gebhart/patrepeval huggingface dataset:
The Unmodified (Apo) Form of Escherichia coli Acyl Carrier Protein Is a Potent Inhibitor of Cell Growth (1995)

Acyl carrier protein (ACP) is the carrier of fatty acids during their synthesis and utilization. ACPs (or ACP-like protein domains) have been found throughout biology and share significant amino acid sequence similarities. All ACPs undergo a post-translational modification in which 4'-phosphopantetheine is transferred from CoA to a specific serine of apo-ACP. This modification is essential for activity because fatty acids are bound in thioester linkage to the sulfhydryl of the prosthetic group. Overproduction of Escherichia coli ACP from multicopy plasmids strongly inhibits growth of E. coli. We report that upon overexpression of ACP in E. coli post-translational modification is inefficient and the apo protein accumulates and blocks cell growth by inhibition of lipid metabolism. Moreover, a mutant form of ACP that is unable to undergo post-translational modification is a potent inhibitor of growth. Finally, we observed that an increase in the efficiency of modification of overexpressed ACP results in decreased toxicity. The accumulated apo-ACP acts as a potent in vitro inhibitor of the sn-glycerol-3-phosphate acyltransferase resulting in an inability to transfer the completed fatty acid to sn-glycerol 3-phosphate. The degree of inhibition depended upon the species of donor acyl chain. Utilization of cis-vaccenoyl-ACP by the sn-glycerol-3-phosphate acyltransferase was inhibited to a much greater extent by apo-ACP than was utilization of palmitoyl-ACP. 1-Acyl glycerol-3-phosphate acyltransferase was also inhibited in vitro by apo-ACP, although not at physiologically relevant concentrations. These in vitro data are supported by in vivo labeling data, which showed a large decrease in cis-vaccenate incorporation into phospholipid during overproduction of ACP, but no decrease in the rate of synthesis of long chain acyl-ACPs. These data indicate that acylation of sn-glycerol 3-phosphate is the major site of inhibition by apo-ACP.
RANTES and Monocyte Chemoattractant Protein–1 (MCP-1) Play an Important Role in the Inflammatory Phase of Crescentic Nephritis, but Only MCP-1 Is Involved in Crescent Formation and Interstitial Fibrosis (1997)

The involvement of chemokines in inflammation is well established, but their functional role in disease progression, and particularly in the development of fibrosis, is not yet understood. To investigate the functional role that the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES play in inflammation and the progression to fibrosis during crescentic nephritis we have developed and characterized a murine model for this syndrome. Significant increases in T-lymphocytes and macrophages were observed within glomeruli and interstitium, paralleled by an induction of mRNA expression of MCP-1 and RANTES, early after disease initiation. Blocking the function of MCP-1 or RANTES resulted in significant decreases in proteinuria as well as in numbers of infiltrating leukocytes, indicating that both MCP-1 and RANTES (regulated upon activation in normal T cells expressed and secreted) play an important role in the inflammatory phase of crescentic nephritis. In addition, neutralization of MCP-1 resulted in a dramatic decrease in both glomerular crescent formation and deposition of type I collagen. These results highlight a novel role for MCP-1 in crescent formation and development of interstitial fibrosis, and indicate that in addition to recruiting inflammatory cells this chemokine is critically involved in irreversible tissue damage.
Human Fc gamma RII, in the absence of other Fc gamma receptors, mediates a phagocytic signal. (1991)

Fc gamma receptors are important components in the binding and phagocytosis of IgG-sensitized cells. Studies on the role of these receptors have been limited by the fact that most hematopoietic cells express more than one Fc gamma receptor. We studied the role of Fc gamma RIIA in isolation on a human erythroleukemia cell line (HEL) which expresses Fc gamma RIIA as its only Fc gamma receptor. HEL cells were observed to bind and phagocytose IgG-sensitized red blood cells (RBCs) in a dose-dependent manner. We then examined the role of Fc gamma RI and Fc gamma RII in isolation and in combination, in transfected COS-1 cells. Fc gamma RIIA-transfected COS cells also mediated both the binding and phagocytosis of IgG-sensitized RBCs. In contrast, phagocytosis was not observed in Fc gamma RI-transfected cells, although these cells avidly bound IgG-sensitized RBCs. Furthermore, coexpression of both receptors by doubly transfected cells did not affect the phagocytic efficiency of Fc gamma RIIA. These studies establish that Fc gamma RIIA can mediate phagocytosis and suggest that transfected COS-1 cells provide a model for examining this process. Since HEL cells exhibit characteristics of cells of the megakaryocyte-platelet lineage, including expression of Fc gamma RII as the only Fc gamma receptor, Fc gamma RIIA on megakaryocytes and platelets may be involved in the ingestion of IgG-containing immune complexes. Furthermore, these studies indicate that Fc gamma RI and Fc gamma RIIA differ in their requirements for transduction of a phagocytic signal.
Brillouin scattering in systems of biological significance (1979)

Abstract Brillouin scattering spectra, with a single mode argon-ion laser and triple-pass Fabry-Perot interferometer, have been measured for natural biological fibres and for films of synthetic polypeptides. For wet unstretched rat tail collagen, with the scattering vector parallel and perpendicular to the fibre axis, single Brillouin shifts of ± 7.9 GHz and ± 6.3 GHz respectively were observed. With the scattering vector at 45° to the fibre axis, two peaks ( ± 6.35 GHz and ± 7.7 GHz) were found. For horse hair keratin the shifts for the scattering vector parallel and perpendicular to the fibre axis were ± 8.7 GHz and ± 7.7 GHz respectively. A single peak only was found with the vector at 40° to the fibre axis. Two synthetic polypeptides poly(DL-caprylic acid) and poly(Y-ethyl-L-glutamate), known to have the a-helix conformation, gave shifts of ± 6.36 and ± 6.1 GHz. The results are discussed.
Fibrotic sequelae in pulmonary paracoccidioidomycosis: histopathological aspects in BALB/c mice infected with viable and non-viable Paracoccidioides brasiliensis propagules (2000)

Patients with paracoccidioidomycosis often present pulmonary fibrosis and exhibit important respiratory limitations. Based on an already established animal model, the contribution of viable and non-viable P. brasiliensis propagules to the development of fibrosis was investigated. BALB/c male mice, 4-6 weeks old were inoculated intranasally either with 4x10(6) viable conidia (Group I), or 6. 5x10(6) fragmented yeast cells (Group II). Control animals received PBS. Six mice per period were sacrificed at 24, 48, 72h (initial) and 1, 2, 4, 8, 12 and 16 weeks post-challenge (late). Paraffin embedded lungs were sectioned and stained with H&E, trichromic (Masson), reticulin and Grocot&tacute;s. During the initial period PMNs influx was important in both groups and acute inflammation involving 34% to 45% of the lungs was noticed. Later on, mononuclear cells predominated. In group I, the inflammation progressed and granulomas were formed and by the 12th week they fussed and became loose. Thick collagen I fibers were observed in 66.6% and 83.3% of the animals at 8 and 12 weeks, respectively. Collagen III, thick fibers became apparent in some animals at 4 weeks and by 12 weeks, 83% of them exhibited alterations in the organization and thickness of these elements. In group II mice, this pattern was different with stepwise decrease in the number of inflammatory foci and lack of granulomas. Although initially most animals in this group had minor alterations in thin collagen I fibers, they disappeared by the 4th week. Results indicate that tissue response to fragmented yeast cells was transitory while viable conidia evoked a progressive inflammatory reaction leading to granuloma formation and to excess production and/or disarrangement of collagens I and III; the latter led to fibrosis.
OFDM blind carrier offset estimation: ESPRIT (2000)

In orthogonal frequency-division multiplex (OFDM) communications, the loss of orthogonality due to the carrier-frequency offset must be compensated before discrete Fourier transform-based demodulation can be performed. This paper proposes a new carrier offset estimation technique for OFDM communications over a frequency-selective fading channel. We exploit the intrinsic structure information of OFDM signals to derive a carrier offset estimator that offers the accuracy of a super resolution subspace method, ESPRIT.
Competitive Triplex/Quadruplex Equilibria Involving Guanine-Rich Oligonucleotides (1995)

Oligonucleotide-directed triple helix formation in the purine motif involves the binding of guanine-rich oligonucleotides to duplex DNA. Although this approach has been proposed for in vivo gene inhibition, triple helix formation by guanine-rich oligonucleotides is severely inhibited by physiological concentrations of certain monovalent cations (M+), especially K+. To clarify the mechanism of this inhibition, electrophoretic gel mobility shift titrations were performed to analyze the formation and stability of a purine motif triple helix in the presence of M+ and to monitor oligonucleotide aggregation under these conditions. M+ inhibition of triplex formation exhibited a concentration and ionic radius dependence that correlates with the ability of M+ to stabilize guanine quartet structures. In the presence of inhibitory [M+], guanine-rich oligonucleotides formed aggregates having characteristics consistent with the involvement of guanine quartets. The inhibitory effects of K+ on triplex formation could not be reversed by addition of the physiological polyamines spermidine3+ or spermine4+. M+ reduced the equilibrium concentration of the triplex primarily by decreasing the rate of triplex formation, but M+ also caused a detectable increase in the rate of triplex dissociation. Together, these results suggest that triplex inhibition under physiological ionic conditions is caused by competing equilibria wherein guanine-rich oligonucleotides form aggregates involving guanine quartets. Approaches to destabilizing aggregates of guanine-rich oligonucleotides under physiological conditions will be required before in vivo applications can be realistically considered.
Separation of cochannel signals under imperfect timing and carrier synchronization (2001)

We propose a complete receiver for separating cochannel signals in a time-division multiple-access type system when the timing and carrier synchronization are imperfect or only nominally accomplished. The receiver is all digital, data aided, assumes the presence of multiple antennas at the receiver, and has three functional components. The first part computes the timing offsets of the different cochannel users through a maximum likelihood search. The second part uses a bank of filters on an oversampled version of the baseband signals to obtain a new symbol rate sampled signal in which the different users are all synchronous but are still spatially mixed and rotated with unknown carrier offsets. The third part uses an extended Kalman-filter-based algorithm to estimate the parameters of this model and to separate and decode the transmitted signals of the different users. The performance of this receiver is demonstrated with simulations. This work is significant in the context of smart antenna technology, considered as a potentially significant improvement to wireless systems, since it is a complete solution encompassing flat fading, timing error, and frequency offsets for multiple cochannel users.
A novel neutrophil-activating factor produced by human mononuclear phagocytes. (1988)

The biological properties of a neutrophil-activating factor (NAF), which was recently identified as a novel peptide of approximately 6,000 mol wt, are described. NAF is produced de novo by human blood monocytes upon stimulation with LPS, PHA, and Con A. It induces two main responses in human neutrophils, i.e., exocytosis (release from specific granules in normal, and from specific and azurophil granules in cytochalasin B-treated cells) and the respiratory burst (formation of superoxide and hydrogen peroxide). The action of NAF appears to be mediated by a surface receptor as shown by the following observations. (a) NAF induces a rapid and transient rise in cytosolic free Ca2+; (b) interaction with NAF results in desensitization, since the cells do not respond to a second NAF challenge; and (c) the respiratory burst elicited by NAF is similar in onset, and time course to that induced by C5a or FMLP. The NAF receptor can be distinguished from the receptors of C5a, FMLP, platelet-activating factor, and leukotriene B4 by the lack of cross-desensitization. Unlike C5a, the other host-derived neutrophil-activating peptide, NAF is not inactivated by serum and thus presumably accumulates in inflamed tissue.
Electrostatic potentials and protein partitioning in aqueous two‐phase systems (1991)

Abstract A thermodynamic analysis unambiguously relates interfacial‐electrostatic‐potential differences measured with Ag/AgCl capillary electrodes to the equilibrium properties of an aqueous two‐phase system. Interfacial electrostatic potentials were measured as a function of total α‐cyclodextrin concentration in an aqueous two‐phase system containing 9.1 wt. % poly (ethylene glycol), 6.1 wt. % Dextran T‐70, and 1‐mM potassium iodide. An order‐of‐magnitude increase in the interfacial electrostatic potential was observed as the total concentration of α‐cyclodextrin increased from 0 to 1 mM. Measured partition coefficients for α‐chymotrypsin, lysozyme, and bovine serum albumin depend strongly on α‐cyclodextrin concentration. For example, as the concentration of α‐cyclodextrin rises from 0 to 1 mM, the partition coefficient of lysozyme decreases from 1.7 to 0.55. These measurements are in good agreement with theoretical expectations.
Spindle Multipolarity Is Prevented by Centrosomal Clustering (2005)

Most tumor cells are characterized by increased genomic instability and chromosome segregational defects, often associated with hyperamplification of the centrosome and the formation of multipolar spindles. However, extra centrosomes do not always lead to multipolarity. Here, we describe a process of centrosomal clustering that prevented the formation of multipolar spindles in noncancer cells. Noncancer cells needed to overcome this clustering mechanism to allow multipolar spindles to form at a high frequency. The microtubule motor cytoplasmic dynein was a critical part of this coalescing machinery, and in some tumor cells overexpression of the spindle protein NuMA interfered with dynein localization, promoting multipolarity.
Catalytic efficiency determines the in-vivo efficacy of PON1 for detoxifying organophosphorus compounds (2000)

Human paraoxonase (PON1) is a polymorphic, high-density lipoprotein (HDL)-associated esterase that hydrolyzes the toxic metabolites of several organophosphorus (OP) insecticides and nerve agents. The activity polymorphism is determined by a Gln/Arg (Q/R) substitution at position 192. Injection of purified PON1 protects animals from OP poisoning. In the present study, we investigated the in-vivo function of PON1 for detoxifying organophosphorus insecticides in PON1-knockout mice that were challenged via dermal exposure with diazoxon, diazinon and paraoxon. PON1-knockout mice were extremely sensitive to diazoxon. Doses (2 and 4 mg/kg) that caused no cholinesterase (ChE) inhibition in wild-type mice were lethal to the knockout mice, which also showed slightly increased sensitivity to the parent compound diazinon. Surprisingly, these knockout mice did not show increased sensitivity to paraoxon. In-vitro assays indicated that the PON1R192 isoform hydrolyzed diazoxon less rapidly than did the PON1Q192 isoform. In-vivo analysis, where PON1-knockout mice received the same amount of either PON1(192) isoform via intraperitoneal (i.p.) injection 4 h prior to exposure, showed that both isoforms provided a similar degree of protection against diazoxon, while PON1R192 conferred better protection against chlorpyrifos-oxon than PON1Q192. Injection of purified rabbit PON1 or either human PON1(192) isoform did not protect PONI-knockout mice from paraoxon toxicity, nor did over-expression of the human PON1R192 transgene in wild-type mice. Kinetic analysis of the two human PON1(192) isoforms revealed that the catalytic efficiency (Vmax/Km) determines the in-vivo efficacy of PON1 for organophosphorus detoxication. The results indicate that PON1 plays a major role in the detoxication of diazoxon and chlorpyrifos oxon but not paraoxon.
Role of Oxidants and Antioxidants in the Induction of AP-1, NF-κB, and Glutathione S-Transferase Gene Expression (1996)

Transcription factors AP-1 and NF-kappaB have been implicated in the inducible expression of a variety of genes in response to oxidative stress. Recently, based on the observation that butylated hydroxyanisole (BHA) and pyrrolidine dithiocarbamate (PDTC) induce AP-1 binding activity and AP-1-dependent gene expression and assuming that these compounds exert an antioxidant effect, it was claimed that AP-1 is an antioxidant-responsive factor. To determine whether AP-1 can be responsive to both oxidant and antioxidant, we examined the nature of BHA and PDTC inducing activity. Using EPR spectroscopy to detect semiquinone radicals, we demonstrate the autoxidation of BHA metabolite tert-butylhydroquinone (TBHQ) to tert-butylquinone. The kinetics of TBHQ-mediated generation of .OH radicals were monitored in intact hepatoma HepG2 cells by EPR spin trapping technique. Exogenous catalase inhibited the rate and amount of .OH radical formation and the induction of AP-1-mediated glutathione S-transferase (GST) Ya gene expression by BHA and TBHQ, thus indicating the intermediate formation of H2O2 in the metabolism of these chemicals. Furthermore, we show that the induction of AP-1 and NF-kappaB activities and GST Ya gene expression by BHA and TBHQ is due to a pro-oxidant activity, since this induction was inhibited by thiol compounds N-acetyl cysteine and GSH. Similarly, induction of AP-1 and GST Ya gene expression by PDTC was inhibited by N-acetyl cysteine and GSH. The present findings do not support the notion that the induction of AP-1 by BHA, TBHQ, or PDTC is an antioxidant response and demonstrate that both AP-1 and NF-kappaB activities are induced by oxygen radicals.
Glycosylidene Carbenes. Part 27. Glucosidation of titanium dioxide with 1‐aziglucoses: Preparation and characterization of modified titanium‐dioxide surfaces (1998)

Abstract Titanium‐dioxide surfaces have been glycosylated with the benzyl‐, 4‐fluorobenzyl‐, and acetyl‐protected diazirines 1 – 3 . The modified TiO 2 surfaces were characterized by contact‐angle measurement, X‐ray photoelectron spectroscopy (XPES), and time‐of‐flight secondary‐ion mass spectrometry (ToF‐SIMS). The main by‐products of the glucosidation (mostly azines and trehaloses) were identified. Their physisorption slightly reduces the efficiency of the glucosidation by 1 m M solution of 1 or 2 in CH 2 Cl 2 , but this influence is neutralized by repeating the glucosidation, or by using a 100 m M solution of the diazirines. The immobilized, acetylated glucosyl moieties were deacetylated in situ . Calculations based on the XPES peaks of Ti 2p and F 1s for the TiO 2 surface modified with 2 indicated 1.5 ± 0.9 immobilized glucosyl moieties per nm 2 .
Regulation of human intestinal mast cells by stem cell factor and IL‐4 (2001)

Mature human mast cells are tissue-residing, key effector cells of immediate allergic reactions. Moreover, mast cells have been recognized as a potent cellular source of multiple cytokines, suggesting an important role in immunoregulation and host defense. Here, we report on the regulation of mature human mast cells isolated from intestinal tissues by stem cell factor (SCF) and interleukin (IL)-4. SCF is substantially necessary for mast cell survival and induces marginal mast cell proliferation in vitro, whereas IL-4 by itself has no effects on mast cell survival or proliferation. Most interestingly, in synergy with SCF, IL-4 strongly enhances mast cell proliferation. In the presence of SCF, mast cells predominantly produce pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6, IL-8, IL-16, and IL-18. Addition of IL-4 to the culture medium induces the expression of Th2-type cytokines (IL-3, IL-5 and IL-13), and a downregulation of pro-inflammatory cytokines, namely IL-6. Furthermore, SCF by itself supports the predominance of the tryptase/chymase double-positive mast cell subtype MCTC whereas the addition of IL-4 supports the chymase negative MCT subtype. In conclusion, SCF may primarily regulate resident mast cell survival, whereas IL-4 may promote local proliferation of mast cells and their expression of Th2-type cytokines.
Determination of Glucose in Submicroliter Samples by CE−LIF Using Precolumn or On-Column Enzymatic Reactions (1997)

Two enzymatic reactions combined with capillary electrophoresis (CE) are used to determine glucose contained in sample volumes of ≤500 nL. In the first enzymatic reaction, glucose is oxidized in the presence of glucose oxidase producing hydrogen peroxide, which reacts quantitatively with the fluorogenic compound homovanillic acid catalyzed by the enzyme peroxidase. The second reaction generates a fluorescent species that is proportional to the glucose concentration. The reaction product is determined by CE using laser-induced fluorescence (LIF) as the detection mode. The overall reaction scheme is faster than commonly used precolumn derivatization procedures and can be performed using very small sample quantities. Alternatively, the enzymatic reactions can be performed on-column, similar to the electrophoretically mediated microanalysis approach, accommodating sample quantities in the nanoliter range. The on-column reaction is a simple and practical approach for the determination of glucose contained in low-volume samples by CE-LIF, where samples are injected directly into the capillary column without any pretreatment. However, sample handling and detectability of the precolumn approach proved to be superior. Determination of glucose using the precolumn and on-column reactions showed detection limits of 50 and 800 nM, respectively. The methods were shown to be linear in the range tested, 1−100 μM and 100 nM−30 μM, for the on-column and precolumn reactions, respectively. The reproducibility for each scheme was <5% RSD. To determine the possibility of using a noninvasive procedure for glucose monitoring, we used the CE−LIF methods to analyze human tear samples for glucose. The tear fluid samples were contained in a volume of ∼200 nL. The concentration of glucose in the human tear samples analyzed using the precolumn and on-column procedures was ∼138 μM.