKN2B. Expression of ANRIL mainly coclustered with p14/ARF both in physiologic (various normal human tissues) and in pathologic conditions (human breast tumors). This study points to the existence of a new gene within the p15/CDKN2B-p16/CDKN2A-p14/ARF locus putatively involved in melanoma-NST syndrome families and in melanoma-prone families with no identified p16/CDKN2A mutations as well as in somatic tumors.
Simultaneous rapid culture for four respiratory viruses in the same cell monolayer using a differential multicolored fluorescent confirmatory stain (1996)

A simultaneous rapid culture for influenza virus types A and B, parainfluenza virus, and respiratory syncytial virus was developed in a 96-well plate format with a culture-confirmatory stain using multiple fluorescent tags. Performance characteristics were comparable to those of standard and/or single rapid-culture methods as shown by parallel testing of 590 fresh clinical specimens and retrospective testing of 190 previously positive frozen specimens. The quadruple culture required less specimen volume than separate cultures, was significantly quicker than standard tube culture, was less labor intensive than separate cultures, and was less expensive than the other methods.
HERG Channel Dysfunction in Human Long QT Syndrome (1998)

Mutations in HERG are associated with human chromosome 7-linked congenital long QT (LQT-2) syndrome. We used electrophysiological, biochemical, and immunohistochemical methods to study the molecular mechanisms of HERG channel dysfunction caused by LQT-2 mutations. Wild type HERG and LQT-2 mutations were studied by stable and transient expression in HEK 293 cells. We found that some mutations (Y611H and V822M) caused defects in biosynthetic processing of HERG channels with the protein retained in the endoplasmic reticulum. Other mutations (I593R and G628S) were processed similarly to wild type HERG protein, but these mutations did not produce functional channels. In contrast, the T474I mutation expressed HERG current but with altered gating properties. These findings suggest that the loss of HERG channel function in LQT-2 mutations is caused by multiple mechanisms including abnormal channel processing, the generation of nonfunctional channels, and altered channel gating.
Expressão de proteínas reguladoras do complemento CD55, CD59, CD35 e CD46 na artrite reumatoide (2011)

Rheumatoid arthritis (RA) is an autoimmune disease associated with polyarticular inflammatory synovitis affecting mainly peripheral joints. It affects approximately 1% of the world population, being two to three times more prevalent in women. Rheumatoid arthritis has a complex and multifactorial pathogenesis. The synovium of the affected joints is infiltrated by T and B lymphocytes, macrophages, and granulocytes. The rheumatoid synovium has proliferative characteristics, forming the pannus, which invades cartilage and bone, leading to normal architecture destruction and function loss. The decreased expression of complement regulatory proteins (CRP) seems to play an important role in RA activity, and is associated with worsening of the clinical symptoms. In several models of autoimmune diseases, the overactivation of the complement system (CS) is the cause of disease exacerbation. This article aimed at reviewing the main aspects related to CS regulation in RA in order to provide a better understanding of the potential role of this system in the pathophysiology and activity of the disease.
Design of a Novel Fibronectin-Mimetic Peptide−Amphiphile for Functionalized Biomaterials (2006)

The interaction of the alpha5beta1 integrin with its ligand, fibronectin, supports numerous adhesive functions and has an important role in health and disease. In recent years, there has been a considerable effort in designing fibronectin-mimetic peptides to target the integrin. However, to date, the therapeutic use of these peptides has been limited, as they cannot accurately mimic fibronectin's binding affinity for alpha5beta1. A peptide-amphiphile (PR_b) was synthesized with a peptide headgroup composed of four building blocks: a spacer; RGDSP, the primary recognition site for alpha5beta1; PHSRN, the synergy binding site; and a linker. The linker was designed to mimic two important criteria: the distance and the hydrophobicity/hydrophilicity between PHSRN and RGD in fibronectin. Human umbilical vein endothelial cells were seeded on different substrates and evaluated in terms of adhesion, spreading, specificity, cytoskeleton organization, focal adhesions, and secretion of extracellular fibronectin. This peptide was shown to perform comparably to fibronectin, indicating that a biomimetic approach can result in the design of novel peptides with therapeutic potential for biomaterial functionalization.
Utility of metabolic stability screening: comparison ofin vitroandin vivoclearance (2001)

1. The ability of hepatic microsomal metabolic stability assessments to predict in vivo clearance in rat has been retrospectively evaluated for 1,163 compounds from 48 programmes of chemistry. Using a simple binary classification system, the in vivo clearances of approximately 64% of the compounds were correctly classified. 2. About 24% of compounds were metalbolically stable yet had clearance greater than half of liver blood flow in vivo. This might be expected as microsomes only contain a limited number of fully functioning drug-metabolizing enzymes and cannot be expected to account for extrahepatic or non-metabolic clearance processes. 3. About 13% of compounds had in vivo clearances of less than half liver blood flow despite being classified as metabolically unstable. Despite overcoming metabolic instability, these compounds had other undesirable properties and were generally more highly bound to plasma proteins, had smaller volumes of distribution (and shorter half-lives despite their clearance) and were more inhibitory against the major human cytochrome P450s. 4. Taking plasma protein binding into consideration reduced the proportion of misclassified low-clearance compounds but did not improve the overall success appreciably. Somewhat surprisingly, human microsomes were nearly as effective as rat microsomes at classifying rat in vivo clearance.
Identification of a gene that regulates expression of M protein, the major virulence determinant of group A streptococci. (1987)

By using Tn916 insertional mutagenesis, we have identified mry (M protein RNA yield), a gene required for high-level expression of the M protein, an essential virulence determinant of the group A streptococcus. The mry::Tn916 mutation causes a reduction by a factor of approximately equal to 50 in the amount of M protein produced, in the original strain and in a nonmutagenized host to which the mutation was transferred by transduction. The insertion is located approximately 1.8 kilobases upstream of the structural gene for M protein (emm) and its promoter. The genomic region including mry::Tn916 and emm was cloned on a cosmid vector and introduced into Escherichia coli. When the transposon excised precisely from the chimeric cosmid in E. coli, the resulting streptococcal DNA showed the same restriction pattern as the homologous chromosomal region in the parental nonmutagenized streptococcus. The sequence of the promoter for emm was not altered in the mry mutant. The reduction in protein correlates with a decrease in the amount of M protein-specific mRNA, indicating that mry regulates transcription of emm.
Homogeneous and heterogenized Au(iii) Schiff base-complexes as selective and general catalysts for self-coupling of aryl boronic acids (2005)

A series of homogeneous and heterogenized gold metal complexes show high activity and selectivity for the homocoupling of a large variety of aryl boronic acids, being of general utility for the synthesis of C2-symmetric biaryls.
Association of Asthma with Serum IgE Levels and Skin-Test Reactivity to Allergens (1989)

We investigated the association of self-reported asthma or allergic rhinitis with serum IgE levels and skin-test reactivity to allergens in 2657 subjects in a general-population study. Regardless of the subjects' status with respect to atopy or their age group, the prevalence of asthma was closely related to the serum IgE level standardized for age and sex (P less than 0.0001), and no asthma was present in the 177 subjects with the lowest IgE levels for their age and sex (greater than 1.46 SD below the mean). The log odds ratio increased linearly with the serum IgE level after we controlled for possible confounders and the degree of reactivity to skin tests. In contrast, allergic rhinitis appeared to be associated primarily with skin-test reactions to common aeroallergens, independently of the serum IgE level. We conclude that asthma is almost always associated with some type of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in the battery of common aeroallergens we used to assess atopic status. These findings challenge the concept that there are basic differences between so-called allergic ("extrinsic") and nonallergic ("intrinsic") forms of asthma.
The Association of Mutans Streptococci and Non-Mutans Streptococci Capable of Acidogenesis at a Low pH with Dental Caries on Enamel and Root Surfaces (1993)

Coronal dental plaque from each of 12 caries-positive subjects (Group I) was pooled from "white spot" tooth surface areas and, separately, from sound surface areas; sound surface areas in each of 18 caries-free subjects (Group II) were sampled similarly. Two samples, one consisting of material from a root-surface lesion and another of plaque from a sound root-surface area, were obtained from each of another 10 subjects (Group III). The samples from Groups I and II were evaluated for: (1) pH-lowering potential in vitro with dispersed plaque suspensions, excess glucose supply, and a 60-minute test; (2) the levels of mutans streptococci (MS) and lactobacilli; and (3) the distribution of the predominant non-mutans streptococci (non-MS) according to their final pH in glucose broth; only microbial analysis was done for the Group III samples. The levels of the MS were generally positively associated with caries. A weaker positive association was found for the levels of those non-MS capable of acidogenesis at low pH (final pH < 4.4). The latter generally far outnumbered the MS in all types of samples. The levels of lactobacilli were nearly always very low. The pH-lowering potential (final pH and pH drop rate) was higher for plaque from "white spot" areas than for plaque from sound surface areas (Group I). The samples from caries-free subjects (Group II), however, exhibited a pH-lowering potential which was not significantly different from that of both types of samples from the caries-active subjects (Group I).(ABSTRACT TRUNCATED AT 250 WORDS)
New developments on the cheminformatics open workflow environment CDK-Taverna (2011)

CDK-Taverna 2.0 as an open-source cheminformatics workflow solution matured to become a freely available and increasingly powerful tool for the biosciences. The combination of the new CDK-Taverna worker family with the already available workflows developed by a lively Taverna community and published on myexperiment.org enables molecular scientists to quickly calculate, process and analyse molecular data as typically found in e.g. today's systems biology scenarios.
Analysis of least congested path routing in WDM lightwave networks (2002)

Analyzes an adaptive routing rule in a WDM lightwave network. Each switching node in the network may have a number of wavelength converters which can be used to resolve wavelength conflicts in multi-hop paths. The authors found that without any wavelength converters, the wavelength conflict possesses an inherent blocking to alternate route traffic and that the use of wavelength converter to resolve wavelength conflicts does not give any significant reduction of blocking probability.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The translation in vitro of rat ornithine decarboxylase mRNA is blocked by its 5′ untranslated region in a polyamine-independent way (1991)

The enzyme ornithine decarboxylase (ODC, EC 4.1.1.17) is believed to play an essential role in the growth and differentiation of cells by regulating the biosynthesis of polyamines. The 5′ untranslated region (5′ UTR) of the ODC mRNA of different species is rather unusual in length and GC content, and may therefore be involved in translational control of ODC protein synthesis. We cloned the rat ODC cDNA downstream of the phage T7 promoter in order to perform transcription/translation studies in vitro. Our results show that the intact 5′ UTR of rat ODC mRNA, which is 303 nt in length, is a potent inhibitor of translation. Efficient synthesis in vitro of ODC protein is obtained when either 172 nt from the 5′-end or 236 nt from the 3′-end of the 5′ UTR are removed. A truncated 5′ UTR with a calculated free energy of less than -272 kJ (-65 kcal/mol) is unable to support the synthesis in vitro of ODC protein. The short open reading frame (ORF) present in the 5′ UTR of rat ODC mRNA does not contribute to the observed inhibitory effect on translation efficiency in vitro. At low polyamine concentration the efficiency of translation in vitro of intact ODC mRNA is not relatively increased compared with that of an ODC mRNA having a truncated 5′ UTR or with that of control globin mRNA. From this we conclude that the well-documented negative feedback control of intracellular polyamines on ODC expression is not regulated by effects of polyamines on the secondary structure of the 5′ UTR of ODC mRNA.
Influence of Specific Signal Peptide Mutations on the Expression and Secretion of the α-Amylase Inhibitor Tendamistat in (1996)

The Streptomyces alpha-amylase inhibitor tendamistat is secreted by a signal peptide with an amino-terminal charge of +3. To elucidate the influence of the charged residues on protein secretion in Streptomyces, the amino-terminal charge was varied from +6 to neutral net charge. The effects of charge variation were analyzed in combination with three Streptomyces promoters and two transcriptional terminators. Introduction of additional positive charges significantly decreased the amount of secreted tendamistat. On the contrary, a charge reduction to +2 resulted in the doubling of inhibitor production. After exclusion of transcriptional effects, the observed alterations of inhibitor secretion by the mutants with a charge of +6 to +2 were attributed to a modulation of precursor synthesis. Furthermore, a tight coupling of synthesis and export was stated. Charge reduction to +1 or neutral charge generally reduced the yield of secreted tendamistat, yet remarkable differences were found for mutants with identical net charge. Elimination of the positive charge at a defined position resulted in the release of tendamistat precursor protein, which suggested a specific uncoupling of synthesis and translocation.
Highly Potent and Selective Ligands for a New Class H3 of Histamine Receptor (1988)

The third histamine receptor was first indentified on brain neurons and seems to be present in other cells such as lung mast cells. Hence the novel and potent H3-receptor agonist (R) alpha-methylhistamine might find therapeutic applications in allergic diseases.