1 We have studied the effects of muscarinic cholinoceptor agonists and specific antagonists on both phasic activity and basal tone of the isolated intravesical ureter of the pig by means of isometric techniques in vitro. 2 Acetylcholine in the presence and absence of physostigmine increased both phasic activity and basal tone of ureteral strips in a concentration-dependent manner. Moreover carbachol, methacholine and oxotremorine-M increased both contractile parameters while bethanechol and McN-A-343 evoked only increases in tone without affecting the frequency of the phasic contractions. 3 The nicotinic receptor blocker, hexamethonium (106-1 0-4 M), failed to modify the contractions evoked by a single dose of carbachol (10-5 M), whilst the muscarinic antagonist, atropine inhibited both phasic and tonic responses.4 The muscarinic M, (pirenzepine), M2 (AF-DX 116 and methoctramine), M3 (4-DAMP, HHSiD and p-F-HHSiD), and putative M4 receptor (tropicamide) antagonists significantly reversed increases in both frequency of phasic activity and baseline tone induced by a submaximal dose of carbachol (10-5 M). The pICs values for inhibition of the induced phasic activity were: atropine (10.16)>4-DAMP (9.12)> HHSiD (8.22) = methoctramine (7.98) = p-F-HHSiD (7.88> tropicamide (7.62) = pirenzepine (7.53) = AF-DX 116 (7.45) and for inhibition of basal tone were: atropine (10.73)>4-DAMP (9.32)> HHSiD (8.65) = pirenzepine (8.43) = p-F-HHSiD (8.38)> methoctramine (7.79)> tropicamide (7.53)>AF-DX 116 (7.04). 5 The antagonist profile indicates that an M, receptor mediates the tonic response while the phasic activity could involve either both M2 and M3 or an M4 muscarinic receptor. These results suggest that different muscarinic receptor subtypes mediate the phasic and tonic contractile activity induced by a submaximal concentration of carbachol in the porcine intravesical ureter.

The papers in this Special Issue raise a number of relevant and important questions, of which three particularly deserve comment. Are indicators reductionist? They might be indeed, both regarding the process of defining them and in their use, which is why it is essential that each be based on a deep and sufficient knowledge of the phenomenon concerned. The human development index illustrates both the pitfalls and potential of global indicators. Are there dark forces behind the selection of indicators? The agreement of the 2030 Agenda was the outcome of a political process that led to a negotiated consensus accomplished by the Open Working Group. In determining the indicators, the Inter‐Agency and Expert Group on Sustainable Development Goal Indicators (IAEG SDG) was asked for a simple and robust framework which would not affect the political equilibrium reached in the Open Working Group (OWG); no easy task. Is the IAEG SDG an arcane bureaucratic entity? In the face of this immensely challenging task, it has sought a balance between what is feasible in the short term and what is required in the long term. The IAEG SDG has become a space for open and constructive dialog between national statistical offices and international agencies.

The stereospecific L-2-haloacid dehalogenase DehCI from Pseudomonas CBS3 was tagged with a peptide tail containing six histidines and overexpressed in Escherichia coli. The His-tagged protein was purified after a single-step affinity chromatography on Zn(2+)-chelating sepharose. The activity of the modified protein was tested after immobilization on Zn(2+)-chelating sepharose and on covalently bound acrylic polymer. Both immobilization systems were used for the transformation of racemic 2-chloropropionic acid into D-lactate and D-chloropropionic acid. Although immobilization on chelating sepharose produced a limited increase in stability, covalent immobilization on acrylic polymer significantly extended the operational temperature and pH range of the enzyme: up to 60% of activity was recovered at either 80 degrees C or pH 11, whereas no activity could be detected under these conditions in the soluble or chelate-immobilized enzyme. Both forms of immobilization extended the enzyme effective storage periods, and after 10 cycles of reutilization, 70% and 20% of the initial activity was recovered in the covalent- and chelate-immobilized enzyme, respectively.

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