Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ transplantation. Both compounds are still widely used in the clinic as well as for basic research, even though they have dramatic side effects and modulate other pathways than calcineurin-NFATc, too. To answer the major open question - whether the adverse side effects are secondary to the actions of the drugs on the calcineurin-NFATc pathway - alternative inhibitors were developed. Ideal inhibitors should discriminate between the inhibition of (i) calcineurin and peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii) NFATc and other transcription factors. In this review we summarize the current knowledge about novel inhibitors, synthesized or identified in the last decades, and focus on their mode of action, specificity, and biological effects

Are Territorial Use Rights in Fisheries (TURFs) sufficiently large?

Territorial Use Rights in Fisheries (TURFs) are gaining renewed attention as a potential tool for sustainable fisheries management in small-scale fisheries. This growing popularity comes despite the fact that there are still unresolved questions about the most effective TURF designs. One of the key questions is the role of TURF size in their efficacy both from ecological and social standpoints. This study explores the expected effects of existing TURF sizes on yields for TURF systems in Chile, México and Japan. The expected effect of larval dispersal and adult movement on yields was simulated for TURFs in each system. The results show that the analyzed TURF systems fall into three main categories: (a) TURFs that are of adequate size to eliminate the expected negative effects of both adult and larval movement, (b) TURFs that are large enough to eliminate the expected negative effects of adult movement, but not the effects of larval dispersal, and c) TURFs that are too small to eliminate the expected impacts on yield of both adult and larval movement. These analyses suggest that either existing models of TURF performance are incomplete or that there is significant scope for improved performance with altered TURF designs. Considering these alternatives, empirical evidence from the TURFs deemed too small suggests that complementary management tools can enhance TURF performance when natural or social constraints prevent the construction of TURFs of optimal size

The biodiversity of fishes at the Islas Marías Biosphere Reserve, Mexico, as determined by baited remote underwater video

The Islas Marías Biosphere Reserve, made up of 4 islands in Pacific waters off central Mexico, supports a large diversity of marine life. However, scientific research was restricted for decades by the occupation of Isla María Madre by the Federal Penitentiary Colony of Mexico from 1905 to 2019. Aside from a list of coastal fish species published in 2011, little has been published about the fish biodiversity in the area. While the limited access to the archipelago may have acted as a de-facto marine reserve, there is evidence that fishing continued both legally for the benefit of the colony and illegally by trespassing vessels. In order to establish baseline ecological data for future conservation planning, we used baited remote underwater video (BRUV) surveys at all 4 islands during 3 expeditions to the archipelago in 2018. A total of 131 BRUV surveys representing ~150 h of footage were analyzed to create the most current compilation of species and abundance data on coastal marine fishes at Islas Marías. Ninety-nine species were identified, 3 of which were additions to the previous assessment. We found strong separation of fish communities based on both habitat and depth, and an association between hard-bottom habitats and high biodiversity of reef fishes. With the declaration of Islas Marías as a natural reserve and relocation of the prison in 2019, there is an opportunity for the reserve to become a priority area for marine conservation on the Pacific coast of Mexico. Spatial analyses of fish biodiversity at Isla María Cleofas can help develop sustainable management strategies at a time when the governmental jurisdiction of the iconic archipelago is uncertain

Fibroblast growth factor (FGF)-23 induces ventricular arrhytmogenesis through Ca2+ handling dysregulation

Resumen del trabajo presentado al European Society of Cardiology (ESC) Congress, celebrado en Barcelona (España) del 26 al 30 de agosto de 2017.[Introduction] Fibroblast growth factor (FGF)-23 is a hormone synthesized in bones in response of an increase in circulating phosphate levels. It is known that patients with chronic kidney disease (CKD) show high serum levels of FGF-23 and this increment is gradual as CKD progresses. Despite of FGF-23 has been classically associated to renal dysfunction, during the last years is also considered as a non-conventional risk factor of cardiovascular (CV) disease. However, it is completely unknown whether FGF-23 might alter cardiac contractile function, especially in advanced stages of renal disease in which circulating FGF-23 levels are strongly increased.[Purpose] 1) Analyze whether FGF-23 impairs calcium (Ca2+) handling, a key regulator of contractile function and consequently the ventricular rhythm. 2) Analyze the circulating levels of FGF-23 in dialysis patients and its relationship with the ventricular rhythm.[Methods] Enzymatically isolated adult rat ventricular myocytes (n=9) were perfused firstly with a vehicle solution and subsequently with a FGF-23 solution (100 ng/mL). L-type Ca2+ current (ICaL) was recorded by the whole-cell patch-clamp technique. Ca2+ handling and contractile function were analyzed using confocal microscopy. To determinate FGF-23-dependent pathways, cardiomyocytes were pre-incubated with the FGF-receptors inhibitor PD173074 (10 μmol/mL) or soluble klotho (s-klotho) (100 ng/mL). In addition, FGF-23 serum levels were measured by the FGF-23 (C-term) ELISA-kit in samples from patients under dialysis (n=52).[Results] FGF-23 induced a significant decline of ICaL (p1000 RU/mL of FGF-23 in 68% of total dialysis patients.[Conclusion] Our study uncovers FGF-23 as new target in the intracellular Ca2+ handling, able to impair contractile function and induce a pro-arrhythmogenic phenotype in adult cardiomyocytes.[Future perspectives] Alterations evoked by FGF-23 in cardiomyocytes could explain the CV events observed in patients with CKD, especially those in dialysis. The next step will be to analyze in CKD patients whether high FGF-23 levels impair cardiac function and heart rhythm.This work was supported by grants CP15/00129 from ISCIII, Fundaciόn SENEFRO and Fondos FEDER.Peer reviewe

Citizen Science as an Approach for Overcoming Insufficient Monitoring and Inadequate Stakeholder Buy-in in Adaptive Management: Criteria and Evidence

Adaptive management is broadly recognized as critical for managing natural resources, yet in practice it often fails to achieve intended results for two main reasons: insufficient monitoring and inadequate stakeholder buy-in. Citizen science is gaining momentum as an approach that can inform natural resource management and has some promise for solving the problems faced by adaptive management. Based on adaptive management literature, we developed a set of criteria for successfully addressing monitoring and stakeholder related failures in adaptive management and then used these criteria to evaluate 83 citizen science case studies from peer-reviewed literature. The results suggest that citizen science can be a cost-effective method to collect essential monitoring information and can also produce the high levels of citizen engagement that are vital to the adaptive management learning process. The analysis also provides a set of recommendations for citizen science program design that addresses spatial and temporal scale, data quality, costs, and effective incentives to facilitate participation and integration of findings into adaptive management