gebhart/patrepeval huggingface dataset:
Mapping the Functional Anatomy of BgK on Kv1.1, Kv1.2, and Kv1.3 (1999)

BgK is a peptide from the sea anemone Bunodosoma granulifera, which blocks Kv1.1, Kv1.2, and Kv1.3 potassium channels. Using 25 analogs substituted at a single position by an alanine residue, we performed the complete mapping of the BgK binding sites for the three Kv1 channels. These binding sites included three common residues (Ser-23, Lys-25, and Tyr-26) and a variable set of additional residues depending on the particular channel. Shortening the side chain of Lys-25 by taking out the four methylene groups dramatically decreased the BgK affinity to all Kv1 channels tested. However, the analog K25Orn displayed increased potency on Kv1.2, which makes this peptide a selective blocker for Kv1.2 (K(D) 50- and 300-fold lower than for Kv1.1 and Kv1.3, respectively). BgK analogs with enhanced selectivity could also be made by substituting residues that are differentially involved in the binding to some of the three Kv1 channels. For example, the analog F6A was found to be >500-fold more potent for Kv1.1 than for Kv1.2 and Kv1.3. These results provide new information about the mechanisms by which a channel blocker distinguishes individual channels among closely related isoforms and give clues for designing analogs with enhanced selectivity.
Mannose-Binding Lectin Is a Regulator of Inflammation That Accompanies Myocardial Ischemia and Reperfusion Injury (2005)

The mannose-binding lectin (MBL), a circulating pattern recognition molecule, recognizes a wide range of infectious agents with resultant initiation of the complement cascade in an Ab-independent manner. MBL recognizes infectious non-self and altered self in the guise of apoptotic and necrotic cells. In this study, we demonstrate that mice lacking MBL, and hence are devoid of MBL-dependent lectin pathway activation but have fully active alternative and classical complement pathways, are protected from cardiac reperfusion injury with resultant preservation of cardiac function. Significantly, mice that lack a major component of the classical complement pathway initiation complex (C1q) but have an intact MBL complement pathway, are not protected from injury. These results suggest that the MBL-dependent pathway of complement activation is a key regulator of myocardial reperfusion ischemic injury. MBL is an example of a pattern recognition molecule that plays a dual role in modifying inflammatory responses to sterile and infectious injury.
Direct Measurement of the Polarized Optical Absorption Cross Section of Single-Wall Carbon Nanotubes (2004)

We determine optical absorption cross sections of single-wall carbon nanotubes for visible light copolarized and cross polarized with respect to the nanotube axis. The need for perfectly aligned ensembles in absorbance measurements is eliminated by using Raman scattering to measure the nematic order parameter in magnetically aligned nanotube suspensions. The absorbance data allow the first quantitative, spectral comparisons with theories of local field depolarization, and provide benchmark spectra for simple, rapid, and quantitative measurements of alignment within nanotube dispersions.
Distinct patterns of expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial-leukocyte adhesion molecule-1 in renal disease. (1993)

These results show for the first time (a) endothelial vascular cell adhesion molecule-1 induction in various glomerulonephritides and (b) endothelial-leukocyte adhesion molecule-1 induction in the kidney. Complementary to earlier in vitro work, our findings indicate that these molecules play distinct roles in the pathogenesis of immune-mediated renal disease.
Excitation and direct imaging of surface plasmon polariton modes in the near-infrared (2004)

This paper describes techniques for the simultaneous excitation and imaging of various SPP modes in a 2-D periodic hole array, and show that these features are consistent with the dispersion relation for SPPs on a periodically modulated surface.
Cloning and Characterization of the Human PAX7 Promoter (2000)

PAX7, a member of the PAX transcription factor gene family, is normally expressed at high levels during development in the neural tube and in skeletal muscle precursor cells. Interestingly, PAX7 expression was also identified in tumor cells developing from these cell types. To date not much is known about the molecular mechanisms controlling the regulation of PAX7 expression. Therefore, we have cloned and sequenced part of the proximal 5'-flanking region of the human PAX7 gene. Computer-based sequence analysis identified putative binding sites for basic transcription factors. Analysis of a series of deletion constructs in different cell types suggested that a distal region containing several E-boxes might be involved in muscle-specific expression of PAX7, and that a distinct proximal region can enhance basal PAX7 expression in tumor cells.
Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E (2015)

This study expands the spectrum of phenotype in β-sarcoglycanopathy and provides strong evidence that severity of clinical involvement may be predicted by SGCB gene mutation and sarcoglycan protein expression.
ChemInform Abstract: Pheromone Synthesis. Part 100. New Synthesis of Both the Enantiomers of Grandisol, the Boll Weevil Pheromone. (1987)

Abstract The mixture of the isomeric bicyclic ketones (VIII), obtained starting from the ester (I), can be separated via the chromatographically separable reduction products (IXa) and (IXb).
Tick anticoagulant peptide: kinetic analysis of the recombinant inhibitor with blood coagulation factor X.alpha. (1990)

Tick anticoagulant peptide (TAP) is a 60 amino acid protein which is a highly specific inhibitor of human blood coagulation factor Xa (fXa) isolated from the tick Ornithodoros moubata [Waxman, L., Smith, D. E., Arcuri, K. E., & Vlasuk, G. P. (1990) Science 248, 593-596]. Due to the limited quantities of native TAP, a recombinant version of TAP produced in Saccharomyces cerevisiae was used for a detailed kinetic analysis of the inhibition interaction with human fXa. rTAP was determined to be a reversible, slow, tight-binding inhibitor of fXa, displaying a competitive type of inhibition. The binding of rTAP to fXa is stoichiometric with a dissociation constant of (1.8 +/- 0.02) x 10(-10) M, a calculated association rate constant of (2.85 +/- 0.07) x 10(6) M-1 s-1, and a dissociation rate constant of (0.554 +/- 0.178) x 10(-3) s-1. Binding studies show that 35S-rTAP binds only to fXa and not to DFP-treated fXa or zymogen factor X, which suggests the active site of fXa is required for rTAP inhibition. That rTAP is a unique serine proteinase inhibitor is suggested both by its high specificity for its target enzyme, fXa, and also by its unique structure.
Comparison of two bromovinyl nucleoside analogs, 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil and E-5-(2-bromovinyl)-2'-deoxyuridine, with acyclovir in inhibition of Epstein-Barr virus replication (1988)

The effect of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU), a new antiviral drug, on Epstein-Barr virus (EBV) was studied and compared with those of E-5-(2-bromovinyl)-2'-deoxyuridine (BVdU) and acyclovir (ACV). BV-araU effectively inhibited EBV replication both in superinfected Raji cells and in virus producer P3HR-1(LS) cells, as determined by density gradient centrifugation, in situ cytohybridization with an EBV DNA probe, and cRNA-DNA hybridization. The 50% effective doses for viral DNA replication were 0.26, 0.06, and 0.3 microM for BV-araU, BVdU, and ACV, respectively. The relative efficacy on the basis of the in vitro therapeutic index was BVdU (6,500) greater than BV-araU (1,500) greater than ACV (850). Synthesis of EBV-induced polypeptides with molecular weights of 145,000 and 140,000 was inhibited by these drugs. Kinetic analysis of reversibility of inhibition of EBV DNA replication after removal of the drugs indicated that BV-araU, like BVdU, has a more prolonged inhibitory effect than ACV. These results indicate that the 2' OH group in the arabinosyl configuration of BV-araU results in marked reduction in anti-EBV activity while slightly diminishing cytotoxicity.
In Vitro Cellular Toxicity Predicts Pseudomonas aeruginosa Virulence in Lung Infections (1998)

The role of quorum sensing by Pseudomonas aeruginosa in producing cytotoxicity has not been fully investigated. Strains of P. aeruginosa have been characterized as having an invasive or a cytotoxic phenotype (S. M. J. Fleiszig et al., Infect. Immun. 65:579-586, 1997). We noted that the application of a large inoculum of the invasive strain 6294 caused cytotoxicity of cultured epithelial cells. To investigate this dose-related cytotoxicity, we compared the behavior of 6294 to that of another invasive strain, PAO1, and determined whether the cytotoxicity could be related to quorum sensing. Both invasive strains, 6294 and PAO1, appear to have quorum-sensing systems that were operative when large doses of bacteria were applied to cultured lung epithelial cells or instilled into the lungs of animals. Nonetheless, only 6294 was cytotoxic. Cytotoxicity induced by 6294 correlated with increased elastase production. These experiments suggest that there are multiple mechanisms for the induction of cytotoxicity, pathology, and mortality in vivo. However, in vivo cytotoxicity and mortality, but not pathology, could be predicted by quantitative in vitro cellular damage experiments utilizing a range of bacteria-to-cell ratios. It appears that quorum sensing may inversely correlate with virulence in that strains that produced PAI [N-(3-oxododecanoyl) homoserine lactone] also appeared to attract more polymorphonuclear leukocytes in vivo and were possibly eliminated more quickly. In addition, exoproduct production in bacteriological medium in vitro may differ significantly from exoproduct expression from infections in vivo or during cocultivation of bacteria with tissue culture cells.
Use of T7 RNA Polymerase in an Optimized Escherichia coli Coupled in vitro Transcription‐Translation System (1996)

An Escherichia coli coupled in vitro transcription-translation system has been modified to allow efficient expression of genes under the control of a T7 promoter. We describe both the characterization and use of two S30 crude extracts prepared from E. coli, namely S30 BL21(DE3) (containing endogenous T7 RNA polymerase) and S30 BL21 (supplemented with exogenous T7 RNA polymerase). Since transcription by the highly active T7 RNA polymerase is known to overload the translational machinery of E. coli, the ratio between mRNA and ribosomes has to be regulated in the coupled in vitro system. For this purpose, the level of mRNA is controlled by varying the amount of DNA template (S30 extract with endogenous T7 RNA polymerase) or by limited amounts of exogenously added T7 RNA polymerase. The coupled in vitro system described in this paper provides two especially useful applications. First, it is most suitable for studying the regulation of gene expression in vitro, second, it can be used to express DNA templates carrying up to 10 genes. We show that genes which are not well expressed in E. coli in vivo because of unfavourable codon usage or plasmid instability are synthesized efficiently in the coupled in vitro system.
Experimental Carotid Stenosis and Endothelial Injury in the Rabbit: An In Vivo Model to Study Intravascular Platelet Aggregation (1992)

Previous studies have shown that experimental canine coronary artery stenosis associated with endothelial injury results in a typical pattern of coronary flow characterized by gradual decreases in coronary flow to almost zero values followed by restorations of flow to normal values. This pattern of flow, called cyclic flow reductions (CFRs), is the consequence of recurrent platelet aggregation at the site of the stenosis and endothelial injury and subsequent dislodgement of the thrombus. In the present study, platelet activation and aggregation in vivo was induced by placing an external constrictor around carotid arteries with endothelial injury in anesthetized rabbits. Carotid blood flow velocity was measured continuously with a Doppler flow probe positioned proximally to the constrictor. After placement of the constrictor, CFRs developed in 14 of 14 rabbits with a mean frequency of 16.5 +/- 2.3 cycles/h. CFRs were observed for 30 min, and the animals were treated with either an i.v. bolus of aspirin (10 mg/kg) or R 68070 (20 mg/kg), a drug with simultaneous TxA2 synthase and TxA2/PGH2 receptor blocking properties. Aspirin completely inhibited CFRs in 4 of 7 rabbits, whereas R 68070 eliminated CFRs in 7 of 7 animals. In the 3 animals that did not respond to aspirin, administration of ketanserin (0.25 mg/kg i.v.), a selective serotonin S2 receptor antagonist, completely abolished CFRs. Both aspirin and R 68070 resulted in a marked reduction in serum TxB2 formation and in a complete inhibition of ex vivo platelet aggregation in response to arachidonic acid, whereas aggregation in response to U46619, a TxA2 mimetic, was inhibited only in R 68070-treated rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
Design, synthesis, and testing toward a 57-codon genome (2016)

Recoding--the repurposing of genetic codons--is a powerful strategy for enhancing genomes with functions not commonly found in nature. Here, we report computational design, synthesis, and progress toward assembly of a 3.97-megabase, 57-codon Escherichia coli genome in which all 62,214 instances of seven codons were replaced with synonymous alternatives across all protein-coding genes. We have validated 63% of recoded genes by individually testing 55 segments of 50 kilobases each. We observed that 91% of tested essential genes retained functionality with limited fitness effect. We demonstrate identification and correction of lethal design exceptions, only 13 of which were found in 2229 genes. This work underscores the feasibility of rewriting genomes and establishes a framework for large-scale design, assembly, troubleshooting, and phenotypic analysis of synthetic organisms.
Pyrazolo[1,5-a][1,3,5]triazines (5-Aza-9-deazapurines): Synthesis and Biological Activity (2008)

10.3987/REV-08-629
Protective action of the peroxisome proliferator‐activated receptor‐γ agonist pioglitazone in a mouse model of Parkinson's disease (2002)

We examined the effect of pioglitazone, a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist of the thiazolidinedione class, on dopaminergic nerve cell death and glial activation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. The acute intoxication of C57BL/6 mice with MPTP led to nigrostriatal injury, as determined by tyrosine hydroxylase (TH) immunocytochemistry, and HPLC detection of striatal dopamine and metabolites. Damage to the nigrostriatal dopamine system was accompanied by a transient activation of microglia, as determined by macrophage antigen-1 (Mac-1) and inducible nitric oxide synthase (iNOS) immunoreactivity, and a prolonged astrocytic response. Orally administered pioglitazone (approximately 20 mg/kg/day) attenuated the MPTP-induced glial activation and prevented the dopaminergic cell loss in the substantia nigra pars compacta (SNpc). In contrast, there was little reduction of MPTP-induced dopamine depletion, with no detectable effect on loss of TH immunoreactivity and glial response in the striatum of pioglitazone-treated animals. Low levels of PPARgamma expression were detected in the ventral mesencephalon and striatum, and were unaffected by MPTP or pioglitazone treatment. Since pioglitazone affects primarily the SNpc in our model, different PPARgamma-independent mechanisms may regulate glial activation in the dopaminergic terminals compared with the dopaminergic cell bodies after acute MPTP intoxication.
Fast and simple purification of chemically modified hammerhead ribozymes using a lipophilic capture tag (1999)

A new type of 5'-lipophilic capture tag is described, enabling the facile reverse phase HPLC purification of chemically modified hammerhead ribozymes (oligozymes) whilst still carrying the 2'-O-tert.-butyldimethylsilyl protection of the essential riboses. In its most convenient form, the capture tag consists of a simple diol, such as hexan-1,6-diol, which at one end is attached via a silyl residue to a highly lipophilic entity such as tocopherol (vitamin E) or cholesterol, and the other end is functionalized as a phosphoramidite. This lipophilic capture tag is added as the last residue in the solid-phase synthesis of chemically modified hammerhead ribozymes. Cleavage from the support and release of all protecting groups except for the silyl groups is achieved with ethanolamine/ethanol. The crude product is then loaded directly on to a reverse phase HPLC column. Separation of failure peaks from full length product is achieved easily using a short run time. The retarded product peak is collected, lyophilized, desilylated in the normal way and then desalted. This method removes the lipophilic capture tag yet leaves behind the hexanediol entity which helps protect the compound against degradation by 5'-exonucleases. The purity of the product as judged by analytical anion-exchange HPLC and capillary gel electrophoresis is generally better than 95% full-length, and yields of 2-4 mg from a 1 micromol scale synthesis are routine. In addition, the method can be readily scaled up, an important feature for the development of such chemically modified ribozymes as potential therapeutics.
Laminin-1 and Laminin-2 G-domain Synthetic Peptides Bind Syndecan-1 and Are Involved in Acinar Formation of a Human Submandibular Gland Cell Line (1998)

The culture of human submandibular gland (HSG) cells on laminin-1 induces acinar differentiation. We identified a site on laminin involved in acinar differentiation using synthetic peptides derived from the C-terminal G-domain of the laminin alpha1 and alpha2 chains. The alpha1 chain peptide AG73 (RKRLQVQLSIRT) decreases the size of acini formed on laminin-1. Cells cultured with either AG73 or the homologous alpha2 chain peptide MG73 (KNRLTIELEVRT) form structures that appear acinar-like, but the cell nuclei are not polarized to the basal surface and no lumen formation occurs, indicating that additional sites on laminin are required for complete differentiation. The G-domain of laminin-1 contains both integrin and heparin binding sites, and anti-beta1-integrin antibodies disrupt acinar formation. Cell adhesion to the peptides and to E3, an elastase digest fragment of laminin-1 containing AG73, is specific, since other laminin peptides or EDTA do not compete the binding. Heparin and heparan sulfate decrease cell adhesion to AG73 and MG73 but anti-beta1-integrin antibodies have no effect. Treating the cell surface with heparitinase inhibits adhesion to both AG73 and MG73. We isolated cell surface ligands using both peptide affinity chromatography and laminin-1 affinity chromatography. Treating the material bound to the affinity columns with heparitinase and chondroitinase enriches for a core protein identified as syndecan-1 by Western blot analysis, thus identifying a syndecan-1 binding site in the globular domain of laminin-1 and laminin-2. In summary, multiple interactions between laminin and HSG cells contribute to acinar differentiation, involving both beta1-integrins and syndecan-1.
Noninvasive detection of skeletal muscle underperfusion with near-infrared spectroscopy in patients with heart failure. (1989)

The present study was undertaken to determine whether near-infrared spectroscopy can be used to noninvasively assess skeletal muscle oxygenation in patients with heart failure. The difference between light absorption at 760 and 800 nm was used to assess hemoglobin-myoglobin oxygenation. Initial studies conducted in isolated canine gracilis muscle demonstrated that 760-800-nm absorption correlated closely (r = -0.97 +/- 0.01) with venous hemoglobin O2 saturation when the muscle was stimulated to contract at 0.25-5.0 Hz. In normal subjects (n = 6) and patients with heart failure (n = 8), 760-800-nm absorption changes from the vastus lateralis muscle were monitored at rest, during progressive maximal bicycle exercise, and during thigh cuff inflation to suprasystolic pressure, an intervention designed to assess minimal hemoglobin-myoglobin oxygenation. Absorption changes were expressed relative to the full physiologic range noted from rest to thigh cuff inflation. During exercise, normal subjects exhibited an initial increase in hemoglobin-myoglobin oxygenation followed by a progressive decrease in oxygenation to 27 +/- 13% of the physiologic range at the peak exercise workload of 140 +/- 9 W. In contrast, patients exhibited an initial decrease in hemoglobin-myoglobin oxygenation with the first workload, followed by a progressive further decrease to 26 +/- 13% of the physiologic range at a peak exercise workload of 60 +/- 8 W, less than half the peak workload noted in the normal subjects. At all exercise loads, hemoglobin-myoglobin oxygenation was significantly less in the patients than in the normal subjects. These data suggest that near-infrared spectroscopy can detect impaired skeletal muscle O2 delivery in patients with heart failure. This technique could provide a valuable method of assessing muscle O2 delivery in patients, particularly before and after therapeutic interventions.
Inhibition of colony-stimulating factor-1 activity by monoclonal antibodies to the human CSF-1 receptor (1989)

Four of 12 monoclonal antibodies (MoAbs) directed to different epitopes in the extracellular domain of the human colony-stimulating factor-1 receptor (CSF-1R, the c-fms proto-oncogene product) specifically inhibit CSF-1 binding to receptor-bearing cells. All four antibodies abrogated CSF-1-dependent colony formation by human bone marrow-derived macrophage precursors and by mouse NIH-3T3 cells expressing a transduced human c-fms gene. In addition, one of these antibodies (designated MoAb 2-4A5) interfered with the ligand-independent proliferation of NIH-3T3 cells transformed by an oncogenic, mutant c-fms allele. Unlike CSF-1 itself, neither MoAb 2-4A5 nor the other three inhibitory antibodies (MoAbs 12-2D6, 12-3A1, and 12-3A3) induced CSF-1R internalization or degradation. These antibodies should prove useful not only for identifying and quantitating CSF-1R on receptor-bearing cells but for abrogating specific receptor signals that govern the proliferation and survival of human mononuclear phagocytes.
Analytical chemistry and oceanography (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAnalytical chemistry and oceanographyKenneth S. Johnson, Kenneth H. Coale, and Hans W. JannaschCite this: Anal. Chem. 1992, 64, 22, 1065A–1075APublication Date (Print):November 15, 1992Publication History Published online22 September 2008Published inissue 15 November 1992https://pubs.acs.org/doi/10.1021/ac00046a001https://doi.org/10.1021/ac00046a001research-articleACS PublicationsRequest reuse permissionsArticle Views340Altmetric-Citations21LEARN 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