gebhart/patrepeval huggingface dataset:
The Pharmacological Activities of the Metabolites ofN‐[(Trimethylamineboryl)‐Carbonyl]‐L‐Phenylalanine Methyl Ester (1996)

The metabolites of N-[(trimethylamineboryl)-carbonyl]-L-phenylalanine methyl ester 1 proved to be active in a number of pharmacological screens where the parent had previously demonstrated potent activity. The proposed metabolites demonstrated significant activity as cytotoxic, hypolipidemic, and anti-inflammatory agents. In cytotoxicity screens several of the proposed metabolites afforded better activity than the parent compound against the growth of suspended and solid tumor cell lines. Evaluation of in vivo hypolipidemic activity demonstrated that the proposed metabolites of 1 were only moderately active and were generally less effective than the parent compound. Interestingly, L-phenylalanine methyl ester hydrochloride 3, which contains no boron atom, demonstrated equivalent hypolipidemic activity as the parent at 8 mg/kg/day in CF(1) male mice. As anti-inflammatory agents the proposed metabolites demonstrated variable capacities to reduce foot pad inflammation. These compounds were similarly effective as the parent 1 at blocking local pain and were generally better than the parent at protecting CF(1) male mice from LPS induced sepsis.
Down-Regulation of Wee1 Kinase by a Specific Subset of microRNA in Human Sporadic Pituitary Adenomas (2010)

To our knowledge, this is the first report suggesting that regulation of Wee1 kinase by miRs may be linked to pituitary tumorigenesis.
Origins of circulating endothelial cells and endothelial outgrowth from blood (2000)

Normal adults have a small number of circulating endothelial cells (CEC) in peripheral blood, and endothelial outgrowth has been observed from cultures of blood. In this study we seek insight into the origins of CEC and endothelial outgrowth from cultures of blood. Fluorescence in situ hybridization analysis of blood samples from bone marrow transplant recipients who had received gender-mismatched transplants 5-20 months earlier showed that most CEC in fresh blood had recipient genotype. Endothelial outgrowth from the same blood samples after 9 days in culture (5-fold expansion) was still predominantly of the recipient genotype. In contrast, endothelial outgrowth after approximately 1 month (102-fold expansion) was mostly of donor genotype. Thus, recipient-genotype endothelial cells expanded only approximately 20-fold over this period, whereas donor-genotype endothelial cells expanded approximately 1000-fold. These data suggest that most CEC in fresh blood originate from vessel walls and have limited growth capability. Conversely, the data indicate that outgrowth of endothelial cells from cultures of blood is mostly derived from transplantable marrow-derived cells. Because these cells have more delayed outgrowth but a greater proliferative rate, our data suggest that they are derived from circulating angioblasts.
Peripheral Nerve Injury Induces Persistent Vascular Dysfunction and Endoneurial Hypoxia, Contributing to the Genesis of Neuropathic Pain (2015)

Nerve injury is associated with microvascular disturbance; however, the role of the vascular system has not been well characterized in the context of neuropathic pain. Furthermore, ischemia is thought to play a role in a number of neuropathic pain conditions, and yet the role of hypoxia has also not been characterized in neuropathic pain conditions. In this study, we observed the presence of persistent endoneurial hypoxia in a mouse model of traumatic peripheral nerve injury, causing painful mononeuropathy. We attribute the ongoing hypoxia to microvascular dysfunction, endoneurial fibrosis, and increased metabolic requirements within the injured nerve. Increased lactate levels were observed in injured nerves, as well as increased oxygen consumption and extracellular acidification rates, suggesting that anaerobic glycolysis is required to maintain cellular ATP levels. Hypoxia causes a reduction in levels of the Na(+)/K(+) ATPase ion transporter in both cultured primary dorsal root ganglion neurons and injured peripheral nerve. A reduction of Na(+)/K(+) ATPase ion transporter levels likely contributes to the hyperexcitability of injured nerves. Physiological antagonism of hypoxia with hyperbaric oxygen alleviated mechanical allodynia in nerve-injured animals. These results suggest that hypoxia and the Na(+)/K(+) ATPase ion transporter may be a novel mechanistic target for the treatment of neuropathic pain. In addition, the findings support the possibility of using hypoxia activated pro-drugs to localize treatments for neuropathic pain and nerve injury to injured nerves.
Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts (2002)

To provide a global analysis of gene expression in the aging heart, we monitored the expression of 9,977 genes simultaneously in 5- and 30-month-old male B6C3F(1) mice by using high-density oligonucleotide microarrays and several statistical techniques. Aging was associated with transcriptional alterations consistent with a metabolic shift from fatty acid to carbohydrate metabolism, increased expression of extracellular matrix genes, and reduced protein synthesis. Caloric restriction (CR) started at 14 months of age resulted in a 19% global inhibition of age-related changes in gene expression. Interestingly, CR also resulted in alterations in gene expression consistent with preserved fatty acid metabolism, reduced endogenous DNA damage, decreased innate immune activity, apoptosis modulation, and a marked cytoskeletal reorganization. These observations provide evidence that aging of the heart is associated with specific transcriptional alterations, and that CR initiated in middle age may retard heart aging by inducing a profound transcriptional reprogramming.
Expression of the vertebrate Gli proteins in Drosophila reveals a distribution of activator and repressor activities (2000)

The Cubitus interruptus (Ci) and Gli proteins are transcription factors that mediate responses to Hedgehog proteins (Hh) in flies and vertebrates, respectively. During development of the Drosophila wing, Ci transduces the Hh signal and regulates transcription of different target genes at different locations. In vertebrates, the three Gli proteins are expressed in overlapping domains and are partially redundant. To assess how the vertebrate Glis correlate with Drosophila Ci, we expressed each in Drosophila and monitored their behaviors and activities. We found that each Gli has distinct activities that are equivalent to portions of the regulatory arsenal of Ci. Gli2 and Gli1 have activator functions that depend on Hh. Gli2 and Gli3 are proteolyzed to produce a repressor form able to inhibit hh expression. However, while Gli3 repressor activity is regulated by Hh, Gli2 repressor activity is not. These observations suggest that the separate activator and repressor functions of Ci are unevenly partitioned among the three Glis, yielding proteins with related yet distinct properties.
Interaction of ribonucleotide reductase with ribonucleotide analogs (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteraction of ribonucleotide reductase with ribonucleotide analogsHenricus P. C. Hogenkamp and Hartmut FollmannCite this: Biochemistry 1971, 10, 1, 186–192Publication Date (Print):January 5, 1971Publication History Published online1 May 2002Published inissue 5 January 1971https://pubs.acs.org/doi/10.1021/bi00777a027https://doi.org/10.1021/bi00777a027research-articleACS PublicationsRequest reuse permissionsArticle Views107Altmetric-Citations16LEARN 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
Acceptor Specificity of Different Length Constructs of Human Recombinant α1,3/4-Fucosyltransferases (1995)

The acceptor specificity of recombinant full-length, membrane-bound fucosyltransferases, expressed in COS-7 cells, and soluble, protein-A chimeric forms of alpha 1,3-fucosyltransferase (Fuc-T) III, Fuc-TIV, and Fuc-TV was analyzed toward a broad panel of oligosaccharide, glycolipid, and glycoprotein substrates. Our results on the full-length enzymes confirm and extend previous studies. However, chimeric Fuc-Ts showed increased activity toward glycoproteins, whereas chimeric Fuc-TIII and Fuc-TV had a decreased activity with glycosphingolipids, compared to the full-length enzymes. Unexpectedly, chimeric Fuc-TV exhibited a GDP-fucose hydrolyzing activity. In substrates with multiple acceptor sites, the preferred site of fucosylation was identified. Fuc-TIII and Fuc-TV catalyzed fucose transfer exclusively to OH-3 of glucose in lacto-N-neotetraose and lacto-N-tetraose, respectively, as was demonstrated by 1H NMR spectroscopy. Thin layer chromatography immunostaining revealed that FucT-IV preferred the distal GlcNAc residue in nLc6Cer, whereas Fuc-TV preferred the proximal Gl-cNAc residue. Incubation of Fuc-TIV or Fuc-TV with VI3NeuAcnLc6Cer resulted in products with the sialyl-LewisX epitope as well as the VIM-2 structure. To identify polar groups on acceptors that function in enzyme binding, deoxygenated substrate analogs were tested as acceptors. All three Fuc-Ts had an absolute requirement for a hydroxyl at C-6 of galactose in addition to the accepting hydroxyl at C-3 or C-4 of GlcNAc.
Marked antiangiogenic and antitumor efficacy of AG3340 in chemoresistant human non-small cell lung cancer tumors: single agent and combination chemotherapy studies. (1999)

Effective therapy is needed to improve the survival of patients with advanced lung cancers. We studied the effects of a selective metalloprotease inhibitor, AG3340, on chemoresistant human non-small cell lung cancer tumors (line MV522) in vivo. Mice bearing s.c. tumors were given twice-daily oral doses of AG3340. As a single agent, AG3340 inhibited angiogenesis (up to 77%) and tumor growth (up to 65%) in a dose-dependent manner at well-tolerated daily doses up to 400 mg/kg/day and induced significant tumor necrosis. In contrast, tumors were relatively insensitive to carboplatin with approximately 25% growth inhibition observed at a maximum tolerated dose of approximately 30 mg/kg/week (given i.p., twice weekly). Carboplatin inhibited tumor growth markedly only at toxic doses, demonstrating a superior therapeutic index of AG3340 to carboplatin in this tumor model. A suboptimal dose of AG3340, when used in combination with an ineffective maximum tolerated dose of carboplatin, resulted in greater tumor growth inhibitions than those produced by either agent alone. Similarly, growth inhibition was enhanced when AG3340 was used in combination with paclitaxel. Cotreatment with carboplatin did not alter AG3340 plasma concentrations achieved acutely after oral dosing. These data demonstrate an antiangiogenic and antitumor effect of AG3340 when used as a single agent and enhanced growth inhibitions when AG3340 is used in combination with cytotoxic agents. These data suggest that treatment with this novel matrix metalloprotease inhibitor may be beneficial in advanced lung cancers and other chemoresistant malignancies.
The Antigenicity of the Tumor Cell — Context Matters (2017)

When is a neoantigen not a neoantigen? A recent study suggests that T cells in a patient with cancer are more likely to “miss” mutant peptides generated by somatic mutations than are the T cells in a healthy person.
Solubility of -Ca3(PO4)2 in the system Ca(OH)2-H3PO4-H2O at 5, 15, 25, and 37 C (1974)

Solubility isotherms of beta-tricalcium phosphate, <i>β</i>-Ca(PO<sub>4</sub>)<sub>2</sub>, prepared by heating mixtures of CaCO<sub>3</sub> and CaHPO<sub>4</sub> above 800 °C, were determined in the ternary system Ca(OH)<sub>2</sub>-H<sub>3</sub>PO<sub>4</sub>-H<sub>2</sub>O at 5, 15, 25, and 37 °C in the pH range 6.0-7.5 by equilibration with dilute H<sub>3</sub>PO<sub>4</sub> solutions. The results indicate that <i>β</i>-Ca<sub>3</sub>(PO<sub>4</sub>)<sub>2</sub> has a negative thermal coefficient of solubility. The solubility product, <i>K</i> <sub><i>s</i></sub> , was determined as a function of temperature by a generalized least-squares procedure; the resulting equation is <DispFormula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mtext>log</mml:mtext> <mml:msub><mml:mi>K</mml:mi> <mml:mi>s</mml:mi></mml:msub> <mml:mo>=</mml:mo> <mml:mo>-</mml:mo> <mml:mn>45723.26</mml:mn> <mml:mo>/</mml:mo> <mml:mi>T</mml:mi> <mml:mo>+</mml:mo> <mml:mn>287.4536</mml:mn> <mml:mo>-</mml:mo> <mml:mn>0.546763</mml:mn> <mml:mi>T</mml:mi> <mml:mo>;</mml:mo></mml:mrow> </mml:math> </DispFormula> the values of <i>K</i> <sub><i>s</i></sub> and its dispersion at 25 and 37 °C are 1.20(0.056), and 0.283(0.011) × 10<sup>-29</sup>. Thermodynamic functions for the dissolution of the salt at the four experimental temperatures are reported. When treated as an adjustable constant, the Ca/P ratio in these <i>β</i>-Ca<sub>3</sub>(PO<sub>4</sub>)<sub>2</sub> solutions was found to have the value 1.514(0.010), confirming that the stoichiometry of the high temperature form of this salt is correctly indicated by the above formula. The computed isotherms at 25 °C for several calcium phosphates are compared; it is shown that <i>β</i>-Ca<sub>3</sub>(PO<sub>4</sub>)<sub>2</sub> is, next to Ca<sub>5</sub>(PO<sub>4</sub>)<sub>3</sub>OH, the most stable at pH's above 6.36. The singular points of the <i>β</i>-Ca<sub>3</sub>(PO<sub>4</sub>)<sub>2</sub> isotherm with those of CaHPO<sub>4</sub> · 2H<sub>2</sub>O and CaHPO<sub>4</sub> are at pH's 5.88 and 6.36, respectively.
Interaction of influenza virus NS1 protein and the human homologue of Staufen in vivo and in vitro (1999)

A screening for human proteins capable of interacting with influenza virus NS1 has been carried out using the two-hybrid genetic trap in yeast. A cDNA corresponding to the human homologue of Drosophila melanogaster Staufen protein (hStaufen) was isolated that fulfilled all genetic controls of the two-hybrid protocol. Using a hStaufen cDNA isolated from a lambda human library, the interaction of hStaufen and NS1 proteins was characterised in vivo and in vitro. Co-transfection of NS1 cDNA and a partial cDNA of hStaufen led to the relocalisation of recombinant hStaufen protein from its normal accumulation site in the cytoplasm to the nuclear location of NS1 protein. NS1 and hStaufen proteins could be co-immunoprecipitated from extracts of co-transfected cells and from mixtures of extracts containing either protein, as well as from extracts of influenza virus-infected cells. Furthermore, both proteins co-localised in the ribosomal and polysomal fractions of influenza virus-infected cells. The interaction was also detected in pull-down experiments using a resin containing purified hStaufen and NS1 protein translated in vitro. Deletion mapping of the NS1 gene indicated that a mutant protein containing the N-terminal 81 amino acids is unable to interact with hStaufen, in spite of retaining full RNA-binding capacity. These results are discussed in relation to the possible mechanisms of action of hStaufen and its relevance for influenza virus infection.
Total Synthesis of [Ψ[C(═S)NH]Tpg4]Vancomycin Aglycon, [Ψ[C(═NH)NH]Tpg4]Vancomycin Aglycon, and Related Key Compounds: Reengineering Vancomycin for Dual d-Ala-d-Ala and d-Ala-d-Lac Binding (2011)

The total synthesis of [Ψ[C(═S)NH]Tpg(4)]vancomycin aglycon (8) and its unique AgOAc-promoted single-step conversion to [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon (7), conducted on a fully deprotected substrate, are disclosed. The synthetic approach not only permits access to 7, but it also allows late-stage access to related residue 4 derivatives, alternative access to [Ψ[CH(2)NH]Tpg(4)]vancomycin aglycon (6) from a common late-stage intermediate, and provides authentic residue 4 thioamide and amidine derivatives of the vancomycin aglycon that will facilitate ongoing efforts on their semisynthetic preparation. In addition to early stage residue 4 thioamide introduction, allowing differentiation of one of seven amide bonds central to the vancomycin core structure, the approach relied on two aromatic nucleophilic substitution reactions for formation of the 16-membered diaryl ethers in the CD/DE ring systems, an effective macrolactamization for closure of the 12-membered biaryl AB ring system, and the defined order of CD, AB, and DE ring closures. This order of ring closures follows their increasing ease of thermal atropisomer equilibration, permitting the recycling of any newly generated unnatural atropisomer under progressively milder thermal conditions where the atropoisomer stereochemistry already set is not impacted. Full details of the evaluation of 7 and 8 along with several related key synthetic compounds containing the core residue 4 amidine and thioamide modifications are reported. The binding affinity of compounds containing the residue 4 amidine with the model D-Ala-D-Ala ligand 2 was found to be only 2-3 times less than the vancomycin aglycon (5), and this binding affinity is maintained with the model d-Ala-d-Lac ligand 4, representing a nearly 600-fold increase in affinity relative to the vancomycin aglycon. Importantly, the amidines display effective dual, balanced binding affinity for both ligands (K(a)2/4 = 0.9-1.05), and they exhibit potent antimicrobial activity against VanA resistant bacteria ( E. faecalis , VanA VRE) at a level accurately reflecting these binding characteristics (MIC = 0.3-0.6 μg/mL), charting a rational approach forward in the development of antibiotics for the treatment of vancomycin-resistant bacterial infections. In sharp contrast, 8 and related residue 4 thioamides failed to bind either 2 or 4 to any appreciable extent, do not exhibit antimicrobial activity, and serve to further underscore the remarkable behavior of the residue 4 amidines.
DBASS3 and DBASS5: databases of aberrant 3'- and 5'-splice sites (2010)

DBASS3 and DBASS5 provide comprehensive repositories of new exon boundaries that were induced by pathogenic mutations in human disease genes. Aberrant 5'- and 3'-splice sites were activated either by mutations in the consensus sequences of natural exon-intron junctions (cryptic sites) or elsewhere ('de novo' sites). DBASS3 and DBASS5 currently contain approximately 900 records of cryptic and de novo 3'- and 5'-splice sites that were produced by over a thousand different mutations in approximately 360 genes. DBASS3 and DBASS5 data can be searched by disease phenotype, gene, mutation, location of aberrant splice sites in introns and exons and their distance from authentic counterparts, by bibliographic references and by the splice-site strength estimated with several prediction algorithms. The user can also retrieve reference sequences of both aberrant and authentic splice sites with the underlying mutation. These data will facilitate identification of introns or exons frequently involved in aberrant splicing, mutation analysis of human disease genes and study of germline or somatic mutations that impair RNA processing. Finally, this resource will be useful for fine-tuning splice-site prediction algorithms, better definition of auxiliary splicing signals and design of new reporter assays. DBASS3 and DBASS5 are freely available at http://www.dbass.org.uk/.
New Chromogenic Identification and Detection of Staphylococcus aureus and Methicillin-Resistant S. aureus (2000)

This paper describes a new chromogenic plate medium, CHROMagar Staph aureus (CHROMagar, Paris, France), for the identification of Staphylococcus aureus on the basis of colony pigmentation. The abilities of CHROMagar Staph aureus, thermostable nuclease (DNase), and mannitol salt agar (MSA) to identify S. aureus isolates (n = 114) and discriminate between S. aureus and coagulase-negative staphylococci (CoNS; n = 22) were compared. CHROMagar Staph aureus proved to be more sensitive and specific than DNase and MSA, allowing a reliable, simple, and rapid method for the identification of S. aureus isolates. All CoNS encountered in this study with the exception of S. chromogenes could be easily differentiated from S. aureus on this medium. The supplementation with 4 microgram of oxacillin or methicillin per ml allowed simple identification of methicillin resistance in hospital-acquired S. aureus strains which show multiple-drug resistance profiles. Community-acquired methicillin-resistant S. aureus strains showing non-multi-drug resistance profiles require further evaluation on this new chromogenic medium. Methicillin or oxacillin resistance of all S. aureus isolates was confirmed by the detection of penicillin-binding protein 2a, encoded by the mecA gene, using the latex slide agglutination MRSA-Screen test (PBP 2' Test, DR900M; Oxoid).
Conformationally Rigid Diamide Complexes: Synthesis and Structure of Tantalum(III) Alkyne Derivatives (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformationally Rigid Diamide Complexes: Synthesis and Structure of Tantalum(III) Alkyne DerivativesFrederic Guerin, David H. McConville, and Jagadese J. VittalCite this: Organometallics 1995, 14, 7, 3154–3156Publication Date (Print):July 1, 1995Publication History Published online1 May 2002Published inissue 1 July 1995https://doi.org/10.1021/om00007a013RIGHTS & PERMISSIONSArticle Views240Altmetric-Citations54LEARN 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 InReddit PDF (1 MB) Get e-AlertsSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Domain structure of vaccinia DNA ligase (1997)

The 552 amino acid vaccinia virus DNA ligase consists of three structural domains defined by partial proteolysis: (i) an amino-terminal 175 amino acid segment that is susceptible to digestion with chymotrypsin and trypsin; (ii) a protease-resistant central domain that contains the active site of nucleotidyl transfer (Lys-231); (iii) a protease-resistant carboxyl domain. The two protease-resistant domains are separated by a protease-sensitive interdomain bridge from positions 296 to 307. Adenylyltransferase and DNA ligation activities are preserved when the N-terminal 200 amino acids are deleted. However, the truncated form of vaccinia ligase has a reduced catalytic rate in strand joining and a lower affinity for DNA than does the full-sized enzyme. The 350 amino acid catalytic core of the vaccinia ligase is similar in size and protease-sensitivity to the full-length bacteriophage T7 DNA ligase.