Jose Santiago

Responses to adrenomedullin, a newly discovered hypotensive peptide isolated from human pheochromocytoma cells, and the carboxy terminal 15–52 (adrenomedullin-(15–52)) and 22–52 (adrenomedullin-(22–52)) amino acid fragments of adrenomedullin were investigated in the mesenteric vascular bed of the cat. Under constant flow conditions, injections of adrenomedullin, adrenomedullin-(15–52), and calcitonin gene-related peptide (CGRP) in doses of 0.003–1 nmol into the perfused superior mesenteric artery caused significant dose-related decreases in mesenteric arterial perfusion pressure. Mesenteric vasodilator responses to adrenomedullin and adrenomedullin-(15–52) were similar in magnitude and duration, while vasodilator responses to CGRP were greater in magnitude and longer in duration than those produced by adrenomedullin or adrenomedullin-(15–52) when these agents were injected in doses of 0.1–1 nmol. Adrenomedullin-(22–52) caused no significant change in mesenteric arterial perfusion pressure when injected in doses up to 10 nmol. These results suggest that amino acids 15–52 and the six-membered ring structure of adrenomedullin are important for the expression of vasodilator activity in the mesenteric vascular bed of the cat.

methyl ester has been reported to have muscarinic receptor blocking activity whereas the nonesterified analog does not bind to muscarinic receptors. The present study was, therefore, undertaken to compare the inhibitory effects of methyl ester with those of on baseline tone and on vasodilator responses to acetylcholine, bradykinin, and substance P in the mesenteric vascular bed of the cat under constant flow conditions. Administration of methyl ester and in doses of 100 mg/kg i.v. increased baseline tone in the mesenteric vascular bed and inhibited mesenteric vasodilator responses to acetylcholine, bradykinin, and substance P. The increase in mesenteric arterial perfusion pressure and the decrease in vasodilator responses to the three endothelium-dependent vasodilator agents following administration of methyl ester and did not differ significantly. The nitric oxide synthase inhibitors did not attenuate vasodilator responses to agents that induce vasodilation by nonendothelium-dependent mechanisms and enhanced responses to the nitrovasodilators. Atropine blocked vasodilator responses to acetylcholine but did not alter responses to bradykinin or substance P. The similarity inthe inhibitory effects of methyl ester and on responses to acetylcholine, bradykinin, and substance P suggest that the L-arginine analog, , as well as the methyl ester of , are useful probes for studying endothelium-dependent vasodilator responses in the mesenteric vascular bed of the cat.

An immense variety of fish may, on occasions, aggregate around or beassociated with floating structures such as drifting algae, jelliedzooplankton, whales, floats or anchored fish aggregating devices (ineffect, there are over 333 fish species belonging to 96 familiesrecorded in the literature). Several hypotheses have been advanced to explain this behaviour ofpelagic fish, although the most widely accepted theory is that fish usefloating materials, to some extent, to protect themselves frompredators. However, we think that aggregation under floats may be theresult of behaviour that has evolved to safeguard the survival of eggs,larvae and juvenile stages, during dispersion to other areas. Naturalfloating structures (e.g., algae, branches of trees) drift in seacurrents that originate in places where the floating objects arefrequently found (e.g., river estuaries, coastal areas). These same seacurrents also introduce some of the planktonic production generated inthese areas into the oligotrophic pelagic environment. Fish associatedwith drifting floating structures probably feed on invertebratesassociated with the structures. However, they may also benefit from theaccumulated plankton in the converging waters. Adult fish of somemigratory species (tuna, dolphinfish, etc.) have also developed similarassociative behaviour around drifting objects for other reasons (e.g.,resting places, presence of bait fish, geographical references andschool recomposition). In this context, the meeting point hypothesis isonly applicable to one specific case, the tuna and tuna-like species. Aggregative and associative behaviour, under and around floatingdevices, may be the result of convergent behaviors that result fromdifferent motivations. However, generally this behaviour can beexplained by the fact that drifting floating objects represent a meansof reaching relatively rich areas, where larvae and juvenile fish havean increased chance of survival.

Models with warped extra dimensions, and their strongly coupled duals, offer a nice solution to the hierarchy problem and a very appealing realisation of flavour. Compatibility with the very stringent electroweak and flavour tests have made a generic picture emerge, with a composite Higgs, partial compositeness and custodial symmetry as the main ingredients. We review the main features of this picture and discuss how -and when- models with warped extra dimensions could be discovered at the Large Hadron Collider.

It has been recently argued that realistic models with warped extra dimensions can have Kaluza-Klein particles accessible at the Large Hadron Collider if a custodial symmetry, SU(2)_V \times P_{LR}, is used to protect the T parameter and the coupling of the left-handed bottom quark to the Z gauge boson. In this article we emphasize that such a symmetry implies that the loop corrections to both the T parameter and the Z b_L \bar{b}_L coupling are calculable. In general, these corrections are correlated, can be sizable, and should be considered to determine the allowed parameter space region in models with warped extra dimensions and custodial symmetry, including Randall-Sundrum models with a fundamental Higgs, models of gauge-Higgs unification and Higgsless models. As an example, we derive the constraints that arise on a representative model of gauge-Higgs unification from a global fit to the precision electroweak observables. A scan over the parameter space typically leads to a lower bound on the Kaluza-Klein excitations of the gauge bosons of about 2-3 TeV, depending on the configuration. In the fermionic sector one can have Kaluza-Klein excitations with masses of a few hundred GeV. We present the constraints on these light fermions from recent Tevatron searches, and explore interesting discovery channels at the LHC.