gebhart/patrepeval huggingface dataset:
GaN Nanowire Functionalized with Atomic Layer Deposition Techniques for Enhanced Immobilization of Biomolecules (2010)

We report the use of atomic layer deposition (ALD) coating as a nanobiosensor functionalization strategy for enhanced surface immobilization that may enable higher detection sensitivity. Three kinds of ALD coating films, Al(2)O(3), TiO(2), and SiO(2), were grown on the gallium nitride nanowire (GaN NW) surfaces and characterized with high-resolution transmission electron microscopy (HRTEM) and vacuum Fourier transform infrared spectroscopy (FTIR). Results from HRTEM showed that the thicknesses of ALD-Al(2)O(3), ALD-TiO(2) and ALD-SiO(2) coatings were 4-5 nm, 5-6 nm, and 12-14 nm, respectively. Results from FTIR showed that the OH contents of these coatings were, respectively, ∼6.9, ∼7.4, and ∼9.3 times that of piranha-treated GaN NW. Furthermore, to compare protein attachments on the different surfaces, poly(ethylene glycol) (PEG)-biotin was grafted on the OH-functionalized GaN NW surfaces through active Si-Cl functional groups. Streptavidin protein molecules were then attached to the biotin ends via specific binding. The immobilized streptavidin molecules were examined with scanning electron microscopy, HRTEM, and fluorescent imaging. Results from HRTEM and energy-dispersive X-ray revealed that the nitrogen concentrations on the three ALD coatings were significantly higher than that on the piranha-treated surface. Results from fluorescent imaging further showed that the protein attachments on the Al(2)O(3), TiO(2), and SiO(2) ALD coatings were, respectively, 6.4, 7.8, and 9.8 times that of piranha-treated surface. This study demonstrates that ALD coating can be used as a functionalization strategy for nanobiosensors because it is capable of creating functional groups with much higher density compared to widely used acid modifications, and among the three ALD coatings, ALD-SiO(2) yielded the most promising results in OH content and protein attachment.
Mir-148a and Mir-25 Target TULA-2 and Regulate Human Platelet FcγRIIA Signaling (2014)

Abstract FcγRIIA-mediated platelet activation is important in the pathogenesis of heparin-induced thrombocytopenia (HIT) and other immune-mediated thrombocytopenia and thrombosis disorders. FcgRIIa is also the major transmembrane signaling adapter for the human platelet fibrinogen receptor, integrin aIIbb3. In HIT, antibody to PF4/heparin is necessary but not sufficient for the disease. There is considerable inter-individual variation in platelet FcγRIIA activation; the reasons remain unclear. To identify potential regulators in the FcγRIIA pathway, we determined the platelet RNA expression profile in 154 healthy human donors who were phenotyped for platelet aggregation via FcgRIIA. 87 mRNAs and 4 DE miRNAs were identified as differentially expressed (DE) between hyper- and hypo-responsive donors by microarray and Nanostring analysis, respectively. Among them, hyper-responders show significantly lower T-cell ubiquitin ligand-2 (TULA-2) mRNA level and higher miR-148a-3p and miR-25-3p levels than hyporesponders. TULA-2, also known as UBASH3B, is a known protein tyrosine phosphatase for Syk, and thus a biologically plausible regulator of platelet FcgRIIA. Both miR-148a-3p and miR-25-3p are predicted to target the 3’UTR region on TULA-2 mRNA (Fig., A). Overexpression of miR-148a-3p or miR-25-3p results in down-regulation of the TULA-2 protein level in HCT116 cells and HEL cells (Fig., B). Inhibition of miR-148a-3p by anti-miR (LNA) leads to elevated TULA-2 expression. A luciferase construct with the 3’UTR miR binding sites was generated. A decrease in luciferase activity was observed in assays with co-transfection of the construct and a miR, supporting the binding between miR-148a-3p and miR-25-3p with TULA-2 3’UTR (Fig., C). Finally, we show that knockdown of TULA-2 caused increased Syk-pY (Y323) level in HEL megakaryocytic cell line in response to FcγRIIA crosslinking by IV.3 (mAb against FcγRIIA) + GAM (Goat anti-mouse F(ab)’2)(Fig., D). These results for the first time show that TULA-2 serves as a negative regulator of the FcγRIIA pathway and that miR-25 and miR-148a may contribute to HIT susceptibility. Studies are in progress for the translation of these findings in vivo. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
The Sodium/Iodide Symporter (NIS): Characterization, Regulation, and Medical Significance (2003)

The Na(+)/I(-) symporter (NIS) is an integral plasma membrane glycoprotein that mediates active I(-) transport into the thyroid follicular cells, the first step in thyroid hormone biosynthesis. NIS-mediated thyroidal I(-) transport from the bloodstream to the colloid is a vectorial process made possible by the selective targeting of NIS to the basolateral membrane. NIS also mediates active I(-) transport in other tissues, including salivary glands, gastric mucosa, and lactating mammary gland, in which it translocates I(-) into the milk for thyroid hormone biosynthesis by the nursing newborn. NIS provides the basis for the effective diagnostic and therapeutic management of thyroid cancer and its metastases with radioiodide. NIS research has proceeded at an astounding pace after the 1996 isolation of the rat NIS cDNA, comprising the elucidation of NIS secondary structure and topology, biogenesis and posttranslational modifications, transcriptional and posttranscriptional regulation, electrophysiological analysis, isolation of the human NIS cDNA, and determination of the human NIS genomic organization. Clinically related topics include the analysis of congenital I(-) transport defect-causing NIS mutations and the role of NIS in thyroid cancer. NIS has been transduced into various kinds of cancer cells to render them susceptible to destruction with radioiodide. Most dramatically, the discovery of endogenous NIS expression in more than 80% of human breast cancer samples has raised the possibility that radioiodide may be a valuable novel tool in breast cancer diagnosis and treatment.
The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle (2000)

Loss of genomic integrity is a defining feature of many human malignancies, including human papillomavirus (HPV)-associated preinvasive and invasive genital squamous lesions. Here we show that aberrant mitotic spindle pole formation caused by abnormal centrosome numbers represents an important mechanism in accounting for numeric chromosomal alterations in HPV-associated carcinogenesis. Similar to what we found in histopathological specimens, HPV-16 E6 and E7 oncoproteins cooperate to induce abnormal centrosome numbers, aberrant mitotic spindle pole formation, and genomic instability. The low-risk HPV-6 E6 and E7 proteins did not induce such abnormalities. Whereas the HPV-16 E6 oncoprotein has no immediate effects on centrosome numbers, HPV-16 E7 rapidly induces abnormal centrosome duplication. Thus our results suggest a model whereby HPV-16 E7 induces centrosome-related mitotic disturbances that are potentiated by HPV-16 E6.
Phase I study of oral topotecan in hematological malignancies. (2003)

In this Phase I, dose-seeking study, we investigated the dose-limiting toxicities (DLTs) and maximal tolerated dose (MTD) of oral topotecan in patients with hematological malignancies.Patients with myelodysplastic syndromes, myeloproliferative disorders, or relapsed acute myelogenous leukemia were treated with 0.6-1.9 mg/m(2)/day oral topotecan for 5 consecutive days on and 2 days off, for 3 weeks (15 doses/course) followed by 2-4 weeks of rest. The DLTs occurring during the first course of treatment were considered for defining the MTD. Preliminary results of antitumor activity were assessed by examining bone marrow status and peripheral blood cell counts.All 26 patients enrolled in the study were evaluable for toxicity, and 24 patients were evaluable for response. A total of 54 courses were administered. The most frequently reported nonhematological toxicities (percentage of courses) were diarrhea (57%), nausea/vomiting (50%), fatigue (24%), and mucositis (9%). DLTs included grade 3 or 4 nausea/vomiting and diarrhea at 1.9 mg/m(2)/day. The MTD for oral topotecan in patients with hematological malignancies was defined at 1.4 mg/m(2)/day. Hematological toxicity was noted in all 26 patients and with all courses but was not considered dose-limiting. Four (17%) patients achieved a complete response, and six (25%) patients experienced hematological improvement.Protracted administration of oral topotecan is safe and well tolerated in patients with hematological malignancies. At the dose-schedule used, single-agent oral topotecan has a definite activity in patients with myelodysplastic syndrome and acute myelogenous leukemia and warrants further investigation alone or in combination with other agents.
Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine-induced hepatic fibrosis in rats (2004)

Monocyte chemoattractant protein-1 (MCP-1) has been implicated in the process of hepatic inflammation, recruiting monocytes and lymphocytes during liver injury. MCP-1 also activates directly hepatic stellate cells, which play a major role in hepatic fibrosis. However, it remains unclear whether blockage of MCP-1 signaling could prevent hepatic fibrosis in vivo. We evaluated a strategy for anti-MCP-1 gene therapy against hepatic fibrosis by transfecting an amino-terminal deletion mutant, lacking the amino-terminal codons 2 to 8 of the human MCP-1 gene and designated 7ND, into skeletal muscle in a rat experimental model of dimethylnitrosamine (DMN)-induced fibrosis. Anti-MCP-1 gene therapy decreased significantly the occurrence of DMN-induced hepatic fibrosis, evaluated by computed image analysis and by measurement of hydroxyproline contents of the liver, accompanied by a reduction in the expressions of alpha-smooth muscle actin. This treatment also caused a significant decrease in hepatic tissue levels of interleukin (IL)-12 (Th1 cytokine) and an increase in those of IL-10 (Th2 cytokine), indicating a change in the Th1/Th2 cytokine balance in the liver. In conclusion, blockade of MCP-1 after intramuscular transfer of the 7ND gene suppressed hepatic fibrosis, and this strategy may be a useful and feasible gene therapy against hepatic fibrosis.
Zinc and the Msc2 zinc transporter protein are required for endoplasmic reticulum function (2004)

In this report, we show that zinc is required for endoplasmic reticulum function in Saccharomyces cerevisiae. Zinc deficiency in this yeast induces the unfolded protein response (UPR), a system normally activated by unfolded ER proteins. Msc2, a member of the cation diffusion facilitator (CDF) family of metal ion transporters, was previously implicated in zinc homeostasis. Our results indicate that Msc2 is one route of zinc entry into the ER. Msc2 localizes to the ER when expressed at normal levels. UPR induction in low zinc is exacerbated in an msc2 mutant. Genetic and biochemical evidence indicates that this UPR induction is due to genuine ER dysfunction. Notably, we found that ER-associated protein degradation is defective in zinc-limited msc2 mutants. We also show that the vacuolar CDF proteins Zrc1 and Cot1 are other pathways of ER zinc acquisition. Finally, zinc deficiency up-regulates the mammalian ER stress response indicating a conserved requirement for zinc in ER function among eukaryotes.
[The retinoblastoma gene: from its basic understanding as a signal mediator for growth and differentiation to its use in the treatment of cancer]. (1997)

The retinoblastoma gene (RB) plays important roles in the genesis of human cancers. Several pieces of evidence have shown that the retinoblastoma protein (Rb) has dual roles in gating cell cycle progression and promoting cellular differentiation. The molecular mechanisms involved in these roles have been elucidated in some biological systems: Rb sequesters the transcription factors of E2F-1 to regulate entry of cell cycle, but enhances the activities of transcription factors such as C/ EBPs to initiate terminal differentiation. Thus, the Rb protein can serve as a mediator of extracellular signals for growth or differentiation. RB also has a tumor suppression function. Introduction of wild-type RB into human tumor cells deficient for RB suppresses their tumorigenicity in nude mice. Similarly, mice with RB+/- genotypes created by gene knockout methods spontaneously develop melanotrophic tumors with complete penetrance. Immune-competent RB+/- mice benefited significantly from adenovirus-mediated RB gene therapy. The fundamental knowledge of Rb function will allow us to take the next steps toward the use of tumor suppressor genes in the treatment of human cancer.
The potential distribution generated by the fetal heart at the maternal abdomen (1986)

The pathways along which the electrical currents generated by the fetal heart are conducted to the surface of the maternal abdomen are not known. As a consequence, in recording the fetal electrocardiogram (FECG) it is hard to predict where electrodes should be placed in order to obtain an optimal signal. The amplitude of the FECG varies with gestation, and there is a large interindividual variability in the amplitude of the FECG and in the optimal recording site among subjects within the same gestational age. Attempts have been made to explain these phenomena in terms of volume conduction. In this research the complete potential distribution on the maternal abdomen is studied in connection with the geometrical configuration of the electrical source (fetal heart) and the volume conductor (surrounding tissues). For a small group of pregnant women the abdominal FECG is recorded simultaneously in 32 leads during a period of about one minute, once every two weeks from 20 weeks of gestation onwards. A spatial filtering technique which combines information of all 32 leads is used to provide a trigger of the fetal QRS complexes. Using this trigger, an average fetal complex is constructed for each lead by time coherent averaging, after subtraction of the maternal contribution. These average fetal complexes are combined to plot the complete potential distribution generated by the fetal heart at the maternal abdomen (fetal body surface map, FBSM) at any given time instant during the fetal cardiac cycle. At these recording sessions the geometry is carefully quantified by making transverse scans every 2 cm with a compound echo scanner. The contours of fetal head and body, the placenta and the uterus are manually drawn on hardcopies of the video display images. Real time echoscopy is used to support the identification of the geometry. The contours are fed into a computer using a graphics tablet. The three dimensional surfaces of fetus, placenta and uterus are separately represented by a triangulation of the respective contour lines. Figures 5 and 6 show an example of the triangulated representation of the recorded geometry. Figure 7 shows the average fetal complexes of an individual at 26 weeks of gestation, plotted at the site where they have been recorded.(ABSTRACT TRUNCATED AT 400 WORDS)
Sucrose Metabolism in Tubers of Potato (Solanum tuberosum L.) (1992)

Excision of developing potato (Solanum tuberosum L.) tubers from the mother plant, followed by storage at 10 degrees C, resulted in a rapid, substantial decrease in sucrose synthase activity and considerable increases in hexose content and acid invertase activity. A comparison of the response of three genotypes, known to accumulate different quantities of hexoses in storage, showed that both sucrose synthase activity and the extent to which activity declined following excision were similar in all cases. However, there was significant genotypic variation in the extent to which acid invertase activity developed, with tubers accumulating the highest hexose content also developing the highest extractable activity of invertase. Similar effects were found in nondetached tubers when growing plants were maintained in total darkness for a prolonged period. Furthermore, supplying sucrose to detached tubers through the cut stolon surface prevented the decline in sucrose synthase activity. Maltose proved to be ineffective. Western blots using antibodies raised against maize sucrose synthase showed that the decline in sucrose synthase activity was associated with the loss of protein rather than the effect of endogenous inhibitors. Although there were indications that maintaining a flux of sucrose into isolated tubers could prevent the increase in acid invertase activity, the results were not conclusive.
Amino-terminal basic residues of Src mediate membrane binding through electrostatic interaction with acidic phospholipids. (1994)

Membrane targeting of pp60src (Src) is mediated by its myristoylated amino terminus. We demonstrate that, in addition to myristate, six basic residues in the amino terminus are essential for high-affinity binding to the lipid bilayer via electrostatic interaction with acidic phospholipids. Specifically, c-Src was shown to bind 2500-fold more strongly to vesicles composed of the physiological ratio of 2:1 phosphatidylcholine (PC)/phosphatidylserine (PS) than to neutral PC bilayer vesicles. The apparent Kd for binding of c-Src to the PC/PS bilayer was 6 x 10(-7) M. This interaction is sufficiently strong to account for c-Src membrane targeting. Mutants of c-Src in which the amino-terminal basic residues were replaced by neutral asparagine residues exhibited binding isotherms approaching that of wild-type binding to neutral bilayers (apparent Kd of 2 x 10(-3) M). The transforming v-Src and activated c-Src (Y527F) proteins also bound more strongly to PC/PS bilayers (apparent Kd of approximately 1 x 10(-5) M) than to neutral PC bilayers. In vivo experiments with Src mutants confirmed the role of positive charge in mediating membrane binding and cellular transformation.
Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth (2020)

Most tumor cells take up more glucose than normal cells but metabolize glucose via glycolysis even in the presence of normal levels of oxygen, a phenomenon known as the Warburg effect. Tumor cells commonly express the embryonic M2 isoform of pyruvate kinase (PKM2) that may contribute to the metabolism shift from oxidative phosphorylation to aerobic glycolysis and tumorigenesis. Here we show that PKM2 is acetylated on lysine 305 and that this acetylation is stimulated by high glucose concentration. PKM2 K305 acetylation decreases PKM2 enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy (CMA). Acetylation increases PKM2 interaction with HSC70, a chaperone for CMA, and association with lysosomes. Ectopic expression of an acetylation mimetic K305Q mutant accumulates glycolytic intermediates and promotes cell proliferation and tumor growth. These results reveal an acetylation regulation of pyruvate kinase and the link between lysine acetylation and CMA.
Process Analytical Chemistry (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProcess Analytical ChemistryWayne W. Blaser, Robert A. Bredeweg, Richard S. Harner, Mark A. LaPack, Anne. Leugers, Daniel P. Martin, Randy J. Pell, Jerome. Workman, and Larry G. WrightCite this: Anal. Chem. 1995, 67, 12, 47–70Publication Date (Print):June 15, 1995Publication History Published online1 May 2002Published inissue 15 June 1995https://pubs.acs.org/doi/10.1021/ac00108a004https://doi.org/10.1021/ac00108a004research-articleACS PublicationsRequest reuse permissionsArticle Views558Altmetric-Citations53LEARN 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
Most of the substrates of oncogenic viral tyrosine protein kinases can be phosphorylated by cellular tyrosine protein kinases in normal cells. (1988)

The cellular transformation induced by viral tyrosine protein kinases may result from the excessive phosphorylation of the normal polypeptide substrates of endogenous cellular tyrosine kinases, from the phosphorylation of proteins that are not normal substrates of cellular tyrosine protein kinases in uninfected cells, or from the phosphorylation of proteins of each type. To differentiate between these possibilities, antibodies to phosphotyrosine were used with immunoblotting to compare the substrates of p60v-src, the transforming tyrosine protein kinase of Rous sarcoma virus (RSV), with those of cellular tyrosine protein kinases. Specifically, the substrates of p60v-src were compared with those of (1) p60c-src, (2) the tyrosine protein kinases activated by the binding of platelet-derived growth factor and (3) normal cellular tyrosine protein kinases in fibroblasts treated with sodium orthovanadate, an inhibitor of phosphatases. Comparison of the patterns observed on the immunoblots with the pattern of phosphotyrosine-containing proteins isolated by immunoaffinity chromatography with antiphosphotyrosine antibodies demonstrated that the proteins detected by Western blotting did indeed contain phosphotyrosine. Cells transformed by a variant of c-src activated by a single point mutation had an almost identical pattern of tyrosine protein phosphorylation as cells transformed by v-src. The several mutations and carboxyl-terminal substitution that differentiate p60v-src from p60c-src appear therefore to affect the enzymatic activity, but not the polypeptide substrate specificity, of the viral protein. In cells transformed by v-src, 27 of the 35 phosphotyrosine-containing proteins were also phosphorylated on tyrosine in normal uninfected fibroblasts treated with sodium orthovanadate. The phosphorylation of the large majority of the substrates of p60v-src can therefore occur in uninfected cells. Nine of the substrates of p60v-src were also phosphorylated by the viral tyrosine protein kinases encoded by the oncogenes, v-abl, v-fps, v-fes, and v-fgr. Together these data are consistent with the idea that viral tyrosine protein kinases induce transformation largely by intervening in cellular regulatory pathways that are normally controlled by tyrosine protein phosphorylation.
A Prospective Analysis of the Prognostic Value of Biomarkers (FibroTest) in Patients with Chronic Hepatitis C (2006)

The FibroTest measurement of HCV biomarkers has a 5-year prognostic value similar to that of liver biopsy.