gebhart/patrepeval huggingface dataset:
Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. (1995)

The metabolism of glucagon-like peptide-1 (GLP-1) has not been studied in detail, but it is known to be rapidly cleared from the circulation. Measurement by RIA is hampered by the fact that most antisera are side-viewing or C-terminally directed, and recognize both intact GLP-1 and biologically inactive. N-terminally truncated fragments. Using high pressure liquid chromatography in combination with RIAs, methodology allowing specific determination of both intact GLP-1 and its metabolites was developed. Human plasma was shown to degrade GLP-1-(7-36)amide, forming an N-terminally truncated peptide with a t1/2 of 20.4 +/- 1.4 min at 37 C (n = 6). This was unaffected by EDTA or aprotinin. Inhibitors of dipeptidyl peptidase-IV or low temperature (4 C) completely prevented formation of the metabolite, which was confirmed to be GLP-1-(9-36)amide by mass spectrometry and sequence analysis. High pressure liquid chromatography revealed the concentration of GLP-1-(9-36)amide to be 53.5 +/- 13.7% of the concentration of endogenous intact GLP-1 in the fasted state, which increased to 130.8 +/- 10.0% (P < 0.01; n = 6) 1 h postprandially. Metabolism at the C-terminus was not observed. This study suggests that dipeptidyl peptidase-IV is the primary mechanism for GLP-1 degradation in human plasma in vitro and may have a role in inactivating the peptide in vivo.
Protein antigens of normal and malignant human cells identified by immunoprecipitation with monoclonal antibodies. (1980)

Spleen cells from a mouse immunized with human melanoma cells were fused with mouse myeloma cells, and somatic cell hybrids were grown in selective medium. Eight hybrids, which secreted antibodies to protein antigens of the melanoma cell line, were identified by immunoprecipitation of a 125I-labeled melanoma cell lysate followed by sodium dodecyl sulfate-gel electrophoresis of the immunoprecipitates and autoradiography. Seven of the eight melanoma proteins identified in this way were present at the cell surface. Two of the cell surface proteins, p80 and p97, were not detected in autologous fibroblasts.
Kinetic Comparison of the Specificity of the Vancomycin Resistance Kinase VanS for Two Response Regulators, VanR and PhoB (1996)

Induction of vancomycin resistance in the Gram-positive Enterococci requires a two-componet regulatory system, VanS and VanR, for transcriptional activation of three genes (vanH, A, X) that encode enzymes for a cell wall biosynthetic pathway that produces an altered peptidoglycan intermediate with lower affinity for the antibiotic. The catalytic efficiency (kcat/KM) has been determined for phosphotransfer from the phosphohistidyl form of VanS to both its homologous partner VanR and the heterologous (Escherichia coli) response regulator Phob. The rate of formation of the phosphoaapartyl forms of VanR and PhoB were determined as well as the rate of appearance of inorganic phosphate. Using PhoB in excess of P-VanS, a pseudo-first-order rate constant (kxfer) of 0.2 min-1 for phosphotransfer and a KM for PhoB of 100 microM were readily determined. The corresponding kxfer of 96 min-1 for phosphotransfer from P-VanS to VanR required quench kinetics. A KM of 3 microM was estimated for VanR, leading to a 10(4)-fold preference in kxfer/KM for phosphotransfer to VanR compared to PhoB. No phosphotransfer was detachable to three other E. coli response regulators, OmpR, ArcB, or CreB, providing some sense of the selectivity against two-component regulatory system cross-talk. In the phosphotransfer from P-VanS to PhoB and VanR, there was evidence of competition between water, to give Pi, and the specific aspartyl beta-COO- moiety of either PhoB or VanR with about 25% of the initial flux generating inorganic phosphate. The kinetics of phosphotransfer from P-VanS to VanR were complicated by inhibition by free VanS but, the inhibition pattern could be modeled to yield at KD of 30 nM for VanR binding to free VanS, an affinity similar to that of the CheA-CheY pair in E. coli chemotaxis.
Von Willebrand Disease: A Database of Point Mutations, Insertions, and Deletions (1993)

The current system for the diagnosis and classification of von Willebrand disease (vWD) is quite complex, with more than 20 distinct variants described. Over the past few years considerable progress has been made toward an understanding of vWD at the molecular level. A small cluster of mutations within the vWF A1 homologous repeat appears responsible for over 90% of type IIB vWD. A similar cluster of mutations in the vWF A2 homologous repeat accounts for the majority of type IIA vWD. By RFLP analysis, several type II vWD mutations have been shown to be recurrent on distinct haplotype backgrounds, suggesting independent genetic origins (see accompanying manuscript for a complete list of known polymorphisms). Several mutations at the N-terminus of the mature vWF subunit have been identified in association with abnormal factor VIII binding. Homozygotes for this abnormal vWF present with a hemophilia-like phenotype that is autosomal recessive in inheritance. In a small subset of patients with type III vWD large gene deletions have been identified on one or both vWF alleles. Carriers heterozygous for a deleted locus and one normal vWF gene are generally asymptomatic. Nonsense mutations and other defects resulting in loss of vWF mRNA expression from one allele have also been associated with a recessive type III vWD phenotype. No distinct molecular defect responsible for classic type I vWD has yet been defined.
Neuroprotective Role of Lactate after Cerebral Ischemia (2009)

It is well established that lactate can be used as an energy substrate by the brain by conversion to pyruvate and a subsequent oxidation in the mitochondria. Knowing the need for readily metabolizable substrates directly after ischemia and the protective effect of lactate after excitotoxicity, the aim of this study was to investigate whether lactate administration directly after ischemia could be neuroprotective. In vitro, the addition of 4 mmol/L L-lactate to the medium of rat organotypic hippocampal slices, directly after oxygen and glucose deprivation (OGD), protected against neuronal death, whereas a higher dose of 20 mmol/L was toxic. In vivo, after middle cerebral artery occlusion in the mouse, an intracerebroventricular injection of 2 microL of 100 mmol/L L-lactate, immediately after reperfusion, led to a significant decrease in lesion size, which was more pronounced in the striatum, and an improvement in neurologic outcome. A later injection 1 h after reperfusion did not reduce lesion size, but significantly improved neurologic outcome, which is an important point in the context of a potential clinical application. Therefore, a moderate increase in lactate after ischemia may be a therapeutic tool.
Host–Guest Interactions: Design Strategy and Structure of an Unusual Cobalt Cage That Encapsulates a Tetrafluoroborate Anion (2005)

Stuck in the middle: Supramolecular host–guest cages of general formula [BF4⊂(RCN)2Co2L4](BF4)3 with L being a di(benzimidazole)-1,4-phenylene derivative (R=Me, Et, Ph) have been prepared. An encapsulated BF4− anion (B yellow, F pale green; see structure) is locked firmly inside the cage and plays a pivotal role as a template around which the CoII ions (gray) and L ligands (ball-and-stick representation) self-assemble.
The impact of data normalisation on unsupervised continuous classification of landforms (2004)

Although most clustering techniques that characterise output classes by mean vectors and a covariance matrix require that features are roughly Gaussian, feature assessment for normality is often ignored in the classification process. This paper presents an example of the effect of data transformation on unsupervised continuous classification of landforms using the fuzzy k-means with extragrades algorithm on morphometric variables (MVs) derived from a DEM. Results show that after being transformed all MVs distributions become more normal and homogeneous. The optimised solution of number of classes given by the minimisation of FPI and MPE show significant changes between untransformed and normalised results. The use of normalised data achieved better results in terms of finding more distinct and less disorganised substructures for the same optimal number of classes. However, class separability was reduced due to data homogenisation. Furthermore, the resulting classes produced using the two different data sets show a small degree of overlap. Thus, not only data transformation affected the optimal solution pair in terms of number of classes and degree of fuzziness, it also has a major impact on the classification of each individual pixel, demonstrating the importance of data normalisation in the unsupervised classification process and in the delineation of landforms.
Metalloenzyme inspired dizinc catalyst for the polymerization of lactide (2002)

A new dizinc-monoalkoxide complex supported by a dinucleating ligand was structurally characterized and shown to be a highly active catalyst for the controlled polymerization of lactide.
Low-dose clozapine improves dyskinesias in Parkinson's disease (1997)

The severity of parkinsonian motor disability and dyskinesias was evaluated in seven levodopa-responsive patients with Parkinson's disease after an acute challenge with the mixed dopamine agonist apomorphine, before and after low-dose clozapine (50 mg) for 18 +/- 2 days. There was a significant 59% improvement (p < 0.05) of apomorphine-induced dyskinesias without aggravation of parkinsonian motor disability following clozapine treatment. The results suggest that low-dose clozapine, already shown to improve psychotic symptoms, may help to reduce severe levodopa-induced dyskinesias in parkinsonian patients.
A LexA-related protein regulates redox-sensitive expression of the cyanobacterial RNA helicase, crhR (2006)

Expression of the cyanobacterial DEAD-box RNA helicase, crhR, is regulated in response to conditions, which elicit reduction of the photosynthetic electron transport chain. A combination of electrophoretic mobility shift assay (EMSA), DNA affinity chromatography and mass spectrometry identified that a LexA-related protein binds specifically to the crhR gene. Transcript analysis indicates that lexA and crhR are divergently expressed, with lexA and crhR transcripts accumulating differentially under conditions, which respectively oxidize and reduce the electron transport chain. In addition, expression of the Synechocystis lexA gene is not DNA damage inducible and its amino acid sequence lacks two of three residues required for activity of prototypical LexA proteins, which repress expression of DNA repair genes in a range of prokaryotes. A direct effect of recombinant LexA protein on crhR expression was confirmed from the observation that LexA reduces crhR expression in a linear manner in an in vitro transcription/translation assay. The results indicate that the Synechocystis LexA-related protein functions as a regulator of redox-responsive crhR gene expression, and not DNA damage repair genes.
The tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone is a beta-adrenergic agonist and stimulates DNA synthesis in lung adenocarcinoma via beta-adrenergic receptor-mediated release of arachidonic acid. (1999)

Lung cancer is the leading cause of death in the United States, and it demonstrates a strong etiological association with smoking. The nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) reproducibly induces pulmonary adenocarcinomas (ACs) in laboratory rodents and is considered an important contributing factor to the high lung cancer burden observed in smokers. It has been shown that the development of NNK-induced ACs in mice is reduced by inhibitors of cyclooxygenase and lipoxygenase and that the growth of human AC cell lines is regulated by beta-adrenergic receptors. On the basis of structural similarities of NNK with classic beta-adrenergic agonists, we tested the hypothesis that NNK stimulates the growth of human AC cells via agonist-binding to beta-adrenergic receptors, resulting in the release of arachidonic acid (AA). In support of this hypothesis, radioreceptor assays with transfected CHO cell lines stably expressing the human beta1- or beta2-adrenergic receptor demonstrated high affinity binding of NNK to each of these receptors. Two human AC cell lines expressed beta1- and beta2-adrenergic receptors by reverse transcription-PCR and responded to NNK with the release of AA and an increase in DNA synthesis. Beta-adrenergic antagonists completely blocked the release of AA and increase in DNA synthesis. The cyclooxygenase inhibitor aspirin and the 5-lipoxygenase inhibitor MK-886 both partially inhibited DNA synthesis in response to NNK. Our findings identify the direct interaction of NNK with beta-adrenergic, AA-dependent pathways as a novel mechanism of action which may significantly contribute to the high cancer-causing potential of this nitrosamine. Moreover, NNK may also contribute to the development of smoking-related nonneoplastic disease via this mechanism.
Stop codon reassignments in the wild (2014)

The canonical genetic code is assumed to be deeply conserved across all domains of life with very few exceptions. By scanning 5.6 trillion base pairs of metagenomic data for stop codon reassignment events, we detected recoding in a substantial fraction of the >1700 environmental samples examined. We observed extensive opal and amber stop codon reassignments in bacteriophages and of opal in bacteria. Our data indicate that bacteriophages can infect hosts with a different genetic code and demonstrate phage-host antagonism based on code differences. The abundance and diversity of genetic codes present in environmental organisms should be considered in the design of engineered organisms with altered genetic codes in order to preclude the exchange of genetic information with naturally occurring species.
Amplification of cDNA ends based on template-switching effect and step- out PCR (1999)

A new method for amplifying cDNA ends is described which requires only first-strand cDNA synthesis and a single PCR to generate a correct product with very low or no background. The method can be successfully applied to total RNA as well as poly A+ RNA. The same first-strand cDNA can be used to amplify flanking sequences of any cDNA species present in the sample.
Expression of a synthetic bovine rhodopsin gene in monkey kidney cells. (1987)

We report here the high-level expression of a synthetic gene for bovine rhodopsin in transfected monkey kidney COS-1 cells. Rhodopsin is produced in these cells to a level of 0.3% of the cell protein, and it binds exogenously added 11-cis-retinal to generate the characteristic rhodopsin absorption spectrum. We describe a one-step immunoaffinity procedure for purification of the rhodopsin essentially to homogeneity. The COS-1 cell rhodopsin activates the GTPase activity of bovine transducin in a light-dependent manner with the same specific activity as that of purified bovine rhodopsin. Electron microscopy of immunogold-stained cells indicates that rhodopsin is located in the plasma membrane of the transfected cells and is oriented with the amino terminus on the extracellular side of the membrane. This orientation is analogous to that of rhodopsin in the disk membranes of photoreceptor cells in the bovine retina.
The 5‐HT2A receptor antagonist M100,907 prevents extracellular glutamate rising in response to NMDA receptor blockade in the mPFC (2004)

We recently found that intracortical injection of the selective and competitive N-methyl-D-aspartate (NMDA) receptor antagonist 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) impaired attentional performance in rats and blockade of 5-hydroxytryptamine (5-HT)2A receptors antagonized this effect. Here, we used the microdialysis technique in conscious rats to study the effect of CPP on extracellular glutamate (GLU) in the medial prefrontal cortex (mPFC) and the regulation of this effect by 5-HT2A receptors. Intraperitoneal injection of 20 mg/kg CPP increased extracellular GLU in the mPFC (201% of basal levels) but had no effect on 5-HT. Intracortical infusion of 100 microm CPP increased extracellular GLU (230% of basal values) and 5-HT (150% of basal values) in the mPFC, whereas 30 microm had no significant effect. The effect of 100 microm CPP on extracellular GLU was abolished by tetrodotoxin, suggesting that neuronal activity is required. Subcutaneous injection of 40 microg/kg M100,907 completely antagonized the effect of 100 microm cpp on extracellular GLU, whereas 10 microg/kg caused only partial attenuation. Likewise, intracortical infusion of 0.1 microm M100,907 completely reversed the increase of extracellular GLU induced by CPP. These findings show that blockade of NMDA receptors in the mPFC is sufficient to increase extracellular GLU locally. The increase of cortical extracellular GLU may contribute to CPP-induced cognitive deficits and blockade of 5-HT2A receptors may provide a molecular mechanism for reversing these deficits caused by dysfunctional glutamatergic transmission in the mPFC.
Optically pure 1,3-diols from (2R,4R)- and (2S,4S)-1,2:4,5-diepoxypentane (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOptically pure 1,3-diols from (2R,4R)- and (2S,4S)-1,2:4,5-diepoxypentaneScott D. Rychnovsky, George Griesgraber, Sam Zeller, and Donald J. SkalitzkyCite this: J. Org. Chem. 1991, 56, 17, 5161–5169Publication Date (Print):August 1, 1991Publication History Published online1 May 2002Published inissue 1 August 1991https://pubs.acs.org/doi/10.1021/jo00017a032https://doi.org/10.1021/jo00017a032research-articleACS PublicationsRequest reuse permissionsArticle Views2182Altmetric-Citations98LEARN 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
Changes in pulmonary structure and function induced by monocrotaline intoxication (1981)

Monocrotaline, a pyrrolizidine alkaloid derived from Crotalaria spectabilis, is known to be toxic to a variety of domestic and laboratory animals and to humans. Major pathological effects induced by monocrotaline poisoning include hepatic cirrhosis and megalocytosis, venocclusive disease, pulmonary hypertension, and right ventricular hypertrophy. The present investigation explored the structural and functional relationships that exist between pulmonary artery pressure, small pulmonary artery medial thickness, and right ventricular hypertrophy. The results of this physiological and histological study on monocrotaline-intoxicated rats has demonstrated that there is a positive correlation between progressive pulmonary hypertension, thickening of the medical wall of small pulmonary vessels, and right ventricular hypertrophy as a function of time.
In vivo features of signal transduction by the essential response regulator RpaB from Synechococcus elongatus PCC 7942 (2012)

The NblS-RpaB signalling pathway, the most conserved two-component system in cyanobacteria, regulates photosynthesis and acclimatization to a variety of environmental conditions and is involved in negative regulation of high-light-induced genes. However, relevant regulatory details of the NblS-RpaB signalling pathway remain to be elucidated. We recently showed that the response regulator RpaB is regulated by specific (de)phosphorylation from the histidine kinase NblS and that RpaB and its phosphorylatable residue Asp56 are both required for viability of Synechococcus elongatus PCC 7942. We show here that the phosphorylated form of RpaB is present in cells growing under standard laboratory conditions and that high light stress affected the ratio of phosphorylated to non-phosphorylated RpaB. It also decreased the amount of rpaB transcripts without appreciably changing the total levels of RpaB. Quantitative Western blotting and confocal microscopy analyses were consistent with RpaB being a very abundant regulator, with nucleoid localization. A genetically engineered RpaB-GFP (green fluorescent protein) fusion protein rescued lethality of the rpaB null mutant, indicating that it was functional. This is, to our knowledge, the first study demonstrating in a cyanobacterium, and for a two-component response regulator, that the in vivo ratio of phosphorylated to non-phosphorylated protein changes in response to environmental conditions.
A study on the recycling of scrap integrated circuits by leaching (2010)

In order to minimize the problem of pollution and to conserve limited natural resources, a method to recover the valuable metals such as gold, silver and copper) present in the scrap integrated circuits (ICs) was developed in the present study. Roasting, grinding, screening, magnetic separation, melting and leaching were adopted to investigate the efficiency of recovery of gold, silver and copper from scrap ICs. The collected scrap IC samples were roasted at 850 °C to destroy their plastic resin sealing material, followed by screening and magnetic separation to separate the metals from the resin residue. The non-ferrous materials (0.840 mm) were mainly composed of copper and could be melted into a copper alloy. Non-ferrous materials containing gold (860.05 ppm), silver (1323.12 ppm) and copper (37259.7 ppm) (size less than 50 mesh) were recovered 100% by a leaching process and thiourea was used as a leaching reagent.
Endogenous gastric mucosal prostaglandins: their role in mucosal integrity (1982)

These studies were designed to determine the role of endogenous gastric mucosal prostaglandins (PG) in maintaining mucosal integrity. Vagally denervated, separated pouches of gastric fundic mucosa in unanesthetized dogs were irrigated with either acetylsalicylic acid (ASA) or salicylic acid (SA) (0, 2.5, 5.0, 10.0, 20.0, and 40.0 mM) in 150 mM HCl. Transmucosal potential difference (PD) and net H+, Na+, and K+ flux were measured. Mucosal ex vivo generation of 6-oxo-PGF1 alpha, PGE2, and PGF2 alpha was measured by radioimmunoassay in mucosal biopsies taken after exposure to each agent. No difference in PD or net H+, Na+, or K+ flux was observed between pouch irrigation with ASA or SA at 2.5-20.0 mM concentrations. Net H+ and Na+ flux was significantly greater (P less than 0.01) after irrigation with 40 mM SA than with 40 mM ASA. No significant reduction in gastric mucosal ex vivo generation of 6-oxo-PGF1 alpha (range, 65-98 ng.g-.min-1), PGE2 (range, 250-326 ng.g-1.min-1), or PGF2 alpha (range, 115-156 ng.g-1.min-1) was observed after pouch irrigation with all concentrations of SA. In comparison, gastric mucosal ex vivo generation of 6-oxo-PGF1 alpha (range, 75-2 ng.g-1.min-1), PGE2 (range, 22-3 ng.g-1.min-1), and PGF2 alpha (range, 40-2 ng.g-1.min-1) was significantly reduced after irrigation with all concentrations of ASA. From these data, we conclude that the activity of endogenous gastric prostacyclin, PGE2 alpha, and PGF2 alpha is not a prerequisite for mucosal integrity as measured by PD and net cationic flux.