gebhart/patrepeval huggingface dataset:
CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells (2008)

Hepatitis C virus (HCV) infects cells by the direct uptake of cell-free virus following virus engagement with specific cell receptors such as CD81. Recent data have shown that HCV is also capable of direct cell-to-cell transmission, although the role of CD81 in this process is disputed. Here, we generated cell culture infectious strain JFH1 HCV (HCVcc) genomes carrying an alanine substitution of E2 residues W529 or D535 that are critical for binding to CD81 and infectivity. Co-cultivation of these cells with naïve cells expressing enhanced green fluorescent protein (EGFP) resulted in a small number of cells co-expressing both EGFP and HCV NS5A, showing that the HCVcc mutants are capable of cell-to-cell spread. In contrast, no cell-to-cell transmission from JFH1(DeltaE1E2)-transfected cells occurred, indicating that the HCV glycoproteins are essential for this process. The frequency of cell-to-cell transmission of JFH1(W529A) was unaffected by the presence of neutralizing antibodies that inhibit E2-CD81 interactions. By using cell lines that expressed little or no CD81 and that were refractive to infection with cell-free virus, we showed that the occurrence of viral cell-to-cell transmission is not influenced by the levels of CD81 on either donor or recipient cells. Thus, our results show that CD81 plays no role in the cell-to-cell spread of HCVcc and that this mode of transmission is shielded from neutralizing antibodies. These data suggest that therapeutic interventions targeting the entry of cell-free HCV may not be sufficient in controlling an ongoing chronic infection, but need to be complemented by additional strategies aimed at disrupting direct cell-to-cell viral transmission.
The role of recombination signal sequences in the preferential joining by deletion in DH-JH recombination and in the ordered rearrangement of the IgH locus (1997)

The bias favoring deletion over inversion in DH-JH rearrangement has been known for years, but the underlying mechanism has yet to be fully defined. It has been suggested that the ratio of deletion/inversion is determined by the combined effect of two factors: (i) the relative strengths of 5' and 3' recombination signal sequences (RSS) of a DH segment, and (ii) the efficiency with which the deletional product (one joint) forms relative to the inversional product (two joints). In this study, we analyzed for the first time the effect of factor 1 alone on the biased 3' RSS utilization in DH-JH joining by using deletional plasmids in an extrachromosomal substrate V(D)J recombination assay. It was found that the 3' RSS and associated coding end (12 bp) mediate recombination more efficiently than the 5' RSS/coding end DH-JH plasmids. These results demonstrate that the effect of the RSS/coding end alone can account, at least partially, for the predominant deletion in DH-JH recombination. The potential effect of the relative strength of RSS and associated coding end on the ordered rearrangement of DH-JH followed by VH to DH-JH was also assessed. When recombination frequencies of D-->J (3' DH to J3) were compared with frequencies of V-->D (VHPJ14 to 3' DH or VHOX2 to 3' DH), it was found that V-->D joining was, if anything, more efficient than D-->J joining. Therefore, if all three segments were accessible, RSS/coding end effects would not contribute to the ordered rearrangement of the IgH locus.
Synthetic peptide epitope‐based polymers: controlling size and determining the efficiency of epitope incorporation (2002)

Abstract: The assembly of synthetic peptide‐based vaccines that incorporate multiple epitopes is a major goal of vaccine development, because such vaccines will potentially allow the immunization of outbred populations against a number of different pathogens. We have shown that free radical‐induced polymerization of individual peptide epitopes results in the incorporation of multiple copies of the same or different epitopes into high molecular weight immunogens (O'Brien‐Simpson, N.M., Ede, N.J., Brown, L.E., Swan, J. &amp; Jackson, D.C. (1997) Polymerization of unprotected synthetic peptides: a view toward synthetic peptide vaccines. J. Am. Chem. Soc. 119 , 1183–1188; Jackson, D.C., O'Brien‐Simpson, N., Ede, N.J. &amp; Brown, L.E. (1997) Free radical induced polymerization of synthetic peptides into polymeric immunogens. Vaccine 15 , 1697–1705). The ability to control the size of these polymers, to determine the physical and chemical properties of the backbone material and also to know the extent to which individual peptide epitopes are incorporated are important manufacturing considerations and form the subject of this study. We show here that the polymerization process is highly efficient with at least 70% of peptides incorporated into the resulting polymer, that acrylamide and acryloylated amino acids can be used as comonomers with peptide epitopes in the polymerization reaction and that the choice of the comonomer can influence the properties of the resulting polymer. We also show that the size of chain growth polymers is restricted in the presence of chain transfer agents, that the resulting polymer size can be predicted and that there is little or no difference in the immunogenicity of polymers that range in apparent molecular size between 18 kDa and 335 kDa. The successful polymerization of peptide epitopes with an acryloyl‐amino acid creates the potential for introducing different physical and chemical properties into artificial protein immunogens.
Mortality In Sickle Cell Disease -- Life Expectancy and Risk Factors for Early Death (1994)

Fifty percent of patients with sickle cell anemia survived beyond the fifth decade. A large proportion of those who died had no overt chronic organ failure but died during an acute episode of pain, chest syndrome, or stroke. Early mortality was highest among patients whose disease was symptomatic. A high level of fetal hemoglobin predicted improved survival and is probably a reliable childhood forecaster of adult life expectancy.
The Suzuki, the Heck, and the Stille reaction - three versatile methods for the introduction of new C-C bonds on solid support (2000)

Metal-catalyzed coupling reactions are very efficient and reliable methods for the introduction of new carbon-carbon bonds onto molecules attached to a solid support. This review summarizes recent advances in utilizing the three most used methods, the Suzuki reaction, the Heck reaction, and the Stille reaction, in the field of solid phase organic synthesis resulting in small organic molecule libraries.Key words: metal-catalyzed coupling reactions, carbon-carbon bonds, solid phase synthesis, combinatorial chemistry, drug discovery.
Evidence that vault ribonucleoprotein particles localize to the nuclear pore complex (1993)

Vaults are cytoplasmic ribonucleoprotein organelles that are highly conserved among diverse eukaryotic species. Their mass (12.9 MDa), diameter (26-35 nm) and shape (two halves, each with eightfold radial symmetry) have recently been determined and are similar to those ascribed to the central plug (or transporter) of the nuclear pore complex (NPC). The size and eightfold symmetry of the vault particle make it conducive to interacting physically in a complementary manner with NPCs. The present study demonstrates that vaults specifically associate with nuclei by both immunoblotting and immunofluorescence. Immunogold EM confirmed that vaults associate with the nuclear envelope in tissue sections and with NPCs of isolated nuclei.
Physiological and Molecular Assessment of Altered Expression of Hsc70-1 in Arabidopsis. Evidence for Pleiotropic Consequences (2003)

Hsp70s function as molecular chaperones. The protective chaperone activities of hsp70 help to confer tolerance to heat, glucose deprivation, and drought. Overexpression of hsp70s in many organisms correlates with enhanced thermotolerance, altered growth, and development. To better understand the roles of hsp70 proteins in Arabidopsis, the molecular and physiological consequences of altered expression of the major heat shock cognate, Hsc70-1, were analyzed. Extensive efforts to achieve underexpression of Hsc70-1 mRNA using a full-length antisense cDNA resulted in no viable transgenic plants, suggesting that reduced expression is lethal. Constitutive overexpression of Hsc70-1 also appeared to be deleterious to viability, growth, and development because fewer transformants were recovered, and most were dwarfed with altered root systems. Despite being dwarfed, the overexpression plants progressed normally through four selected developmental stages. Heat treatment revealed that Hsc70-1 overexpression plants were more tolerant to heat shock (44 degrees C for 10 min). The elevated basal levels of HSC70-1 in transgenic plants led to delayed heat shock response of several heat shock genes. The data in this study suggest that tight regulation of Hsc70-1 expression is critical for the viability of Arabidopsis and that the functions of HSC70-1 contribute to optimum growth, development, thermotolerance, and regulation of the heat shock response.
HER2 as a Therapeutic Target in Head and Neck Squamous Cell Carcinoma (2014)

The majority of patients with head and neck squamous cell carcinoma (HNSCC) present with advanced-stage disease. The current standard of care is surgery followed by adjuvant radiotherapy with or without chemotherapy or chemoradiation alone. The addition of cetuximab for the treatment of patients with locally advanced or recurrent/metastatic HNSCC has improved overall survival and locoregional control; however, responses are often modest, and treatment resistance is common. A variety of therapeutic strategies are being explored to overcome cetuximab resistance by blocking candidate proteins implicated in resistance mechanisms such as HER2. Several HER2 inhibitors are in clinical development for HNSCC, and HER2-targeted therapy has been approved for several cancers. This review focuses on the biology of HER2, its role in cancer development, and the rationale for clinical investigation of HER2 targeting in HNSCC.
Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies. (1990)

In an effort to determine the functional activity of anti-HIV-1 human mAb and to define the epitopes against which they are directed, supernatants from 10 EBV-transformed lymphoblastoid cell lines producing mAb to HIV were tested. Five clones producing mAb to gp41 and five producing mAb to p24 were identified. The anti-HIV-1 human mAb were tested in neutralization and cell fusion assays in the form of cell culture supernatants at concentrations ranging from 1.7 to 22.0 micrograms/ml. None of the human mAb were found either to inhibit HIV-1-(IIIB or RF) associated cell fusion or to neutralize HIV-1 (IIIB) infection of AA5 cells. All human mAb were additionally tested in 6 h 51Cr release assays for their ability to direct HIV-1 specific antibody-dependent cellular cytotoxicity (ADCC). For ADCC assays, PBMC were isolated from healthy seronegative donors and used as effector cells. HIV-1 infected (IIIB, RF, and MN) CEM.NKR cells as well as CEM.NKR cells with purified gp120 adsorbed onto their surface served as targets. None of the anti-p24 mAb mediated ADCC. In contrast, three of the anti-gp41 mAb were able to direct a significant level of ADCC against each of the infected targets, but as expected, failed to lyse gp120 adsorbed cells. To define the specific epitopes against which the anti-gp41 mAb were directed, seven small peptides homologous to regions within the extracellular domain of gp41 were synthesized. Using RIA, two of the mAb could be mapped. The most effective ADCC-directing human mAb bound to a peptide comprising amino acids 644-663, whereas the least effective ADCC directing anti-gp41 human mAb bound to a region within the immunodominant portion of gp41 outlined by amino acids 579-604. Together, these results for the first time assign a functional activity to human mAb directed at specific regions within gp41 by demonstrating that areas within this molecule can serve as targets for ADCC.
Genome analysis : a practical approach (1988)

Goodfellow: Techniques for mammalian genome transfer Coulson: Genome mapping by restriction fingerprinting Smith: Pulsed-field gel electrophoresis and the technology of large DNA molecules Collins: Chromosome jumping Myers: Detection of single base changes in DNA Saiki: The polymerase chain reaction Wells: DNA fingerprinting Lander: Mapping complex genetic traits in humans
Effect of bradykinin and kininogens in isolated rat kidney vasoconstricted by angiotensin II (1990)

The hemodynamic and endocrine effects of bradykinin and kininogens were investigated using a closed-circuit isolated rat kidney perfused with angiotensin II (ANG II). ANG II induced vasoconstriction, stimulation of urinary kallikrein release, and inhibition of renin secretion. Bradykinin markedly increased renal perfusate flow (RPF) and produced a slight but significant diuresis and natriuresis. The inhibitory effect of ANG II on renin secretion was delayed. Urinary kallikrein secretion was unchanged. The effect of bradykinin was suppressed by the competitive kinin antagonist [DArg,Hyp3,Thi5,8,DPhe7]bradykinin. Kallikrein-sensitive rat high-molecular-weight kininogen produced a progressive rise in renal perfusate flow. Exocrine function and renin and kallikrein secretions were unchanged. Immunoreactive kinins, identified as bradykinin by high-pressure liquid chromatography, were liberated into the perfusate. Perfusate immunoreactive high-molecular-weight kininogen decreased in parallel as a result of consumption. The kalikrein-resistant T-kininogen was not hydrolyzed to release a kinin, had no effect on renal function, and its concentration in the perfusate remained constant. These results suggest that kinin can be produced in the renal circulation from kallikrein-sensitive circulating kininogens and can antagonize the vasoconstrictor effect of ANG II and alter renal hemodynamics. They provide evidence that the kallikrein-kinin system can participate with the renin-angiotensin system in the control of renal blood flow.
Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution. (1989)

Human neutrophil elastase (HNE) has been implicated as a major contributor to tissue destruction in various disease states, including emphysema. The structure of HNE, at neutral pH, in complex with methoxysuccinyl-Ala-Ala-Pro-Ala chloromethyl ketone (MSACK), has been solved and refined to an R factor of 16.4% at 1.84-A resolution. Results are consistent with the currently accepted mechanism of peptide chloromethyl ketone inhibition of serine proteases, in that MSACK cross-links the catalytic residues His-57 and Ser-195. The structure of the HNE-MSACK complex is compared with that of porcine pancreatic elastase in complex with L-647,957, a beta-lactam inhibitor of both elastases. The distribution of positively charged residues on HNE is highly asymmetric and may play a role in its specific association with the underlying negatively charged proteoglycan matrix of the neutrophil granules in which the enzyme is stored.
Multiscale deformations lead to high toughness and circularly polarized emission in helical nacre-like fibres (2016)

Nacre-like composites have been investigated typically in the form of coatings or free-standing sheets. They demonstrated remarkable mechanical properties and are used as ultrastrong materials but macroscale fibres with nacre-like organization can improve mechanical properties even further. The fiber form or nacre can, simplify manufacturing and offer new functional properties unknown yet for other forms of biomimetic materials. Here we demonstrate that nacre-like fibres can be produced by shear-induced self-assembly of nanoplatelets. The synergy between two structural motifs--nanoscale brick-and-mortar stacking of platelets and microscale twisting of the fibres--gives rise to high stretchability (>400%) and gravimetric toughness (640 J g(-1)). These unique mechanical properties originate from the multiscale deformation regime involving solid-state self-organization processes that lead to efficient energy dissipation. Incorporating luminescent CdTe nanowires into these fibres imparts the new property of mechanically tunable circularly polarized luminescence. The nacre-like fibres open a novel technological space for optomechanics of biomimetic composites, while their continuous spinning methodology makes scalable production realistic.
Comparative analysis of the HTLV-I Rex and HIV-1 Rev trans-regulatory proteins and their RNA response elements. (1989)

The Rex proteins of types I and II human T-cell leukemia viruses (HTLV-I, HTLV-II) are required for expression of the viral structural gene products, gag and env and, thus, are essential for the replication of these pathogenic retroviruses. The action of Rex is sequence specific, requiring the presence of a cis-acting Rex response element located in the 3' long terminal repeat. This element corresponds to a predicted RNA secondary structure and functions in an orientation-dependent but position-independent manner. Rex acts through this response element to stimulate the nuclear export of the unspliced or singly spliced viral mRNA species encoding the virion structural proteins that are normally excluded from the cytoplasm. Although the Rex proteins of HTLV-I and HTLV-II can also function via the related Rev response element present in the env gene of the type I human immunodeficiency virus (HIV-1), the analogous HIV-1 Rev protein is unable to act on the HTLV-I Rex response element. This nonreciprocal pattern of genetic complementation by Rex and Rev suggests that these viral trans-regulators may interact directly with their RNA response elements.
Synthetic Multivalent Molecules: Concepts and Biomedical Applications (2004)

Preface.Notes for Organization and Classification.Abbreviations.1 Introduction.1.1 Nomenclature and Definitions.1.2 Mechanistic Aspects of Multivalent Interaction.1.3 Biological Roles of Multivalent Ligands.2 Multivalent Molecules Applied to Viral Targets.2.1 Influenza Virus.2.2 Human Immunodeficiency Virus.2.3 Rotavirus.2.4 Polyoma Virus.2.5 Picorna Virus.2.6 Respiratory Syncytial Virus.2.7 Dengue Virus.2.8 Nucleic Acids of Viruses.2.9 Synthetic Multivalent Vaccines.3 Multivalent Molecules Applied to Bacterial Targets.3.1 Targets in Bacterial Cell Membranes.3.2 Bacterial Toxins.3.3 Bacterial Enzymes.3.4 Bacterial Nucleic Acids.3.5 Multivalent Molecules as Synthetic Vaccines.3.6 Fungal Cells.4 Multivalent Molecules Applied to Cellular Targets.4.1 Carbohydrate-Recognition Receptors on Cell Surfaces.4.2 Peptide and Hormone Recognition Receptors on Cell Surfaces.4.3 Ligand-Mediated Receptor Dimerization.4.4 Enzymes.4.5 G-Protein-Coupled Receptors.4.6 Ion Channels.4.7 Nucleic Acids.4.8 Antibodies.4.9 Cell Surface Engineering.5 Chemical Synthesis of Multivalent Molecules.5.1 Selected Synthetic Methods for Multimerization.5.2 Combinatorial Chemistry.Appendix.Table 1. Divalent Ligands Linked to Enzymes in Human Immunodeficiency Virus (HIV).Table 2. Multivalent Ligands Linked to gp120 Surface Receptors in Human Immunodeficiency Virus.Table 3. Multivalent Ligands Linked to Surface Receptors on Viruses.Table 4. Multivalent Receptors Targeting Multivalent Ligands in Bacterial Cell Walls.Table 5. Multivalent Ligands Targeting Bacterial Receptors in Membrane Surfaces.Table 6. Multivalent Ligands Linked to Bacterial Toxins.Table 7. Multivalent Molecules Targeting Bacterial Enzymes.Table 8. Multivalent Ligands Targeting Carbohydrate-Recognition Receptors on Cellular Surfaces.Table 9. Multivalent Ligands Targeting Noncarbohydrate-Recognition Receptors on Cellular Surfaces.Table 10. Multivalent Ligands Linked to Selectins on Cell Surfaces.Table 11. Multivalent Ligands Linked to Lectins.Table 12. Multivalent Ligands Linked to Cellular Enzymes.Table 13. Multivalent Ligands Linked to G-Protein-Coupled Receptors (GPCRs).Table 14. Multivalent Ion Channel-Binding Molecules.Table 15. Homo- and Heterodivalent Chemical Inducers of Dimerization (CIDs).Table 16. Multivalent Ligands Linked to Nucleic Acids.Table 17. Synthetic Multivalent Antigens.Table 18. Multivalent Ligands Displayed on Self-Assembled Monolayer (SAM) Made of Alkanethiolate on Gold.Table 19. (Bio)chemical Modification of Cell Surface Antigens.Table 20. Multivalent Targets.References.Index.
Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment (2011)

Cancer cells show a broad spectrum of bioenergetic states, with some cells using aerobic glycolysis while others rely on oxidative phosphorylation as their main source of energy. In addition, there is mounting evidence that metabolic coupling occurs in aggressive tumors, between epithelial cancer cells and the stromal compartment, and between well-oxygenated and hypoxic compartments. We recently showed that oxidative stress in the tumor stroma, due to aerobic glycolysis and mitochondrial dysfunction, is important for cancer cell mutagenesis and tumor progression. More specifically , increased autophagy/mitophagy in the tumor stroma drives a form of parasitic epithelial-stromal metabolic coupling. These findings explain why it is effective to treat tumors with either inducers or inhibitors of autophagy, as both would disrupt this energetic coupling. We also discuss evidence that glutamine addiction in cancer cells produces ammonia via oxidative mitochondrial metabolism. Ammonia production in cancer cells, in turn, could then help maintain autophagy in the tumor stromal compartment. In this vicious cycle, the initial glutamine provided to cancer cells would be produced by autophagy in the tumor stroma. Thus, we believe that parasitic epithelial-stromal metabolic coupling has important implications for cancer diagnosis and therapy, for example, in designing novel metabolic imaging techniques and establishing new targeted therapies. In direct support of this notion, we identified a loss of stromal caveolin-1 as a marker of oxidative stress, hypoxia, and autophagy in the tumor microenvironment, explaining its powerful predictive value. Loss of stromal caveolin-1 in breast cancers is associated with early tumor recurrence, metastasis, and drug resistance, leading to poor clinical outcome.
The Effect of Epidural Injection of Betamethasone or Bupivacaine in a Rat Model of Lumbar Radiculopathy (1998)

Epidural steroid injection has a significant effect on the thermal hyperalgesia produced in a model of radiculopathy, which may provide clinical support for advocates of epidural steroids.
Characterization and localization of the Gova/b alloantigens to the glycosylphosphatidylinositol-anchored protein CDw109 on human platelets (1995)

The Gova/b alloantigens are expressed on a 175-kD protein (GP175) on human platelets. Anti-Gov alloantibodies have been implicated in posttransfusion purpura and alloimmune neonatal thrombocytopenia. In this report we characterize the immunochemistry of the alloantigens and identify the platelet protein that expresses the Gov epitopes. Approximately 50% of GP175 containing the Gov epitope was released from platelets treated with phosphatidylinositol-specific phospholipase C, indicating that at least some of this protein exists as a glycosylphosphatidylinositol (GPI)-linked isoform. Radioimmunoprecipitation and immunodepletion studies indicated that the Gova/b alloantigens are expressed on the GPI-anchored CDw109 protein. The Gova/b epitopes were expressed on an extracellular, 120-kD soluble fragment (p120) of CDw109 produced by calcium-dependent protease cleavage. Anti-Gov immunoprecipitates of chymotryptic digests of p120 contained 70- and 52-kD fragments of CDw109. Deglycosylation of native CDw109 had no effect on recognition by Gov alloantisera; however, the epitopes were destroyed after exposure to sodium dodecyl sulfate. Gova/b alloantigens were expressed on platelets and PHA-activated T-cells, cultured human umbilical vein endothelial cells, and by many different tumor cell lines, consistent with the tissue distribution of CDw109.