gebhart/patrepeval huggingface dataset:
Polypurine Tract Primer Generation and Utilization by Moloney Murine Leukemia Virus Reverse Transcriptase (1999)

During reverse transcription, the RNase H activity of reverse transcriptase specifically cleaves the viral genome within the polypurine tract (PPT) to create the primer used for the initiation of plus-strand DNA synthesis and nonspecifically cleaves the viral genome to facilitate synthesis of plus-strand DNA. To understand how primer length and sequence affect generation and utilization of the PPT, we employed short hybrid substrates containing or lacking the PPT to evaluate cleavage, extension, and binding by reverse transcriptase. Substrates containing RNAs with the correct 3' end for initiation of plus-strand synthesis were extended equally well by reverse transcriptase, but primer length affected susceptibility to RNase H cleavage. RNA substrates with 3' ends extending beyond the plus-strand initiation site were extended poorly but were specifically cleaved to generate the correct 3' end for initiation of plus-strand synthesis. Substrates containing RNAs lacking the PPT were cleaved nonspecifically and extended inefficiently. Specific cleavages to generate the plus-strand primer and 5'-end-directed cleavages were kinetically favored over cleavages that destroyed the PPT primer or degraded other short RNA fragments. The PPT was not intrinsically resistant to cleavage by the isolated RNase H domain, and the isolated polymerase domain extended RNA primers containing the PPT sequence irrespective of the primer 3' end. These results provide insights into how reverse transcriptase generates and selectively utilizes the PPT primer for initiation of plus-strand DNA synthesis.
Biofilm formation by nontypeable Haemophilus influenzae: strain variability, outer membrane antigen expression and role of pili (2002)

Nontypeable H. influenzae forms biofilms in vitro. Clinical isolates show substantial variability in their ability to grow as biofilms. Three major outer membrane proteins (P2, P5 and P6) are expressed during growth as a biofilm. Expression of lipooligosaccharide is altered during growth as a biofilm compared to planktonic growth. Pili are important in biofilm formation. As the role of biofilms in human infection becomes better defined, characterization of biofilms may be important in understanding the pathogenesis of infection and immune response to nontypeable H. influenzae in children with otitis media and adults with COPD.
Mast Cells Mobilize Myeloid-Derived Suppressor Cells and Treg Cells in Tumor Microenvironment via IL-17 Pathway in Murine Hepatocarcinoma Model (2010)

Tumor immunosuppression is commonly braided with chronic inflammation during tumor development. However, the relationship between immunosuppression and inflammation in tumor microenvironment is still unclear. We have demonstrated that mast cells are accumulated and exacerbate the inflammation and immunosuppression in tumor microenvironment via SCF/c-kit signaling pathway. Here, we further elucidate the underlying mechanism, which involves both myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells. Our data showed that mast cells mobilized the infiltration of MDSCs to tumor and induced the production of IL-17 by MDSCs; MDSCs-derived IL-17 indirectly attracted Treg cells, enhanced their suppressor function, and induced the IL-9 production by Treg cells; in turn, IL-9 strengthened the survival and protumor effect of mast cells in tumor microenvironment. Our findings disclose a closed loop among mast cells, MDSCs and Treg cells in tumor microenvironment, which provides a new insight into the paralleled developments of inflammation and immunosuppression in tumor microenvironment. Based on these findings, we propose that targeting tumor inflammation might be a potential strategy to reverse the immunosuppression of tumor microenvironment, thus facilitating cancer immunotherapy.
Structure of cloned DNA complementary to rat prolactin messenger RNA. (1980)

Prolactin (Prl), growth hormone (GH), and chorionic
In Vitro Selection of RNA Aptamers That Bind to Cell Adhesion Receptors of Trypanosoma cruzi and Inhibit Cell Invasion (2002)

Trypanosoma cruzi causing Chagas' disease needs to invade host cells to complete its life cycle. Macromolecules on host cell surfaces such as laminin, thrombospondin, heparan sulfate, and fibronectin are believed to be important in mediating parasite-host cell adhesions and in the invasion process of the host cell by the parasite. The SELEX technique (systematic evolution of ligands by exponential enrichment) was used to evolve nuclease-resistant RNA ligands (aptamer = to fit) that bind with affinities of 40-400 nm to parasite receptors for the host cell matrix molecules laminin, fibronectin, thrombospondin, and heparan sulfate. After eight consecutive rounds of in vitro selection four classes of RNA aptamers based on structural similarities were isolated and sequenced. All members of each class shared a common sequence motif and competed with the respective host cell matrix molecule that was used for displacement during the selection procedure. RNA pools following seven and eight selection rounds as well as individual aptamers sharing consensus motifs were active in inhibiting invasion of LLC-MK(2) monkey kidney cells by T. cruzi in vitro.
Detection of capsule tampering by near-infrared reflectance analysis (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetection of capsule tampering by near-infrared reflectance analysisRobert A. Lodder, Mark. Selby, and Gary M. HieftjeCite this: Anal. Chem. 1987, 59, 15, 1921–1930Publication Date (Print):August 1, 1987Publication History Published online1 May 2002Published inissue 1 August 1987https://pubs.acs.org/doi/10.1021/ac00142a008https://doi.org/10.1021/ac00142a008research-articleACS PublicationsRequest reuse permissionsArticle Views197Altmetric-Citations43LEARN 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
Role of the physical state of Salmonella lipopolysaccharide in expression of biological and endotoxic properties (1993)

Lipopolysaccharide (LPS) extracted from three strains of Salmonella typhimurium, i.e., the rough Re mutant SL1102, the rough Ra mutant TV119, and the smooth strain SH4809, was first electrodialyzed (eLPS) and then divalent cation deprived by EDTA treatment and finally made monomeric by deoxycholate solubilization. The removal of excess detergent by extensive dialysis in the absence of mineral cations resulted in the reassociation of LPS subunits into monodisperse micelles of reduced aggregation number (dLPS) as estimated by electron microscopy and gel filtration chromatography. For all LPS chemotypes tested, the developed procedure reproducibly results in stable and clear solutions of dLPS in concentrations of up to 100 mg/ml. The dLPS and eLPS preparations possessed the same reactivity with monoclonal antibodies (MAbs) raised against different LPS domains. The 100% lethal dose in galactosamine-sensitized mice of 0.01 microgram for the smooth eLPS was from 10- to 100-fold lower than that of dLPS at 0.1 to 1.0 microgram. dLPS from both the smooth strain and the Ra mutant had a significantly reduced capacity to activate the proenzyme cascade in the Limulus amoebocyte lysate assay in comparison with the slightly reduced activity of dLPS from the Re mutant. In contrast, dLPS as well as the deoxycholate-dispersed and then diluted eLPS from the smooth strain had a higher mitogenic activity on splenocytes than eLPS. The results indicate that the biological and endotoxic properties of LPS are significantly influenced by the physical state of its aggregates in aqueous solutions. The approach developed for production of a stable and dispersed form of LPS should further assist in investigation of LPS properties and interpretation of the data of endotoxic research.
Ephrin-A1 Facilitates Mammary Tumor Metastasis through an Angiogenesis-Dependent Mechanism Mediated by EphA Receptor and Vascular Endothelial Growth Factor in Mice (2006)

Ephrin-A1, the prototypic ligand for EphA receptor tyrosine kinases, is overexpressed in vascularized tumors relative to normal tissue. Moreover, ephrin-A1-Fc fusion proteins induce endothelial cell sprouting, migration, and assembly in vitro, and s.c. vascular remodeling in vivo. Based on these data, we hypothesized that native, membrane-bound ephrin-A1 regulates tumor angiogenesis and progression. We tested this hypothesis using a transplantable mouse mammary tumor model. Small interfering RNA-mediated ephrin-A1 knockdown in metastatic mammary tumor cells significantly diminishes lung metastasis without affecting tumor volume, invasion, intravasation, or lung colonization upon i.v. injection in vivo. Ephrin-A1 knockdown reduced tumor-induced endothelial cell migration in vitro and microvascular density in vivo. Conversely, overexpression of ephrin-A1 in nonmetastatic mammary tumor cells elevated microvascular density and vascular recruitment. Overexpression of ephrin-A1 elevated wild-type but not EphA2-deficient endothelial cell migration toward tumor cells, suggesting that activation of EphA2 on endothelial cells is one mechanism by which ephrin-A1 regulates angiogenesis. Furthermore, ephrin-A1 knockdown diminished, whereas overexpression of ephrin-A1 elevated, vascular endothelial growth factor (VEGF) levels in tumor cell-conditioned medium, suggesting that ephrin-A1-mediated modulation of the VEGF pathway is another mechanism by which membrane-tethered ephrin-A1 regulates angiogenic responses from initially distant host endothelium. These data suggest that ephrin-A1 is a proangiogenic signal, regulating VEGF expression and facilitating angiogenesis-dependent metastatic spread.
High Plasma Osteopontin Levels in Patients With Inflammatory Bowel Disease (2007)

Our results indicate that the plasma concentrations of OPN are elevated in patients with UC and that OPN expression is correlated with clinical activity. These results provide insight into UC pathogenesis and suggest that OPN may be a useful tool for assessing disease activity.
A New Broad Range Plasmid for DNA Delivery in Eukaryotic Cells Using Lactic Acid Bacteria: In Vitro and In Vivo Assays (2016)

<i>Lactococcus lactis</i> is well documented as a promising candidate for development of novel oral live vaccines. It has been broadly engineered for heterologous expression, as well as for plasmid expression vector delivery, directly inside eukaryotic cells, for DNA vaccine, or as therapeutic vehicle. This work describes the characteristics of a new plasmid, pExu (extra chromosomal unit), for DNA delivery using <i>L. lactis</i> and evaluates its functionality both by in vitro and in vivo assays. This plasmid exhibits the following features: (1) a theta origin of replication and (2) an expression cassette containing a multiple cloning site and a eukaryotic promoter, the cytomegalovirus (pCMV). The functionality of pExu:<i>egfp</i> was evaluated by fluorescence microscopy. The <i>L. lactis</i> MG1363 (pExu:<i>egfp</i>) strains were administered by gavage to Balb/C mice and the eGFP expression was monitored by fluorescence microscopy. The pExu vector has demonstrated an excellent stability either in <i>L. lactis</i> or in <i>Escherichia coli</i>. The eGFP expression at different times in in vitro assay showed that 15.8% of CHO cells were able to express the protein after transfection. The enterocytes of mice showed the expression of eGFP protein. Thus, <i>L. lactis</i> carrying the pExu is a good candidate to deliver genes into eukaryotic cells.
Very low room-temperature threshold current density dots in a well (DWELL) lasers (2003)

It has been predicted that the threshold current density of quantum dot lasers should be lower than that of quantum well lasers due to the reduction in the density of states. In particular, efforts have been made in the past few years to reduce the threshold current density of quantum dot lasers on GaAs substrates. A recently developed approach is to put the InAs dots in a strained In/sub 0.2/Ga/sub 0.8/As quantum well. This "dots in a well" (DWELL) design not only improves carrier capture by the dots, but also keeps the density of quantum dots high (up to 7/spl times/10/sup 10/ cm/sup -2/). Consequently, ground state lasing from a single layer of dots is possible at reasonable cavity lengths. While competition with radiative quantum well transitions was suggested as a concern, quantum well transitions were not observed in previous work or in this study. In this work, comparisons have been made by putting a single layer of InAs quantum dots into three different quantum wells, In/sub 0.10/Ga/sub 0.9/As, In/sub 0.15/Ga/sub 0.85/As, and In/sub 0.2/Ga/sub 0.8/As. Very low threshold current densities of 40, 26, and 31 A cm/sup -2/ have been achieved with InAs dots in the three systems for the 7.8 mm cavity length, cleaved facet lasers.
The HHQK Domain of β-Amyloid Provides a Structural Basis for the Immunopathology of Alzheimer's Disease (1998)

The beta-amyloid peptide 1-42 (Abeta1-42), a major component of neuritic and core plaques found in Alzheimer's disease, activates microglia to kill neurons. Selective modifications of amino acids near the N terminus of Abeta showed that residues 13-16, the HHQK domain, bind to microglial cells. This same cluster of basic amino acids is also known as a domain with high binding affinity for heparan sulfate. Both Abeta binding to microglia and Abeta induction of microglial killing of neurons were sensitive to heparitinase cleavage and to competition with heparan sulfate, suggesting membrane-associated heparan sulfate mediated plaque-microglia interactions through the HHQK domain. Importantly, small peptides containing HHQK inhibited Abeta1-42 cell binding as well as plaque induction of neurotoxicity in human microglia. In vivo experiments confirmed that the HHQK peptide reduces rat brain inflammation elicited after infusion of Abeta peptides or implantation of native plaque fragments. Strategies which exploit HHQK-like agents may offer a specific therapy to block plaque-induced microgliosis and, in this way, slow the neuronal loss and dementia of Alzheimer's disease.
Race Is On To Develop Sugar-Based Anti-inflammatory, Antitumor Drugs (1992)

RETURN TO ISSUEPREVNewsNEXTRace Is On To Develop Sugar-Based Anti-inflammatory, Antitumor DrugsBiotech companies, academic researchers, devote major efforts to develop therapeutic agents based on sialyl LewisSTU BORMANView Author Information C&EN WashingtonCite this: Chem. Eng. News 1992, 70, 49, 25–28Publication Date (Print):December 7, 1992Publication History Published online10 November 2010Published inissue 7 December 1992https://pubs.acs.org/doi/10.1021/cen-v070n049.p025https://doi.org/10.1021/cen-v070n049.p025newsACS PublicationsCopyright © 1992 AMERICAN CHEMICAL SOCIETYArticle Views9Altmetric-Citations5LEARN 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 options SUBJECTS:Oligosaccharides Get e-Alerts
Cutting Edge: CD28 Controls Dominant Regulatory T Cell Activity during Active Immunization (2006)

Ligation of CD28 during Ag recognition plays an important role in the generation of effective T cell responses. However, its peripheral control of regulatory T cell function remains obscure. In this study, we show that naive wild-type or CD28(-/-) CD4(+)CD25(-) T cells exposed to peptide in vivo develop regulatory activity that suppresses the response of adoptively transferred naive T cells to a subsequent immunogenic challenge. We find that although CD28 is engaged during the initial peptide-priming event and is essential to sustain T cell survival, it is not sufficient to prevent the dominance of regulatory T cell function. Immunization with adjuvant abrogates regulatory dominance, reducing overall Foxp3 expression in a CD28-dependent manner. We conclude that CD28 licenses active immunization by regulating Ag-induced immunoregulation.
Isolation of a cDNA encoding 5T4 oncofetal trophoblast glycoprotein. An antigen associated with metastasis contains leucine-rich repeats. (1994)

The monoclonal antibody 5T4 defines a human oncotrophoblast antigen expressed by a variety of carcinomas but with a restricted pattern of expression in normal adult tissues. The 5T4 antigen has been isolated from term placenta as a 72-kDa glycoprotein consisting of a 42-kDa core protein with extensive N-linked glycosylation. A cDNA has been isolated from a human placental library using pools of oligonucleotides based on amino acid sequence obtained from purified 5T4 molecules. The predicted open reading frame encodes a protein of 420 amino acids with a molecular mass of 46 kDa and 8 potential N-glycosylation sites. There are N- and C-terminal hydrophobic segments corresponding to putative signal and membrane anchorage sequences, respectively. Northern analysis has demonstrated a major 2.5-kilobase mRNA present in cell lines serologically reactive with the monoclonal antibody 5T4. Comparison of the 5T4 protein sequence with current sequence data bases has identified the presence of leucine-rich repeats, which are found in a variety of proteins from yeast, insects, and mammals. The 5T4 antigen expression is strongly associated with metastasis in colorectal and gastric cancer, and, hence, the possible functions of the gene product and its relationship to tumor growth and progression are discussed.
Expression of wild-type p53 during the cell cycle in normal human mammary epithelial cells. (1994)

In this study, we compare the expression patterns of p53 mRNA and protein in normal human mammary epithelial cells following synchronization to different points in the cell cycle using two independent methods. When treated with lovastatin, the cells were blocked in G1 and appeared to express increased levels of wild-type p53 when examined by immunostaining. Upon reversal of the metabolic block, the number of nuclei that stained positively for p53 declined dramatically during mid-G1 and increased again concomitant with the entry of cells into S phase. In contrast to the immunostaining results, Northern and Western blot analyses revealed little change in p53 mRNA and protein levels in the lovastatin-synchronized cells. When normal human mammary epithelial cells were made quiescent by removal of growth factors, the mRNA for p53 showed a biphasic distribution. p53 mRNA levels were increased during growth arrest, decreased during the G1 phase, and rose again concomitant with the entry of cells into S phase. The immunostaining pattern of p53 also showed a biphasic distribution similar to the pattern of mRNA expression. Despite an increase in p53 mRNA and immunostaining levels, growth factor-arrested cells actually had less total p53 protein. Upon stimulation to proliferate, p53 protein levels remained low throughout G1 and increased concomitant with the entry of cells into S phase. Taken together, the results from these studies demonstrate that p53 immunostaining patterns do not correlate with the overall levels of p53 protein at different times during the cell cycle. Therefore, the distinct changes observed in p53 immunostaining patterns are likely due to posttranslational modifications, conformational changes, or interactions of p53 with other cellular proteins during the cell cycle.
Combination Therapy with Amylin and Peptide YY[3–36] in Obese Rodents: Anorexigenic Synergy and Weight Loss Additivity (2007)

Circulating levels of the pancreatic beta-cell peptide hormone amylin and the gut peptide PYY[3-36] increase after nutrient ingestion. Both have been implicated as short-term signals of meal termination with anorexigenic and weight-reducing effects. However, their combined effects are unknown. We report that the combination of amylin and PYY[3-36] elicited greater anorexigenic and weight-reducing effects than either peptide alone. In high-fat-fed rats, a single ip injection of amylin (10 microg/kg) plus PYY[3-36] (1000 microg/kg) reduced food intake for 24 h (P < 0.05 vs. vehicle), whereas the anorexigenic effects of either PYY[3-36] or amylin alone began to diminish 6 h after injection. These anorexigenic effects were dissociable from changes in locomotor activity. Subcutaneous infusion of amylin plus PYY[3-36] for 14 d suppressed food intake and body weight to a greater extent than either agent alone in both rat and mouse diet-induced obesity (DIO) models (P < 0.05). In DIO-prone rats, 24-h metabolic rate was maintained despite weight loss, and amylin plus PYY[3-36] (but not monotherapy) increased 24-h fat oxidation (P < 0.05 vs. vehicle). Finally, a 4 x 3 factorial design was used to formally describe the interaction between amylin and PYY[3-36]. DIO-prone rats were treated with amylin (0, 4, 20, and 100 microg/kg.d) and PYY[3-36] (0, 200, 400 microg/kg.d) alone and in combination for 14 d. Statistical analyses revealed that food intake suppression with amylin plus PYY[3-36] treatment was synergistic, whereas body weight reduction was additive. Collectively, these observations highlight the importance of studying peptide hormones in combination and suggest that integrated neurohormonal approaches may hold promise as treatments for obesity.