gebhart/patrepeval huggingface dataset:
Mice transgenic for a soluble form of murine CTLA-4 show enhanced expansion of antigen-specific CD4+ T cells and defective antibody production in vivo. (1994)

CD4+ T cell responses were analyzed in transgenic mice expressing a soluble form of murine CTLA-4, mCTLA4-H gamma 1, which blocks the interaction of the T cell activation molecules CD28 and CTLA-4 with their costimulatory ligands. Consistent with previous reports (Linsley, P. S., P. M. Wallace, J. Johnson, M. G. Gibson, J. L. Greene, J. A. Ledbetter, C. Singh, and M. A. Tepper. 1992. Science (Wash. DC). 257:792), T cell-dependent antibody production was profoundly inhibited in mCTLA4-H gamma 1 transgenic mice immunized with a protein antigen. Surprisingly, however, transgenic mice could generate quantitatively and qualitatively normal primary T cell responses, as measured by limiting dilution assays and lymphokine production. In addition, in vivo expansion of antigen-specific T cells after secondary or tertiary immunization was enhanced in mCTLA4-H gamma 1 transgenics as compared with normal mice. Although unable to deliver cognate help to B cells in vivo, T cells from mCTLA4-H gamma 1 transgenic mice were not anergic as they could help B cells to produce specific antibodies when adoptively transferred into nude hosts. Taken together, these data suggest that the engagement of CD28 and/or CTLA-4 may not be required for the induction of T cell responses, as is currently understood, but rather for the expression of T cell effector function such as the delivery of T cell help to B cells.
Human Oral Microbial Ecology and Dental Caries and Periodontal Diseases (1996)

In the human oral cavity, which is an open growth system, bacteria must first adhere to a surface in order to be able to colonize. Ability to colonize a non-shedding tooth surface is necessary prior to any odontopathic or periodontopathic process. Complex microbe-host relationships occur and must be studied before the commensal-to-pathogenic nature of the human indigenous oral flora can be understood. Medical pathogens, if present in the appropriate host, always produce specific disease. Caries and periodontal diseases are conditional diseases, requiring numbers of certain indigenous species at various sites, particularly the tooth surface. In the case of caries, the condition is related to sugar consumption. Periodontal disease/s may require certain host and environmental conditions, such as local environment or nutritional factors in gingival crevicular fluids. Nonetheless, critical numbers of certain indigenous species must be present in order for these diseases to occur. The aim of this review is to understand the acquisition of the indigenous oral flora and the development of human dental plaque. The role of the salivary pellicle and adherence of indigenous bacteria to it are critical first steps in plaque development. Bacterial interactions with saliva, nutritional factors, growth factors, and microbial physiologic processes are all involved in the overall process of microbial colonization.
Dipolar cycloaddition of cyclic rhodium carbenoids to aromatic heterocycles (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDipolar cycloaddition of cyclic rhodium carbenoids to aromatic heterocyclesMichael C. Pirrung, Jiancun Zhang, and Andrew T. McPhailCite this: J. Org. Chem. 1991, 56, 22, 6269–6271Publication Date (Print):October 1, 1991Publication History Published online1 May 2002Published inissue 1 October 1991https://doi.org/10.1021/jo00022a010RIGHTS & PERMISSIONSArticle Views580Altmetric-Citations83LEARN 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 (383 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Urease-associated heat shock protein of Helicobacter pylori (1992)

Helicobacter pylori urease is an extracellular, cell-bound enzyme with a molecular weight of approximately 600,000 (600K enzyme) comprising six 66K and six 31K subunits. A 62K protein is closely associated with the H. pylori urease, both in crude preparations and after gel filtration; this protein can be removed from the urease by ion-exchange chromatography without inactivating the enzyme. We purified this urease-associated protein and determined its N-terminal amino acid sequence. The sequence is 80% homologous (identical plus conserved amino acid residues) to the Escherichia coli GroEL heat shock protein (HSP), 75% homologous to the human homolog, and 84% homologous to the HSP homolog found in species of Chlamydia. Thus, the 62K urease-associated protein of H. pylori belongs to the HSP60 family of stress proteins known as chaperonins. Evidently this protein, HSP62, participates in the extracellular assembly and/or protection of the urease against inactivation in the hostile environment of the stomach.
Sugar-Assisted Chirality Control of Tris(2,2′-bipyridine)-Metal Complexes (1994)

Abstract 2,2′-Bipyridine-4,4′-diboronic acid (2), a 2,2′-bipyridine derivative with sugar-binding sites was synthesized. The Δ vs. Λ chirality of the Fe2+·23 complex was selectively generated in correlation with the absolute configuration of added saccharides.
Characterization of the celB gene coding for beta-glucosidase from the hyperthermophilic archaeon Pyrococcus furiosus and its expression and site-directed mutation in Escherichia coli (1995)

The celB gene encoding the cellobiose-hydrolyzing enzyme beta-glucosidase from the hyperthermophilic archaeon Pyrococcus furiosus has been identified, cloned, and sequenced. The transcription and translation gene was overexpressed in Escherichia coli, resulting in high-level (up to 20% of total protein) production of beta-glucosidase that could be purified by a two-step purification procedure. The beta-glucosidase produced by E. coli had kinetic and stability properties similar to those of the beta-glucosidase purified from P. furiosus. The deduced amino acid sequence of CelB showed high similarity with those of beta-glycosidases that belong to glycosyl hydrolase family 1, implicating a conserved structure. Replacement of the conserved glutamate 372 in the P. furiosus beta-glucosidase by an aspartate or a glutamine led to a high reduction in specific activity (200- or 1,000-fold, respectively), indicating that this residue is the active site nucleophile involved in catalysis above 100 degrees C.
Human α-1-antichymotrypsin: interaction with chymotrypsin-like proteinases (1978)

The interaction of human plasma alpha-1-antichymotrypsin with serine proteinases from different tissues has been investigated. The protein was found to form stable complexes with pancreatic chymotrypsin, leukocyte cathepsin G, and mast cell chymotrypsin. No inhibition of pancreatic trypsin or leukocyte elastase could be demonstrated. With mixtures containing both alpha-1-antichymotrypsin and alpha-1-proteinase inhibitor, it was found that the former preferentially inactivated leukocyte cathepsin G, while the latter showed a strong preference for pancreatic chymotrypsin. However, leukocyte elastase was specifically inactivated by alpha-1-proteinase inhibitor even in 1:1 mixtures with chymotrypsin. All of these results taken together suggest that one of the primary functions of alpha-1-antichymotrypsin is to inactivate leukocyte cathepsin G, while alpha-1-proteinase inhibitor controls the activity of other serine proteinases, particularly leukocyte elastase.
Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. (1996)

Dihydropyrimidine dehydrogenase (DPD) deficiency constitutes an inborn error in pyrimidine metabolism associated with thymine-uraciluria in pediatric patients and an increased risk of toxicity in cancer patients receiving 5-fluorouracil (5-FU) treatment. The molecular basis for DPD deficiency in a British family having a cancer patient that exhibited grade IV toxicity 10 d after 5-FU treatment was analyzed. A 165-bp deletion spanning a complete exon of the DPYD gene was found in some members of the pedigree having low DPD catalytic activity. Direct sequencing of lymphocyte DNA from these subjects revealed the presence of a G to A point mutation at the 5'-splicing site consensus sequence (GT to AT) that leads to skipping of the entire exon preceding the mutation during pre-RNA transcription and processing. A PCR-based diagnostic method was developed to determine that the mutation is found in Caucasian and Asian populations. This mutation was also detected in a Dutch patient with thymine-uraciluria and completely lacking DPD activity. A genotyping test for the G to A splicing point mutation could be useful in predicting cancer patients prone to toxicity upon administration of potentially toxic 5-FU and for genetic screening of heterozygous carriers and homozygous deficient subjects.
Organoid Models and Applications in Biomedical Research (2015)

Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ three-dimensional (3D) culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into 3D structures. These systems evolved, methodologically and conceptually, from classical reaggregation experiments, showing that dissociated cells from embryonic organs can reaggregate and re-create the original organ architecture. Since organoids can be grown from human stem cells and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology and drug discovery studies, and in the field of regenerative medicine. Here, we outline historical advances in the field and describe some of the major recent developments in 3D human organoid formation. Finally, we underline current limitations and highlight examples of how organoid technology can be applied in biomedical research.
Cloning and characterization of the gene encoding the IDH1 subunit of NAD(+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae. (1992)

NAD(+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae is composed of two nonidentical subunits, designated IDH1 and IDH2. The gene encoding IDH2 was previously cloned and sequenced (Cupp, J.R., and McAlister-Henn, L. (1991) J. Biol. Chem. 266, 22199-22205), and in this paper we describe the isolation of a yeast genomic clone containing the IDH1 gene. A fragment of the IDH1 gene was amplified by the polymerase chain reaction method utilizing degenerate oligonucleotides based on tryptic peptide sequences of the purified subunit; this fragment was used to isolate a full length IDH1 clone. The nucleotide sequence of the IDH1 coding region was determined and encodes a 360-residue polypeptide including an 11-residue mitochondrial targeting presequence. Amino acid sequence comparison between IDH1 and IDH2 reveals a 42% sequence identity, and both IDH1 and IDH2 show approximately 32% identity to Escherichia coli NAD(P)(+)-dependent isocitrate dehydrogenase. To examine the function of the IDH1 subunit and to determine the metabolic role of NAD(+)-dependent isocitrate dehydrogenase the IDH1 gene was disrupted in a wild type haploid yeast strain and in a haploid strain lacking IDH2. The IDH1 disruption strains expressed no detectable IDH1 as determined by Western blot analysis, and these strains were found to lack NAD(+)-dependent isocitrate dehydrogenase activity indicating that IDH1 is essential for a functional enzyme. Over-expression of IDH1 in a strain containing IDH2 restored wild type activity but did not result in increased levels of activity, suggesting that both IDH1 and IDH2 are required for a functional enzyme. Growth phenotype analysis of the IDH1 disruption strains revealed that they grew at a reduced rate on the nonfermentable carbon sources examined (glycerol, lactate, and acetate), consistent with NAD(+)-dependent isocitrate dehydrogenase performing a critical role in oxidative function of the citric acid cycle. In addition, the IDH1 disruption strains grew at wild type rates in the absence of glutamate, indicating that these strains are not glutamate auxotrophs.
A DNA transposon-based approach to validate oncogenic mutations in the mouse (2008)

Large-scale cancer genome projects will soon be able to sequence many cancer genomes to comprehensively identify genetic changes in human cancer. Genome-wide association studies have also identified putative cancer associated loci. Functional validation of these genetic mutations in vivo is becoming a challenge. We describe here a DNA transposon-based platform that permits us to explore the oncogenic potential of genetic mutations in the mouse. Briefly, promoter-less human cancer gene cDNAs were first cloned into Sleeping Beauty (SB) transposons. DNA transposition in the mouse that carried both the transposons and the SB transposase made it possible for the cDNAs to be expressed from an appropriate endogenous genomic locus and in the relevant cell types for tumor development. Consequently, these mice developed a broad spectrum of tumors at very early postnatal stages. This technology thus complements the large-scale cancer genome projects.
Protein expression profiling identifies macrophage migration inhibitory factor and cyclophilin a as potential molecular targets in non-small cell lung cancer. (2003)

Current diagnostic and therapeutic strategies for lung cancer have had no significant impact on lung cancer mortality over the last several decades. This study used a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) discovery platform to generate protein expression profiles in search of overexpressed proteins in lung tumors as potentially novel molecular targets. Two differentially expressed protein peaks at m/z 12338 and 17882 in the MALDI-TOF spectra were identified in lung tumor specimens as macrophage migration inhibitory factor and cyclophilin A, respectively. Overexpression of both proteins was confirmed by Western blotting, and cyclophilin A was localized to the tumor cells by immunohistochemistry. These data demonstrate the feasibility of using a MALDI-TOF platform to generate protein expression profiles and identify potential molecular targets for cancer diagnostics and therapeutics.
New Polymer Supports for Solid-Liquid-Phase Peptide Synthesis (1986)

New Polymer Supports for Solid-Liquid-Phase Peptide Synthesis was published in Vol. 3 Proceedings of the Fifth USSR-FRG Symposium on Chemistry of Peptides and Proteins, Odessa, USSR, May 16–20, 1985 on page 3.
The vascular biology of macrophage migration inhibitory factor (MIF) (2013)

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with chemokine-like functions. MIF is a critical mediator of the host immune and inflammatory response. Dysregulated MIF expression has been demonstrated to contribute to various acute and chronic inflammatory conditions as well as cancer development. More recently, MIF has been identified as an important pro-atherogenic factor. Its blockade could even aid plaque regression in advanced atherosclerosis. Promotion of atherogenic leukocyte recruitment processes has been recognised as a major underlying mechanism of MIF in vascular pathology. However, MIF's role in vascular biology is not limited to immune cell recruitment as recent evidence also points to a role for this mediator in neo-angiogenesis / vasculogenesis by endothelial cell activation and endothelial progenitor cell recruitment. On the basis of introducing MIF's chemokine-like functions, the current article focusses on MIF's role in vascular biology and pathology.
Tetrazolium reduction as an aid for streptococcal growth detection with agar dilution susceptibility testing (1983)

A dye reduction method for determining a definitive endpoint with agar dilution susceptibility testing has been developed. Bacterial growth was determined by applying to the inoculum spot a dye solution containing 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyltetrazolium chloride and phenazine methosulfate. Viable colonies reduced the tetrazolium salt to a visible red color within 3 to 5 min. The minimum inhibitory concentrations of six antimicrobial agents tested against 167 clinical streptococcal isolates were recorded before and after the addition of the tetrazolium-phenazine methosulfate solution. A total of 252 discrepancies (25%) were observed, and of these, 30 (12%) differed by more than one tested antibiotic concentration. Endpoint reproducibility of the dye procedure was assessed by four technologists in a double-blind study. A 2.7-fold reduction in disagreement was observed when the dye was used. Use of the tetrazolium-phenazine methosulfate solution involves little deviation from standard antimicrobial susceptibility test procedures and yields more accurate, as well as reproducible, susceptibility results.
Role of WRINKLED1 in the transcriptional regulation of glycolytic and fatty acid biosynthetic genes in Arabidopsis (2009)

The WRINKLED1 (WRI1) protein is an important regulator of oil accumulation in maturing Arabidopsis seeds. WRI1 is a member of a plant-specific family of transcription factors (AP2/EREBP) that share either one or two copies of a DNA-binding domain called the AP2 domain. Here, it is shown that WRI1 acts as a transcriptional enhancer of genes involved in carbon metabolism in transgenic seeds overexpressing this transcription factor. PKp-beta1 and BCCP2, two genes encoding enzymes of the glycolysis and fatty acid biosynthetic pathway, respectively, have been chosen to investigate the regulatory action exerted by WRI1 over these pathways. Using the reporter gene uidA, it was possible to demonstrate in planta that WRI1 regulates the activity of both PKp-beta1 and BCCP2 promoters. Electrophoretic mobility-shift assays and yeast one-hybrid experiments showed that WRI1 was able to interact with the BCCP2 promoter. To further elucidate the regulatory mechanism controlling the transcription of these genes, functional dissections of PKp-beta1 and BCCP2 promoters were performed. Two enhancers, of 54 and 79 bp, respectively, have thus been isolated that are essential to direct the activity of these promoters in oil-accumulating tissues of the embryo. A consensus site is present in these enhancers as well as in other putative target promoters of WRI1. Loss of this consensus sequence in the BCPP2 promoter decreases both the strength of the interaction between WRI1 and this promoter in yeast and the activity of the promoter in planta.
The effect of 5-fluorouracil on erythropoiesis (1991)

Abstract The effects of a single dose (150 mg/kg) of 5-fluorouracil on mature erythroid and erythropoietic and multipotential in vitro precursor populations in the bone marrow and spleen and circulating biologically (erythroid colony forming unit [CFU-E] assay) and immunologically active (enzyme-linked immunosorbent assay) erythropoietin (Epo) are described. All mature erythroid (reticulocytes, erythrocytes) and in vitro erythropoietic precursors (CFU-E, erythroid burst-forming unit [BFU-E]) are severely reduced, if not eradicated. Transient repopulation of the pure BFU-E and CFU-E populations on days 6 and 7, respectively, produces a marked reticulocytosis after day 9. Circulating Epo increases to above normal values by day 2. However, whereas biologically active Epo remains constant at this level until day 9, immunologically active Epo continually increases; by day 12, however, both assays detect circulating Epo levels of about 400 mU/mL. In vitro multipotential stem cells (BFU-E mix) are reduced to 32% on day 1, 7.6% on day 2, and return to normal values between days 4 and 5. The survival and repopulation kinetics of the BFU-E mix imply a stem cell population more mature than the high proliferative potential colony-forming cells. However, the BFU-E mix may be responsible for erythropoiesis repopulating ability.
Expression of the peroxisome proliferator-activated receptor γ (PPARγ) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein (1998)

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcription factor that has been demonstrated to regulate fat cell development and glucose homeostasis. PPARgamma is also expressed in a subset of macrophages and negatively regulates the expression of several proinflammatory genes in response to natural and synthetic ligands. We here demonstrate that PPARgamma is expressed in macrophage foam cells of human atherosclerotic lesions, in a pattern that is highly correlated with that of oxidation-specific epitopes. Oxidized low density lipoprotein (oxLDL) and macrophage colony-stimulating factor, which are known to be present in atherosclerotic lesions, stimulated PPARgamma expression in primary macrophages and monocytic cell lines. PPARgamma mRNA expression was also induced in primary macrophages and THP-1 monocytic leukemia cells by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). Inhibition of protein kinase C blocked the induction of PPARgamma expression by TPA, but not by oxLDL, suggesting that more than one signaling pathway regulates PPARgamma expression in macrophages. TPA induced the expression of PPARgamma in RAW 264.7 macrophages by increasing transcription from the PPARgamma1 and PPARgamma3 promoters. In concert, these observations provide insights into the regulation of PPARgamma expression in activated macrophages and raise the possibility that PPARgamma ligands may influence the progression of atherosclerosis.
Asymmetric Hydrogenation of α-Hydroxy Ketones Catalyzed by MsDPEN−Cp*Ir(III) Complex (2007)

Asymmetric hydrogenation of a series of alpha-hydroxy aromatic ketones in methanol catalyzed by Cp*Ir(OTf)(MsDPEN) (MsDPEN = N-(methanesulfonyl)-1,2-diphenylethylenediamine) affords the 1-aryl-1,2-ethanediols in up to 99% ee. The reaction can be conducted with a substrate-to-catalyst molar ratio as high as 6000 under 10 atm of H2. 1-hydroxy-2-propanone is also hydrogenated with high enantioselectivity.
Diverse forms of a receptor for acidic and basic fibroblast growth factors. (1990)

We recently reported the isolation of a chicken cDNA clone encoding a basic fibroblast growth factor (FGF) receptor that has three immunoglobulinlike domains in the extracellular region. We have now identified four unique human cDNA clones encoding previously unknown FGF receptor variants which contain only two immunoglobulinlike domains. Two of the human clones encode membrane-spanning receptors, and two encode putative secreted forms. Both the three- and two-immunoglobulinlike-domain forms mediate biological responsiveness to acidic and basic FGF. Thus, the first immunoglobulinlike domain of the three-domain form may have a function other than binding of acidic and basic FGF.