gebhart/patrepeval huggingface dataset:
Hypothermic effects of a homologous series of short‐chain alcohols in rats (1991)

The purpose of this study was to assess the utility of the thermoregulatory system as an end point in predicting the toxicity of various short-chain alcohols. Male Fischer rats developed significant hypothermia following acute administration (ip) of methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, or 2-butanol. The hypothermic responses to the six alcohols all showed similar segmented responses characterized by a threshold dose below which no change in body temperature occurred, and a suprathreshold regression with increasing dose causing greater hypothermia. Relative potency of the alcohols was assessed using both the threshold dose to cause hypothermia and the dose that would cause body temperature to decrease by 1 degree C. Both measures gave the progression of toxicity from least to most potent of methanol less than ethanol less than 2-propanol less than 1-propanol less than 2-butanol less than 1-butanol. The effective dose of each alcohol was compared to its membrane/buffer partition coefficient (Pm/b), and there was a high inverse correlation between the hypothermic dose of an alcohol and its lipid solubility. That the potency of an alcohol was strongly correlated with its Pm/b suggests that the membrane disordering theory of narcosis may also be used to explain the hypothermic action of alcohols.
Genome sequence of Silicibacter pomeroyi reveals adaptations to the marine environment (2004)

Since the recognition of prokaryotes as essential components of the oceanic food web, bacterioplankton have been acknowledged as catalysts of most major biogeochemical processes in the sea. Studying heterotrophic bacterioplankton has been challenging, however, as most major clades have never been cultured or have only been grown to low densities in sea water. Here we describe the genome sequence of Silicibacter pomeroyi, a member of the marine Roseobacter clade (Fig. 1), the relatives of which comprise approximately 10-20% of coastal and oceanic mixed-layer bacterioplankton. This first genome sequence from any major heterotrophic clade consists of a chromosome (4,109,442 base pairs) and megaplasmid (491,611 base pairs). Genome analysis indicates that this organism relies upon a lithoheterotrophic strategy that uses inorganic compounds (carbon monoxide and sulphide) to supplement heterotrophy. Silicibacter pomeroyi also has genes advantageous for associations with plankton and suspended particles, including genes for uptake of algal-derived compounds, use of metabolites from reducing microzones, rapid growth and cell-density-dependent regulation. This bacterium has a physiology distinct from that of marine oligotrophs, adding a new strategy to the recognized repertoire for coping with a nutrient-poor ocean.
Vesicle and Cell Networks:  Interconnecting Cells by Synthetic Polymers (1996)

Water-soluble polymers carrying a small fraction of hydrophobic groups are able to insert these groups into the hydrophobic interior of lipid bilayers or membranes. Under certain conditions such polymers can interconnect different vesicles or biological cells. With increasing polymer concentration this leads to the formation of a three-dimensional network. In this paper we report about the preparation and a first characterization of the structure and the mechanical properties of these new vesicle−polymer and polymer−cell gels composed of α,ω-cholesterol-modified poly(oxyethylene) and dimethyldioctadecylammonium chloride vesicles or living cells.
Pulse itraconazole vs. continuous terbinafine for the treatment of dermatophyte toenail onychomycosis in patients with diabetes mellitus (2006)

Both continuous terbinafine and itraconazole pulse therapy are effective and safe in the management of dermatophyte toenail onychomycosis in people with diabetes.
MicroRNA regulatory networks in idiopathic pulmonary fibrosis (2015)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal scarring lung disease of unknown etiology, characterized by changes in microRNA expression. Activation of transforming growth factor (TGF-β) is a key event in the development of IPF. Recent reports have also identified epigenetic modification as an important player in the pathogenesis of IPF. In this review, we summarize the main results of studies that address the role of microRNAs in IPF and highlight the synergistic actions of these microRNAs in regulating TGF-β, the primary fibrogenic mediator. We outline epigenetic regulation of microRNAs by methylation. Functional studies identify microRNAs that alter proliferative and migratory properties of fibroblasts, and induce phenotypic changes in epithelial cells consistent with epithelial-mesenchymal transition. Though these studies were performed in isolation, we identify multiple co-operative actions after assembling the results into a network. Construction of such networks will help identify disease-propelling hubs that can be targeted for therapeutic purposes.
Multiple glycosylphosphatidylinositol-anchored Ly-6 molecules and transmembrane Ly-6E mediate inhibition of IL-2 production. (1994)

Cross-linking of Ly-6 molecules on T lymphocytes leads to IL-2 production, whereas costimulation of T cells via Ly-6A/E and the TCR inhibits IL-2 secretion. This study was initiated to determine whether there are unique structural requirements at the level of the Ly-6 molecule for its capacity to activate or block IL-2 production. Functional studies in which transfected EL-4J cells that expressed various Ly-6 proteins or chimeric Ly-6 molecules were used have demonstrated that direct activation of IL-2 secretion or inhibition of anti-CD3-induced IL-2 production occurred after mAb binding to Ly-6A/E, Ly-6C, and Ly-6G and was independent of whether the mAbs bound to amino- or carboxyl-terminal epitopes of Ly-6. The blockade of IL-2 production by costimulation with anti-CD3 and anti-Ly-6 was detected even when the addition of either mAb was temporally delayed for up to 17 h in a reciprocal fashion. Stimulation of mouse Ly-6 proteins expressed in Jurkat cells antagonized PMA/OKT3-induced IL-2 production, thus revealing that the Ly-6 inhibitory pathway is operative in human cells. EL-4J cells were also transfected with a chimeric construct in which the glycosylphosphatidylinositol anchor of Ly-6E was replaced by the transmembrane and a portion of the intracytoplasmic tail of H-2Db. Anti-Ly-6A/E also blocked anti-CD3-induced IL-2 production for these cells, although anti-Ly-6A/E failed to directly induce IL-2 secretion. Thus, anti-Ly-6A/E blockade of IL-2 production is independent of the glycosylphosphatidylinositol anchor of Ly-6E. This finding suggests that there may be aspects of signaling via Ly-6 that are solely dependent on the extracellular amino acid sequence of this protein.
Engineering naturally occurring trans -acting non-coding RNAs to sense molecular signals (2012)

Non-coding RNAs (ncRNAs) are versatile regulators in cellular networks. While most trans-acting ncRNAs possess well-defined mechanisms that can regulate transcription or translation, they generally lack the ability to directly sense cellular signals. In this work, we describe a set of design principles for fusing ncRNAs to RNA aptamers to engineer allosteric RNA fusion molecules that modulate the activity of ncRNAs in a ligand-inducible way in Escherichia coli. We apply these principles to ncRNA regulators that can regulate translation (IS10 ncRNA) and transcription (pT181 ncRNA), and demonstrate that our design strategy exhibits high modularity between the aptamer ligand-sensing motif and the ncRNA target-recognition motif, which allows us to reconfigure these two motifs to engineer orthogonally acting fusion molecules that respond to different ligands and regulate different targets in the same cell. Finally, we show that the same ncRNA fused with different sensing domains results in a sensory-level NOR gate that integrates multiple input signals to perform genetic logic. These ligand-sensing ncRNA regulators provide useful tools to modulate the activity of structurally related families of ncRNAs, and building upon the growing body of RNA synthetic biology, our ability to design aptamer-ncRNA fusion molecules offers new ways to engineer ligand-sensing regulatory circuits.
A Multicenter United States—Canadian Trial to Assess Lamivudine Monotherapy Before and After Liver Transplantation for Chronic Hepatitis B (2001)

Seventy-seven liver transplant candidates were enrolled in a multicenter study in which patients were treated with lamivudine (100 mg daily) without the adjunctive use of hepatitis B immune globulin. Treatment was begun while patients awaited liver transplantation and continued after transplantation. All were hepatitis B surface antigen (HBsAg) positive, and 61% had detectable hepatitis B e antigen (HBeAg) and HBV DNA when treatment was begun. Forty-seven underwent liver transplantation and 30 did not. Median study participation was 38 months (range, 2.7-48.5) in the transplanted patients and 26 months (range, 0.1-37) in the nontransplanted group. Twenty-five of 42 (60%) transplanted patients with 12 or more weeks of posttransplantation follow-up were HBsAg negative at the last study visit. At treatment week 156, 13 of 22 (59%) remained HBsAg negative, and all 9 reinfected patients were HBV-DNA positive before treatment. In the nontransplanted patients, HBeAg was initially detectable in 20 of 27 (74%) but this decreased to 3 of 17 (18%) after 104 weeks of treatment, and significant improvement in biochemical parameters was observed. HBV-DNA polymerase mutants were detected in 15 (21%) and 6 (20%) of the transplanted and nontransplanted patients, respectively. When compared with historical cohorts, lamivudine-treated patients appeared to have improved survival, and transplanted patients had a decrease in the rate of recurrent HBV infection. Lamivudine therapy was partially effective in preventing recurrent HBV infection when given before and after transplantation. Thus, future trials using a combination of HBIg and lamivudine are needed to assess the optimal prophylactic therapy.
Low Seroprevalent Species D Adenovirus Vectors as Influenza Vaccines (2013)

Seasonal and pandemic influenza remains a constant threat. While standard influenza vaccines have great utility, the need for improved vaccine technologies have been brought to light by the 2009 swine flu pandemic, highly pathogenic avian influenza infections, and the most recent early and widespread influenza activity. Species C adenoviruses based on serotype 5 (AD5) are potent vehicles for gene-based vaccination. While potent, most humans are already immune to this virus. In this study, low seroprevalent species D adenoviruses Ad26, 28, and 48 were cloned and modified to express the influenza virus A/PR/8/34 hemagglutinin gene for vaccine studies. When studied in vivo, these species D Ad vectors performed quite differently as compared to species C Ad vectors depending on the route of immunization. By intramuscular injection, species D vaccines were markedly weaker than species C vaccines. In contrast, the species D vaccines were equally efficient as species C when delivered mucosally by the intranasal route. Intranasal adenovirus vaccine doses as low as 10(8) virus particles per mouse induced complete protection against a stringent lethal challenge dose of influenza. These data support translation of species D adenoviruses as mucosal vaccines and highlight the fundamental effects of differences in virus tropism on vaccine applications.
Tyrosinase transfection produces melanin synthesis and growth retardation in glioma cells (1998)

Tyrosinase is the key enzyme in melanin biosynthesis in pigmented cells. We transfected 9L rat glioma cells with human tyrosinase cDNA that had been cloned in a high expression vector. Stable transfectants were selected by their resistance to the antibiotic G418. More than a dozen G418-resistant clones were isolated and were screened for tyrosinase expression using dopa-oxidase activity. The clone with the highest tyrosinase activity was selected and expanded for further studies. Northern blot analyses of total RNA from cells showed that the transfected cells had relatively more tyrosinase transcript than SK-MEL-23 human melanotic melanoma cells. The melanin content of the transfected cells was dependent on the concentration of L-tyrosine in the culture medium. In addition, the growth of transfected cells was inhibited when grown in a medium containing high concentrations of L-tyrosine. These results suggest that tyrosinase activity is cytotoxic in a substrate-dependent manner. This may have far reaching therapeutic use for glioma tumours.
Comparison of antiangiogenic activities using paclitaxel (taxol) and docetaxel (taxotere) (2003)

Tumor growth requires a competent vascular supply and angiogenesis has been considered as a potential target for the treatment of several cancers. The two clinically approved taxanes, paclitaxel and docetaxel, are novel antimitotic agents that are under extensive investigation in clinical trials. Both taxanes have demonstrated significant activity against many solid tumors, but little is known about the effect of paclitaxel and docetaxel on endothelial cell function and angiogenic processes. The purpose of our study was to examine and compare the effects of these drugs on angiogenic processes in vitro and in vivo. These processes include: proliferation, migration and differentiation of cultured human umbilical vein endothelial cells (HUVEC) (in vitro), capillary sprouting of rat aortic ring explants (ex vivo) and HT1080 tumor growth in vivo. Our results demonstrate that endothelial cells are 10-100-fold more sensitive to these drugs than tumor cells. Additionally, comparison of the taxanes demonstrated that angiogenesis is blocked by both drugs primarily via inhibition of proliferation and differentiation (tube assay) and induction of cell death. Docetaxel, however, appears to be more potent at inhibiting angiogenesis, with an IC(50) concentration 10x less than that of paclitaxel. We conclude that these important findings should be taken in account in clinical trials where tumor angiogenesis is being targeted.
Human RNase 7: a new cationic ribonuclease of the RNase A superfamily (2003)

Here we report on the expression and function of RNase 7, one of the final RNase A superfamily ribonucleases identified in the human genome sequence. The human RNase 7 gene is expressed in various somatic tissues including the liver, kidney, skeletal muscle and heart. Recombinant RNase 7 is ribonucleolytically active against yeast tRNA, as expected from the presence of eight conserved cysteines and the catalytic histidine-lysine- histidine triad which are signature motifs of this superfamily. The protein is atypically cationic with an isoelectric point (pI) of 10.5. Expression of recombinant RNase 7 in Escherichia coli completely inhibits the growth of the host bacteria, similar to what has been observed for the cationic RNase, eosinophil cationic protein (ECP/RNase 3, pI 11.4). An in vitro assay demonstrates dose-dependent cytotoxicity of RNase 7 against bacteria E.coli, Pseudomonas aeruginosa and Staphylococcus aureus. While RNase 7 and ECP/RNase 3 are both cationic and share this particular aspect of functional similarity, their protein sequence identity is only 40%. Of particular interest, ECP/RNase 3's cationicity is based on an (over)abundance of arginine residues, whereas RNase 7 includes an excess of lysine. This difference, in conjunction with the independent origins and different expression patterns, suggests that RNase 7 and ECP/RNase 3 may have been recruited to target different pathogens in vivo, if their physiological functions are indeed host defenses.
Inhibition of <i>Candida</i> by Compounds which Inhibit Cholesterol Biosynthesis (1973)

Three compounds which inhibit cholesterol biosynthesis (SKF 525-A, 3301-A and 16467-A) of 7 tested had significant activity against 8 Candida isolates (1 wild-type strain each of C. albicans and C. tropicalis, and polyene-resistant mutants derived from these). The mean minimum inhibitory concentration of SKF 525 and 3301 was 0.62 mg/ml (about 1.7 mm) and of SKF 16467 was 2 mg/ml (about 5.5 mm). The resistant C. albicans isolates tended to be slightly more sensitive to these compounds than was the parent strain. No evidence was obtained for any synergism or antagonism between these drugs and nystatin. The effect of compounds SKF 525 and 3301 on the growth of C. albicans resembled that of nystatin and pyrrolnitrin, and differed from that of 5-fluorocytosine and clotrimazole.
Identifying Critically Ill Patients Who May Benefit From Adjunctive Corticosteroids (2014)

Department of Surgery, University of Cincinnati College of Medicine; and Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center and Cincinnati Children’s Hospital Research Foundation, Cincinnati, OH Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center and Cincinnati Children’s Hospital Research Foundation; and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH * See also p. 698. Dr. Wong received support for article research from the National Institutes of Health (NIH). His institution received grant support from the NIH and disclosed patents (Biomarker patents; U.S. Patent Office). Dr. Atkinson has disclosed that she does not have any potential conflicts of interest.
Adenoviral-Mediated Gene Transfer to Human Adipocytes In Vitro, and Human Adipose Tissue Ex Vivo and Rabbit Femoral Adipose Tissue In Vivo. (1998)

Adenoviral-mediated gene transfer has proven useful in several organ systems to understand gene action and to provide a potential therapeutic modality for localized, organ-specific gene overexpression. However, the application of adenoviral-mediated gene transfer to adipocytes and adipose tissue has not been evaluated. We evaluated the feasibility of in vitro and ex vivo transfer of the beta-galactosidase gene to human adipocytes and adipose tissue by means of adenoviral vectors. The efficiency (percentage of cells transduced) of adenoviral-mediated gene transfer of the beta-galactosidase gene to human adipocytes in vitro and to human adipose tissue ex vivo was 21 +/- 3% and 14 +/- 3%, respectively. Adenoviral-mediated gene transfer in a rabbit femoral adipose tissue was also demonstrated in vivo. Adenoviral-mediated gene transfer may facilitate studies on understanding the biology of adipocytes and provide a potential tool for the modulation of adipocyte function in vivo and thereby for the treatment of obesity.
Cloning of rat type I receptor cDNA for bone morphogenetic protein‐2 and bone morphogenetic protein‐4, and the localization compared with that of the ligands (1996)

A rat homologue cDNA of mouse (Koenig et al. [1994] Mol. Cell Biol. 14:5961–5974; Suzuki et al. [1994] Proc. Natl. Acad. Sci. USA 91: 10255–10259) and human (ten Dijke et al. [1994] J. Biol. Chem. 269:16985–16988) type I receptors for BMP-2 and BMP-4 was cloned. Tissue distribution of the receptor mRNA was studied by in situ hybridization using rats at embryonic days 9, 13, 15, and 18 as well as 1- and 5-day-old postnatal rats. In the rats at embryonic days 9, 13, and 15, the receptor mRNA was diffusely expressed over the embryonic bodies. At embryonic day 18, the receptor mRNA expression was high in the hair and whisker follicles, tooth bud, cartilage, bone, digestive organs, lung, kidney, heart, and meninges. The receptor mRNA was expressed over a much wider area than those of the ligands in many organs. In the lung and digestive organs, the receptor mRNA was diffusely expressed and most highly expressed in the bronchial epithelium and muscle layer, respectively, in both of which mRNA expression of the ligands was undetectable. The receptor mRNA was highly expressed in the meninges, although neither of the ligands was expressed in or near this region. These results suggest that this receptor participates in both mesoderm formation in early embryogenesis and differentiation of mesodermal cells during maturation of organs, and further suggest the presence of another factor(s) that binds the type I receptor. © 1996 Wiley-Liss, Inc.
Establishment of T-helper type 1- and T-helper type 2-like human Toxoplasma antigen-specific T-cell clones. (1995)

As an in vitro model for human cerebral toxoplasmosis, we analysed the interaction between glioblastoma cells, Toxoplasma and Toxoplasma antigen-specific T-helper cells. We established 46 different human CD4+ T-cell clones from four different donors. All T-cell clones responded to Toxoplasma antigen derived from three different Toxoplasma strains. We found that the supernatants of 44 clones induced toxoplasmostasis in glioblastoma cells. The anti-parasitic effector mechanism activated in glioblastoma cells by T-cell supernatants was the induction of the tryptophan-degrading enzyme indolamine 2,3-dioxygenase. Enzyme induction, as well as the anti-parasitic effect, was blocked by a monoclonal antibody directed against interferon-gamma (IFN-gamma), and the addition of L-tryptophan to the cultures completely blocked the anti-parasitic effect induced by T-cell supernatants. The supernatants from two of the 46 established T-cell clones (3A22 and 1A15) were unable to induce indolamine 2,3-dioxygenase activity or, as expected, toxoplasmostasis in glioblastoma cells. We further analysed the supernatants from these two clones, and found that they contained large amounts of IL-4 and no, or only limited amounts of, IFN-gamma. We therefore conclude that Toxoplasma-antigen is able to activate T-helper type 1 (Th1)- and Th2-like human T cells, and only IFN-gamma-producing cells are capable of inducing anti-parasitic effector mechanisms.
Photochemistry of colloidal semiconductors. 20. Surface modification and stability of strong luminescing CdS particles (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotochemistry of colloidal semiconductors. 20. Surface modification and stability of strong luminescing CdS particlesLubomir Spanhel, Markus Haase, Horst Weller, and Arnim HengleinCite this: J. Am. Chem. Soc. 1987, 109, 19, 5649–5655Publication Date (Print):September 1, 1987Publication History Published online1 May 2002Published inissue 1 September 1987https://doi.org/10.1021/ja00253a015Request reuse permissionsArticle Views5216Altmetric-Citations1121LEARN 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 InReddit PDF (817 KB) Get e-Alertsclose Get e-Alerts