gebhart/patrepeval huggingface dataset:
Epitope Mapping of CCR5 Reveals Multiple Conformational States and Distinct but Overlapping Structures Involved in Chemokine and Coreceptor Function (1999)

The chemokine receptor CCR5 is the major coreceptor for R5 human immunodeficiency virus type-1 strains. We mapped the epitope specificities of 18 CCR5 monoclonal antibodies (mAbs) to identify domains of CCR5 required for chemokine binding, gp120 binding, and for inducing conformational changes in Env that lead to membrane fusion. We identified mAbs that bound to N-terminal epitopes, extracellular loop 2 (ECL2) epitopes, and multidomain (MD) epitopes composed of more than one single extracellular domain. N-terminal mAbs recognized specific residues that span the first 13 amino acids of CCR5, while nearly all ECL2 mAbs recognized residues Tyr-184 to Phe-189. In addition, all MD epitopes involved ECL2, including at least residues Lys-171 and Glu-172. We found that ECL2-specific mAbs were more efficient than NH2- or MD-antibodies in blocking RANTES or MIP-1beta binding. By contrast, N-terminal mAbs blocked gp120-CCR5 binding more effectively than ECL2 mAbs. Surprisingly, ECL2 mAbs were more potent inhibitors of viral infection than N-terminal mAbs. Thus, the ability to block virus infection did not correlate with the ability to block gp120 binding. Together, these results imply that chemokines and Env bind to distinct but overlapping sites in CCR5, and suggest that the N-terminal domain of CCR5 is more important for gp120 binding while the extracellular loops are more important for inducing conformational changes in Env that lead to membrane fusion and virus infection. Measurements of individual antibody affinities coupled with kinetic analysis of equilibrium binding states also suggested that there are multiple conformational states of CCR5. A previously described mAb, 2D7, was unique in its ability to effectively block both chemokine and Env binding as well as coreceptor activity. 2D7 bound to a unique antigenic determinant in the first half of ECL2 and recognized a far greater proportion of cell surface CCR5 molecules than the other mAbs examined. Thus, the epitope recognized by 2D7 may represent a particularly attractive target for CCR5 antagonists.
Control of Simian/Human Immunodeficiency Virus Viremia and Disease Progression after IL-2-Augmented DNA-Modified Vaccinia Virus Ankara Nasal Vaccination in Nonhuman Primates (2004)

A successful HIV vaccine may need to stimulate antiviral immunity in mucosal and systemic immune compartments, because HIV transmission occurs predominantly at mucosal sites. We report here the results of a combined DNA-modified vaccinia virus Ankara (MVA) vaccine approach that stimulated simian/human immunodeficiency virus (SHIV)-specific immune responses by vaccination at the nasal mucosa. Fifteen male rhesus macaques, divided into three groups, received three nasal vaccinations on day 1, wk 9, and wk 25 with a SHIV DNA plasmid producing noninfectious viral particles (group 1), or SHIV DNA plus IL-2/Ig DNA (group 2), or SHIV DNA plus IL-12 DNA (group 3). On wk 33, all macaques were boosted with rMVA expressing SIV Gag-Pol and HIV Env 89.6P, administered nasally. Humoral responses were evaluated by measuring SHIV-specific IgG and neutralizing Abs in plasma, and SHIV-specific IgA in rectal secretions. Cellular responses were monitored by evaluating blood-derived virus-specific IFN-gamma-secreting cells and TNF-alpha-expressing CD8+ T cells, and blood- and rectally derived p11C tetramer-positive T cells. Many of the vaccinated animals developed both mucosal and systemic humoral and cell-mediated anti-SHIV immune responses, although the responses were not homogenous among animals in the different groups. After rectal challenge of vaccinated and naive animals with SHIV89.6P, all animals became infected. However a subset, including all group 2 animals, were protected from CD4+ T cell loss and AIDS development. Taken together, these data indicate that nasal vaccination with SHIV-DNA plus IL-2/Ig DNA and rMVA can provide significant protection from disease progression.
Control of white and brown adipose tissues by the autonomic nervous system (1987)

Interest in the neural regulation of the adipose tissues has increased considerably in recent years. In the case of brown adipose tissue (BAT) this reflects the development of the concept that the tissue is important in the regulation of energy balance. The substantial innervation of BAT has been recognized, however, for some considerable time (see In the present paper we have set out to briefly summarize current views on the role of the autonomic nervous system, in practice the sympathetic system, in the control of both white adipose tissue (WAT) and BAT. The regulatory effects of the sympathetic system on these two tissues can be considered in terms of acute effects on the central metabolic pathways, and chronic effects relating to the growth and development of the tissues.
Adsorption isotherm of amorphous trehalose (1997)

The water adsorption isotherm at 25°C of freeze-dried amorphous trehalose and trehalose with the addition of maltodextrin (MD) DE 10.9 was obtained. Moisture uptake as a function of time at various relative humidities (RH) was also measured. At low relative humidities (RH) amorphous trehalose adsorbs moisture but at 44% RH and above the isotherm exhibits a plateau indicating crystallisation (formation of the dihydrate) of amorphous trehalose and this was reflected on the shape of the isotherm. Trehalose crystallisation was delayed in the system containing maltodextrin (50: 50) as compared with pure trehalose. © 1997 SCI.
MicroRNA for circulating tumor cells detection in breast cancer: In silico and in vitro analysis (2009)

e22027 Background: Detection of circulating tumor cells (CTC) may provide diagnostic and prognostic information in breast cancer (bc) patients. Deregulation of microRNAs (miRNAs) is frequent in tumors, including breast cancer. It is suggested miRNAs play a role in tumor progression. We hypothesized that miRNAs may constitute a promising new class of cancer biomarkers for CTC detection. Our objective has been to identify miRNAs potentially useful for CTC detection. Methods: Phase I preclinical study was performed by means of computational tools for miRNAs profiling including MIRGATOR, MIRBASE, SMIRNAdb, GeneHUB-GEPIS, MICRORNA.ORG, and MIRNAMAP. In silico data were used to identify and prioritize miRNAs highly expressed in breast cancer, but absent in hematopoietic-derived sources. Selected miRNAs were evaluated by means of qRT-PCR in breast cancer and Hematopoietic cell lines, normal blood, and blood from breast cancer patients. Results: Computational tools identify a set of miRNAs highly expressed in breast cancer sources in relation to hematopoietic samples. Among these were miR-141, miR-200c, miR-196a, miR-203, miR-200a, miR-200b, miR-32, miR-375, miR-31, miR-193a, and miR-205. For instance, relative expression of miR-32 was 10 4 higher in bc cell lines (N= 5) than in normal PB (N = 19) using qRT-PCR. In a preliminary analysis of PB from bc patients (stage IV) higher relative expression levels for selected miRNAs were found comparing with age-matched controls’ blood. Conclusions: Our results suggest that miRNA bioinformatic approach is a useful high-throughput method to select bc-associated miRNAS. The selected miRNAs should be further evaluated for their potential as markers for CTC detection. We next investigate if blood miRNA profile could predict tumor progression and survival. Supported by grants PI06/1541 and PI07/0477 from Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III. No significant financial relationships to disclose.
The parathyroid is a target organ for FGF23 in rats (2007)

Phosphate homeostasis is maintained by a counterbalance between efflux from the kidney and influx from intestine and bone. FGF23 is a bone-derived phosphaturic hormone that acts on the kidney to increase phosphate excretion and suppress biosynthesis of vitamin D. FGF23 signals with highest efficacy through several FGF receptors (FGFRs) bound by the transmembrane protein Klotho as a coreceptor. Since most tissues express FGFR, expression of Klotho determines FGF23 target organs. Here we identify the parathyroid as a target organ for FGF23 in rats. We show that the parathyroid gland expressed Klotho and 2 FGFRs. The administration of recombinant FGF23 led to an increase in parathyroid Klotho levels. In addition, FGF23 activated the MAPK pathway in the parathyroid through ERK1/2 phosphorylation and increased early growth response 1 mRNA levels. Using both rats and in vitro rat parathyroid cultures, we show that FGF23 suppressed both parathyroid hormone (PTH) secretion and PTH gene expression. The FGF23-induced decrease in PTH secretion was prevented by a MAPK inhibitor. These data indicate that FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH. This bone-parathyroid endocrine axis adds a new dimension to the understanding of mineral homeostasis.
Hydrogen bonding, overlap geometry, and sequence specificity in anthracycline antitumor antibiotic.DNA complexes in solution. (1981)

We have deduced structural aspects of the intercalation complex of the anthracycline antitumor antibiotic daunomycin and its analogs with the synthetic DNA poly(dA-dT) by 1H and 31P NMR in high-salt solution. We demonstrate that the base pairs are intact at the antibiotic binding site and that the anthracycline phenolic hydroxyls form intramolecular hydrogen bonds with the quinone carbonyls and are shielded from solvent in the intercalation complex. The complexation shifts of the exchangeable phenolic and nonexchangeable aromatic protons demonstrate that rings B and C of the anthracycline chromophore overlap with adjacent base pairs, while anthracycline ring D passes right through the intercalation site in the complex. We observe two resolved 31P resonances attributable to the dA-dT and dT-dA phosphodiester linkages in the phosphorus spectra of the neighbor-exclusion daunomycin.poly(dA-dT) complex. This suggests that the anthracycline antitumor antibiotic exhibits a sequence specificity in its intercalation complex with alternating purine-pyrimidine synthetic DNAs in solution. These conclusions on hydrogen bonding and overlap geometry at the intercalation site and sequence specificity for the daunomycin.poly(dA-dT) complex in solution are in agreement with the structure of the daunomycin.dC-dG-dT-dA-dC-dG hexanucleotide duplex crystalline complex at atomic resolution published recently [Quigley, G. J., Wang, A. H.-J., Ughetto, G., van der Marel, G., van Boom, J. H. & Rich, A. (1980) Proc. Natl. Acad. Sci. USA 77, 7204-7208].
Hedonic Hot Spot in Nucleus Accumbens Shell: Where Do μ-Opioids Cause Increased Hedonic Impact of Sweetness? (2005)

Mu-opioid systems in the medial shell of the nucleus accumbens contribute to hedonic impact ("liking") for sweetness, food, and drug rewards. But does the entire medial shell generate reward hedonic impact? Or is there a specific localized site for opioid enhancement of hedonic "liking" in the medial shell? And how does enhanced taste hedonic impact relate to opioid-stimulated increases in food intake? Here, we used a functional mapping procedure based on microinjection Fos plumes to localize opioid substrates in the medial shell of the nucleus accumbens that cause enhanced "liking" reactions to sweet pleasure and that stimulate food intake. We mapped changes in affective orofacial reactions of "liking"/"disliking" elicited by sucrose or quinine tastes after D-Ala2-N-Me-Phe4-Glycol5-enkephalin (DAMGO) microinjections in rats and compared hedonic increases to food intake stimulated at the same sites. Our maps indicate that opioid-induced increases in sucrose hedonic impact are generated by a localized cubic millimeter site in a rostrodorsal region of the medial shell. In contrast, all regions of the medial shell generated DAMGO-induced robust increases in eating behavior and food intake. Thus, our results identify a locus for opioid amplification of hedonic impact and reveal a distinction between opioid mechanisms of food intake and hedonic impact. Opioid circuits for stimulating food intake are widely distributed, whereas hedonic "liking" circuits are more tightly localized in the rostromedial shell of the nucleus accumbens.
ortho-Alkylation of Aromatic Amines1 (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTortho-Alkylation of Aromatic Amines1GEORGE G. ECKE, JOHN P. NAPOLITANO, ALLEN H. FILBEY, and ALFRED J. KOLKACite this: J. Org. Chem. 1957, 22, 6, 639–642Publication Date (Print):June 1, 1957Publication History Published online1 May 2002Published inissue 1 June 1957https://pubs.acs.org/doi/10.1021/jo01357a013https://doi.org/10.1021/jo01357a013research-articleACS PublicationsRequest reuse permissionsArticle Views489Altmetric-Citations25LEARN 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
Multiple and sensitive fluorescence in situ hybridization with rhodamine-, fluorescein-, and coumarin-labeled DNAs (1993)

We have tested the use of several newly developed red, green, and blue fluorescent dUTPs in direct, multiple, and sensitive fluorescence in situ hybridization procedures. Among the ones tested, the tetramethylrhodamine-dUTP proved to give the best sensitivity; using conventional epifluorescence microscopy, cosmids could be visualized with a hybridization efficiency of 90%. Fluorescein-dUTP permitted visual cosmid detection with 50% efficiency, and, to the human eye, the green signals appeared less bright. With a blue fluorescent coumarin-labeled dUTP, only highly repetitive target sequences could be visualized directly. Imaging with a cooled CCD (charged coupled device) camera for prolonged integration times permitted localization of small targets using probes labeled with red and green fluorochromes. Visualization of a 1.8-kb single copy sequence with a rhodamine-labeled cDNA proved feasible. The strategy of identifying hybridization sites with multiple colors was successfully applied for multiple hybridizations to repetitive and unique targets, using the red and green labels directly and the biotin label indirectly with one layer of avidin-coumarin.
Atomic force microscope study of chromatic transitions in polydiacetylene thin films (1996)

Despite decades of study, the exact mechanism for chromatic transitions in polydiacetylene materials remains somewhat elusive. The mechanism of the blue to red color transition for overcompressed mixed lipid thin films of 10,12 pentacosadiynoic acid has been investigated by atomic force microscopy. Blue layers were prepared by the horizontal Langmuir–Schaefer deposition method. The red form was attained by thermal annealing of blue films (thermochromism). The blue films reveal micro-sized domains. Each domain shows a stripelike morphology on top of a nearly complete layer. The polymer backbone direction shows a high degree of order. A partial disorder is shown to exist along the interbackbone direction. Our study of the red form films indicates that changes occur in the micron-scale morphology of the films. Interestingly the alkyl side chains rearrange into a completely ordered structure and remain ordered well beyond the transition temperature (70 °C&amp;lt;T&amp;lt;90 °C). Our results strongly suggest that the reorganization of the side chains is the origin of the thermochromic effect for these films.
Bacterial Biofilm Formation on a Human Cochlear Implant (2005)

Cochlear implant material can provide a surface for bacterial biofilm formation. Impressions can provide an environment conducive to biofilm establishment and growth, ultimately necessitating device removal, with loss of implant function. Biofilm characterization should aid in design of cochlear implant devices less susceptible to biofilm formation.
Bacteria in cancer therapy: a novel experimental strategy (2010)

Resistance to conventional anticancer therapies in patients with advanced solid tumors has prompted the need of alternative cancer therapies. Moreover, the success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity to normal tissues. Several decades after Coley's work a variety of natural and genetically modified non-pathogenic bacterial species are being explored as potential antitumor agents, either to provide direct tumoricidal effects or to deliver tumoricidal molecules. Live, attenuated or genetically modified non-pathogenic bacterial species are capable of multiplying selectively in tumors and inhibiting their growth. Due to their selectivity for tumor tissues, these bacteria and their spores also serve as ideal vectors for delivering therapeutic proteins to tumors. Bacterial toxins too have emerged as promising cancer treatment strategy. The most potential and promising strategy is bacteria based gene-directed enzyme prodrug therapy. Although it has shown successful results in vivo yet further investigation about the targeting mechanisms of the bacteria are required to make it a complete therapeutic approach in cancer treatment.
Isolation of the amplified dihydrofolate reductase domain from methotrexate-resistant Chinese hamster ovary cells. (1987)

We isolated overlapping recombinant cosmids that represent the equivalent of two complete dihydrofolate reductase amplicon types from the methotrexate-resistant CHO cell line CHOC400. The type I amplicons are 260 kilobases long, are arranged in head-to-tail fashion, and represent 10 to 15% of the amplicons in the CHOC400 genome. The type II amplicons are 220 kilobases long, are arranged in head-to-head and tail-to-tail configurations, and constituted the majority of the remaining amplicons in CHOC400 cells. The type II amplicon sequences are represented entirely within the type I unit. These are the first complete amplicons to be cloned from a mammalian cell line.
Anandamide-Evoked Activation of Vanilloid Receptor 1 Contributes to the Development of Bladder Hyperreflexia and Nociceptive Transmission to Spinal Dorsal Horn Neurons in Cystitis (2004)

The role of anandamide in the development of inflammatory hyperalgesia and visceral hyperreflexia was studied in the rat urinary bladder. Animals were given intraperitoneal cyclophosphamide injection, which evokes painful hemorrhagic cystitis accompanied by increased bladder reflex activity. The vanilloid receptor 1 [transient receptor potential vanilloid 1 (TRPV1)] antagonist capsazepine, applied onto the serosal surface of bladders, significantly reduced the hyperreflexia. Mass spectrometric analysis revealed that cyclophosphamide injection significantly and persistently increased the anandamide content of bladder tissues. The increase in the anandamide content paralleled the development of reflex hyperactivity. Anandamide (1-100 microm), applied onto the serosal surface of naive bladders, increased the reflex activity in a concentration-dependent manner. Repeated anandamide applications did not produce desensitization of the response. The anandamide-evoked effect was blocked by capsazepine or by instillation of resiniferatoxin, the ultrapotent TRPV1 agonist, into the bladders 24 hr before the anandamide challenge. The cannabinoid 1 receptor antagonist SR141716A [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide] significantly increased the potency of anandamide in enhancing bladder reflex activity in naive but not in cyclophosphamide-injected animals. Application of the fatty acid amide hydrolyze inhibitor palmitoylisopropylamine onto the serosal surface of bladders also increased the reflex activity both in naive and cyclophosphamide-injected rats. This latter effect in naive animals was blocked by capsazepine and by resiniferatoxin pretreatment. Finally, intravesical instillation of anandamide (50 microm) increased c-fos expression in the spinal cord, which was reduced by capsazepine or by resiniferatoxin pretreatment. These results suggest that anandamide, through activating TRPV1, contributes to the development of hyperreflexia and hyperalgesia during cystitis.
Overexpression of glucosylceramide synthase and P-glycoprotein in cancer cells selected for resistance to natural product chemotherapy (2004)

Resistance to natural product chemotherapy drugs is a major obstacle to successful cancer treatment. This type of resistance is often acquired in response to drug exposure; however, the mechanisms of this adverse reaction are complex and elusive. Here, we have studied acquired resistance to Adriamycin, Vinca alkaloids, and etoposide in MCF-7 breast cancer cells, KB-3-1 epidermoid carcinoma cells, and other cancer cell lines to determine if there is an association between expression of glucosylceramide synthase, the enzyme catalyzing ceramide glycosylation to glucosylceramide, and the multidrug-resistant (MDR) phenotype. This work shows that glucosylceramide levels increase concomitantly with increased drug resistance in the KB-3-1 vinblastine-resistant sublines KB-V.01, KB-V.1, and KB-V1 (listed in order of increasing MDR). The levels of glucosylceramide synthase mRNA, glucosylceramide synthase protein, and P-glycoprotein (P-gp) also increased in parallel. Increased glucosylceramide levels were also present in Adriamycin-resistant KB-3-1 sublines KB-A.05 and KB-A1. In breast cancer, detailed analysis of MCF-7 wild-type and MCF-7-AdrR cells (Adriamycin-resistant) demonstrated enhanced glucosylceramide synthase message and protein, P-gp message and protein, and high levels of glucosylceramide in resistant cells. Similar results were seen in vincristine-resistant leukemia, etoposide-resistant melanoma, and Adriamycin-resistant colon cancer cell lines. Cell-free glucosylceramide synthase activity was higher in lysates obtained from drug-resistant cells. Lastly, glucosylceramide synthase promoter activity was 15-fold higher in MCF-7-AdrR compared with MCF-7 cells. We conclude that selection pressure for resistance to natural product chemotherapy drugs selects for enhanced ceramide metabolism through glucosylceramide synthase in addition to enhanced P-gp expression. A possible connection between glucosylceramide synthase and P-gp in drug resistance biology is suggested.