gebhart/patrepeval huggingface dataset:
Comprehensive Analysis of Phosphorylation Sites in Tensin1 Reveals Regulation by p38MAPK (2010)

Tensin1 is the archetype of a family of focal adhesion proteins. Tensin1 has a phosphotyrosine binding domain that binds the cytoplasmic tail of β-integrin, a Src homology 2 domain that binds focal adhesion kinase, p130Cas, and the RhoGAP called deleted in liver cancer-1, a phosphatase and tensin homology domain that binds protein phosphatase-1α and other regions that bind F-actin. The association between tensin1 and these partners affects cell polarization, migration, and invasion. In this study we analyzed the phosphorylation of human S-tag-tensin1 expressed in HEK293 cells by mass spectrometry. Peptides covering >90% of the sequence initially revealed 50 phosphorylated serine/phosphorylated threonine (pSer/pThr) but no phosphorylated tyrosine (pTyr) sites. Addition of peroxyvanadate to cells to inhibit protein tyrosine phosphatases exposed 10 pTyr sites and addition of calyculin A to cells to inhibit protein phosphatases type 1 and 2A gave a total of 62 pSer/pThr sites. We also characterized two sites modified by O-linked N-acetylglucosamine. Tensin1 F302A, which does not bind protein phosphatase-1, showed > twofold enhanced phosphorylation of seven sites. The majority of pSer/pThr have adjacent proline (Pro) residues and we show endogenous p38 mitogen activated protein kinase (MAPK) associated with and phosphorylated tensin1 in an in vitro kinase assay. Recombinant p38α MAPK also phosphorylated S-tag-tensin1, resulting in decreased binding with deleted in liver cancer-1. Activation of p38 MAPK in cells by sorbitol-induced hyperosmotic stress increased phosphorylation of S-tag-tensin1, which reduced binding to deleted in liver cancer-1 and increased binding to endogenous pTyr proteins, including p130Cas and focal adhesion kinase. These data demonstrate that tensin1 is extensively phosphorylated on Ser/Thr residues in cells and phosphorylation by p38 MAPK regulates the specificity of the tensin1 Src homology 2 domain for binding to different proteins. Tensin1 provides a hub for connecting signaling pathways involving p38 MAP kinase, tyrosine kinases and RhoGTPases.
Mechanisms of receptor-mediated rhinovirus neutralization defined by two soluble forms of ICAM-1 (1991)

The majority of human rhinoviruses use intercellular adhesion molecule 1 (ICAM-1) as a cell surface receptor. Two soluble forms of ICAM-1, one corresponding to the entire extracellular portion [tICAM(453)] and one corresponding to the two N-terminal immunoglobulin-like domains [tICAM(185)], have been produced, and their effects on virus-receptor binding, virus infectivity, and virus integrity have been examined. Results from competitive binding experiments indicate that the virus binding site is largely contained within the two N-terminal domains of ICAM-1. Virus infectivity studies indicate that tICAM(185) prevents infection by direct competition for receptor binding sites on virus, while tICAM(453) prevents infection at concentrations 10-fold lower than that needed to inhibit binding and apparently acts at the entry or uncoating steps. Neutralization by both forms of soluble ICAM-1 requires continual presence of ICAM-1 during the infection and is largely reversible. Both forms of soluble ICAM-1 can alter rhinovirus to yield subviral noninfectious particles lacking the viral subunit VP4 and the RNA genome, thus mimicking virus uncoating in vivo, although this irreversible modification of rhinovirus is not the major mechanism of virus neutralization.
hnRNP G: sequence and characterization of a glycosylated RNA-binding protein (1993)

The autoantigen p43 is a nuclear protein initially identified with autoantibodies from dogs with a lupus-like syndrome. Here we show that p43 is an RNA-binding protein, and identify it as hnRNP G, a previously described component of heterogeneous nuclear ribonucleoprotein complexes. We demonstrate that p43/hnRNP G is glycosylated, and identify the modification as O-linked N-acetylglucosamine. A full-length cDNA clone for hnRNP G has been isolated and sequenced, and the predicted amino acid sequence for hnRNP G shows that it contains one RNP-consensus RNA binding domain (RBD) at the amino terminus and a carboxyl domain rich in serines, arginines and glycines. The RBD of human hnRNP G shows striking similarities with the RBDs of several plant RNA-binding proteins.
Hybridization of Peptide Nucleic Acid (1998)

The thermodynamics of hybridization and the conformations of decameric mixed purine-pyrimidine sequence PNA/PNA, PNA/DNA, and DNA/DNA duplexes have been studied using fluorescence energy transfer (FET), absorption hypochromicity (ABS), isothermal titration calorimetry (ITC), and circular dichroism (CD) techniques. The interchromophoric distances determined in the FET experiments on fluorescein- and rhodamine-labeled duplexes indicate that the solution structures of the duplexes are extended helices in agreement with available NMR (PNA/DNA) and crystal X-ray data (PNA/PNA). The melting thermodynamics of the duplexes was studied with both FET and ABS. The thermodynamic parameters obtained with ABS are in good agreement with the parameters from calorimetric measurements while FET detection of duplex melting gives in most cases more favorable free energies of hybridization. This discrepancy between FET and ABS detection is ascribed to the conjugated dyes which affect the stability of the duplexes substantially. Especially, the dianionic fluorescein attached via a flexible linker either to PNA or to DNA seems to be involved in an attractive interaction with the opposite dicationic lysine when hybridized to a PNA strand. This interaction leads to an increased thermal stability as manifested as a 3-4 degreesC increase of the melting temperature. For the PNA/DNA duplex where fluorescein is attached to the PNA strand, a large destabilization (DeltaTm = -12 degreesC) occurs relative to the unlabeled duplex, probably originating from electrostatic repulsion between the fluorescein and the negatively charged DNA backbone. In the case of the PNA/PNA duplex, the sense of helicity of the duplex is reversed upon conjugation of fluorescein via a flexible linker arm, but not when the fluorescein is attached without a linker to the PNA.
Local names in SPKI/SDSI (2002)

We analyze the notion of "local names" in SPKI/SDSI. By interpreting local names as distributed groups, we develop a simple logic program for SPKI/SDSI's linked local-name scheme and prove that it is equivalent to the name-resolution procedure in SDSI 1.1 and the 4-tuple-reduction mechanism in SPKI/SDSI 2.0. This logic program is itself a logic for understanding SDSI's linked local-name scheme and has several advantages over previous logics. We then enhance our logic program to handle authorization certificates, threshold subjects, and certificate discovery. This enhanced program serves both as a logical characterization and an implementation of SPKI/SDSI 2.0's certificate reduction and discovery. We discuss the way SPKI/SDSI uses the threshold subjects and names for the purpose of authorization and show that, when used in a certain restricted way, local names can be interpreted as distributed roles.
The Soy Isoflavone Genistein Decreases Adipose Deposition in Mice (2003)

Adipose tissue is responsive to estrogen and expresses both estrogen receptor alpha and beta. To test the hypothesis that the estrogenic soy isoflavone genistein can have effects on adipose tissue, juvenile or adult C57/BL6 mice were ovariectomized and given daily injections of vehicle, 17beta-estradiol (5 microg/kg.d) or genistein (8-200 mg/kg.d) sc for 21-28 d. To test effects of dietary genistein, 25- to 27-d-old mice were fed diets containing 0-1500 parts per million (ppm) genistein for 12 d. Mice were killed and fat pads weighed. Parametrial fat pads were used for morphometric and Northern analysis. Genistein injections decreased adipose weight and adipocyte circumference at higher doses; effects in adult and juvenile mice were similar. Genistein decreased lipoprotein lipase mRNA, which may be a critical aspect of its adipose effects. Juveniles fed 500-1500 ppm dietary genistein had dose-responsive decreases in fat pad weights of 37-57%, compared with controls; 300 ppm genistein did not cause decreases. Genistein doses of 300, 500, 1000, and 1500 ppm produced serum genistein concentrations of 1.02 +/- 0.14 microM, 1.79 +/- 0.32 microM, 2.55 +/- 0.18 microM, and 3.81 +/- 0.39 microM, respectively. These results indicate dietary genistein at 500-1500 ppm produces antilipogenic effects in mice at serum levels that humans are realistically exposed to.
Cyclic AMP response element-binding protein and the catalytic subunit of protein kinase A are present in F9 embryonal carcinoma cells but are unable to activate the somatostatin promoter. (1992)

The cyclic AMP (cAMP) response elements (CREs) of the somatostatin and vasoactive intestinal peptide (VIP) promoters contain binding sites for CRE-binding protein (CREB) that are essential for cAMP-regulated transcription. Using F9 embryonal carcinoma cells, we show that the somatostatin and VIP promoters exhibit a differentiation-dependent cAMP response, demonstrating that these promoters are regulated by transcription factors that become active during differentiation. Lack of cAMP responsiveness of the somatostatin promoter in undifferentiated cells is not due to the absence of known positive-acting factors (the catalytic subunit of protein kinase A [cPKA] and CREB) or a general inhibition of protein kinase A activity. Since overexpression of exogenous cPKA and CREB is sufficient to activate the somatostatin promoter in undifferentiated cells, these findings suggest that a negative factor(s) represses endogenous cPKA and CREB. In contrast to their effects on somatostatin, exogenous CREB and cPKA do not activate the VIP promoter. Thus, despite coregulation during differentiation and the ability to bind CREB, the somatostatin and VIP promoters are not coordinately activated by CREB in undifferentiated F9 cells.
Idiotypic DNA Vaccines Against B‐cell Lymphoma (1995)

Idiotypic antigens are clearly defined tumor-associated protein antigens, which can induce protective immunity against lymphoma. Because each patient requires an individual vaccine, idiotypic antigens also provide ideal candidates for exploring the feasibility of replacing protein antigens by DNA vaccines. Component idiotypic variable region genes can be identified in patients' tumor biopsies and rapidly assembled as scFv sequences. These can be used to produce recombinant scFv protein in bacteria, or as direct naked DNA vaccines. A preliminary small trial of DNA vaccines for chemotherapy-resistant patients with lymphoma has begun. Intramuscular idiotypic DNA vaccination in a mouse model induces low levels of anti-idiotypic antibody in serum. Levels can be increased dramatically by coinjection of DNA plasmids encoding either IL-2 or GM-CSF, and specific proliferative anti-idiotypic T cells are induced. However protective immunity remains to be demonstrated, and a possible reason for this may lie in the continued secretion of idiotypic scFv antigen which blocks antibody activity by formation of immune complexes. Methods for regulating secretion of antigen are required before this category of tumor antigen can be fully exploited as a vaccine. The power of DNA technology should allow analysis and manipulation of pathways of antigen presentation to induce maximal therapeutic attack on neoplastic B cells. In addition, lymphoma presents a model for application of DNA technology to the wide range of human tumors known to harbor potential tumor antigens.
Binary Source Estimation Using a Two-Tiered Wireless Sensor Network (2011)

Binary source estimation using indirect observation by a cluster of wireless sensors in a two-tiered architecture is considered. The high correlation among sensors' observation is exploited in order to implement an efficient distributed Joint Source Channel Coding (DJSCC) scheme based on Parallel Concatenated Convolutional Codes (PCCC). A novel approach employing two sink nodes per cluster providing a Distributed Space-Time Block Coding (DSTBC) is proposed to get diversity gain over fading channels without need to set up an extra link between two sinks. The proposed iterative decoding algorithm is easily scalable to a large number of sensors and outperforms independent RSC decoders followed by a Maximum Likelihood (ML) detector.
Recognition of the Different Structural Forms of the Capsid Protein Determines the Outcome following Infection with Porcine Circovirus Type 2 (2012)

Porcine circovirus type 2 (PCV2) capsid protein (CP) is the only protein necessary for the formation of the virion capsid, and recombinant CP spontaneously forms virus-like particles (VLPs). Located within a single CP subunit is an immunodominant epitope consisting of residues 169 to 180 [CP(169-180)], which is exposed on the surface of the subunit, but, in the structural context of the VLP, the epitope is buried and inaccessible to antibody. High levels of anti-CP(169-180) activity are associated with porcine circovirus-associated disease (PCVAD). The purpose of this study was to investigate the role of the immune response to monomer CP in the development of PCVAD. The approach was to immunize pigs with CP monomer, followed by challenge with PCV2 and porcine reproductive and respiratory syndrome virus (PRRSV). To maintain the CP immunogen as a stable monomer, CP(43-233) was fused to ubiquitin (Ub-CP). Size exclusion chromatography showed that Ub-CP was present as a single 33-kDa protein. Pigs immunized with Ub-CP developed a strong antibody response to PCV2, including antibodies against CP(169-180). However, only low levels of virus neutralizing activity were detected, and viremia levels were similar to those of nonimmunized pigs. As a positive control, immunization with baculovirus-expressed CP (Bac-CP) resulted in high levels of virus neutralizing activity, small amounts of anti-CP(169-180) activity, and the absence of viremia in pigs following virus challenge. The data support the role of CP(169-180) as an immunological decoy and illustrate the importance of the structural form of the CP immunogen in determining the outcome following infection.
Frequency of Anxiety Disorders in Psychiatric Outpatients With Major Depressive Disorder (2000)

The majority of patients with a principal diagnosis of unipolar major depressive disorder have a comorbid anxiety disorder. Because antidepressant medications have differential efficacies for anxiety disorders, knowledge of the presence of a comorbid anxiety disorder in a depressed patient may have treatment implications.
A parasitism gene from a plant‐parasitic nematode with function similar to CLAVATA3/ESR (CLE) of Arabidopsis thaliana (2005)

SUMMARY The Hg-SYV46 parasitism gene is expressed exclusively in the dorsal oesophageal gland cell of parasitic stages of the soybean cyst nematode, Heterodera glycines, and it encodes a secretory protein that contains a C-terminal motif of the CLAVATA3/ESR-related (CLE) family in Arabidopsis thaliana. In shoot and floral meristems of Arabidopsis, the stem cells secret CLV3, a founding member of the CLE protein family, that activates the CLV1/CLV2 receptor complex and negatively regulates WUSCHEL expression to restrict the size of the stem cell population. Mis-expression of Hg-SYV46 in Arabidopsis (ecotype Columbia-0) under control of the CaMV35S promoter resulted in a wus-like phenotype including premature termination of the shoot apical meristem and the development of flowers lacking the central gynoecium. The wus-like phenotype observed was similar to reports of over-expression of CLV3 and CLE40 in Arabidopsis, as was down-regulation of WUS expression in the shoot apices of 35S::Hg-SYV46/Col-0 plants. Expression of 35S::Hg-SYV46 in a clv3-1 mutant of Arabidopsis was able partially or fully to rescue the mutant phenotype, probably dependent upon localization and level of transgene expression. A short root phenotype, as reported for over-expression of CLV3, CLE40 and CLE19 in roots, was also produced in primary 35S::Hg-SYV46/Col-0 transgenic plants. The results suggest a functional similarity of HG-SYV46 to plant-secreted CLE ligands that may play a role in the differentiation or division of feeding cells induced in plant roots by parasitic nematodes.
Exchange of Histidine Spacing between Sp1 and GLI Zinc Fingers:  Distinct Effect of Histidine Spacing-Linker Region on DNA Binding (2004)

In the DNA recognition mode of C(2)H(2)-type zinc fingers, the finger-finger connection region, consisting of the histidine spacing (HX(3-5)H) and linker, would be important for determining the orientation of the zinc finger domains. To clarify the influence of spacing between two ligand histidines in the DNA binding, we exchanged the histidine spacing between Sp1 and GLI zinc fingers, which have an HX(3)H-TGEKK linker (typical) and an HX(4)H-SNEKP linker (atypical), respectively. A significant decrease in the DNA binding affinity and specificity is found in Sp1-type peptides, whereas GLI-type peptides show a mild reduction. To evaluate the effect of the linker characteristics, we further designed Sp1-type mutants with an SNEKP linker. As a result, the significant effect of the histidine spacing in Sp1-type peptides was reduced. These results demonstrate that (1) the histidine spacing significantly affects the DNA binding of zinc finger proteins and (2) the histidine spacing and the following linker regions are one effective target for regulating the DNA recognition mode of zinc finger proteins.
Reactive Oxygen-Mediated Protein Oxidation in Aging and Disease (1998)

Highly reactive oxygen species that are formed during normal metabolism and under conditions of oxidative stress are able to oxidize proteins or convert lipid and carbohydrate derivatives to compounds that react with functional groups on proteins. Among other changes, these ROS-mediated reactions lead to the formation of protein carbonyl derivatives, which serves as a marker of ROS-mediated protein damage. On the basis of this marker, it is established that oxidatively damaged protein is associated with aging and some diseases. The accumulation of oxidatively damaged protein reflects the balance among a myriad of factors that govern the rates of ROS generation and the rate at which damaged protein is degraded. Peroxynitrite, which is formed under normal physiological conditions, is able to oxidize methionine residues in proteins and to nitrate tyrosine residues; however, its ability to do so is dependent on the availability of CO2, which stimulates the nitration of tyrosine residues but inhibits the oxidation of methionine residues. Nitration of tyrosine residues may contribute to peroxynitrite toxicity, as nitration precludes the phosphorylation or nucleotidylation of tyrosine residues and thereby seriously compromises one of the most important mechanisms of cellular regulation and signal transduction.
Structural probing and damage selection of citrullineand arginine-specific RNA aptamers identify base positions required for binding (1995)

In a recent study, an RNA aptamer for the specific recognition of the amino acid L-arginine was evolved from an in vitro selected L-citrulline binding parent sequence [M. Famulok (1994) J. Am. Chem. Soc. 116, 1698-1706]. We have now carried out a structural analysis of these aptamers by using chemical modification experiments. Footprinting experiments and a damage selection approach were performed to identify those positions protected from modification in the presence of the amino acids and modifications that interfere with the binding of the ligand. It is shown that of the two bulged regions present in both aptamers one can be modified without loss of binding activity whereas in the other bulge nearly every position is shown to be involved in the recognition of the ligands. This might be indicative for non-canonical base pairing to occur within the non-Watson-Crick paired regions which might be stabilized by the complexed amino acid. Binding to the cognate amino acid significantly enhances the conformational stability of the RNA. We also tested the sensitivity of both aptamers towards lead (II) ion induced cleavage and identified a hypersensitive cleavage site within the invariant bulged region. Lead cleavage is inhibited by the complexed amino acid, indicating a conformational change of the aptamer upon ligand binding. NMR titration data obtained with both aptamers and their cognate ligands confirm the proposed conformational changes and indicate the formation of a 1:1 complex of RNA:amino acid.
Quantitative investigation of optical phase-measuring techniques for ultrashort pulse lasers (1996)

We have performed a quantitative investigation into the capabilities and the limitations of two phase-measuring techniques: second-harmonic-generation frequency-resolved optical gating and direct optical spectral phase measurement. In particular, we have studied the reproducibility and the accuracy of these techniques in measuring the frequency-dependent phase of ultrashort pulses with varying amounts of cubic and quadratic phase. We find that both of these techniques are accurate to within 5% in measuring phase distortions in optical pulses.
Generation and characterization of an anti-GP73 monoclonalantibody for immunoblotting and sandwich ELISA (2012)

Recently, serum Golgi protein 73 (GP73) levels have been found to be elevated in patients with hepatocellular carcinoma (HCC), and GP73 has been proposed as a novel marker for HCC. However, GP73 levels in patients remain controversial due to the specificity of the anti-GP73 antibody-based enzyme linked immunosorbent assay (ELISA). Therefore, an anti-GP73 antibody with high specificity was highly demanded. In the present study, by hybridoma screening, we generated an anti-GP73 monoclonal antibody (mAb) designated as 6A2 using recombinant GP73 protein produced by prokaryotic expression. The specificity of 6A2 was evaluated by Western blotting, immunohistochemistry and immunoprecipitation. The results showed that 6A2 recognized GP73 in both native and denatured forms. In addition, we have developed a sandwich ELISA using 6A2 and GP73 polyclonal antibody generated in New Zealand white rabbits according to standard procedures, and measured the serum GP73 level of patients using this assay. Our results showed that serum GP73 levels of HCC patients were significantly higher than those of healthy controls (P = 0.0036). Furthermore, for the first time, GP73 serum level was found to be elevated in patients with breast cancer compared with healthy controls (P = 0.0172).
WebWatcher: A Learning Apprentice for the World Wide Web (1995)

We describe an information seeking assistant for the world wide web. This agent, called WebWatcher, interactively helps users locate desired information by employing learned knowledge about which hyperlinks are likely to lead to the target information. Our primary focus to date has been on two issues: (1) organizing WebWatcher to provide interactive advice to Mosaic users while logging their successful and unsuccessful searches as training data, and (2) incorporating machine learning methods to automatically acquire knowledge for selecting an appropriate hyperlink given the current web page viewed by the user and the user’s information goal. We describe the initial design of WebWatcher, and the results of our preliminary learning experiments.