gebhart/patrepeval huggingface dataset:
A Chemoenzymatic Approach toward the Rapid and Sensitive Detection of O -GlcNAc Posttranslational Modifications (2003)

We report a new chemoenzymatic strategy for the rapid and sensitive detection of O-GlcNAc posttranslational modifications. The approach exploits the ability of an engineered mutant of beta-1,4-galactosyltransferase to selectively transfer an unnatural ketone functionality onto O-GlcNAc glycosylated proteins. Once transferred, the ketone moiety serves as a versatile handle for the attachment of biotin, thereby enabling chemiluminescent detection of the modified protein. Importantly, this approach permits the rapid visualization of proteins that are at the limits of detection using traditional methods. Moreover, it bypasses the need for radioactive precursors and captures the glycosylated species without perturbing metabolic pathways. We anticipate that this general chemoenzymatic strategy will have broad application to the study of posttranslational modifications.
Functional Protein Delivery into Neurons Using Polymeric Nanoparticles (2009)

An efficient route for delivering specific proteins and peptides into neurons could greatly accelerate the development of therapies for various diseases, especially those involving intracellular defects such as Parkinson disease. Here we report the novel use of polybutylcyanoacrylate nanoparticles for delivery of intact, functional proteins into neurons and neuronal cell lines. Uptake of these particles is primarily dependent on endocytosis via the low density lipoprotein receptor. The nanoparticles are rapidly turned over and display minimal toxicity to cultured neurons. Delivery of three different functional cargo proteins is demonstrated. When primary neuronal cultures are treated with recombinant Escherichia coli beta-galactosidase as nanoparticle cargo, persistent enzyme activity is measured beyond the period of nanoparticle degradation. Delivery of the small GTPase rhoG induces neurite outgrowth and differentiation in PC12 cells. Finally, a monoclonal antibody directed against synuclein is capable of interacting with endogenous alpha-synuclein in cultured neurons following delivery via nanoparticles. Polybutylcyanoacrylate nanoparticles are thus useful for intracellular protein delivery in vitro and have potential as carriers of therapeutic proteins for treatment of neuronal disorders in vivo.
MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation (2008)

In response to Toll-like receptor ligands, dendritic cells (DCs) dramatically enhance their antigen presentation capacity by stabilizing at the cell-surface MHC II molecules. We demonstrate here that, in human monocyte-derived DCs, the RING-CH ubiquitin E3 ligase, membrane-associated RING-CH I (MARCH I), promotes the ubiquitination of the HLA-DR beta-chain. Thus, in nonactivated DCs, MARCH I induces the surface internalization of mature HLA-DR complexes, therefore reducing their stability and levels. We further demonstrate that the maturation-dependent down-regulation of MARCH I is a key event in MHC class II up-regulation at the surface of LPS-activated DCs. MARCH I is, therefore, a major regulator of HLA-DR traffic, and its loss contributes to the acquisition of the potent immunostimulatory properties of mature human DCs.
Vulnerability of oligodendroglia to glutamate: pharmacology, mechanisms, and prevention (1993)

Periventricular white matter injury, the principal variety of brain injury of the human premature infant, involves differentiating oligodendroglia. Nothing is known of the biochemical mechanism of oligodendroglial death in this disorder. Because an early event in periventricular white matter injury is ischemia-induced axonal disruption and because such axonal destruction could lead to a marked increase in local concentrations of glutamate, we evaluated the vulnerability of differentiating oligodendroglia to glutamate in a culture model. Oligodendroglia were isolated from mixed-glial primary cultures by a selective detachment technique and grown in a primary culture under conditions that lead to differentiation. These oligodendroglia were found to be highly vulnerable to glutamate-induced cell death. The EC50 for glutamate for a 24 hr exposure was approximately 200 microM, comparable to the value reported for neurons in conventional cerebral cortical cultures. Astrocytes, in contrast, were shown to be resistant to as much as 5 mM glutamate. Study of glutamate receptor antagonists and glutamate transport substrates showed that the glutamate-induced oligodendroglial death was not related to a receptor mechanism, as operates in neurons, but rather was secondary to glutamate uptake by the oligodendroglia. Glutamate transport by high-affinity, sodium-dependent and by sodium-independent systems was shown. The central importance of glutamate uptake for the toxic effect of glutamate was shown by total prevention of the oligodendroglial toxicity by the simultaneous inhibition of glutamate uptake by the specific inhibitor D,L-threo-beta-hydroxyaspartate. Subsequent observations showed that the toxicity of glutamate was mediated by free radical attack, the consequence of glutathione depletion, apparently caused by the action of a glutamate-cystine exchange mechanism that results in cystine and thereby glutathione depletion. Thus, addition of cystine or cysteine totally prevented the glutamate toxicity to oligodendroglia. Second, glutamate exposure led to cystine efflux. Third, glutathione levels decreased markedly in cells exposed to glutamate, and this marked decrease preceded the loss of cell viability. Fourth, glutamate toxicity could be prevented totally by exposure to different free radical scavengers, vitamin E and idebenone. The data thus show that glutamate is highly toxic to oligodendroglia. Moreover, the findings raise the possibilities that such glutamate toxicity is operative in the oligodendroglial cell death associated with ischemic processes that disrupt axons, such as periventricular white matter injury of the premature infant, and that novel therapies directed against glutamate transport, glutathione depletion, and free radical attack might be beneficial in prevention of that injury.
[Optimization of separation of purine and pyrimidine compounds using ion-pair reversed-phase high performance chromatography (HPLC)]. (1988)

Utilization of ion-air reagents in a reversed-phase chromatographic system allows solving a number of problems related to the separation of purine and pyrimidine derivatives. Simultaneous analysis of nucleotides, nucleosides and their bases was carried out by acetonitrile gradient elution using tetrabutyl ammonium phosphate as a counterion in the mobile phase. Besides, optimal conditions were selected for isocratic separation of adenine nucleotides and their metabolites. Furthermore, isocratic separation of certain purines and pyrimidines was achieved by modifying the stationary C18-phase with pentane- and heptane sulphonic acids.
JUAN JOSE SANCHEZ SOSA, DIRECTOR DE LA FACULTAD DE PSICOLOGIA PARA 93-97 (1993)

EL MARTES 25 DE MAYO EL DOCTOR JUAN JOSE SANCHEZ SOSA ASUMIO LA DIRECCION DE LA FACULTAD DE PSICOLOGIA. EL MAESTRO JAVIER URBINA, AHORA EX DIRECTOR DE LA FP, AFIRMO QUE TERMINA SATISFECHO SU PERIODO AL FRENTE DE ESA DEPENDENCIA.
Administration of interleukin-2 (IL-2) results in increased plasma concentrations of IL-5 and eosinophilia in patients with cancer (1991)

Peripheral eosinophilia is almost invariably observed during the course of interleukin-2 (IL-2) therapy and is frequently accompanied by the development of a capillary leak syndrome characterized by edema, weight gain, and oliguria. We studied five patients with advanced malignancy treated with IL-2. Eosinophilia was not present initially but developed in all patients late in the course of therapy, with counts ranging from 2,328/mm3 to 15,958/mm3. In all patients, there was a temporal relationship between the infusion of IL-2 and the appearance of elevated plasma concentrations of IL-5, a growth factor for eosinophils. Granulocyte-macrophage colony-stimulating factor was not detectable in plasma. IL-4 and gamma-interferon plasma levels were variably elevated. Plasma concentrations of major basic protein, a toxic eosinophil granule protein, began increasing before eosinophil counts increased. By the time of the third IL-2 infusion, high concentrations of major basic protein were present in all five patients (up to 5,600 ng/mL) and skin biopsies showed major basic protein deposition in the dermis. Four patients developed significant capillary leak syndrome and all of these patients showed markedly elevated major basic protein levels. The lowest peak plasma concentration of major basic protein (1,751 ng/mL) was observed in the one patient who did not develop edema and weight gain. These results suggest that IL-2 induces IL-5 leading to marked peripheral eosinophilia and extravascular eosinophil degranulation. The release of toxic eosinophil products at extravascular sites and in the circulation may contribute to the pathogenesis of the capillary leak syndrome complicating IL-2 therapy.
ChemInform Abstract: RING TRANSFORMATION OF 3‐(2‐AMINOARYL)‐1,2,4‐OXADIAZOLES INTO 3‐ACYLAMINOINDAZOLES; EXTENSION OF THE BOULTON‐KATRITZY SCHEME (1982)

Abstract Das Prinzip der bereits früher beschriebenen Umwandlung von 3‐(2‐Aminoethyl)‐l ,2,4‐oxadiazolen in Acylaminopyrazoline wird auf die 4‐substituierten 3‐(Aminoaryl bzw. ‐heteroaryl)‐l ,2,4‐oxadiazo1e (I), (III), (V) bzw. (VII) ausgedehnt [ ‐+ (II), (IV), (VI), (VIII)].
Synthesis of nitrosourea derivatives of pyridine and piperidine as potential anticancer agents (1980)

Nitrosourea derivatives 18-22 which utilize either a piperidine or pyridine ring as a carrier group were synthesized and evaluated for anticancer activity. N'-(1-Benzyl-4-piperidinyl)-N-(2-chloroethyl)-N-nitosourea hydrogen maleate (19) exhibited good activity against intracranial L1210 leukemia as well as the mouse ependymoblastoma brain tumor system. Compound 19 exhibited comparable activity in the Lewis lung carcinoma system to N,N'-bis(2-chloroethyl)-N-nitrosourea. Replacement of the N-benzyl group in both the 3-piperidinyl- and 4-piperidinylnitrosoureas resulted in less active compounds in all tumor systems tested. The 3-pyridylnitrosourea 22 was inactive in the L-1210 leukemia system.
Synthesis and anticonvulsant activity of 2-iminohydantoins (1991)

Iminohydantoins selectively substituted at position C-5 and their 1-carbobenzoxy derivatives have been synthesized, and their anticonvulsant activity was evaluated in mice. In general, the more lipophilic 1-carbobenzoxy iminohydantoins were more potent than the unsubstituted counterparts. Evaluation of the individual enantiomers of the chiral iminohydantoins showed that the anticonvulsant activity resided primarily in the S isomers. In this study, (S)-(+)-1-carbobenzoxy-5-isobutyl-2-iminohydantoin (9a) was the most active member. This compound was not nearly as active as phenytoin against electrically induced convulsions, but was also active against pentylenetetrazole-induced seizures, suggesting a broader clinical potential. The closest analogue of phenytoin, viz., 5,5-diphenyl-2-iminohydantoin (1), failed to show any significant activity. Methylation on N-3 or the imino nitrogen of 1 also did not provide a compound with substantial activity. 2-Thiophenytoin was not active against electroshock seizures and showed only a weak activity against pentylenetetrazole. This study suggested that the structure-activity relationship of 2-iminohydantoins was quite different from that of 2-hydantoins.
Electronically asymmetric bis(porphyrin) sandwich complexes (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectronically asymmetric bis(porphyrin) sandwich complexesGregory S. Girolami, Philip A. Gorlin, and Kenneth S. SuslickCite this: Inorg. Chem. 1994, 33, 4, 626–627Publication Date (Print):February 1, 1994Publication History Published online1 May 2002Published inissue 1 February 1994https://pubs.acs.org/doi/10.1021/ic00082a002https://doi.org/10.1021/ic00082a002research-articleACS PublicationsRequest reuse permissionsArticle Views307Altmetric-Citations29LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Quantification of low-copy transcripts by continuous SYBR Green I monitoring during amplification. (1998)

Continuous fluorescence observation of amplifying DNA allows rapid and accurate quantification of initial transcript copy number. A simple and generic method for monitoring product synthesis with the double-stranded DNA dye, SYBR Green I provides initial template copy number estimation limited only by stochastic effects. To reach this degree of sensitivity, two methods were used. First, specific products generally have a higher melting temperature than nonspecific products, and therefore, specific product formation was monitored by fluorescence acquisition at temperatures at which only specific products are double-stranded. Second, anti-Taq antibodies were used to reduce nonspecific product generation. The log-linear portion of the fluorescence vs. cycle plot was extended to determine a fractional cycle number at which a threshold fluorescence was obtained. These fractional cycle numbers were plotted against the log of starting template copies to give linear standard curves from purified PCR products, allowing easy estimation of cDNA unknowns over a 10(6)-fold range. A single template molecule per reaction could be distinguished from the absence of template, although stochastic effects increased the variance of concentration estimates below 10 copies. Above 10 copies per reaction, typical replicate coefficients of variation were 6%-37%, with better precision at higher copy numbers.
Inhibition by Cardiac Natriuretic Peptides of Rat Vascular Endothelial Cell Migration (1995)

Vascular endothelial cell migration is proposed to be an important process in the initiation and progression of atherosclerosis. We designed the present study to examine the effects of atrial and brain natriuretic peptides on fetal calf serum-stimulated migration of cultured rat aortic endothelial cells using Boyden's chamber method. Fetal calf serum clearly stimulated migration in a concentration- and time-dependent manner. Rat atrial natriuretic peptide-(1-28) and rat brain natriuretic peptide-45, which are the major circulating forms of atrial and brain natriuretic peptides in rats, inhibited fetal calf serum-stimulated migration in a concentration-dependent manner between 10(-10) and 10(-6) mol/L. Such inhibition by these natriuretic peptides was paralleled by an increase in the cellular level of cGMP. The addition of a cGMP analogue 8-bromo-cGMP, significantly inhibited fetal calf serum-stimulated migration in a concentration-dependent manner between 10(-7) and 10(-3) mol/L. Rat atrial natriuretic peptide-(5-25) was much less effective than atrial natriuretic peptide-(1-28) or rat brain natriuretic peptide-45 with respect to inhibiting migration and increasing cGMP levels. These results indicate that atrial and brain natriuretic peptides inhibit fetal calf serum-stimulated vascular endothelial cell migration, probably through a cGMP-dependent process.
Assessment of corneal hydration sensing in the terahertz band:in vivoresults at 100 GHz (2012)

Terahertz corneal hydration sensing has shown promise in ophthalmology applications and was recently shown to be capable of detecting water concentration changes of about two parts in a thousand in ex vivo corneal tissues. This technology may be effective in patient monitoring during refractive surgery and for early diagnosis and treatment monitoring in diseases of the cornea. In this work, Fuchs dystrophy, cornea transplant rejection, and keratoconus are discussed, and a hydration sensitivity of about one part in a hundred is predicted to be needed to successfully distinguish between diseased and healthy tissues in these applications. Stratified models of corneal tissue reflectivity are developed and validated using ex vivo spectroscopy of harvested porcine corneas that are hydrated using polyethylene glycol solutions. Simulation of the cornea's depth-dependent hydration profile, from 0.01 to 100 THz, identifies a peak in intrinsic reflectivity contrast for sensing at 100 GHz. A 100 GHz hydration sensing system is evaluated alongside the current standard ultrasound pachymetry technique to measure corneal hydration in vivo in four rabbits. A hydration sensitivity, of three parts per thousand or better, was measured in all four rabbits under study. This work presents the first in vivo demonstration of remote corneal hydration sensing.
Vascular endothelial growth factor can signal through platelet-derived growth factor receptors (2007)

Vascular endothelial growth factor (VEGF-A) is a crucial stimulator of vascular cell migration and proliferation. Using bone marrow-derived human adult mesenchymal stem cells (MSCs) that did not express VEGF receptors, we provide evidence that VEGF-A can stimulate platelet-derived growth factor receptors (PDGFRs), thereby regulating MSC migration and proliferation. VEGF-A binds to both PDGFRalpha and PDGFRbeta and induces tyrosine phosphorylation that, when inhibited, results in attenuation of VEGF-A-induced MSC migration and proliferation. This mechanism was also shown to mediate human dermal fibroblast (HDF) migration. VEGF-A/PDGFR signaling has the potential to regulate vascular cell recruitment and proliferation during tissue regeneration and disease.
Toll-like receptors: lessons from knockout mice (2000)

The Toll signalling pathway, which is required for establishment of dorsoventral polarity in Drosophila embryos, plays an important role in the response to microbial infections. Recently, Toll-like receptors (TLRs) have also been identified in mammals. TLR4 has been shown to function as the transmembrane component of the lipopolysaccharide receptor, while TLR2 recognizes peptidoglycans from Gram-positive bacteria, lipoproteins and yeast. Although various microbial cell-wall components are recognized by different receptors, all of these responses are abrogated in MyD88-deficient cells. These results show that different TLRs recognize different microbial cell-wall components, and that MyD88 is an essential signalling molecule shared among interleukin-1 receptor/Toll family members.
Synthesis, Biological Evaluation, and Molecular Docking of Ugi Products Containing a Zinc-Chelating Moiety as Novel Inhibitors of Histone Deacetylases (2009)

HDAC inhibitors show great promise for the treatment of cancer. As part of a broader effort to explore the SAR of HDAC inhibitors, synthesis, biological evaluation, and molecular docking of novel Ugi products containing a zinc-chelating moiety are presented. One compound shows improved inhibitory potencies compared to SAHA, demonstrating that hindered lipophilic residues grafted on the peptide scaffold of the alpha-aminoacylamides can be favorable in the interaction with the enzyme.
Prevalence, Significance, and Specificity of Antibodies to Phospholipids in Q Fever (1994)

A cross-sectional study of the prevalence, significance, and specificity of antibodies to phospholipids (aPL) in patients with Q fever was undertaken in a university-based tertiary care medical center. The results of the lupus anticoagulant (LA) test, VDRL test, fluorescent treponemal antibody absorption test, and ELISA with different phospholipid antigens were determined for 26 patients with Q fever diagnosed by clinical and serological criteria. Plasma from four patients with Q fever and antibodies to cardiolipin (aCL) was purified by affinity chromatography in a cardiolipin column and tested against all phospholipids. For 17 patients with high levels of aCL, a modified ELISA without fetal calf serum was performed to determine if the serum cofactor was needed for a CL activity. Fisher's exact test was used for the statistical analysis. From the results of our study we conclude the following: patients with Q fever have a high incidence of aPL, with techniques with aCL or LA being the most sensitive to determine aPL (these antibodies can help diagnose Q fever presenting only as a fever); antibodies (phase II) to Coxiella burnetii and aCL are different antibodies; and the aCL activity in patients with Q fever is cofactor-independent.
CrossSearch, a User-friendly Search Engine for Detecting Chemically Cross-linked Peptides in Conjugated Proteins (2008)

Chemical cross-linking and high resolution MS have been integrated successfully to capture protein interactions and provide low resolution structural data for proteins that are refractive to analyses by NMR or crystallography. Despite the versatility of these combined techniques, the array of products that is generated from the cross-linking and proteolytic digestion of proteins is immense and generally requires the use of labeling strategies and/or data base search algorithms to distinguish actual cross-linked peptides from the many side products of cross-linking. Most strategies reported to date have focused on the analysis of small cross-linked protein complexes (<60 kDa) because the number of potential forms of covalently modified peptides increases dramatically with the number of peptides generated from the digestion of such complexes. We report herein the development of a user-friendly search engine, CrossSearch, that provides the foundation for an overarching strategy to detect cross-linked peptides from the digests of large (>or=170-kDa) cross-linked proteins, i.e. conjugates. Our strategy combines the use of a low excess of cross-linker, data base searching, and Fourier transform ion cyclotron resonance MS to experimentally minimize and theoretically cull the side products of cross-linking. Using this strategy, the (alpha beta gamma delta)(4) phosphorylase kinase model complex was cross-linked to form with high specificity a 170-kDa betagamma conjugate in which we identified residues involved in the intramolecular cross-linking of the 125-kDa beta subunit between its regulatory N terminus and its C terminus. This finding provides an explanation for previously published homodimeric two-hybrid interactions of the beta subunit and suggests a dynamic structural role for the regulatory N terminus of that subunit. The results offer proof of concept for the CrossSearch strategy for analyzing conjugates and are the first to reveal a tertiary structural element of either homologous alpha or beta regulatory subunit of phosphorylase kinase.