gebhart/patrepeval huggingface dataset:
Selective tolerization of Th1-like cells after nasal administration of a cholera toxoid-LACK conjugate (1998)

Recent reports have suggested that after infection of BALB/c mice with Leishmania major, CD4+ T cells responding to a single antigen, LACK (Leishmaniahomologue of receptors for activated C kinase), drive the differentiation of other responding T cells to the Th2 phenotype and so allow lesion development to occur. Transgenic mice expressing LACK in the thymus are tolerant to LACK and thus resolve infection with L. major. The oral administration of soluble protein to mice has been shown to result in the peripheral tolerance of antigen-specific CD4+ T cells. We therefore sought to tolerize LACK reactive T cells in non-transgenic BALB/c mice in order to determine the effectiveness of this tolerization approach as an alternative to standard vaccination protocols againist L. majorinfection. Surprisingly, oral or nasal administration of up to 8 mg of recombinant LACK did not affect the outcome of infection. We therefore conjugated LACK to cholera toxin β subunit (CTB-LACK) which has previously been shown to improve the effectiveness of oral tolerance to conjugated antigens. Nasal administration of as little as 12 μg of CTB-LACK effectively diminished the capacity of mice to mount a subsequent proliferative response to LACK and further delayed the onset of lesion development in infected mice. However, pretreatment with CTB-LACK did not prevent the eventual onset and progression of disease in these mice. An examination of cytokine responsiveness to LACK after tolerization with CTB-LACK revealed that while the Th1 response to LACK was suppressed, Th2 cytokine production was unaffected. Similar experiments using an ovalbumin-CTB conjugate suggested that this selective tolerance of Th1 cells was not specific to the LACK protein but may be an effect common to CTB-conjugated proteins.
Escherichia coliType 1 Pili (2014)

This chapter concentrates on what the author thinks are the essential features of Escherichia coli type 1 pili as models of host-pathogen interactions, gene regulation, supramolecular assembly, and receptor binding. The majority of E. coli strains fell into group 1, which had the structures that were to become known as type 1 pili. Type 1 pili grow from the base. That is, new pilin monomers (fimA gene products) are added to the bottom of the growing fiber rather than at the tip. There are only two additional gene products required for this polymerization process. These are the products of the fimC and fimD genes. A chaperone molecule is believed to be necessary in order to keep the pilin molecules from aggregating prematurely and to stabilize the minor pilus components during their time in the periplasm. Type 1 pili have provided paradigms for a number of central biological processes including host-pathogen interactions, gene regulation, assembly of supramolecular structures, and receptor-ligand interactions. The chapter highlights areas that still present interesting challenges to understanding of type 1 pili structures and their function.
Apolipoprotein A-I Regulates Lipid Hydrolysis by Hepatic Lipase (2000)

Association of hepatic lipase (HL) with pure heparan sulfate proteoglycans (HSPG) has little effect on hydrolysis of high density lipoprotein (HDL) particles, but significantly inhibits (>80%) the hydrolysis of low (LDL) and very low density lipoproteins (VLDL). Lipolytic inhibition is associated with a differential ability of the lipoproteins to remove HL from the HSPG. LDL and VLDL are unable to displace HL, whereas HDL readily displaces HL from the HSPG. These data show that HSPG-bound HL is inactive. Purified apolipoprotein (apo) A-I is more efficient than HDL at liberating HL from HSPG, and HL displacement is associated with the direct binding of apoA-I to HSPG. However, displacement of HL by apoA-I does not enhance hydrolysis of VLDL particles. This appears due to the direct inhibition of HL by apoA-I. Both apoA-I and HDL are able to inhibit VLDL lipid hydrolysis by up to 60%. Inhibition of VLDL hydrolysis is associated with the binding of apoA-I to the surface of the VLDL particle and a concomitant decreased affinity for HL. These data show that apoA-I can regulate lipid hydrolysis by HL by liberating/activating the enzyme from cell surface proteoglycans and by directly modulating lipoprotein binding and hydrolysis.
Monitoring protease activity in biological tissues using antibody prodrugs as sensing probes (2020)

Proteases have been implicated in the development of many pathological conditions, including cancer. Detection of protease activity in diseased tissues could therefore be useful for diagnosis, prognosis, and the development of novel therapeutic approaches. Due to tight post-translational regulation, determination of the expression level of proteases alone may not be indicative of protease activities, and new methods for measuring protease activity in biological samples such as tumor biopsies are needed. Here we report a novel zymography-based technique, called the IHZ<sup>TM</sup> assay, for the detection of specific protease activities in situ. The IHZ assay involves imaging the binding of a protease-activated monoclonal antibody prodrug, called a Probody<sup>®</sup> therapeutic, to tissue. Probody therapeutics are fully recombinant, masked antibodies that can only bind target antigen after removal of the mask by a selected protease. A fluorescently labeled Probody molecule is incubated with a biological tissue, thereby enabling its activation by tissue endogenous proteases. Protease activity is measured by imaging the activated Probody molecule binding to antigen present in the sample. The method was evaluated in xenograft tumor samples using protease specific substrates and inhibitors, and the measurements correlated with efficacy of the respective Probody therapeutics. Using this technique, a diverse profile of MMP and serine protease activities was characterized in breast cancer patient tumor samples. The IHZ assay represents a new type of in situ zymography technique that can be used for the screening of disease-associated proteases in patient samples from multiple pathological conditions.
Characterization of the gene encoding heat-stable toxin II and preliminary molecular epidemiological studies of enterotoxigenic Escherichia coli heat-stable toxin II producers (1983)

The gene encoding heat-stable toxin II (STII) was cloned into an Escherichia coli K-12 strain, and its nucleotide sequence was determined. The deduced amino acid sequence indicates that STII is synthesized within the cell as a 71-amino-acid protein and that neither the DNA nor amino acid sequence bears any similarity to that of heat-stable toxin I. A DNA fragment containing the STII gene was used to probe enterotoxigenic E. coli clinical isolates with various toxin phenotypes and was shown to be useful in detecting all STII and only STII producers.
Refinement of Macromolecular Structures by the Maximum-Likelihood Method (1997)

This paper reviews the mathematical basis of maximum likelihood. The likelihood function for macromolecular structures is extended to include prior phase information and experimental standard uncertainties. The assumption that different parts of a structure might have different errors is considered. A method for estimating sigma(A) using 'free' reflections is described and its effects analysed. The derived equations have been implemented in the program REFMAC. This has been tested on several proteins at different stages of refinement (bacterial alpha-amylase, cytochrome c', cross-linked insulin and oligopeptide binding protein). The results derived using the maximum-likelihood residual are consistently better than those obtained from least-squares refinement.
Fertility of Bull Spermatozoa Frozen in Whole Milk Extender with Trehalose, Taurine, or Blood Serum (1993)

Fertility of bull semen processed in heated whole milk-glycerol control semen extender with various additives was compared in six field trials. The additive in field trials 1 and 2 was 25.6 g of trehalose/L of the glycerol fraction of whole milk. Whole milk was heated to 95 degrees C for 10 min, cooled, and filtered 1 d before use (trial 1) or 3 d before use (trial 2). In field trial 3, 3.0 g/L of taurine were added to the glycerol fraction of whole milk. In field trial 4, specially prepared bovine serum (15% vol/vol) was included in the glycerol fraction of whole milk. Field trials 5 and 6 were larger fertility studies with trehalose in extenders prepared the day before use (trial 5) and 1 and 3 d before use (trial 6). Control and treated semen were coded and distributed randomly over a large group of professional inseminators. The 59-d nonreturn rates for control and treated semen, respectively, were as follows: trial 1, 74.1 and 73.7%; trial 2, 71.3 and 73.1%; trial 3, 74.9 and 70.9%; and trial 4, 75.1 and 71.6%. No significant differences resulted in trials 1 to 3, but bovine serum decreased the non-return rate in trial 4. Trials 5 and 6 resulted in nonsignificant improvement in fertility with added trehalose. Thus, these additives, useful as cryopreservatives or membrane protectors in other systems, did not enhance the fertility of sperm frozen in whole milk.
Six X-Linked Agammaglobulinemia-Causing Missense Mutations in the Src Homology 2 Domain of Bruton’s Tyrosine Kinase: Phosphotyrosine-Binding and Circular Dichroism Analysis (2000)

Src homology 2 (SH2) domains recognize phosphotyrosine (pY)-containing sequences and thereby mediate their association to ligands. Bruton's tyrosine kinase (Btk) is a cytoplasmic protein tyrosine kinase, in which mutations cause a hereditary immunodeficiency disease, X-linked agammaglobulinemia (XLA). Mutations have been found in all Btk domains, including SH2. We have analyzed the structural and functional effects of six disease-related amino acid substitutions in the SH2 domain: G302E, R307G, Y334S, L358F, Y361C, and H362Q. Also, we present a novel Btk SH2 missense mutation, H362R, leading to classical XLA. Based on circular dichroism analysis, the conformation of five of the XLA mutants studied differs from the native Btk SH2 domain, while mutant R307G is structurally identical. The binding of XLA mutation-containing SH2 domains to pY-Sepharose was reduced, varying between 1 and 13% of that for the native SH2 domain. The solubility of all the mutated proteins was remarkably reduced. SH2 domain mutations were divided into three categories: 1) Functional mutations, which affect residues presumably participating directly in pY binding (R307G); 2) structural mutations that, via conformational change, not only impair pY binding, but severely derange the structure of the SH2 domain and possibly interfere with the overall conformation of the Btk molecule (G302E, Y334S, L358F, and H362Q); and 3) structural-functional mutations, which contain features from both categories above (Y361C).
Electrical Performances of Low Temperature Annealed Hafnium Oxide Deposited at Room Temperature (2006)

In this work, HfO2 was deposited by r.f. sputtering at room temperature and then annealed for different times at 200°C in a forming gas atmosphere. After annealing for 2 hours the HfO2 layers present a reduction on the flat band voltage of about 1 V, relatively to the as deposited film, decreasing from -2.23V down to -1.28 V. This means an improvement of the interface properties and a reduction on the oxide charge density from 1.33×1012 cm-2 to 7.62×1011 cm-2. The dielectric constant reaches a maximum of 18.3 after 5h annealing due to film’s densification. When annealing for longer times such as 10h a small degradation of the electrical properties is observed. After 10h annealing the dielectric constant, flat band voltage and fixed charge density are respectively, 14.9, -2.96 V and 1.64 ×1012 cm-2 and the leakage current also increases due to film’s crystallization.
Accumulation of natural and synthetic betaines by a mammalian renal cell line (1996)

Intracellular accumulation of different betaines was compared in osmotically stressed Madin Darby canine kidney (MDCK) cells to model the betaine accumulation specificity of the mammalian inner medulla and to show how this accumulation differed from that of bacteria. All betaines accumulated less than glycine betaine. Arsenobetaine (the arsenic analogue of glycine betaine) accumulated to 12% of the glycine betaine levels and the sulphur analogue dimethylthetin accumulated to >80%. Most substituted glycine betaine analogues accumulated to 2-5% of intracellular glycine betaine concentrations, however, serine betaine accumulated to <0.5% of glycine betaine levels. Inhibition studies to distinguish the betaine ports were performed by the addition of proline. Butyrobetaine and carnitine accumulation was not proline sensitive, whereas that of other betaines was. As with glycine betaine, the accumulation of propionobetaine and dimethylthetin was proline sensitive and osmoregulated. Pyridinium betaine was accumulated by both proline-sensitive and -insensitive systems, with a small increase under osmotic stress. High concentrations (10 times that of glycine betaine) of the dietary betaines proline betaine and trigonelline inhibited total betaine accumulation. Because alpha-substituted betaines are accumulated by bacteria and not by MDCK cells, these betaines may be the basis for design of antimicrobial agents.
Search for new cyclic AMP‐binding proteins (2003)

Today, there is evidence that the cAMP-dependent kinases (PKA) are not the only intracellular receptors involved in intracellular cAMP signalling in eukaryotes. Other cAMP-binding proteins have been recently identified, including some cyclic nucleotide-gated channels and Epac (exchange protein directly activated by cAMP) proteins. All these proteins bind cAMP through conserved cyclic nucleotide monophosphate-binding domains. However, all putative cAMP-binding proteins having such domains, as revealed by computer analysis, do not necessarily bind cAMP, indicating that their presence is not a sufficient criteria to predict cAMP-binding property for a protein.
The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents (2009)

The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents. The comparison of the dog, human and rodent repertoires revealed several examples of species-specific gene duplications and deletions. This information is useful in the selection of model organisms for pharmacological experiments.
The Effect of Dietary N-3 Fatty Acids on Osmotic Fragility and Membrane Fluidity of Human Erythrocytes (1993)

Sixteen healthy females were randomly assigned to receive fish oil or corn oil double blind in a 28 days intervention period. Osmotic fragility of erythrocytes was decreased in the fish-oil supplemented group and not affected in the corn-oil group. The decrease in osmotic fragility was maximal after 14 days and approached the pre-intervention level after 24 and 28 days of n-3 supplementation. No change was observed in erythrocyte membrane fluidity in either of the groups. The level of n-3 fatty acids increased significantly in erythrocytes from the fish oil supplemented subjects, mainly at the expense of linoleic acid (18:2, n-6) and oleic acid (18:1). No significant change was seen in the relative amount of arachidonic acid (20:4,n-6) or in the phospholipid/cholesterol ratio in erythrocytes, while the ratio between the sum of phoshatidylcholine and sphingomyeline/phosphatidylethanolamine (PC+SM/PE) increased during the intervention period. This study does not verify the hypothesis of a relationship between osmotic fragility and membrane fluidity. It is concluded that increased level of n-3 fatty acids in erythrocyte membranes decreases osmotic fragility, and that this effect is counteracted by increased PC+SM/PE ratio.
SwiftLib: rapid degenerate-codon-library optimization through dynamic programming (2014)

Degenerate codon (DC) libraries efficiently address the experimental library-size limitations of directed evolution by focusing diversity toward the positions and toward the amino acids (AAs) that are most likely to generate hits; however, manually constructing DC libraries is challenging, error prone and time consuming. This paper provides a dynamic programming solution to the task of finding the best DCs while keeping the size of the library beneath some given limit, improving on the existing integer-linear programming formulation. It then extends the algorithm to consider multiple DCs at each position, a heretofore unsolved problem, while adhering to a constraint on the number of primers needed to synthesize the library. In the two library-design problems examined here, the use of multiple DCs produces libraries that very nearly cover the set of desired AAs while still staying within the experimental size limits. Surprisingly, the algorithm is able to find near-perfect libraries where the ratio of amino-acid sequences to nucleic-acid sequences approaches 1; it effectively side-steps the degeneracy of the genetic code. Our algorithm is freely available through our web server and solves most design problems in about a second.
A model for multiple-query processing based upon strong factoring (2004)

This paper proposes a model for interleaving the execution of multiple queries simultaneously. The queries are rewritten, in the context of each other, in order to induce common subexpressions (CSEs). A CSE will then need to be evaluated once only and its result is used in the evaluation of the queries that contain it, thereby leading to cost saving over the conventional query-at-a-time scenario. Two important aspects characterize the proposed model. First, it rewrites the queries in such a way that the isolated CSEs are, themselves, heuristically efficient to evaluate during query execution. Second, it reduces the optimization overhead (due to query rewriting) by using a divide-and-conquer approach to deduce relationships among inter-query selection conditions on base relations while using only pattern matching to find relationships among higher-order subexpressions (those involving an arbitrary number of joins).
Arterial cannulation: a critical review. (2004)

Arterial catheterization for hemodynamic monitoring is used widely in clinical management. Complications of connulation have been recognized since introduction of the technique. This review examines radial, brachial, axillary, and femoral cannulation sites. Waveform distortion, adjacent structure injury, and the incidence of thrombus are described. Computerized subject heading searches were executed using CINAHL and MEDLINE databases. Searches encompassed English-language, randomized, controlled trials, reviews, practice guidelines, and meta-analyses published from January 1997 to February 2002. Additional studies were identified via review of retrieved literature. Radial cannulation is subject to inaccuracy and thrombus formation, although a benefit is dual circulation. The brachial site is subject to inaccuracy, lacks collateral circulation, and is associated with median nerve injury. Axillary cannulation provides data closely approximating aortic pressure and poses minimal thrombotic risk but is associated with brachial plexus compression. Femoral cannulation provides a pulse contour approximating aortic with minimal thrombotic risk. There is little evidence to show increased incidence of catheter-related systemic infection at this site.
EvgA of the Two-Component Signal Transduction System Modulates Production of the YhiUV Multidrug Transporter in Escherichia coli (2002)

Overexpression of the EvgA regulator of the two-component signal transduction system was previously found to modulate multidrug resistance of Escherichia coli by increasing efflux of drugs (K. Nishino and A. Yamaguchi, J. Bacteriol. 183:1455-1458, 2001). Here we present data showing that EvgA contributes to multidrug resistance through increased expression of the multidrug transporter yhiUV gene.
GLVR1, a receptor for gibbon ape leukemia virus, is homologous to a phosphate permease of Neurospora crassa and is expressed at high levels in the brain and thymus (1992)

The human gene GLVR1 has been shown to render mouse cells sensitive to infection by gibbon ape leukemia virus. This indication that the GLVR1 protein acts as a virus receptor does not reveal the protein's normal physiological role. We now report that GLVR1 is homologous to pho-4+, a phosphate permease of Neurospora crassa, at a level sufficiently high to predict that GLVR1 is also a transport protein, although the substrate transported remains unknown. To characterize the gene further, we have cloned cDNA for the mouse homolog of the gene, Glvr-1. The sequence of the murine protein differs from that of the human protein in 10% of residues, and it may be presumed that some of these differences are responsible for the inability of gibbon ape leukemia virus to infect mouse fibroblasts. Glvr-1 RNA is most abundant in mouse brain and thymus, although it is present in all tissues examined. The pattern of RNA expression found in mouse tissues was also found in rat tissues, in which the RNA was expressed at high levels in all compartments of the brain except the caudate nucleus and was expressed most abundantly early in embryogenesis. Thus, high-level expression of Glvr-1 appears to be restricted to specific tissues and may have developmental consequences.
Glycerol Monolaurate Inhibits the Effects of Gram-Positive Select Agents on Eukaryotic Cells (2006)

Many exotoxins of Gram-positive bacteria, such as superantigens [staphylococcal enterotoxins, toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxins] and anthrax toxin are bioterrorism agents that cause diseases by immunostimulation or cytotoxicity. Glycerol monolaurate (GML), a fatty acid monoester found naturally in humans, has been reported to prevent synthesis of Gram-positive bacterial exotoxins. This study explored the ability of GML to inhibit the effects of exotoxins on mammalian cells and prevent rabbit lethality from TSS. GML (>or=10 microg/mL) inhibited superantigen (5 microg/mL) immunoproliferation, as determined by inhibition of (3)H-thymidine incorporation into DNA of human peripheral blood mononuclear cells (1 x 10(6) cells/mL) as well as phospholipase Cgamma1, suggesting inhibition of signal transduction. The compound (20 microg/mL) prevented superantigen (100 microg/mL) induced cytokine secretion by human vaginal epithelial cells (HVECs) as measured by ELISA. GML (250 microg) inhibited rabbit lethality as a result of TSST-1 administered vaginally. GML (10 microg/mL) inhibited HVEC and macrophage cytotoxicity by anthrax toxin, prevented erythrocyte lysis by purified hemolysins (staphylococcal alpha and beta) and culture fluids containing streptococcal and Bacillus anthracis hemolysins, and was nontoxic to mammalian cells (up to 100 microg/mL) and rabbits (250 microg). GML stabilized mammalian cell membranes, because erythrocyte lysis was reduced in the presence of hypotonic aqueous solutions (0-0.05 M saline) or staphylococcal alpha- and beta-hemolysins when erythrocytes were pretreated with GML. GML may be useful in the management of Gram-positive exotoxin illnesses; its action appears to be membrane stabilization with inhibition of signal transduction.