gebhart/patrepeval huggingface dataset:
The Pattern of Disulfide Linkages in the Extracellular Loop Regions of Connexin 32 Suggests a Model for the Docking Interface of Gap Junctions (1998)

Connexins, like true cell adhesion molecules, have extracellular domains that provide strong and specific homophilic, and in some cases, heterophilic interactions between cells. Though the structure of the binding domains of adhesion proteins have been determined, the extracellular domains of connexins, consisting of two loops of approximately 34-37 amino acids each, are not easily studied in isolation from the rest of the molecule. As an alternative, we used a novel application of site-directed mutagenesis in which four of the six conserved cysteines in the extracellular loops of connexin 32 were moved individually and in all possible pairwise and some quadruple combinations. This mapping allowed us to deduce that all disulfides form between the two loops of a single connexin, with the first cysteine in one loop connected to the third of the other. Furthermore, the periodicity of movements that produced functional channels indicated that these loops are likely to form antiparallel beta sheets. A possible model that could explain how these domains from apposed connexins interact to form a complete channel is discussed.
Impairment, disability, and handicap in multiple sclerosis (1994)

We studied functional status of MS patients in a geographically based cohort in Olmsted County, Minnesota. The 162 definite MS patients who were alive and residing in the study area on December 1, 1991, constituted the MS prevalence disability cohort. We identified 179 cases of definite or probable MS, providing an overall sex- and age-adjusted prevalence rate of 167.5 per 100,000. Median duration of MS from onset was 15.4 years, and median age on prevalence date was 47.5 years. The Minimal Record of Disability for MS determined the degree of impairment, disability, and handicap of the entire cohort within 4 months of the prevalence date. The frequency of Expanded Disability Status Scale scores of the MS prevalence cohort showed a bimodal distribution with peaks at 1 and 6.5 (3.5 [1 to 9.5], median [range]). Approximately one-third of the cohort had marked paraparesis, paraplegia, or quadriplegia. One-fourth of all patients needed intermittent or almost constant catheterization for bladder dysfunction. Few patients (3.7%) reported severe decrease in mentation or dementia requiring supervision. Many patients (53.1%) were working full-time. Most patients (72.2%) maintained their usual financial standard without external support. There were no differences in level of impairment, disability, or handicap observed between the subgroup of 122 patients (75.3%) who are incident cases (onset of disease as residents of Olmsted County) compared with the entire prevalence cohort. This geographically based study of MS demonstrates that the functional status is more favorable than previously recognized.
Epidermal growth factor-induced apoptosis in A431 cells can be reversed by reducing the tyrosine kinase activity. (1996)

A431 cells overexpress epidermal growth factor receptors (EGF-Rs) and are inhibited by EGF. We show that treatment of A431 cells with 10 nM EGF induced a 15-fold increase in EGF-R autophosphorylation, leading to inhibition of cell proliferation and morphological features of apoptosis. However, at a lower concentration of EGF (0.01 nM), there is a 2-fold increase in EGF-R autophosphorylation and increased cell proliferation when compared to untreated cells. EGF treatment is associated with increased expression of c-myc and decreased expression of mutant p53 and p21/WAF protein. When A431 cells were simultaneously treated with 10 nM EGF and EGF-R antibody, there was a significant reduction in EGF-R autophosphorylation that was associated with increased cell proliferation. Based on these results, we postulate that overexpression of EGF-R could allow for selective growth advantage for tumor cells in the presence of normal or decreased ligand availability. However, excessive ligand binding would result in deregulated growth signaling, leading to growth inhibition and programmed cell death.
Intradermal Influenza Vaccine Administered Using a New Microinjection System Produces Superior Immunogenicity in Elderly Adults: A Randomized Controlled Trial (2008)

Clinicaltrials.gov registry number: NCT00296829.
Characterization of the Acid Stability of Glycosidically Linked Neuraminic Acid (2002)

The glycosidic linkage of sialic acids is much more sensitive to acid hydrolysis than those of other monosaccharides in vertebrates. The commonest sialic acids in nature are neuraminic acid (Neu)-based and are typically N-acylated at the C5 position. Unsubstituted Neu is thought to occur on native gangliosides of certain tumors and cell lines, and synthetic de-N-acetyl-gangliosides have potent biological properties in vitro. However, claims for their natural existence are based upon monoclonal antibodies and pulse-chase experiments, and there have been no reports of their chemical detection. Here we report that one of these antibodies shows nonspecific cross-reactivity with a polypeptide epitope, further emphasizing the need for definitive chemical proof of unsubstituted Neu on naturally occurring gangliosides. While pursuing this, we found that alpha2-3-linked Neu on chemically de-N-acetylated G(M3) ganglioside resists acid hydrolysis under conditions where the N-acetylated form is completely labile. To ascertain the generality of this finding, we investigated the stability of glycosidically linked alpha- and beta-methyl glycosides of Neu. Using NMR spectroscopy to monitor glycosidic linkage hydrolysis, we find that only 47% of Neualpha2Me is hydrolyzed after 3 h in 10 mm HCl at 80 degrees C, whereas Neu5Acalpha2Me is 95% hydrolyzed after 20 min under the same conditions. Notably, Neubeta2Me is hydrolyzed even slower than Neualpha2Me, indicating that acid resistance is a general property of glycosidically linked Neu. Taking advantage of this, we modified classical purification techniques for de-N-acetyl-ganglioside isolation using acid to first eliminate conventional gangliosides. We also introduce a phospholipase-based approach to remove contaminating phospholipids that previously hindered efforts to study de-N-acetyl-gangliosides. The partially purified sample can then be N-propionylated, allowing acid release and mass spectrometric detection of any originally existing Neu as Neu5Pr. These advances allowed us to detect covalently bound Neu in lipid extracts of a human melanoma tumor, providing the first chemical proof for naturally occurring de-N-acetyl-gangliosides.
Single-fibre surface-enhanced Raman sensors with angled tips (2000)

Single-fibre surface-enhanced Raman sensors were prepared by depositing rough metal films at the tips of optical fibres. Different deposition techniques such as slow evaporation of metal island films and vacuum deposition of metal films over nanoparticles or on pre-roughened surfaces were applied and compared. The superposition of surface Raman spectra from the tips with Raman spectra of the fibre core made maximum enhancements necessary for the construction of long fibre sensors. The enhancement was improved significantly by altering the tip geometry. Angled polishing has enhanced the SERS intensity by up to a factor of 6. The intensity increases monotonically with increase in the angle, reaching its maximum value at the largest prepared angle of 40°. Copyright © 2000 John Wiley & Sons, Ltd.
The grpE protein of Escherichia coli. Purification and properties. (1987)

The grpE gene of Escherichia coli was first identified because a mutation in it, grpE280, prevented bacteriophage lambda DNA replication in vivo. Subsequent work resulted in the identification of the grpE protein in two-dimensional gels and its classification as a heat shock protein. Here we report the purification of the grpE protein. We show that overproduction of grpE occurs in dnaK 103 bacteria which do not produce a functional Mr 72,000 dnaK protein. The grpE protein was purified from this strain primarily by its specific retention on a dnaK affinity column. The interaction between these two proteins, which is stable in the presence of 2 M KCl, allowed other proteins to be washed from this column. grpE was then eluted by ATP, which disrupts the interaction. During purification, grpE activity was monitored by its ability to complement an in vitro lambda dv DNA replication system dependent on the lambda O and lambda P proteins. The effect of ATP on the dnaK-grpE complex was also observed during sedimentation of the two proteins in glycerol gradients. Purified grpE protein has a Mr of approximately 23,000 under both denaturing and native conditions, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and sedimentation, respectively. However, in the presence of dnaK under native conditions, grpE cosediments with dnaK. When ATP is added to the gradient, the complex is disrupted, and the two proteins sediment independently as monomers.
Propene Polymerization with Silica-Supported Metallocene/MAO Catalysts (2000)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPropene Polymerization with Silica-Supported Metallocene/MAO CatalystsGerhard Fink, Bernd Steinmetz, Joachim Zechlin, Christian Przybyla, and Bernd TescheView Author Information Max Planck Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim/Ruhr, Germany Cite this: Chem. Rev. 2000, 100, 4, 1377–1390Publication Date (Web):March 18, 2000Publication History Received9 September 1999Published online18 March 2000Published inissue 1 April 2000https://pubs.acs.org/doi/10.1021/cr9804689https://doi.org/10.1021/cr9804689research-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views3879Altmetric-Citations341LEARN 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 SUBJECTS:Catalysts,Polymer particles,Polymerization,Polymers,Silica Get e-Alerts
Histidine regulation of cyclic AMP metabolism in cultured renal epithelial LLC-PK1 cells. (1990)

L-Histidine and imidazole (the histidine side chain) significantly increase cAMP accumulation in intact LLC-PK1 cells. This effect is completely inhibited by isobutylmethylxanthine (IBMX). Histidine and imidazole stimulate cAMP phosphodiesterase activity in soluble and membrane fractions of LLC-PK1 cells suggesting that the IBMX-sensitive effect of these agents to stimulate cAMP formation is not due to inhibition of cAMP phosphodiesterase. Histidine and imidazole but not alanine (the histidine core structure) increase basal, GTP-, forskolin-, and AVP-stimulated adenylate cyclase activity in LLC-PK1 membranes. Two other amino acids with charged side chains (aspartic and glutamic acids) increase AVP-stimulated but neither basal- nor forskolin-stimulated adenylate cyclase activity. This suggests that multiple amino acids with charged side chains can regulate selected aspects of adenylate cyclase activity. To better define the mechanism of histidine regulation of adenylate cyclase, membranes were detergent-solubilized which prevents histidine and imidazole potentiation of forskolin-stimulated adenylate cyclase activity and suggests that an intact plasma membrane environment is required for potentiation. Neither pertussis toxin nor indomethacin pretreatment alter imidazole potentiation of adenylate cyclase. IBMX pretreatment of LLC-PK1 membranes also prevents imidazole to potentiate adenylate cyclase activity. Since IBMX inhibits adenylate cyclase coupled adenosine receptors, LLC-PK1 cells were incubated in vitro with 5'-N-ethylcarboxyamideadenosine (NECA) which produced a homologous pattern of desensitization of NECA to stimulate adenylate cyclase activity. Despite homologous desensitization, histidine and imidazole potentiation of adenylate cyclase was unaltered. These data suggest that histidine, acting via an imidazole ring, potentiates adenylate cyclase activity and thereby increases cAMP formation in cultured LLC-PK1 epithelial cells. This potentiation requires an intact plasma membrane environment, occurs independent of a pertussis toxin-sensitive substrate and of products of cyclooxygenase, and is inhibited by IBMX. This IBMX-sensitive pathway does not involve either inhibition of cAMP phosphodiesterase activity or a stimulatory adenosine receptor coupled to adenylate cyclase.
Chemoprotective Properties of Phenylpropenoids, Bis(benzylidene)cycloalkanones, and Related Michael Reaction Acceptors:  Correlation of Potencies as Phase 2 Enzyme Inducers and Radical Scavengers (1998)

Induction of phase 2 enzymes (e.g., glutathione transferases, NAD(P)H:quinone reductase, glucuronosyltransferases, epoxide hydrolase) is a major strategy for reducing the susceptibility of animal cells to neoplasia and other forms of electrophile toxicity. In a search for new chemoprotective enzyme inducers, a structure-activity analysis was carried out on two types of naturally occurring and synthetic substituted phenylpropenoids: (a) Ar-CH=CH-CO-R, where R is OH, OCH3, CH3, or Ar, including cinnamic, coumaric, ferulic, and sinapic acid derivatives, their ketone analogues, and chalcones; and (b) bis(benzylidene)cycloalkanones, Ar-CH=C(CH2)n(CO)C=CH-Ar, where n = 5, 6, or 7. The potencies of these compounds in inducing NAD(P)H:quinone reductase activity in murine hepatoma cells paralleled their Michael reaction acceptor activity (Talalay, P.; De Long, M. J.; Prochaska, H. J. Proc. Natl. Acad. Sci. U.S.A. 85, 1988, 8261-8265). Unexpectedly, the bis(benzylidene)cycloalkanones also powerfully quenched the lucigenin-derived chemiluminescence evoked by superoxide radicals. Introduction of o-hydroxyl groups on the aromatic rings of these phenylpropenoids dramatically enhanced their potencies not only as inducers for quinone reductase but also as quenchers of superoxide. These potentiating o-hydroxyl groups are hydrogen-bonded, as shown by moderate downfield shift of their proton NMR resonances and their sensitivities to the solvent environment. The finding that the potencies of a series of bis(benzylidene)cycloalkanones in inducing quinone reductase appear to be correlated with their ability to quench superoxide radicals suggests that the regulation of phase 2 enzymes may involve both Michael reaction reactivity and radical quenching mechanisms.
INHIBITION OF PROLIFERATION OF CONTAMINATING FIBROBLASTS BY D‐VALINE IN CULTURES OF SMOOTH MUSCLE CELLS FROM HUMAN MYOMETRIUM (2000)

Replacement of L-valine with D-valine in a standard culture medium can selectively inhibit fibroblast proliferation. The aim of the present study was to investigate whether human myometrial cells cultured with D-valine instead of L-valine can survive and express their characteristics. Cultured cells (95-98%) maintain expression of the intermediate filament desmin, which is the specific marker for mature muscle cells. By transmission electron microscopy, the cells showed the general morphology of smooth muscle cells in culture. Oxytocin in serum-free culture medium at 37 degrees C (5 min) caused a concentration-dependent increase in cellular Na and total Ca, and a decrease in K content as determined by X-ray microanalysis. The percentage of cells cultured with D-valine responding to oxytocin stimulation was larger than that of cells cultured with L-valine, suggesting less contamination of smooth muscle cells by fibroblasts in the presence of D-valine. As shown by measurements with fura-2, D-valine-cultured cells retained the characteristic increase in intracellular free Ca2+ ions after oxytocin stimulation.
A Plant-Derived Ligand Favoring Monomeric Glucocorticoid Receptor Conformation with Impaired Transactivation Potential Attenuates Collagen-Induced Arthritis (2008)

The glucocorticoid receptor (GR) is a transcription factor regulating its target genes either positively, through direct binding to the promoter of target genes, or negatively by the interference with the activity of transcription factors involved in proinflammatory gene expression. The well-known adverse effects of glucocorticoids are believed to be mainly caused by their GR-mediated gene-activating properties. Although dimerization of GR is thought to be essential for gene-activating properties, no compound has yet been described which selectively imposes GR monomer formation and interference with other transcription factors. In the present study, we report on a GR-binding, plant-derived compound with marked dissociative properties in rheumatoid arthritis fibroblast-like synoviocytes, which are important effector cells in inflammation and matrix degradation in rheumatoid arthritis. In addition, these findings could be extended in vivo in murine collagen-induced arthritis, in which joint inflammation was markedly inhibited without inducing hyperinsulinemia. Therefore, we conclude that GR monomers are sufficient for inhibition of inflammation in vivo.
Activins and Inhibins in Endocrine and Other Tumors (2001)

Inhibin and activin are members of the TGF beta superfamily of growth and differentiation factors. They were first identified as gonadal-derived regulators of pituitary FSH and were subsequently assigned multiple actions in a wide range of tissues. More recently, the inhibin alpha subunit was considered as a tumor suppressor based on functional studies employing transgenic mouse models. This review evaluates the functional and molecular evidence that the inhibin alpha subunit is a tumor suppressor in endocrine cancers. The evaluation highlights the discrepant results from the human and mouse studies, as well as the differences between endocrine tumor types. In addition, we examine the evidence that the activin-signaling pathway is tumor suppressive and identify organ-specific differences in the actions and putative roles of this pathway in endocrine tumors. In summary, there is a considerable body of evidence to support the role of inhibins and activins in endocrine-related tumors. Future studies will define the mechanisms by which inhibins and activins contribute to the process of initiation, promotion, or progression of endocrine-related cancers.
Diastereoselective Cationic Tandem Cyclizations to N-Heterocyclic Scaffolds:  Total Synthesis of (−)-Dysibetaine PP (2005)

[reaction: see text] Herein, we report a short and diastereoselective synthesis of the natural product (-)-dysibetaine PP. The key step in the synthetic sequence is a novel highly diastereoselective tandem-cyclization reaction of an enantiomerically pure dipeptide. This cyclization methodology is applied in the synthesis of a broader range of N-heterocyclic scaffolds.
Induction of Neutralizing Antibodies to T-Cell Line-Adapted and Primary Human Immunodeficiency Virus Type 1 Isolates with a Prime-Boost Vaccine Regimen in Chimpanzees (1998)

ABSTRACT Five chimpanzees were immunized by administration of one or more intranasal priming doses of one to three recombinant adenoviruses containing a gp160 insert from human immunodeficiency virus type 1 (HIV-1) MN (HIV-1 MN ) followed by one or more boosts of recombinant HIV-1 SF2 gp120 delivered intramuscularly with MF59 adjuvant. This regimen resulted in humoral immune responses in three of five animals. Humoral responses included immunochemically active anti-HIV-1 antibodies (Abs) directed to recombinant gp120 and neutralizing Abs reactive with T-cell-line-adapted HIV-1 MN and HIV-1 SF2 . In addition, neutralizing activity was detected to the two homologous primary isolates and to two of three heterologous primary isolates which, like the immunizing strains, can use CXCR4 as a coreceptor for infection. The three animals with detectable neutralizing Abs and a fourth exhibiting the best cytotoxic T-lymphocyte response were protected from a low-dose intravenous challenge with a cell-free HIV-1 SF2 primary isolate administered 4 weeks after the last boost. Animals were rested for 46 weeks and then rechallenged, without a boost, with an eightfold-higher challenge dose of HIV-1 SF2 . The three animals with persistent neutralizing Abs were again protected. These data show that a strong, long-lived protective Ab response can be induced with a prime-boost regimen in chimpanzees. The data suggest that in chimpanzees, the presence of neutralizing Abs correlates with protection for animals challenged intravenously with a high dose of a homologous strain of HIV-1, and they demonstrate for the first time the induction of neutralizing Abs to homologous and heterologous primary isolates.
Specific Inhibition of Insulin-Like Growth Factor-1 and Insulin Receptor Tyrosine Kinase Activity and Biological Function by Tyrphostins (1997)

A series of the synthetic protein tyrosine kinase inhibitors known as tyrphostins were studied for their effect on insulin-like growth factor-1 and insulin-stimulated cellular proliferation on NIH-3T3 fibroblasts overexpressing either receptor, as well as for their ability to inhibit ligand-stimulated receptor autophosphorylation and tyrosine kinase activity toward exogenous substrates. Several of the tyrphostins tested demonstrated a dramatic effect by inhibiting hormone-stimulated cell proliferation, with IC50s in the submicromolar range, while being unable to block serum-stimulated cell proliferation. The tyrphostins also inhibited receptor autophosphorylation and tyrosine kinase activity, with a higher IC50, in the micromolar range. Most of the tyrphostins tested presented no clear preference for either receptor, although two of them (AG1024 and AG1034) showed significantly lower IC50s for IGF-1 than for insulin receptors. These results suggest that, in spite of the high homology of the kinase regions of both receptors, it could be possible to design and synthesize small molecules capable of discriminating between them. The synthesis of such specific inhibitors could be an excellent tool to establish the precise signalling mechanisms that distinguish between the different effects of these two hormones.
Frequent Detection of Human Adenovirus from the Lower Gastrointestinal Tract in Men Who Have Sex with Men (2010)

HAdV shedding was highly prevalent and diverse, including types presently under consideration as HIV vaccine vectors. Subclinical HAdV infection of the GI tract is common among MSM in Peru; the prevalence of HAdV in the enteric tract should be evaluated in other populations. The association between ongoing recent enteric HAdV and the immune response to recombinant HAdV vaccines should be evaluated.