Galaxy bulges and their massive black holes: a review

With references to both key and oft-forgotten pioneering works, this article starts by presenting a review into how we came to believe in the existence of massive black holes at the centres of galaxies. It then presents the historical development of the near-linear (black hole)-(host spheroid) mass relation, before explaining why this has recently been dramatically revised. Past disagreement over the slope of the (black hole)-(velocity dispersion) relation is also explained, and the discovery of sub-structure within the (black hole)-(velocity dispersion) diagram is discussed. As the search for the fundamental connection between massive black holes and their host galaxies continues, the competing array of additional black hole mass scaling relations for samples of predominantly inactive galaxies are presented.Comment: Invited (15 Feb. 2014) review article (submitted 16 Nov. 2014). 590 references, 9 figures, 25 pages in emulateApJ format. To appear in "Galactic Bulges", E. Laurikainen, R.F. Peletier, and D.A. Gadotti (eds.), Springer Publishin

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Purification And Characterization Of A Low-molecular-weight Bovine Kidney Acid Phosphatase

A relative low molecular mass bovine kidney acid phosphatase was purified 1,640-fold to homogeneity, with 7% recovery. The purified enzyme (specific activity 100 μmol min-1 mg-1) was electrophoretically homogeneous with a relative molecular mass of 17.8 kDa, as determined by SDS-polyacrylamide gel electrophoresis. A broad pH optimum of 4.0-5.5 and a maximal enzyme activity at 60°C were determined for the p-nitrophenyl phosphate hydrolysis. Apparent Km values of 0.14 mM, 0.4 mM, 0.3 mM and 7.9 mM were obtained, at 37°C and pH 5.0, for the best substrates p-nitrophenyl phosphate, β-naphtyl-phosphate, flavin mononucleotide and tyrosine-phosphate, respectively. The enzyme activity was enhanced by guanosine but inhibited by ZnCl2 and CuSO4, p-cloromercuribenzoate and ammonium molybdate. Vanadate (Ki 0.47 μM), pyridoxal 5′-phosphate (Ki 2.2 μM), inorganic phosphate (Ki 0.77 mM) are competitive inhibitors. Both glycerol and methanol increased significantly the acid phosphatase activity, acting as good phosphate acceptors in the transphosphorylation reaction.694451460Araújo, P.S., Mies, V., Miranda, O., Subcelular distribution of low-molecular-weight acid phosphatases (1976) Biochim. Biophys. Acta, 452, pp. 121-130Baldijão, C.E.M., Guija, E., Bittencourt, H.M.S., Chaimovich, H., Steady state kinetics and effects of inhibitors on acid phosphatase from bovine brain (1975) Biochim. Biophys. Acta, 391, pp. 316-325Bhargava, R., Sachar, R.C., Induction of acid phosphatase in cotton seedlings enzyme purification, subunit structure and kinetic properties (1987) Phytochemistry, 26, pp. 1293-1297Baxter, J.H., Suelter, C.H., Resolution of the low-molecular-weight acid phosphatase in avian pectoral muscle into distinct enzyme forms (1985) Arch. Biochem. Biophys., 239, pp. 29-37Berti, A., Rigacci, S., Raugei, G., Degl'innocenti, D., Ramponi, G., Inhibition of cellular esponse to platelet-derived growth factor by low Mr phosphotyrosine protein phosphatase overexpression (1994) FEBS Lett., 349, pp. 7-12Camici, G., Manao, G., Cappugi, G., Modesti, A., Stefani, M., Ramponi, G., The complete amino acid sequence of the low molecular weight cytosolic acid phosphatase (1989) J. Biol. Chem., 264, pp. 2560-2567Chaimovich, H., Nome, F., Purification and properties of an acid phosphatase from bovine brain (1970) Arch. Biochem. Biophys., 139, pp. 9-16Chernoff, J., Li, H.C., A major phosphotyrosyl-protein phosphatase from bovine heart is associated with a low-molecular-weight acid phosphatase (1985) Arch. Biochem. Biophys., 240, pp. 135-145Chiarugi, P., Marzocchini, R., Raugei, G., Pazzagli, C., Berti, A., Camici, G., Manao, G., Ramponi, G., Differential role of four cysteines residues on the activity of a low Mr phosphotyrosine protein phosphatase (1992) FEBS Lett., 310, pp. 9-12Chiarugi, P., Cirri, P., Camici, G., Manao, G., Fiaschi, T., Raugei, G., Cappugi, G., Ramponi, G., The role of His66 and His72 in the reaction mechanism of bovine low-Mr phosphotyrosine protein phosphatase (1994) Biochem. J., 298, pp. 427-433Chiarugi, P., Cirri, P., Raugei, G., Camici, G., Dolfi, F., Berti, A., Ramponi, G., PDGF receptor as a specific in vivo target for low Mr phosphotyrosine protein phosphatase (1995) FEBS Lett., 372, pp. 49-53Davis, J.P., Zhou, M.-M., Van Etten, R.L., Kinetic and site directed mutagenesis studies of the cysteine residues of bovine low molecular weight phosphotyrosyl protein phosphatase (1994) J. Biol. Chem., 269, pp. 8734-8740De-Kundu, P., Banerjee, A.C., Multiple forms of acid phosphatase from seedlings axes of Vigna radiata (1990) Phytochemistry, 29, pp. 2825-2828Dissing, J., Svensmark, O., Human red cell acid phosphatase: Purification and properties of the A, B and C isoenzymes (1990) Biochim. Biophys. Acta, 1041, pp. 232-242Dissing, J., Johnsen, A.H., Human red cell acid phosphatase (ZCP1): The primary structure of two pairs of isoenzymes encoded by the ACP1*A and ACP1*C alleles (1992) Biochim. Biophys. Acta, 1121, pp. 261-268Dissing, J., Rangaard, B., Christensen, U., Activity modulation of the fas and slow isoenzymes of human cytosolic low-molecular-weight acid phosphatase (ACP1) by purines (1993) Biochim. Biophys. Acta, 1162, pp. 275-282Dixon, M., Webb, E.C., (1979) Enzymes, 3rd Edn, p. 1116. , Academic Press, New YorkDuff, S.M.G., Sarath, G., Plaxton, W.C., The role of acid phosphatases in plant phosphorus metabolism (1994) Physiol. Plant., 90, pp. 791-800Fauman, E.B., Saper, M.A., Structure and function of the protein tyrosine phosphatase (1996) Trends Biochem. Sci., 21, pp. 413-417Fuchs, K.R., Shekels, L.L., Bernlohr, D.A., Analysis of the ACP1 gene product: Classification as an FMN phosphatase (1992) Biochem. Biophys. Res. Commun., 189, pp. 1598-1605Fujimoto, S., Urata, Y., Nakagawa, T., Ohara, A., Characterization of intermediate-molecular-weight acid phosphatase from bovine kidney cortex (1984) J. Biochem., 96, pp. 1079-1088Galka, M., Dziembor-Gryszkiewicz, E., Kos, S., Ostrowski, W., Properties of low-molecular-weight acid phosphatases isolated from cytosol and chromatin of rat liver (1980) Acta Biochim. Pol., 27, pp. 281-293Hollander, V.P., Acid phosphatases (1971) The Enzymes, pp. 449-455. , BOYER, P. D. ed. New York, Academic PressKlarlund, J.K., Transformation of cells by an inhibitor of phosphatases acting on phosphotyrosine in proteins (1985) Cell, 41, pp. 707-717Kumagai, A., Dunphy, W.G., The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system (1991) Cell, 64, pp. 903-914Logan, T.M., Zhou, M.-M., Nettesheim, D.G., Meadows, R.P., Van Etten, R.L., Fesik, S.W., Solution structure of a low molecular weight protein tyrosine phosphatase (1994) Biochemistry, 33, pp. 11087-11096Lowry, O.H., Lopez, J., The determination of inorganic phosphate in the presence of labile phosphate esters (1946) J. Biol. Chem., 162, pp. 421-424Lowry, O.H., Rosebrough, N., Farr, A., Randal, R., Protein measurement with the phenol reagent (1951) J. Biol. Chem., 193, pp. 265-275Panara, F., Angiolillo, A., Fagotti, A., Di Rosa, I., Francesca, S., Pascolini, R., Acid phosphatases in mammalian tissues. 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NMR, 22, pp. 81-94Su, X.-D., Taddei, N., Stefani, M., Ramponi, G., Nordlund, P., The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase (1994) Nature, 370, pp. 575-578Taga, E.M., Van Etten, R.L., Human liver acid phosphatase: Purification and properties of a low molecular weight isoenzymes (1982) Arch. Biochem. Biophys., 214, pp. 505-515Tantzaki, M.M., Bittencourt, H.M.S., Chaimovich, H., Activation of low molecular weight acid phosphatase from bovine brain by purines and glycerol (1976) Biochim. Biophys. Acta, 485, pp. 116-123Ullah, A.H.J., Gibson, D.M., Purification and characterization of acid phosphatase from cotyledons of germinating soybean seeds (1988) Arch. Biochem. 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Repair of the anophthalmic cavity of rats with synthetic hydroxyapatite

We placed spheres of synthetic hydroxyapatite (calcium chloride combined with sodium phosphate) in the eviscerated or enucleated orbital cavity of rats in order to evaluate the biocompatibility of this material with the orbital cavity. The study was conducted on 50 albino rats, 25 of which were submitted to enucleation and 25 to evisceration of one eye. The animals were sacrificed 7, 15, 21, 30 and 60 days after surgery and the orbital content was submitted to histopathological examination. A reaction of the young granulation tissue type was observed first. The hydroxyapatite was gradually surrounded by a granulomatous macrophage inflammatory response and covered with dense connective tissue that formed a sort of" mesh" septating and supporting progressively smaller blocks of the substance. The same type of reaction was observed in the enucleated and eviscerated cavities. We conclude that synthetic hydroxyapatite is an inert nonallergenic material which is appropriate for volume replacement in the anophthalmic cavit

Repair of the anophthalmic cavity of rats with synthetic hydroxyapatite

We placed spheres of synthetic hydroxyapatite (calcium chloride combined with sodium phosphate) in the eviscerated or enucleated orbital cavity of rats in order to evaluate the biocompatibility of this material with the orbital cavity. The study was conducted on 50 albino rats, 25 of which were submitted to enucleation and 25 to evisceration of one eye. The animals were sacrificed 7, 15, 21, 30 and 60 days after surgery and the orbital content was submitted to histopathological examination. A reaction of the young granulation tissue type was observed first. The hydroxyapatite was gradually surrounded by a granulomatous macrophage inflammatory response and covered with dense connective tissue that formed a sort of" mesh" septating and supporting progressively smaller blocks of the substance. The same type of reaction was observed in the enucleated and eviscerated cavities. We conclude that synthetic hydroxyapatite is an inert nonallergenic material which is appropriate for volume replacement in the anophthalmic cavit

Synergistic Effects of Methotrexate and Suberoylanilide Hydroxamic Acid in Triggering Apoptosis of Chronic Myeloid Leukemia Cells

In this study, we have investigated the effects of suberoylanilide hydroxamic acid (SAHA) against chronic myeloid leukemia (CML) cells in combination studies with methotrexate (MTX), which is a dihydrofolate reductase inhibitor used in combination therapy with other agents or alone. Combination of synergistic ratios of MTX and SAHA led to apoptotic cell death of CML cells via PARR cleavage, cytochrome c release and ROS increase in vitro. We suggest that combination of MD( and SAHA may minimize the toxicity and side effects of SAHA treatment, thus providing lower amounts of each drug in CML treatment

Purification And Kinetic Properties Of A Castor Bean Seed Acid Phosphatase Containing Sulfhydryl Groups

An acid phosphatase (EC 3.1.3.2) has been identified and purified from castor bean (Ricinus communis L., IAC-80) seed through sulphopropyl (SP)-Sephadex, diethylaminoethyl (DEAE)-Sephadex, Sephacryl S-200, and Concanavalin A-Sepharose chromatography. The enzyme was purified 2000-fold to homogeneity, with a final specific activity of 3.8 μkat mg-1 protein. The purified enzyme revealed a single diffuse band with phosphatase activity on nondenaturing polyacrylamide gel electrophoresis, at pH 8.3. The relative molecular mass, determined by high-performance liquid chromatography (HPLC), was found to be 60 kDa. The acid phosphatase had a pH optimum of 5.5 and an apparent K(m) value for p-nitrophenylphosphate of 0.52 mM. The enzyme-catalyzed reaction was inhibited by inorganic phosphate, fluoride, vanadate, molybdate, p-chloromercuribenzoate (pCMB), Cu2+ and Zn2+. The strong inhibition by pCMB, Cu2+ and vanadate suggests the presence of sulfhydryl groups essential for catalysis. The castor bean enzyme also recognized tyrosine-phosphate and inorganic pyrophosphate (PP(i)) as substrate. The highest specificity constant (V(max)/K(m)) was observed with PP(i), making it a potential physiological substrate.1072151158Barrett-Lennard, E.G., Robson, A.D., Greenway, H., Effect of phosphorus deficiency and water deficit on phosphatase activities from wheat leaves (1982) J Exp Bot, 33, pp. 682-693Basha, S.M., Purification and characterization of an acid phosphatase from peanut (Arachis hypogaea) seed (1984) Can J Bot, 62, pp. 385-391Biswas, T.K., Cundiff, C., Multiple forms of acid phosphatase in germinating seeds of Vigna sinensis (1991) Phytochemistry, 30, pp. 2119-2125Ching, T.M., Lin, T., Metzger, R.J., Purification and properties of acid phosphatase from plump and shriveled seeds of Triticale (1987) Plant Physiol, 84, pp. 789-795Conrad, F., Rüdiger, H., The lectin from pleurotus ostreatus: Purification, characterization and interaction with a phosphatase (1994) Phytochemistry, 30, pp. 277-283Duff, S.M.G., Lefebvre, D.D., Plaxton, W.C., Purification, characterization and subcellular localization of an acid phosphatase from Brassica nigra suspension cells. Comparison with phosphoenolpyruvate phosphatase (1991) Arch Biochem Biophys, 286, pp. 226-232Duff, S.M.G., Sarath, G., Plaxton, W.C., The role of acid phosphatases in plant phosphorus metabolism (1994) Physiol Plant, 90, pp. 791-800Ferreira, C.V., Granjeiro, J.M., Taga, E.M., Aoyama, H., Multiple forms of soybean seeds acid phosphatases (1998) Plant Physiol Biochem, 36, pp. 487-494Gellatly, K., Moorhead, G.B.G., Duff, S.M.G., Lefebvre, D.D., Plaxton, W.C., Purification and characterization of a potato tuber acid phosphatase having significant phosphotyrosine phosphatase activity (1994) Plant Physiol, 106, pp. 223-232Guo, J., Pesacreta, J.C., Purification and characterization of an acid phosphatase from the bulb of Allium cepa L., var. Sweet Spanish (1997) J Plant Physiol, 151, pp. 520-527Haraguchi, H., Yamauchi, D., Minamikawa, T., Multiple forms of acid phosphatase in cotyledons of Vigna mungo seedlings: Immunological detection and quantitation (1990) Plant Cell Physiol, 31, pp. 917-923Hartree, E.F., Determination of proteins: A modification of the Lowry method that gives a linear photometric response (1972) Anal Biochem, 48, pp. 422-427Hollander, V.P., Acid phosphatases (1971) The Enzymes, 4, pp. 449-498. , Boyer PD (ed) A. Academic Press, New York, NYHuyer, G., Liu, S., Kelly, J., Moffat, J., Payette, P., Kennedy, B., Tsaprailis, G., Ramachandran, C., Mechanism of inhibition of protein tyrosine phosphatase by vanadate and pervanadate (1997) J Biol Chem, 272, pp. 843-851Kawarasaki, Y., Nakano, H., Yamane, T., Purification and some properties of wheat germ acid phosphatase (1996) Plant Sci, 119, pp. 67-77Kruzel, M., Morawiecka, B., Acid phosphatase of potato tubers (Solanum tuberosum L.). Purification, properties, sugar and amino acid composition (1982) Acta Biochim Pol, 29, pp. 321-330Lebansky, B.R., McKnight, T.D., Griffing, L.R., Purification and characterization of a secreted purple phosphatase from soybean suspension cultures (1992) Plant Physiol, 99, pp. 391-395Lowry, O.H., Lopez, J.A., The determination of inorganic phosphate in the presence of labile phosphate esters (1945) J Biol Chem, 162, pp. 421-424Pan, S., Characterization of multiple acid phosphatase in salt, stressed spinach leaves (1987) Aust J Plant Physiol, 14, pp. 117-124Panara, F., Pasqualini, S., Antonielli, M., Multiple forms of barley root acid phosphatase: Purification and some characteristics of the major cytoplasmic isoenzyme (1990) Biochim Biophys Acta, 1037, pp. 73-80Park, H.S.C., Van Etten, R.L., Purification and characterization of homogeneous sunflower seed acid phosphatase (1986) Phytochemistry, 25, pp. 351-357Penheiter, A.R., Duff, S.M.G., Sarath, G., Soybean root nodule acid phosphatase (1997) Plant Physiol, 114, pp. 597-604Polya, G.M., Wetlenhall, R.E.H., Rapid purification and N-terminal sequencing of a potato tuber cyclic nucleotide binding phosphatase (1992) Biochim Biophys Acta, 1159, pp. 179-184Reisfeld, R.A., Lewis, V.J., Williams, D.E., Disk electrophoresis of basic proteins and peptides on polyacrylamide gels (1962) Nature, 195, pp. 281-283Staswick, P.E., Papa, C., Huang, J., Rhee, Y., Purification of the major soybean leaf acid phosphatase that is increased by seed. Pod removal (1994) Plant Physiol, 104, pp. 49-57Swarup, G., Cohen, S., Garbers, D.L., Inhibition of membrane phosphotyrosyl protein phosphate activity by vanadate (1982) Biochem Biophys Res Commun, 107, pp. 1104-1109Taga, E.M., Van Etten, R.L., Human liver acid phosphatase: Purification and properties of a low, molecular weight isoenzyme (1982) Arch Biochem Biophys, 214, pp. 505-515Ullah, A.H.J., Gibson, D.M., Purification and characterization of acid phosphatase from cotyledons of germinating soybean seeds (1988) Arch Biochem Biophys, 260, pp. 514-520Yumagata, H., Tanaka, K., Kasai, Z., Purification and characterization of acid phosphatase in aleurone particles of rice grains (1980) Plant Cell Physiol, 21, pp. 1449-1460Yupsanis, T., Eleftheriou, P., Pantazaki, A., Georgatsos, J.G., Multiplicity of metal independent protein phosphatases of germinated alfafa seeds (1993) J Plant Physiol, 141, pp. 257-26