gebhart/patrepeval huggingface dataset:
Rab GTPases coordinate endocytosis (2000)

Endocytosis is characterized by vesicular transport along numerous pathways. Common steps in each pathway include membrane budding to form vesicles, transport to a particular destination, and ultimately docking and fusion with the target membrane. Specificity of vesicle targeting is rendered in part by associated Rab GTPases. This review summarizes current knowledge about Rab GTPase functions in the endocytic pathways and provides insight into the regulation of Rab GTPase activity and mechanisms of Rab protein function. Functional assays have identified some Rab proteins that operate on individual pathways, but Rab proteins in several pathways remain controversial or have not been identified. Control of Rab GTPase activity is exerted through multiple levels of regulation. Significant new information pertaining to Rab protein function in regulating transport has emerged. Remarkably, Rab5 GTPase links budding, cytoskeletal transport and docking/fusion activities. This paradigm will most likely be generally applicable to other Rab GTPase pathways. Together with the cross-talk between different Rab proteins and their effectors, this may provide an integrated system for the general coordination of endocytic pathways to maintain organelle homeostasis.
Simple, high yield syntheses of molybdenum(VI) bis(imido) complexes of the type Mo(NR)2Cl2(1,2-dimethoxyethane) (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSimple, high yield syntheses of molybdenum(VI) bis(imido) complexes of the type Mo(NR)2Cl2(1,2-dimethoxyethane)Harold H. Fox, Kimo B. Yap, Jennifer Robbins, Shiang Cai, and Richard R. SchrockCite this: Inorg. Chem. 1992, 31, 11, 2287–2289Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1 May 1992https://pubs.acs.org/doi/10.1021/ic00037a056https://doi.org/10.1021/ic00037a056research-articleACS PublicationsRequest reuse permissionsArticle Views1269Altmetric-Citations131LEARN 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
Recent Advances in the Applications of Radioisotopes in Drug Metabolism,Toxicology and Pharmacokinetics (2000)

Radioisotopes have proven to be an indispensable tool in biomedical research and have played a pivotal role in the investigation of absorption, distribution, metabolism and excretion (ADME) properties of new chemical entities over the past several decades. The main advantage of using radioisotopes in studying the disposition of new drug candidates is the ease of detection and the achievement of high sensitivity, especially when compounds with high specific activity are used. The recent advances and applications of radioisotopes in designing and conducting ADME studies and its impact in the field of drug metabolism and pharmacokinetics are discussed in this review.
Stimulation of human T-cell proliferation by specific activation of the 75-kDa tumor necrosis factor receptor. (1993)

TNF-alpha can enhance the proliferation of human thymocytes stimulated by the comitogen Con A. To determine which of the two different TNF receptors is responsible for signaling this cellular response, we investigated the proliferation of human thymocytes in response to agonistic antibodies specific for the two TNF receptor types. In contrast to previously examined TNF activities in human cells, thymocyte proliferation was stimulated in response to rabbit polyclonal antibodies directed against the 75-kDa TNF receptor (TNF-R2), but not those directed against the 55-kDa TNF receptor (TNF-R1). Lymphotoxin (TNF-beta) was also shown to stimulate human thymocyte proliferation, demonstrating that TNF-beta can initiate a biologic response that is mediated by TNF-R2. TNF-R2-mediated T-cell proliferation was not restricted to the immature T cells within the thymus, as the anti-TNF-R2 antibodies also stimulated the proliferation of peripheral T cells. As a first step toward identifying a specific agonist of TNF-R2 with therapeutic potential, 10 anti-TNF-R2 mAb were examined for potential agonist activity. Nine of these significantly stimulated human thymocyte proliferation with maximal responses ranging from twofold to significantly greater than that obtained with TNF-alpha by itself.
VEGF(121), VEGF(165) overexpression enhances tumorigenicity in U251 MG but not in NG-1 glioma cells. (2002)

Vascular endothelial growth factor (VEGF) is a multifunctional cytokine with important roles in angiogenesis. VEGF is overexpressed in human cancers, including highly vascularized and infiltrative brain tumors. In our previous study of seven glioma cell lines, VEGF expression levels correlated with blood vessel density and tumorigenicity, and U251 MG and NG-1 cells were recognized as low-tumorigenic glioma cell lines. We hypothesized that low-tumorigenic cells can become highly tumorigenic when high levels of VEGF are expressed. To test this hypothesis, we constructed VEGF expression vectors containing 564 bp or 696 bp of VEGF(121) or VEGF(165) cDNA, respectively, and transfected them into U251 MG and NG-1 cells. In comparison to parental cells, the 20 VEGF-expressing clones examined had on average 8-10-fold more VEGF mRNA and 12-88-fold more secreted VEGF proteins. Four VEGF-overexpressing clones (U251 MG/V121-C2, U251 MG/V165-C3, NG-1/V121-C6, and NG-1/V165-C3) were selected for additional study. As VEGF production increased with population growth, U251 MG/V121-C2 and U251 MG/V165-C3 cells accumulated 47.9 and 22.0 ng of VEGF during a 5-day culture of 10(4) cells, a 313- and 144-fold overexpression when compared with that in parental U251 MG cells. NG-1/V121-C6 and NG-1/V165-C3 cells secreted 30.4 and 9.4 ng of VEGF, respectively, or 138- and 43-fold more than did the parental NG-1 cells. Subcutaneous implantation of the VEGF-overexpressing U251 MG cells into nude mice caused huge, soft hemorrhagic tumors to form, whereas controls maintained very small tumors. Intracranial implantation of the VEGF-overexpressing cell lines significantly shortened survival of the mice when compared with controls, and it caused formation of solid brain tumors with variable sized hemorrhages, whereas the controls had no apparent brain tumors. Tumorigenicity of U251 MG cells was synergized by co-overexpression of VEGF(121) and VEGF(165). In addition, VEGF(165) seemed to be more potent to the brain endothelium than was VEGF(121). More interestingly, except when an admixture of cells was implanted s.c., VEGF overexpression in NG-1 cells did not promote hemorrhagic tumor formation. These data suggested that a switch from a phenotype of low tumorigenicity to one of high tumorigenicity is possible when VEGF overexpression occurs, although other factors may also be required.
Lentiviral Vectors--the Promise of Gene Therapy Within Reach? (1999)

The goal of gene therapy is to modify the genetic material of cells by introducing a therapeutic gene to treat or prevent disease. However, gene therapy has been hampered by the lack of suitable delivery systems (vectors). Existing vectors (all based on viruses) have major problems including poor transduction efficiency, inability to infect nondividing cells, short-term expression of the therapeutic gene and induction of a host immune response. In a Perspective,
 Amado and Chen
 discuss the new generation of vectors that are based on lentiviruses such as HIV. They discuss the advantages of such lentiviral vectors but also raise the safety concerns inherent in using such vectors and how these can be overcome.
Prussian Blue and Its Analogues: Electrochemistry and Analytical Applications (2001)

This article reviews fundamental aspects of deposition, structure and electrochemistry of Prussian Blue and its analogues. Special attention is given to the metal hexacyanoferrates with potential analytical applications. Prussian Blue and its analogues as advanced sensing materials for nonelectroactive ions are discussed. In contrast to common ‘smart materials’, the sensitivity and selectivity of metal hexacyanoferrates to such ions is provided by thermodynamic background. Prussian Blue itself is recognized as the most advantageous low-potential transducer for hydrogen peroxide over all known systems. Both high sensitivity (ca. 1 A M−1 cm−2) and selectivity in relation to oxygen reduction are more than three orders of magnitude higher, than for platinum electrodes. Biosensors based on different transducing principles containing enzymes oxidases are compared, and the devices operated due to hydrogen peroxide detection with the Prussian Blue based transducer are shown to be the most advantageous ones. The future prospects of chemical and biological sensors based on metal hexacyanoferrates are outlined.
Delivery of optical contrast agents using Triton-X100, part 1: reversible permeabilization of live cells for intracellular labeling (2009)

Effective delivery of optical contrast agents into live cells remains a significant challenge. We sought to determine whether Triton-X100, a detergent commonly used for membrane isolation and protein purification, could be used to effectively and reversibly permeabilize live cells for delivery of targeted optical contrast agents. Although Triton-X100 is widely recognized as a good cell permeabilization agent, no systematic study has evaluated the efficiency, reproducibility, and reversibility of Triton-X100-mediated permeabilization in live mammalian cells. We report a series of studies to characterize macromolecule delivery in cells following Triton-X100 treatment. Using this approach, we demonstrate that molecules ranging from 1 to 150 kDa in molecular weight can be reproducibly delivered into live cells by controlling the moles of Triton-X100 relative to the number of cells to be treated. When Triton-X100 is administered at or near the minimum effective concentration, cell permeabilization is generally reversed within 24 h, and treated cells continue to proliferate and show metabolic activity during the restoration of membrane integrity. We conclude that Triton-X100 is a promising permeabilization agent for efficient and reproducible delivery of optical contrast agents into live mammalian cells.
Timed Release of Flurprimidol from a Granular Formulation in Mulches and Sand (2009)

Flurprimidol is a plant growth regulator that can be applied as a granular formulation. Understanding flurprimidol release from a granular formulation and movement in various mediums will impact how it is used. Dissipation of flurprimidol from a granular formulation and movement through organic media and sand were evaluated in a greenhouse and laboratory experiment. Experimental variables included media type, depth, and irrigation event. Dissipation isotherms were determined by applying nonlinear regression. Mobility was evaluated using columns filled with media, which was surface-spiked with the granular formulation and then irrigated once daily for 22 consecutive days. Leachate was collected and analyzed by high-performance liquid chromatography–mass spectroscopy. Half-life (DT 50 ), defined as time to 50% reduction, varied among sand, media, and media depth. Flurprimidol dissipation was rapid through sand with DT 50 of 6 days. DT 50 increased with increasing media depth from 5 to 10 cm for pine bark plus sand, 18 and 35 days, and hardwood bark plus sand, 77 and 173 days, respectively. Maximum flurprimidol leaching was a cumulative 71% of applied amounts over 22 irrigation events through the sand. Hardwood and pine bark media allowed less than 25% of flurprimidol to escape through the column. Data for all media indicated that flurprimidol was mobile through the substrates but exhibited hysteresis with pine bark and hard wood bark media. An initial pulse of flurprimidol will release slowly from this formulation over time. These results indicate that flurprimidol will dissipate from a granular formulation over time and that it will have movement through sand soil and pine bark and hardwood bark media to reach the roots of growing plants.
Improving the efficiency of CHO cell line generation using glutamine synthetase gene knockout cells (2011)

Although Chinese hamster ovary (CHO) cells, with their unique characteristics, have become a major workhorse for the manufacture of therapeutic recombinant proteins, one of the major challenges in CHO cell line generation (CLG) is how to efficiently identify those rare, high-producing clones among a large population of low- and non-productive clones. It is not unusual that several hundred individual clones need to be screened for the identification of a commercial clonal cell line with acceptable productivity and growth profile making the cell line appropriate for commercial application. This inefficiency makes the process of CLG both time consuming and laborious. Currently, there are two main CHO expression systems, dihydrofolate reductase (DHFR)-based methotrexate (MTX) selection and glutamine synthetase (GS)-based methionine sulfoximine (MSX) selection, that have been in wide industrial use. Since selection of recombinant cell lines in the GS-CHO system is based on the balance between the expression of the GS gene introduced by the expression plasmid and the addition of the GS inhibitor, L-MSX, the expression of GS from the endogenous GS gene in parental CHOK1SV cells will likely interfere with the selection process. To study endogenous GS expression's potential impact on selection efficiency, GS-knockout CHOK1SV cell lines were generated using the zinc finger nuclease (ZFN) technology designed to specifically target the endogenous CHO GS gene. The high efficiency (∼2%) of bi-allelic modification on the CHO GS gene supports the unique advantages of the ZFN technology, especially in CHO cells. GS enzyme function disruption was confirmed by the observation of glutamine-dependent growth of all GS-knockout cell lines. Full evaluation of the GS-knockout cell lines in a standard industrial cell culture process was performed. Bulk culture productivity improved two- to three-fold through the use of GS-knockout cells as parent cells. The selection stringency was significantly increased, as indicated by the large reduction of non-producing and low-producing cells after 25 µM L-MSX selection, and resulted in a six-fold efficiency improvement in identifying similar numbers of high-productive cell lines for a given recombinant monoclonal antibody. The potential impact of GS-knockout cells on recombinant protein quality is also discussed.
A transcriptional network signature characterizes lung cancer subtypes (2010)

These results suggest the existence of a robust signature localized in a relatively small area of the genome, and show the clinical potential of reverse engineering transcriptional networks from molecular profiles.
Immunoglobulin heavy chain constant regions regulate immunity and tolerance to idiotypes of antibody variable regions (2002)

Particular syngeneic adjuvant-free monoclonal antibodies are immunogenic and elicit antibody responses against the variable region idiotypes (Ids). We here study how heavy-chain constant regions (C(H)) regulate immune responses to Ids of free, uncomplexed monoclonal antibodies. To this end, we selected two hybridomas, called Id(3) and Id(A.01), that produce immunogenic IgM(lambda)2 directed toward 2,4,6-trinitrophenyl, and subcloned rare IgG1, IgG3, IgE, or IgA class switch variants. The purified switch variants, which possessed the Ids of their IgM progenitors, were injected repeatedly without added adjuvant into BALB/c mice, and anti-Id IgG responses were determined. These repeated injections revealed that the immunogenicity of Ids was lost by switching to IgG1 and IgG3, restored when the Fc piece of IgG1 was removed, maintained by switching to IgE and monomeric IgA, and lost in polymeric IgA. Loss of immunogenicity was associated with acquisition of Id-specific tolerogenicity, as determined by immunization challenge with Id borne by IgM. An Id borne by IgG induced tolerance when injected at least 90 days before or 3-21 days after immunization with IgM Id was begun. Ids of IgG were also tolerogenic in mice deficient in Fc(gamma)RIIB or Fc(gamma)RI + III. The results suggest that Ids that have switched to IgG and pIgA negatively control immune responses to shared Ids, including the Ids of their IgM progenitors.
Dendritic cell vaccines: A review of recent developments and their potential pediatric application (2016)

For many cancers the use of conventional chemotherapy has been maximized, and further intensification of chemotherapy generally results in excess toxicity with little long-term benefit for cure. Many tumors become resistant to chemotherapy, making the investigation of novel approaches such as immunotherapy of interest. Because the tumor microenvironment is known to promote immune tolerance and down regulate the body's natural defense mechanisms, modulating the immune system with the use of dendritic cell (DC) therapy is an attractive approach. Thousands of patients with diverse tumor types have been treated with DC vaccines. While antigen specific immune responses have been reported, the duration and magnitude of these responses are typically weak, and objective clinical responses have been limited. DC vaccine generation and administration is a multi-step process with opportunities for improvement in source of DC for vaccine, selection of target antigen, and boosting effector cell response via administration of vaccine adjuvant or concomitant pharmacologic immunomodulation. In this review we will discuss recent developments in each of these areas and highlight elements that could be moved into pediatric clinical trials.
Two members of the Arabidopsis CLC (chloride channel) family, AtCLCe and AtCLCf, are associated with thylakoid and Golgi membranes, respectively (2007)

Though numerous pieces of evidence point to major physiological roles for anion channels in plants, progress in the understanding of their biological functions is limited by the small number of genes identified so far. Seven chloride channel (CLC) members could be identified in the Arabidopsis genome, amongst which AtCLCe and AtCLCf are both more closely related to bacterial CLCs than the other plant CLCs. It is shown here that AtCLCe is targeted to the thylakoid membranes in chloroplasts and, in agreement with this subcellular localization, that the clce mutants display a phenotype related to photosynthesis activity. The AtCLCf protein is localized in Golgi membranes and functionally complements the yeast gef1 mutant disrupted in the single CLC gene encoding a Golgi-associated protein.
Interaction of Mesoporous Silica Nanoparticles with Human Red Blood Cell Membranes: Size and Surface Effects (2011)

The interactions of mesoporous silica nanoparticles (MSNs) of different particle sizes and surface properties with human red blood cell (RBC) membranes were investigated by membrane filtration, flow cytometry, and various microscopic techniques. Small MCM-41-type MSNs (∼100 nm) were found to adsorb to the surface of RBCs without disturbing the membrane or morphology. In contrast, adsorption of large SBA-15-type MSNs (∼600 nm) to RBCs induced a strong local membrane deformation leading to spiculation of RBCs, internalization of the particles, and eventual hemolysis. In addition, the relationship between the degree of MSN surface functionalization and the degree of its interaction with RBC, as well as the effect of RBC-MSN interaction on cellular deformability, were investigated. The results presented here provide a better understanding of the mechanisms of RBC-MSN interaction and the hemolytic activity of MSNs and will assist in the rational design of hemocompatible MSNs for intravenous drug delivery and in vivo imaging.
Percutaneous Autologous Bone-Marrow Grafting for Nonunions<sbt aid="1015500">Influence of the Number and Concentration of Progenitor Cells</sbt> (2005)

Percutaneous autologous bone-marrow grafting is an effective and safe method for the treatment of an atrophic tibial diaphyseal nonunion. However, its efficacy appears to be related to the number of progenitors in the graft, and the number of progenitors available in bone marrow aspirated from the iliac crest appears to be less than optimal in the absence of concentration.
Intrathecal polymer-based interleukin-10 gene delivery for neuropathic pain (2006)

Research on communication between glia and neurons has increased in the past decade. The onset of neuropathic pain, a major clinical problem that is not resolved by available therapeutics, involves activation of spinal cord glia through the release of proinflammatory cytokines in acute animal models of neuropathic pain. Here, we demonstrate for the first time that the spinal action of the proinflammatory cytokine, interleukin 1 (IL-1) is involved in maintaining persistent (2 months) allodynia induced by chronic-constriction injury (CCI). The anti-inflammatory cytokine IL-10 can suppress proinflammatory cytokines and spinal cord glial amplification of pain. Given that IL-1 is a key mediator of neuropathic pain, developing a clinically viable means of long-term delivery of IL-10 to the spinal cord is desirable. High doses of intrathecal IL-10-gene therapy using naked plasmid DNA (free pDNA-IL-10) is effective, but the dose required limits its potential clinical utility. Here we show that intrathecal gene therapy for neuropathic pain is improved sufficiently using two, distinct synthetic polymers, poly(lactic-co-glycolic) and polyethylenimine, that substantially lower doses of pDNA-IL-10 are effective. In conclusion, synthetic polymers used as i.t. gene-delivery systems are well-tolerated and improve the long-duration efficacy of pDNA-IL-10 gene therapy.