Tubulin and its assembly promoting factor(s) during maturation of avian erythrocytes

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Role of B-ring of colchicine in its binding to Zn(II)-induced tubulin-sheets

Colchicine-tubulin dimer complex, a potent inhibitor of normal microtubule assembly undergoes extensive self-assembly in the presence of 1 X 10-4 M zinc sulphate. Polymers assembled from colchicine-tubulin dimer complexes are sensitive to cold. Although colchicine can be accomodated within the polymeric structure, the drug cannot bind to tubulin subunits in the intact polymers. This is evidenced by the fact that (a) the colchicine binding activity of tubulin is lost when allowed to polymerize with zinc sulphate, (b) the loss in colchicine binding could be prevented by preincubation of tubulin with 1 X 10-3 M CaCl2 or 1 X 10-5 M vinblastine sulphate and finally (c) no loss in colchicine binding activity is found when tubulin is kept at a concentration far below the critical concentration for polymerization. Unlike colchicine, its B-ring analogues desacetamido colchicine (devoid of the B-ring subtituent) and 2-methoxy-5-(2', 3', 4'-trimethoxyphenyl) tropone (devoid of the B-ring) can bind to tubulin subunits in the intact polymers. Thus we conclude that the colchicine binding domain on the tubulin molecule is mostly (if not completely) exposed in the Zn(II) -induced polymers and the B-ring substituent plays a major role in determining the binding ability of a colchicine analogue to tubulin in the intact Zn(II) -induced sheets

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Cardiovascular effects of serotonin on the pigeon Columba livia

The effect of serotonin on the blood pressure and the heart rate of the pigeon Columba livia was investigated in anaesthetised condition. The effect of histamine was also investigated to understand the mechanism of action of serotonin. Serotonin and histamine were both depressors. Serotonin produced bradycardia while histamine produced tachycardia. Atropine treatment reversed the serotonin-induced depressor response but only partially blocked the histamine-induced fall in blood pressure. Atropine treatment completely abolished the serotonin-induced bradycardia but partially inhibited the histamine-induced tachycardia. A reflex vagal activity and a direct vasoconstrictor activity were proposed on the action of serotonin

Magnetic-field-induced intensification of a forbidden A<SUB>1</SUB> &#8594; A<SUB>1</SUB> transition in the trigonal Na<SUB>3</SUB>Pr(C<SUB>4</SUB>H<SUB>4</SUB>O<SUB>5</SUB>)<SUB>3</SUB>&#183;2NaClO<SUB>4</SUB>&#183;6H<SUB>2</SUB>O crystal

The mixing of states induced by a high magnetic field is exploited to intensify and locate a forbidden A1 &#8594; A1 transition in Na3Pr(C4H4O5)3&#183;2NaClO4&#183;6H2O single crystal

Zinc-induced self-assembly of goat brain tubulin: some novel aspects

Unlike normal microtubule assembly, the in vitro assembly of DEAE-purified goat brain tubulin in presence of Zn(II) is not inhibited by suprastoichiometric concentrations of antimicrotubular drugs like colchicine and podophyllotoxin. However, assembly in the presence of Zn(II) is inhibited by vinblastine. Vinblastine sensitivity of the assembly process depends on the Mg(II) concentration in the assembly medium. Like normal microtubules, Zn(II)-induced polymers are sensitive to cold. The polymers assembled in presence of Zn(II) are readily disassembled on treatment with Zn(II)-chelators like EDTA or o-phenanthroline, indicating that the binding of Zn(II) to tubulin is essential for maintaining the polymeric structure. MAPs, Microtubule-associated proteins; MES, 2-(N-Morpholino) ethane sulfonic acid; MT, Microtubule; CD, Colchicine-tubulin dimer complex; GTP, Guanosine-5'-triphosphate; SDS, Sodium dodecyl sulphate; EDTA, Ethylenediamine-tetraacetic acid; Buffer A, 0.1 M MES (pH 6.4), 0.5 mM MgCl2, 1 mM GTP; Buffer B, 4 M glycerol in buffer A

Charge effect on the colchicine binding-site of tubulin

Poly (L-lysine) was found to enhance colchicine binding activity of brain tubulin to a several folds. Bases of biological interests that were tested and found to be inactive were spermine, spermidine and even L-lysine. Part of this enhance binding is due to the increase in the affinity of colchicine-tubulin interaction in the presence of poly (L-lysine). Moreover, poly (L-lysine) stabilized the colchicine binding site of tubulin against thermal denaturation