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Summary Cyclic AMP acts as an aggregative attractant in Dictyostelium discoideum and possibly in other cellular slime molds. There is good evidence that extra-cellular cyclic AMP is also involved in the control of morphogenetic movement and of differentiation throughout the D. discoideum life cycle. In this paper we review what is known of the cyclic AMP signal, of the responses to it and of cyclic AMP metabolism in D. discoideum.

Lectin-like oxidized LDL receptor-1 (LOX-1), a lectin-like 50-kD receptor for oxidized low-density lipoproteins (ox-LDL), is present primarily on endothelial cells. Oxidatively modified low-density lipoprotein (oxLDL) is implicated in the pathogenesis of atherosclerosis. Endothelial dysfunction is the initial change in the vascular wall that induces morphological changes for atheroma-formation. LOX-1 was identified as the receptor for oxLDL that was thought to be a major cause of endothelial dysfunction. LOX-1 has been demonstrated to contribute not only to endothelial dysfunction, but also to atherosclerotic-plaque formation, hypertension, myocardial infarction and intimal thickening after balloon injury. Studies with transgenic and knockout mouse models have elucidated in part the role of LOX-1 in the pathogenesis of atherosclerosis and cardiac remodeling. Recently, a circulating soluble form of LOX-1(sLOx-1), corresponding solely to its extracellular domain, has been identified in human serum. Circulating levels of sLOX-1 are increased in inflammatory and atherosclerotic conditions and are associated with acute coronary syndrome, with the severity of coronary artery disease, and with serum biomarkers for oxidative stress and inflammation, suggesting that they could be useful marker for vascular injury. Identification and regulation of this receptor and understanding of signal transduction pathways might open new gateways from diagnosis to therapeutics for cardiovascular diseases. Keywords: Atherosclerosis; Endothelial dysfunction; LOX-1; ox-LDL; Signal transduction. DOI: http://dx.doi.org/10.3329/cardio.v3i2.9187 Cardiovasc. J. 2011; 3(2): 169-177

Newly revealed ShcD has been characterized as an intracellular phosphotyrosine adaptor protein belonging to the Src homology and collagen (Shc) family. These scaffolding molecules facilitate receptor-mediated signal transduction through their ability to selectively recognize and bind, via PTB and SH2 domains, to phosphorylated tyrosine residues in the cytoplasmic tails of a variety of activated receptors. A central CH1 domain couples to downstream signaling molecules including Grb2. ShcD is most similar in form to ShcA; however, unlike the latter, its expression in the mouse is localized to the brain and skeletal muscle. Consistent with this observation, we report that human ShcD is able to bind the TrkA neurotrophin receptor responsive to nerve growth factor (NGF). This interaction is similar to that of other Shc proteins in that it is strongly influenced by the TrkA Tyr 490 residue, and results in ShcD phosphorylation. Surprisingly, we find that both the PTB and SH2 domains of ShcD impact its ability to complex with TrkA, in contrast to the PTB-mediated interaction documented for traditional Shc proteins. TrkA binding analyses performed with different ShcD mutants suggest that the contributions of the PTB and SH2 domains supercede simple co operativity, and are in fact reminiscent of auto-regulatory mechanisms. Here we report both the canonical and atypical characteristics of the ShcD / TrkA interaction, including novel proposed models of adaptor-receptor interactions.

The exchange of Ca45 was studied in dog myocardium by means of a newly developed perfusion technique whereby an excised papillary muscle was perfused through its own artery. This makes possible the sequential and simultaneous correlation of ionic flux with ventricular myocardial function with each muscle serving as its own control. Calcium exchange has the following characteristics: (a) The major component of calcium flux is independent of the frequency of contraction. It demonstrates a rapidly equilibrating phase (half-time, 4 to 6 minutes) and a more slowly equilibrating phase with a progressively decreasing rate constant. The flux characteristics of the more rapidly equilibrating compartment are determined by a factor or factors, in addition to simple diffusion, which increase the time required for this compartment to achieve a steady-state with respect to the vascular compartment. (b) A lesser component of exchange is stimulus-rate dependent and is characterized by an alteration in the rate of calcium turnover such that the altered influx: efflux ratio requires 20 to 25 minutes to achieve equilibrium. After this time, despite the higher stimulus rate, there is no evidence of change in total tissue calcium. (c) The initial rate of the transient response is approximately proportional to the change in stimulus rate.

Insulin resistance is associated with a defect in protein tyrosine phosphorylation in the insulin signal transduction cascade. PTPase enzyme dephosphorylates the active form of insulin receptor and thus attenuates its tyrosine kinase activity, therefore the need of potent PTPase inhibitor is there with that intention the QSAR was performed. Quantitative structure-activity relationship (QSAR) has been established on a series of compounds of novel benzofuran biphenyl/naphthalene’s analogs using SYSTAT (Version 7.0) software, for their protein tyrosine phosphatase (PTPase-1B) inhibitor activity, in order to understand the essential structural requirement for binding with the receptor. Among several 2D QSAR models, one for a series was selected on the basis of high correlation coefficient, least standard deviation, & high value of significance for maximum number of subject was considered. The interpreted data signify the essentiality of hydrophobic character at X in the designing of the new PTPase -1B inhibitors of naphthalene analogs but not in biphenyl derivatives as shown in earlier result.

Histamine was bound strongly by heparin in 1% acetic acid, distilled water, or 0.01 N HCl in the absence of cations. The histamine-heparin complex was unstable in salt solutions. Polyamines, in equimolar concentration as histamine, interfered with the ability of heparin to bind histamine. Histamine was bound selectively by heparin in the presence of equimolar amounts of cadaverine, serotonin, and adrenaline. Desulfated heparin failed to bind any histamine. Proteins containing a high percentage of glutamic and aspartic acids showed little histamine-binding activity. A hypothesis for the histamine-binding mechanism of the mast cell and the release of histamine by Compound 48–80 is presented.

Insulin resistance is associated with a defect in protein tyrosine phosphorylation in the insulin signal transduction cascade. Protein tyrosine phosphatase (PTPase) enzyme dephosphorylates the active form of insulin receptor and thus attenuates its tyrosine kinase activity, therefore the need of potent PTPase inhibitor is there with that intention the Quantitative structure-activity relationship QSAR was performed. QSAR has been established on a series of compounds of novel sulfono biphenyl analogs using SYSTAT (Version 7.0) software, for their PTPase-1B inhibitor activity, in order to understand the essential structural requirement for binding with the receptor. Among several 2D QSAR models, one for a series was selected on the basis of high correlation coefficient, least standard deviation, & high value of significance for maximum no. of subject was considered. The interpreted data signify the essentiality of Benzofuran ring in the designing of the new PTPase -1B inhibitors and any substitution on the biphenyl and sulfonyl phenyl is going to decrease its activity. Key words: QSAR, PTPase-1B inhibitor, Sulfono biphenyl analog. Dhaka Univ. J. Pharm. Sci. 6(2): 77-80, 2007 (December)

Copyright © 2015 The Korean Society of Phycology 147 http://e-algae.kr pISSN: 1226-2617 eISSN: 2093-0860 The fucose containing polymer (FCP) rich fraction of Ascophyllum nodosum (L.) Le Jol. protects Caenorhabditis elegans against Pseudomonas aeruginosa by triggering innate immune signaling pathways and suppression of pathogen virulence factors Saveetha Kandasamy, Wajahatullah Khan, Garima Kulshreshtha, Franklin Evans, Alan T. Critchley, J. H. Fitton, Damien N. Stringer, Vicki-Anne Gardiner and Balakrishnan Prithiviraj* Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, P.O. Box 550, Truro, NS B2B 5E3, Canada Basic Sciences Department, College of Science and Health Professions (COSHP), King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), P.O. Box 22490, Riyadh 11426, Saudi Arabia Acadian Seaplants Limited, 30 Brown Avenue, Dartmouth, NS B3B 1X8, Canada Marinova Pty Ltd., 249, Kennedy Drive, Cambridge, Tasmania 7170, Australia

(1) The influence of various anions on activity of gustatory receptors was investigated by adapting the tongue of a frog to modified anion-Ringer, in which all Cl was substituted for Br, I, NO3, SCN, SO4 and H2PO4.(2) Immediately after exchange of normal Ringer with one of these modified anion-Ringers the response of the tongue was not appreciably changed in its threshold to various taste solutions and in its magnitude.(3) 1-2 hours after exchange of the bathing medium the response of the tongue to salt solutions was reduced and its threshold was raised, while the threshold concentration of sodium salts to depress water response was raised. The sensitivity of the tongue to other kinds of taste stimuli was not very much modified compared with that to salts.(4) Sooner or later all the sensitivities of the tongue to various taste stimuliwere reduced or abolished.(5) The effects of anions mentioned above depended on the anions used; the effectiveness was in the order of SCN>NO3>I>Br. Sulphate had no marked effects on gustatory receptors, while their response was readily abolished in phosphate Ringer.(6) The sensitivity of the tongue was rapidly restored when the phosphate Ringer immersing the tongue was replaced by normal Ringer, whereas the effect of other monovalent anions was irreversible.(7) The following hypothesis was presented on the mechanism of salt reception and of the depressing action of salts on water response: Entry of cations inside gustatory receptor from the exterior is the initial step for the initiation of salt receptor activity and withdrawal of the intracellular potassium ions may initiate water response, which is prevented by exsistence of a sufficient amount of cations permeable to the membrane outside the cell. Anions reduce the permeability of the membrane to cations in the order of SCN>NO3>I>Br> Cl, or alternatively the cellular potassium reduces in the presence of SCN, NO3, Ior Br.

SummaryRabbit platelets decarboxylate C14 L-histidine and bind the resulting C14 histamine in stable condition. Soluble histi-dine decarboxylase has been prepared from rabbit platelets and a study of its properties reported.

Endogenous somatostatin shows anti-secretory effects in both physiological and pathological settings, as well as inhibitory activity on cell growth. Since somatostatin is not suitable for clinical practice, researchers developed synthetic somatostatin receptor ligands (SRLs) to overcome this limitation. Currently, SRLs represent pivotal tools in the treatment algorithm of neuroendocrine tumors (NETs). Octreotide and lanreotide are the first-generation SRLs developed and show a preferential binding affinity to somatostatin receptor (SST) subtype 2, while pasireotide, which is a second-generation SRL, has high affinity for multiple SSTs (SST5 > SST2 > SST3 > SST1). A number of studies demonstrated that first-generation and second-generation SRLs show distinct functional properties, besides the mere receptor affinity. Therefore, the aim of the present review is to critically review the current evidence on the biological effects of SRLs in pituitary adenomas and neuroendocrine tumors, by mainly focusing on the differences between first-generation and second-generation ligands.

A bioassay for the calcium mobilizing fraction of parathyroid gland extract has been developed using intact rats. This assay is based on the ability of such an extract to promote the withdrawal of radiocalcium from the skeletons of rats which had been injected with radiocalcium at least 40 days before. This pro-cedure meets the requirements of a satisfactory assay in that: (a) The response increases with increasing dose, (b) The response is linear over a particular range of doses when expressed as log dose, (c) The variation among responses at a single dose level is independent of the magnitude of the average response at that dose. Using this technique as little as 4 units of U.S.P. Parathyroid Extract (Lilly)/100 gm. body weight can be detected in the intact rat. The calcium mobilizing fraction is effective in the rat via the intravenous, intraperitoneal and subcutaneous routes but not by mouth

In some patients complaining of chronic fatigue such as those suffering from the chronic fatigue syndrome (CFS), no underlying physical cause can be clearly identified and they typically present a normal thyroid function. Several studies indicate a dysregulation in the type I interferons (IFN-alpha/beta) pathway in CFS resulting in a sustained upregulation of 2('),5(')-oligoadenylate synthetases (2-5OAS). Likewise, patients treated with IFN-alpha/beta usually complain of severe fatigue as a limiting side effect. Beside the 2-5OAS, IFN-alpha/beta induce also the expression of three closely related proteins of unknown function termed the 2-5OAS-like (2-5OASL) proteins. The amino acid sequences of the 2-5OASL proteins display 96% identity with the partial sequence of the thyroid receptor interacting protein (TRIP) 14, further contain two typical thyroid hormone receptor (TR) coregulator domains and feature two ubiquitin C-terminal domains. From these observations, we raise the hypothesis that the 2-5OASL proteins are TRIPs capable of, respectively, repressing TR transactivation and/or signaling the receptor for destruction by the proteasome. Such molecular mechanisms could explain the development of a clinical hypothyroid state in presence of a normal thyroid function.

A simple test to determine whether insulin requiring diabetic patients may benefit by alteration of species source of insulin is described. Close correlation between insulin responsiveness and relative beef/pork/dalanated pork insulin binding capacity was found in all patients investigated.