gebhart/patrepeval huggingface dataset:
Inhibition of hepatic tumour necrosis factor‐α attenuates the anandamide‐induced vasoconstrictive response in cirrhotic rat livers (2009)

Thalidomide decreased the PVP and IHR through the attenuation of anandamide-induced constrictive response, decreasing the production of TNF-alpha, IL-6 and TXA(2) in the liver and the suppression of hepatic fibrogenesis of rats with biliary cirrhosis of this study.
Molecular cloning, expression, and localization of a brain-specific phosphodiesterase I/nucleotide pyrophosphatase (PD-I alpha) from rat brain. (1994)

We have isolated cDNA clones encoding the rat brain phosphodiesterase I/nucleotide pyrophosphatase (PD-I alpha), a novel member of the membrane phosphodiesterase I gene family. PD-I alpha cDNA has a 2,655-nucleotide open reading frame encoding a polypeptide of 885 amino acids with a calculated M(r) of 101,302. Northern blot analysis revealed that PD-I alpha transcript was abundantly present in cerebrum and cerebellum while its level was quite low in other tissues. In situ hybridization analysis revealed that PD-I alpha mRNA is localized in secretory epithelial cells in the brain and the eye including choroid plexus epithelial cells, ciliary epithelial cells, iris pigment epithelial cells, and retinal pigment cells. Localization of PD-I alpha mRNA was also observed in glial cells in the molecular layer of the cerebellum. These results indicate that this protein might be involved in the synthesis of adenosine as well as in the regulation of the secretion/transport of epithelial cells and glial cells in the central nervous system.
Optimality Model of Unsupervised Spike-Timing-Dependent Plasticity: Synaptic Memory and Weight Distribution (2007)

We studied the hypothesis that synaptic dynamics is controlled by three basic principles: (1) synapses adapt their weights so that neurons can effectively transmit information, (2) homeostatic processes stabilize the mean firing rate of the postsynaptic neuron, and (3) weak synapses adapt more slowly than strong ones, while maintenance of strong synapses is costly. Our results show that a synaptic update rule derived from these principles shares features, with spike-timing-dependent plasticity, is sensitive to correlations in the input and is useful for synaptic memory. Moreover, input selectivity (sharply tuned receptive fields) of postsynaptic neurons develops only if stimuli with strong features are presented. Sharply tuned neurons can coexist with unselective ones, and the distribution of synaptic weights can be unimodal or bimodal. The formulation of synaptic dynamics through an optimality criterion provides a simple graphical argument for the stability of synapses, necessary for synaptic memory.
Kallikrein 6 Induces E-Cadherin Shedding and Promotes Cell Proliferation, Migration, and Invasion (2007)

Recently, we described phorbol ester-induced expression of the brain and skin serine proteinase Bssp/kallikrein 6 (Klk6), the mouse orthologue of human KLK6, in mouse back skin and in advanced tumor stages of a well-established multistage tumor model. Here, we show KLK6 up-regulation in squamous skin tumors of human patients and in tumors of other epithelial tissues. Ectopic Klk6 expression in mouse keratinocyte cell lines induces a spindle-like morphology associated with accelerated proliferation, migration, and invasion capacity. We found reduced E-cadherin protein levels in the cell membrane and nuclear translocation of beta-catenin in Klk6-expressing mouse keratinocytes and human HEK293 cells transfected with a KLK6 expression plasmid. Additionally, HEK293 cells exhibited induced T-cell factor-dependent transcription and impaired cell-cell adhesion in the presence of KLK6, which was accompanied by induced E-cadherin ectodomain shedding. Interestingly, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3 interfere with KLK6-induced E-cadherin ectodomain shedding and rescue the cell-cell adhesion defect in vitro, suggesting the involvement of matrix metalloproteinase and/or a disintegrin and metalloproteinase (ADAM) proteolytic activity. In line with this assumption, we found increased levels of the mature 62-kDa ADAM10 proteinase in cells expressing ectopic KLK6 compared with mock controls. Finally, enhanced epidermal keratinocyte proliferation and migration in concert with decreased E-cadherin protein levels are confirmed in an in vivo Klk6 transgenic mouse model.
Adriamycin (1974)

Adriamycin, a new antineoplastic drug, induces objective tumor responses in solid tumors (adenocarcinoma of the breast, malignant sarcomas, bronchogenic carcinoma, and neuroblastoma) as well as in hematologic malignancies (malignant lymphomas and acute leukemia). The responses in specific tumor types are reviewed, and the relative clinical efficacy of adriamycin is compared with that of other antitumor agents. The toxic effects of adriamycin are also reviewed. Adriamycin therapy results in dose-limiting hematologic and cardiac toxicity, as well as stomatitis, nausea, vomiting, and alopecia, but in general these toxicities are predictable and reversible. The theoretical limitations of this type of review are pointed out.
Volatile Components of Peel and Leaf Oils of Lemon and Lime Species (2002)

Peel and leaf oils of 43 taxa of lemons and limes were obtained from fruits and leaves collected from trees submitted to the same pedoclimatic and cultural conditions. Their chemical composition was investigated by capillary GC, GC-MS, and (13)C NMR, and the results were submitted to principal component analysis to check for chemical variability. Three major chemotypes were distinguished for lemon peel oils: limonene; limonene/beta-pinene/gamma-terpinene; and limonene/linalyl acetate/linalool. Two chemotypes were identified for lemon leaf oils: limonene/beta-pinene/geranial/neral and linalool/linalyl acetate/alpha-terpineol. In lime peel oils, four chemotypes were distinguished: limonene; limonene/gamma-terpinene; limonene/beta-pinene/gamma-terpinene; and limonene/gamma-terpinene/beta-pinene/oxygenated products. Four others were identified for lime leaf oils: beta-pinene/limonene; limonene/geranial/neral; limonene/linalool/citronellal; and limonene/sabinene/citronellal/linalool. These results were interpreted using principal component analysis.
Aptamers: Active Targeting Ligands for Cancer Diagnosis and Therapy (2015)

Aptamers, including DNA, RNA and peptide aptamers, are a group of promising recognition units that can specifically bind to target molecules and cells. Due to their excellent specificity and high affinity to targets, aptamers have attracted great attention in various fields in which selective recognition units are required. They have been used in biosensing, drug delivery, disease diagnosis and therapy (especially for cancer treatment). In this review, we summarized recent applications of DNA and RNA aptamers in cancer theranostics. The specific binding ability of aptamers to cancer-related markers and cancer cells ensured their high performance for early diagnosis of cancer. Meanwhile, the efficient targeting ability of aptamers to cancer cells and tissues provided a promising way to deliver imaging agents and drugs for cancer imaging and therapy. Furthermore, with the development of nanoscience and nanotechnology, the conjugation of aptamers with functional nanomaterials paved an exciting way for the fabrication of theranostic agents for different types of cancers, which might be a powerful tool for cancer treatment.
Gain-of-Function Alleles in Caenorhabditis elegans Nuclear Hormone Receptor nhr-49 Are Functionally Distinct (2016)

Nuclear hormone receptors (NHRs) are transcription factors that regulate numerous physiological and developmental processes and represent important drug targets. NHR-49, an ortholog of Hepatocyte Nuclear Factor 4 (HNF4), has emerged as a key regulator of lipid metabolism and life span in the nematode worm Caenorhabditis elegans. However, many aspects of NHR-49 function remain poorly understood, including whether and how it regulates individual sets of target genes and whether its activity is modulated by a ligand. A recent study identified three gain-of-function (gof) missense mutations in nhr-49 (nhr-49(et7), nhr-49(et8), and nhr-49(et13), respectively). These substitutions all affect the ligand-binding domain (LBD), which is critical for ligand binding and protein interactions. Thus, these alleles provide an opportunity to test how three specific residues contribute to NHR-49 dependent gene regulation. We used computational and molecular methods to delineate how these mutations alter NHR-49 activity. We find that despite originating from a screen favoring the activation of specific NHR-49 targets, all three gof alleles cause broad upregulation of NHR-49 regulated genes. Interestingly, nhr-49(et7) and nhr-49(et8) exclusively affect nhr-49 dependent activation, whereas the nhr-49(et13) surprisingly affects both nhr-49 mediated activation and repression, implicating the affected residue as dually important. We also observed phenotypic non-equivalence of these alleles, as they unexpectedly caused a long, short, and normal life span, respectively. Mechanistically, the gof substitutions altered neither protein interactions with the repressive partner NHR-66 and the coactivator MDT-15 nor the subcellular localization or expression of NHR-49. However, in silico structural modeling revealed that NHR-49 likely interacts with small molecule ligands and that the missense mutations might alter ligand binding, providing a possible explanation for increased NHR-49 activity. In sum, our findings indicate that the three nhr-49 gof alleles are non-equivalent, and highlight the conserved V411 residue affected by et13 as critical for gene activation and repression alike.
Biological and biochemical characteristics of murine megakaryoblastic cell line L8057. (1993)

Biological and biochemical characteristics of a murine megakaryoblastic cell line (L8057), derived from an irradiated C3H/He mouse, were studied. The L8057 cells grew in liquid cultures with a doubling time of 24 to 27 hours. By light and electron microscopy, the L8057 cells were small and basophilic with a high nuclear/cytoplasmic ratio, but large cells (approximately 25 to 60 microns) were sometimes seen. Western blot analysis of cell extracts demonstrated that murine megakaryocyte and platelet antigens, glycoprotein (GP) IIb/IIIa, fibronectin, and factor VIII:RAg were expressed in L8057 cells. Acetylcholinesterase (AChE)-positive cells were rare (< 2.0%). Flow cytometric analysis demonstrated that 8.7% of the cells were spontaneously polyploid (> 4N DNA levels). In response to phorbol diester (TPA, 50 nm), L8057 cells showed a decrease in proliferation and a marked increase in cell size and amount of cytoplasm. The morphology of the cells became similar to that of megakaryocytes, with larger and lobulated nuclei and expansion of the demarcation membrane system compartment. The proportion of cells with ploidy levels greater than 4N increased to 40.8% (8N, 21.3 +/- 3.2%; 16N, 13.1 +/- 2.6%; > or = 32N, 6.4 +/- 4.9% [n = 4]). More than 90% of the cells became AChE-positive. TPA also increased the expression of GP IIb/IIIa, fibronectin and factor VIII:RAg. Thus, the L8057 cell line provides a potentially superior model with which to study the characteristics of megakaryocytic biology, differentiation and biochemistry.
Microbial Dysbiosis in Pediatric Patients with Crohn's Disease (2012)

Microbial dysbiosis has been suggested to be involved in the pathogenesis of Crohn's disease (CD); however, many studies of gut microbial communities have been confounded by environmental and patient-related factors. In this study, the microbial flora of fecal samples from 19 children newly diagnosed with CD and 21 age-matched controls were analyzed using high-throughput sequencing to determine differences in the microbial composition between CD patients and controls. Analysis of the microbial composition of specific bacterial groups revealed that Firmicutes percentages were significantly lower in CD patients than in controls and that this was due largely to changes in the class Clostridia. Bacteroidetes and Proteobacteria percentages were higher and significantly higher in CD patients than in controls, respectively. Both the detection frequencies of Bacteroidetes and Firmicutes correlated (positively and negatively, respectively) with the calculated pediatric Crohn's disease activity index scores of patients. Upon further analysis, differences in the microbial compositions of patients with mild disease and moderate to severe disease were identified. Our findings indicate that a combination of different bacterial species or a dynamic interplay between individual species is important for disease and is consistent with the dysbiosis hypothesis of CD.
Interactions of Human hMSH2 with hMSH3 and hMSH2 with hMSH6: Examination of Mutations Found in Hereditary Nonpolyposis Colorectal Cancer (1998)

Mutations in the human mismatch repair protein hMSH2 have been found to cosegregate with hereditary nonpolyposis colorectal cancer (HNPCC). Previous biochemical and physical studies have shown that hMSH2 forms specific mispair binding complexes with hMSH3 and hMSH6. We have further characterized these protein interactions by mapping the contact regions within the hMSH2-hMSH3 and the hMSH2-hMSH6 heterodimers. We demonstrate that there are at least two distinct interaction regions of hMSH2 with hMSH3 and hMSH2 with hMSH6. Interestingly, the interaction regions of hMSH2 with either hMSH3 or hMSH6 are identical and there is a coordinated linear orientation of these regions. We examined several missense alterations of hMSH2 found in HNPCC kindreds that are contained within the consensus interaction regions. None of these missense mutations displayed a defect in protein-protein interaction. These data support the notion that these HNPCC-associated mutations may affect some other function of the heterodimeric complexes than simply the static interaction of hMSH2 with hMSH3 or hMSH2 with hMSH6.
Drag reduction of Newtonian fluid in a circular pipe with a highly water-repellent wall (1999)

Drag reduction phenomena, in which 14% drag reduction of tap water flowing in a 16 mm-diameter pipe occurs in the laminar flow range, have been clarified. Experiments were carried out to measure the pressure drop and the velocity profile of tap water and an aqueous solution of glycerin flowing in pipes with highly water-repellent walls, by using a pressure transducer and a hot-film anemometer, respectively. The same drag reduction phenomena also occurred in degassed tap water when using a vacuum tank. The velocity profile measured in this experiment gives the slip velocity at the pipe wall, and it was shown that the shear stress is directly proportional to the slip velocity. The friction factor formula for a pipe with fluid slip at the wall has been obtained analytically from the exact solution of the Navier–Stokes equation, and it agrees well qualitatively with the experimental data. The main reasons for the fluid slip are that the molecular attraction between the liquid and the solid surface is reduced because the free surface energy of the solid is very low and the contact area of the liquid is decreased compared with a conventional smooth surface because the solid surface has many fine grooves. Liquid cannot flow into the fine grooves owing to surface tension. These concepts are supported by the experimental result that drag reduction does not occur in the case of surfactant solutions.
Antibodies and Lectins in Glycan Analysis (2009)

Antiglycan antibodies and lectins are widely used in glycan analysis because their specificities enable them to discriminate among a variety of glycan structures and their multivalency ensures high-affinity binding to the glycans and cell surfaces containing those glycans. This chapter describes the variety of commonly used antibodies and lectins and the types of analyses to which they may be applied.
Endotoxin removal from water using microporous polyethylene chopped fibres as a new adsorbent (1986)

A new adsorbent, microporous polyethylene chopped fibre, was produced from a high density polyethylene. This can adsorb lipopolysaccharides (LPS) linearly up to 2 h, and showed the highest capacity to adsorb LPS when compared with two other polyethylene-based adsorbents and a polystyrene-based adsorbent. More than twice as much orange II and 4-nitroquinoline N oxide were adsorbed in the new adsorbent as was LPS. The adsorption isotherm of the new adsorbent for LPS was of Ln type, the correlation between adsorption and concentration of solute was proportional; whereas orange II and 4-nitroquinoline N oxide were of L type (greater adsorption than Ln type); tetrachloroethylene adsorption was of S type, less than Ln type. Adsorption of LPS to the new adsorbent increased when temperature rose, whereas adsorption of orange II and 4-nitroquinoline N oxide decreased. These data suggest that the binding of LPS to the new adsorbent is a hydrophobic interaction, whereas the binding of both orange II and 4-nitroquinoline N oxide is not. The new adsorbent has a greater potential for the removal of endotoxin from tap water than other commercially available adsorbents such as charcoal and Amberlite XAD-2.
Role of interleukin-1 in the pathogenesis of diabetic retinopathy (2004)

IL-1beta accelerates apoptosis of retinal capillary cells via activation of NF-kappaB, and the process is exacerbated in high glucose conditions. These studies suggest a possible role of IL-1beta in the development of retinopathy in diabetes, and offer a possible rationale to test IL-1beta receptor antagonists to inhibit the development of diabetic retinopathy.
Early release of glycogen phosphorylase in patients with unstable angina and transient ST-T alterations. (1994)

The early release of glycogen phosphorylase BB may help to identify high risk patients with unstable angina even on admission to an emergency department. Glycogen phosphorylase BB concentrations could help to guide decisions about patient management.
Regulation of Extrinsic Pathway Factor Xa Formation by Tissue Factor Pathway Inhibitor (1998)

Tissue factor (TF) pathway inhibitor (TFPI) regulates factor X activation through the sequential inhibition of factor Xa and the VIIa.TF complex. Factor Xa formation was studied in a purified, reconstituted system, at plasma concentrations of factor X and TFPI, saturating concentrations of factor VIIa, and increasing concentrations of TF reconstituted into phosphatidylcholine:phosphatidylserine membranes (TF/PCPS) or PC membranes (TF/PC). The initial rate of factor Xa formation was equivalent in the presence or absence of 2.4 nM TFPI. However, reaction extent was small (<20%) relative to that observed in the absence of TFPI, implying the rapid inhibition of VIIa.TF during factor X activation. Initiation of factor Xa formation using increasing concentrations of TF/PCPS or TF/PC in the presence of TFPI yielded families of progress curves where both initial rate and reaction extent were linearly proportional to the concentration of VIIa.TF. These observations were consistent with a kinetic model in which the rate-limiting step represents the initial inhibition of newly formed factor Xa. Numerical analyses of progress curves yielded a rate constant for inhibition of VIIa.TF by Xa.TFPI (>10(8) M-1.s-1) that was substantially greater than the value (7.34 +/- 0.8 x 10(6) M-1.s-1) directly measured. Thus, VIIa.TF is inhibited at near diffusion-limited rates by Xa.TFPI formed during catalysis which cannot be explained by studies of the isolated reaction. We propose that the predominant inhibitory pathway during factor X activation may involve the initial inhibition of factor Xa either bound to or in the near vicinity of VIIa.TF on the membrane surface. As a result, VIIa.TF inhibition is unexpectedly rapid, and the concentration of active factor Xa that escapes regulation is linearly dependent on the availability of TF.
Triiodothyronine-mediated myosin heavy chain gene transcription in the heart (2003)

We developed an RT-PCR assay to study both the time course and the mechanism for the triiodothyronine (T(3))-induced transcription of the alpha- and beta-myosin heavy chain (MHC) genes in vivo on the basis of the quantity of specific heterogeneous nuclear RNA (hnRNA). The temporal relationship of changes in transcriptional activity to the amount of alpha-MHC mRNA and the coordinated regulation of transcription of more than one gene in response to T(3) are demonstrated here for the first time. Quantitation of alpha-MHC hnRNA demonstrated that T(3) induced alpha-MHC transcription in hypothyroid rats within 30 min of a single injection of T(3) (0.5 microg/100 g body wt). Maximal transcription rates (135% +/- 15.8 of euthyroid values) occurred 6 h after injection and subsequently declined in parallel with serum T(3) levels. The transcription of beta-MHC was reduced to 86% of peak hypothyroid levels 6 h after a single T(3) injection and reached a nadir of 59% of hypothyroid levels at 36 h. Analysis of the time course of T(3)-mediated induction of alpha-MHC hnRNA and repression of beta-MHC hnRNA indicates that separate molecular mechanisms are involved in the coordinated regulation of these genes.
Masking of Phosphatidylserine Inhibits Apoptotic Cell Engulfment and Induces Autoantibody Production in Mice (2004)

Apoptotic cells are rapidly phagocytosed by professional phagocytes, such as macrophages and dendritic cells. This process prevents the release of potentially noxious or immunogenic intracellular materials from dying cells, and is thought to play a critical role for the maintenance of normal functions in surrounding tissues. Milk fat globule-EGF-factor 8 (MFG-E8), secreted by activated macrophages and immature dendritic cells, links apoptotic cells and phagocytes, and promotes phagocytosis of apoptotic cells. Here, we report that an MFG-E8 mutant, designated as D89E, carrying a point mutation in an RGD motif, inhibited not only the phagocytosis of apoptotic cells by a wide variety of phagocytes, but also inhibited the enhanced production of IL-10 by thioglycollate-elicited peritoneal macrophages phagocytosing apoptotic cells. When intravenously injected into mice, the D89E protein induced the production of autoantibodies including antiphospholipids antibodies and antinuclear antibodies. The production of autoantibodies was enhanced by the coinjection of syngeneic apoptotic thymocytes. After the induction of autoantibody production by D89E, the treated mice showed a long-term elevation of the titer for autoantibodies, and developed IgG deposition in the glomeruli. These results indicated that the impairment of apoptotic cell phagocytosis led to autoantibody production.