Hypophagia induced by salmon calcitonin, but not by amylin, is partially driven by malaise and is mediated by CGRP neurons

Objective: The behavioral mechanisms and the neuronal pathways mediated by amylin and its long-acting analog sCT (salmon calcitonin) are not fully understood and it is unclear to what extent sCT and amylin engage overlapping or distinct neuronal subpopulations to reduce food intake. We here hypothesize that amylin and sCT recruit different neuronal population to mediate their anorectic effects. Methods: Viral approaches were used to inhibit calcitonin gene-related peptide (CGRP) lateral parabrachial nucleus (LPBN) neurons and assess their role in amylin's and sCT's ability to decrease food intake in mice. In addition, to test the involvement of LPBN CGRP neuropeptidergic signaling in the mediation of amylin and sCT's effects, a LPBN site-specific knockdown was performed in rats. To deeper investigate whether the greater anorectic effect of sCT compared to amylin is due do the recruitment of additional neuronal pathways related to malaise multiple and distinct animal models tested whether amylin and sCT induce conditioned avoidance, nausea, emesis, and conditioned affective taste aversion. Results: Our results indicate that permanent or transient inhibition of CGRP neurons in LPBN blunts sCT-, but not amylin-induced anorexia and neuronal activation. Importantly, sCT but not amylin induces behaviors indicative of malaise including conditioned affective aversion, nausea, emesis, and conditioned avoidance; the latter mediated by CGRPLPBN neurons. Conclusions: Together, the present study highlights that although amylin and sCT comparably decrease food intake, sCT is distinctive from amylin in the activation of anorectic neuronal pathways associated with malaise

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Extinction risk, reconstructed catches and management of chondrichthyan fishes in the Western Central Atlantic Ocean

Chondrichthyan fishes are among the most threatened vertebrates on the planet because many species have slow life histories that are outpaced by intense fishing. The Western Central Atlantic Ocean, which includes the Greater Caribbean, is a hotspot of chondrichthyan biodiversity and abundance, but has been characterized by extensive shark and ray fisheries and a lack of sufficient data for effective management and conservation. To inform future research and management decisions, we analysed patterns in chondrichthyan extinction risk, reconstructed catches and management engagement in this region. We summarized the extinction risk of 180 sharks, rays and chimaeras, including 66 endemic and 14 near-endemic species, using contemporary IUCN Red List assessments. Over one-third (35.6%) were assessed as Vulnerable, Endangered or Critically Endangered, primarily due to overfishing. Reconstructed catches from 1950 to 2016 peaked in 1992, then declined by 40.2% thereafter. The United States, Venezuela and Mexico were responsible for most catches in the region and hosted the largest proportions of the regional distributions of threatened species, largely due to having extensive coastal habitats in their Exclusive Economic Zones. The quantity and taxonomic resolution of fisheries landings data were poor in much of the region, and national-level regulations varied widely across jurisdictions. Deepwater fisheries represent an emerging threat, although many deepwater chondrichthyans currently have refuge beyond the depths of most fisheries. Regional collaboration as well as effective and enforceable management informed by more complete fisheries data, particularly from small-scale fisheries, are required to protect and recover threatened species and ensure sustainable fisheries