Geographic and ontogenetic variation in the diet of two commonly exploited batoids (Chilean eagle ray and Pacific guitarfish) off Peru: evidence of trophic plasticity

This study provides information about the diet across geographic areas and throughout ontogeny and sex of two coastal and commercial batoid species in Peru (Chilean eagle ray Myliobatis chilensis and Pacific guitarfish Pseudobatos planiceps). Data was collected in the central coast (13°30′S to 14°30′S; Pisco district, Lima) and in the northern coast (13°12′S to 13°49′S; San Jose district, Lambayeque) off Peru during the second semester of the years 2015 and 2016 (i.e., winter and spring) in an El Niño event. A total of 357 stomach contents were analyzed in northern and central Peru with different oceanographic and ecological conditions. In the central coast, M. chilensis showed a high trophic position (tertiary consumer) due to its high consumption of Peruvian anchoveta (Engraulis ringens), while P. planiceps had a lower trophic position (secondary consumer) and a less specialized diet of benthic invertebrates (i.e., crustaceans and mollusks) and pelagic fish (e.g., E. ringens). In the northern coast, both species preyed mainly upon benthic invertebrates and to a lesser degree on fish; therefore, their trophic position was lower. Dietary variation was influenced by species, geographic location, and ontogeny. The diet variability between geographic locations shows insights of these batoids’ trophic plasticity and opportunistic feeding behavior in response to differences in the local prey availability, an effect that may be amplified during the El Niño–Southern Oscillation (ENSO). The spatial variation in this species diet may indicate that they play different ecological roles in distinct environments. This study contributes to the scarce literature about batoids’ ecology in the southeast Pacific Ocean and presents novel information on habitat-specific diet composition.

     

Arrestin-2 differentially regulates PAR4 and ADP receptor signaling in platelets

Arrestins can facilitate desensitization or signaling by G protein-coupled receptors (GPCR) in many cells, but their roles in platelets remain uncharacterized. Because of recent reports that arrestins can serve as scaffolds to recruit phosphatidylinositol-3 kinases (PI3K)s to GPCRs, we sought to determine whether arrestins regulate PI3K-dependent Akt signaling in platelets, with consequences for thrombosis. Co-immunoprecipitation experiments demonstrate that arrestin-2 associates with p85 PI3Kα/β subunits in thrombin-stimulated platelets, but not resting cells. The association is inhibited by inhibitors of P2Y12 and Src family kinases (SFKs). The function of arrestin-2 in platelets is agonist-specific, as PAR4-dependent Akt phosphorylation and fibrinogen binding were reduced in arrestin-2 knock-out platelets compared with WT controls, but ADP-stimulated signaling to Akt and fibrinogen binding were unaffected. ADP receptors regulate arrestin recruitment to PAR4, because co-immunoprecipitates of arrestin-2 with PAR4 are disrupted by inhibitors of P2Y1 or P2Y12. P2Y1 may regulate arrestin-2 recruitment to PAR4 through protein kinase C (PKC) activation, whereas P2Y12 directly interacts with PAR4 and therefore, may help to recruit arrestin-2 to PAR4. Finally, arrestin2(-/-) mice are less sensitive to ferric chloride-induced thrombosis than WT mice, suggesting that arrestin-2 can regulate thrombus formation in vivo. In conclusion, arrestin-2 regulates PAR4-dependent signaling pathways, but not responses to ADP alone, and contributes to thrombus formation in vivo.     

Drug Development in Conformational Diseases: A Novel Family of Chemical Chaperones that Bind and Stabilise Several Polymorphic Amyloid Structures

The increasing prevalence of conformational diseases, including Alzheimer''s disease, type 2 Diabetes Mellitus and Cancer, poses a global challenge at many different levels. It has devastating effects on the sufferers as well as a tremendous economic impact on families and the health system. In this work, we apply a cross-functional approach that combines ideas, concepts and technologies from several disciplines in order to study, in silico and in vitro, the role of a novel chemical chaperones family (NCHCHF) in processes of protein aggregation in conformational diseases. Given that Serum Albumin (SA) is the most abundant protein in the blood of mammals, and Bovine Serum Albumin (BSA) is an off-the-shelf protein available in most labs around the world, we compared the ligandability of BSA:NCHCHF with the interaction sites in the Human Islet Amyloid Polypeptide (hIAPP):NCHCHF, and in the amyloid pharmacophore fragments (Aβ17–42 and Aβ16–21):NCHCHF. We posit that the merging of this interaction sites is a meta-structure of pharmacophore which allows the development of chaperones that can prevent protein aggregation at various states from: stabilizing the native state to destabilizing oligomeric state and protofilament. Furthermore to stabilize fibrillar structures, thus decreasing the amount of toxic oligomers in solution, as is the case with the NCHCHF. The paper demonstrates how a set of NCHCHF can be used for studying and potentially treating the various physiopathological stages of a conformational disease. For instance, when dealing with an acute phase of cytotoxicity, what is needed is the recruitment of cytotoxic oligomers, thus chaperone F, which accelerates fiber formation, would be very useful; whereas in a chronic stage it is better to have chaperones A, B, C, and D, which stabilize the native and fibril structures halting self-catalysis and the creation of cytotoxic oligomers as a consequence of fiber formation. Furthermore, all the chaperones are able to protect and recondition the cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP_20–29 fragment or by a low potassium medium, regardless of their capacity for accelerating or inhibiting in vitro formation of fibers. In vivo animal experiments are required to study the impact of chemical chaperones in cognitive and metabolic syndromes.