GadCap: A GADGET multispecies model for the Flemish Cap cod, redfish and shrimp.

Since late 1980s, the demersal community of Flemish Cap (NAFO area 3M) has experienced large variations (including the collapse) in the abundance and population structure of its main fishing resources: cod Gadus morhua, redfish Sebastes sp. and shrimp Pandalus borealis, with alternation in their dominant role in the ecosystem. GadCap is an EU project dealing with the development of a GADGET multispecies model for the Flemish Cap cod, redfish and shrimp, as part of the NAFO roadmap for the EAF. The effect of fishing, trophic interactions (including cannibalism) and water temperature in the dynamic of these three major fishing resources has been modeled. The results highlight the interdependent dynamic of these stocks, and reveals strong interactions between recruitment, fishing and predation (including cannibalism), with marked changes in their relative importance by species-age-length over time. The multispecies model shows that disregarding the species interactions would lead to serious underestimates of natural mortality, overestimations of the exploitable biomass, and highlights the need to move beyond single-species management in this highly coupled ecosystem. Preliminary estimates of total SSB and MSY, under different combinations of fishing mortality for all the three stocks, are also presented.Postprint0,000

An Assessment of Beaked Redfish (S. mentella and S. fasciatus) in NAFO Division 3M (With a Revised Approach to Quantify the Increase on Redfish Natural Mortality Determined by the Increase on Cod Predation Observed Over Recent Years, 2006-2012)

The 3M redfish assessment is focused on the beaked redfish, regarded as a management unit composed of two populations from two very similar species: the Flemish Cap S. mentella and S. fasciatus. The reason for this approach is the historical dominance of this group in the 3M redfish commercial catch until 2005. However a new golden redfish fishery (S. marinus) started on September 2005 on shallower depths of the Flemish Cap bank above 300m, and the Flemish Cap cod fishery reopened in 2010. These new realities implied a revision of catch estimates, in order to split recent redfish commercial catch and by-catch from the major fleets on Div. 3M into golden (S. marinus) and beaked (S. mentella and S. fasciatus) redfish catches. An Extended Survivor Analysis (Shepherd, 1999) was used with the same framework of previous assessments and with the tuning of the 1989-2012 EU survey. Survey results suggest that the beaked redfish stock has not been able to hold its growth and sustain an above average level, suffering instead a severe decline on the second half of the 2000’s. The most likely hypothesis to justify this unexpected downward trend on stock size is an increase in natural mortality by cod predation. From the sensitive analysis, natural mortality at 0.4 was applied on ages 4-6 through 2006-2010, and extended to ages 7 plus on 2009 and 2010. It has been kept constant through all ages on 2011 and 2012, but with an overall decline to 0.125.This is the highest possible level of natural mortality giving assessment results in line with the recent survey trends and at the same time with key diagnostics very close to the best ones, obtained with the return on 2011-2012 to the “standard” redfish natural mortality of 0.1. A 2013-2009 retrospective XSA was also carried out, being this assessment very much in line with their immediate predecessors (2012-2011). Above average year classes coupled with low fishing mortalities allowed a rapid growth of biomass and abundance since 2003 that pushed the stock to a 2008-2009 high. Between 2009 and 2011 biomass and abundance of exploitable and 7 plus female stock went down for causes other than fishing. These declines were halted at well above average levels on the terminal year and, at least for biomass, there was some improvement on 2012. The recruitment at age 4 increased from 2002 till 2006 and was kept at a high level until 2009, with 2005 year class as the most abundant year class of the assessment interval. Recruitment to exploitable stock declined since then and is approaching the level of the weak year classes from the 1990’s. Short and medium term stochastic projections were obtained for female spawning stock biomass (SSB) under Fstatusquo , together with SSB and yield medium term probability profiles. As it was documented on the 2011 assessment F0.1 is an unacceptable management option at the current beaked redfish stock status. Keeping on 2014 and 2015 fishing mortality at its present low level will sustain on the short term a high level of female spawning biomass. But on the long term it will be natural mortality to determine the future of beaked redfish as a fishery resource

An Assessment of Beaked Redfish (S. mentella and S. fasciatus) in NAFO Division 3M (at times when natural mortality is driven stock dynamics and fishing mortality reference points are useless to scientific advice)

The 3M redfish assessment is focused on the beaked redfish, regarded as a management unit composed of two populations from two very similar species: the Flemish Cap S. mentella and S. fasciatus. The reason for this approach is the historical dominance of this group in the 3M redfish commercial catch until 2005. However a new golden redfish fishery (S. marinus) started on September 2005 on shallower depths of the Flemish Cap bank above 300m, and the Flemish Cap cod fishery reopened in 2010. These new realities implied a revision of catch estimates, in order to split recent redfish commercial catch and by-catch from the major fleets on Div. 3M into golden (S. marinus) and beaked (S. mentella and S. fasciatus) redfish catches. The Extended Survivor Analysis assessment used as tuning file the 1989-2014 EU survey abundance at age matrix included in a revised input framework. Continuing pressure over Flemish Cap redfish stocks by cod predation, at levels higher, or much higher, than the levels prior to 2006 lead to higher natural mortalities since then. Natural mortality have been tuned to survey at age data 2006 onwards by the sensitivity analysis preceding each assessment, and on 2013-2104 has a best estimate at slightly higher level from previous years. A 2015-2011 retrospective XSA was carried out, confirming that the present assessment is very much in line with their immediate predecessors

Nitrogen Metabolism and Biomass Production in Forest Trees

Low nitrogen (N) availability is a major limiting factor for tree growth and development. N uptake, assimilation, storage and remobilization are key processes in the economy of this essential nutrient, and its efficient metabolic use largely determines vascular development, tree productivity and biomass production. Recently, advances have been made that improve our knowledge about the molecular regulation of acquisition, assimilation and internal recycling of N in forest trees. In poplar, a model tree widely used for molecular and functional studies, the biosynthesis of glutamine plays a central role in N metabolism, influencing multiple pathways both in primary and secondary metabolism. Moreover, the molecular regulation of glutamine biosynthesis is particularly relevant for accumulation of N reserves during dormancy and in N remobilization that takes place at the onset of the next growing season. The characterization of transgenic poplars overexpressing structural and regulatory genes involved in glutamine biosynthesis has provided insights into how glutamine metabolism may influence the N economy and biomass production in forest trees. Here, a general overview of this research topic is outlined, recent progress are analyzed and challenges for future research are discussed

FOSL1 promotes cholangiocarcinoma via transcriptional effectors that could be therapeutically targeted

[EN] Background & Aims: Cholangiocarcinoma (CCA) is a neoplasia of the biliary tract driven by genetic, epigenetic and transcriptional mechanisms. Herein, we investigated the role of the transcription factor FOSL1, as well as its downstream transcriptional effectors, in the development and progression of CCA. Methods: FOSL1 was investigated in human CCA clinical samples. Genetic inhibition of FOSL1 in human and mouse CCA cell lines was performed in in vitro and in vivo models using constitutive and inducible short-hairpin RNAs. Conditional FOSL1 ablation was done using a genetically engineered mouse (GEM) model of CCA (mutant KRAS and Trp53 knockout). Followup RNA and chromatin immunoprecipitation (ChIP) sequencing analyses were carried out and downstream targets were validated using genetic and pharmacological inhibition. Results: An inter-species analysis of FOSL1 in CCA was conducted. First, FOSL1 was found to be highly upregulated in human and mouse CCA, and associated with poor patient survival. Pharmacological inhibition of different signalling pathways in CCA cells converged on the regulation of FOSL1 expression. Functional experiments showed that FOSL1 is required for cell proliferation and cell cycle progression in vitro, and for tumour growth and tumour maintenance in both orthotopic and subcutaneous xenograft models. Likewise, FOSL1 genetic abrogation in a GEM model of CCA extended mouse survival by decreasing the oncogenic potential of transformed cholangiocytes. RNA and ChIP sequencing studies identified direct and indirect transcriptional effectors such as HMGCS1 and AURKA, whose genetic and pharmacological inhibition phenocopied FOSL1 loss. Conclusions: Our data illustrate the functional and clinical relevance of FOSL1 in CCA and unveil potential targets amenable to pharmacological inhibition that could enable the implementation of novel therapeutic strategies. Lay summary: Understanding the molecular mechanisms involved in cholangiocarcinoma (bile duct cancer) development and progression stands as a critical step for the development of novel therapies. Through an inter-species approach, this study provides evidence of the clinical and functional role of the transcription factor FOSL1 in cholangiocarcinoma. Moreover, we report that downstream effectors of FOSL1 are susceptible to pharmacological inhibition, thus providing new opportunities for therapeutic intervention.A.V. was supported by ADA of the University of Navarra, Spain, O.E. by FSE; MINECO; FJCI-2017-34233, Spain, R.E. by a donation from Mauge Burgos de la Iglesia’s family, Spain, and P. Olaizola by the Basque Government (PRE_2016_1_0269), Basque Country, Spain. M.J.P. was funded by ISCIII [FIS PI14; 00399, PI17; 00022] cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER), Spain; Spanish Ministry of Economy and Competitiveness (MINECO: “Ramón y Cajal” Program RYC-2015-17755), Spain. M.A.A was funded by La Caixa Foundation, HEPACARE project, Spain, ISCIII FIS PI16/01126 cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER), Spain, and “Fundación Científica de la Asociación Española Contra el Cáncer’’ (AECC Scientific Foundation) Rare Cancers 2017, Spain. J.M.B. was funded by the Spanish Carlos III Health Institute (ISCIII) (FIS PI15; 01132, PI18; 01075 and Miguel Servet Program CON14; 00129 and CPII19; 00008), Spain, co-financed by “Fondo Europeo de Desarrollo Regional” (FEDER), Spain; “Euskadi RIS3” (2019222054) and BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15; CA; 016; BD), Basque Country, Spain; “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC Scientific Foundation) Rare Cancers 2017, Spain. S.V. was supported by FEDER; MINECO (SAF2017-89944-R), Spain, by the Government of Navarra-Health Research Department (58; 2018), Navarra, Spain, by La Caixa and Caja Navarra Foundation-CIMA agreement, Spain. None of the funding sources were involved in the decision to submit the article for publication. This article is based upon work from COST Action CA18122 European Cholangiocarcinoma Network, supported by COST (European Cooperation in Science and Technology). COST (European Cooperation in Science and Technology) is a funding agency for research and innovation networks (www.cost.eu)

Neddylation inhibition ameliorates steatosis in NAFLD by boosting hepatic fatty acid oxidation via the DEPTOR-mTOR axis

Objective: Neddylation is a druggable and reversible ubiquitin-like post-translational modification upregulated in many diseases, including liver fibrosis, hepatocellular carcinoma, and more recently, non-alcoholic fatty liver disease (NAFLD). Herein, we propose to address the effects of neddylation inhibition and the underlying mechanisms in pre-clinical models of NAFLD. Methods: Hepatic neddylation measured by immunohistochemical analysis and NEDD8 serum levels measured by ELISA assay were evaluated in NAFLD clinical and pre-clinical samples. The effects of neddylation inhibition by using a pharmacological small inhibitor, MLN4924, or molecular approaches were assessed in isolated mouse hepatocytes and pre-clinical mouse models of diet-induced NAFLD, male adult C57BL/6 mice, and the AlfpCre transgenic mice infected with AAV-DIO-shNedd8. Results: Neddylation inhibition reduced lipid accumulation in oleic acid-stimulated mouse primary hepatocytes and ameliorated liver steatosis, preventing lipid peroxidation and inflammation in the mouse models of diet-induced NAFLD. Under these conditions, increased Deptor levels and the concomitant repression of mTOR signaling were associated with augmented fatty acid oxidation and reduced lipid content. Moreover, Deptor silencing in isolated mouse hepatocytes abolished the anti-steatotic effects mediated by neddylation inhibition. Finally, serum NEDD8 levels correlated with hepatic neddylation during the disease progression in the clinical and pre-clinical models. Conclusions: Overall, the upregulation of Deptor, driven by neddylation inhibition, is proposed as a novel effective target and therapeutic approach to tackle NAFLDThis work was supported by grants from Gobierno Vasco-Departamento de Salud 2013111114 (to M.L.M.-C), ELKARTEK 2016, Departamento de Industria del Gobierno Vasco (to M.L.M−C), Ministerio de Ciencia, Innovación y Universidades MICINN: SAF2017-87301-R, and RTI2018-096759-A-100 integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER (to M.L.M− T.C.D respectively); MCIU/AEI/FEDER, UE (RTI2018-095134-B-100) (to P.A.), AECC Bizkaia (M.S-M); Asociación Española contra el Cáncer (T.C.D), Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M, J.M.B., M.A.A., J.J.G.M.), La Caixa Foundation Program (to M.L.M and J.M.B.), 2018 BBVA Foundation Grants for Scientific Research Teams (to M.L.M.-C.), Ayudas para apoyar grupos de investigación del sistema Universitario Vasco IT971-16 (P.A.). MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico (to LV), the European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- “Liver Investigation: Testing Marker Utility in Steatohepatitis” (to LV), Fondazione IRCCS Ca’ Granda “Liver BIBLE” PR-0391, Fondazione IRCCS Ca’ Granda core COVID-19 Biobank (RC100017A) (to LV). This research was funded by the CIBERehd (EHD15PI05/2016) and “Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III”, Spain (PI16/00598 and PI19/00819, co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”); Spanish Ministry of Economy, Industry and Competitiveness (SAF2016-75197-R); “Junta de Castilla y Leon” (SA063P17); AECC Scientific Foundation (2017/2020), Spain; “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER, 0348_CIE_6_E), Spain; University of Salamanca Foundation, Spain (PC-TCUE18-20_051), and Fundació Marato TV3 (Ref. 201916–31), Spain. RB acknowledges BFU2017-84653-P (MINECO/FEDER, EU), SEV-2016-0644 (Severo Ochoa Excellence Program), 765445-EU (UbiCODE Program), SAF2017-90900-REDT (UBIRed Program), and IT1165-19 (Basque Country Government). Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644)S

Promoción, capacitación y acciones en las enfermedades infecciosas emergentes y reemergentes zoonóticas: el cambio global y el desarrollo sustentable

Las enfermedades infecciosas emergentes y reemergentes zoonóticas (EIEYRZ) bacterianas y virales, pueden ser transmitidas a partir de animales, agua, alimentos, o vectores poniendo en riesgo la salud humana. Muchos factores antropogénicos inciden en el surgimiento de estas enfermedades, tales como eventos sociales, comportamiento humano, cambios ambientales, políticas en salud pública y procedimientos médicos entre otros. Los detonantes de estos eventos infecciosos emergentes o reemergentes, son variados y poco conocidos por lo general en la población a lo que se suman conductas higiénico-sanitarias variables que pueden favorecer la transmisión de este tipo de enfermedades. La instrucción y formación educativa, es una herramienta fundamental para el cambio de actitud de la población. La interacción con grupos referenciales especializados puede favorecer de manera sostenible a la reducción, prevención, control y en algunos casos erradicación de muchas enfermedades. Un mayor conocimiento por parte de la comunidad s puede resultar de gran utilidad en la prevención y control de las mismas. Este proyecto tiene como comunidad de aplicación las áreas programáticas de los Centros de Atención Primaria de la Salud (CAPS) de La Plata y gran La Plata.Facultad de Ciencias Veterinaria

Promoción, capacitación y acciones en las enfermedades infecciosas emergentes y reemergentes zoonóticas: el cambio global y el desarrollo sustentable

Las enfermedades infecciosas emergentes y reemergentes zoonóticas (EIEYRZ) bacterianas y virales, pueden ser transmitidas a partir de animales, agua, alimentos, o vectores poniendo en riesgo la salud humana. Muchos factores antropogénicos inciden en el surgimiento de estas enfermedades, tales como eventos sociales, comportamiento humano, cambios ambientales, políticas en salud pública y procedimientos médicos entre otros. Los detonantes de estos eventos infecciosos emergentes o reemergentes, son variados y poco conocidos por lo general en la población a lo que se suman conductas higiénico-sanitarias variables que pueden favorecer la transmisión de este tipo de enfermedades. La instrucción y formación educativa, es una herramienta fundamental para el cambio de actitud de la población. La interacción con grupos referenciales especializados puede favorecer de manera sostenible a la reducción, prevención, control y en algunos casos erradicación de muchas enfermedades. Un mayor conocimiento por parte de la comunidad s puede resultar de gran utilidad en la prevención y control de las mismas. Este proyecto tiene como comunidad de aplicación las áreas programáticas de los Centros de Atención Primaria de la Salud (CAPS) de La Plata y gran La Plata.Facultad de Ciencias Veterinaria

Wildfire incidence throughout the Brazilian Pantanal is driven by local climate rather than bovine stocking density

The Pantanal is the world’s largest and most biodiverse continental sheet-flow wetland. Recently, vast tracts of the Pantanal have succumbed to the occurrence of fires, raising serious concerns over the future integrity of the biodiversity and ecosystem services of this biome, including revenues from ecotourism. These wildfires degrade the baseline of natural ecosystems and the ecotourism economy across the region. Local residents (“Pantaneiros”) anecdotally state that extensive cattle herbivory can solve the contemporary flammability problem of the Pantanal by controlling vegetation biomass, thereby preventing or reducing both fuel loads and fires across the region. Here, we examine the covariation between the presence and density of cattle and the incidence of fires across the Brazilian Pantanal. Variables assessed included bovine cattle density, SPI (Standardized Precipitation Index), GPP (Gross Primary Productivity)/biomass estimate, and fire foci along a 19-year time series (2001 to 2019). Our findings show that fire foci across the Pantanal biome are related to climatic variables, such as lower annual precipitation and higher annual drought indices (SPI) rather than to cattle stocking rates. Therefore, the notion of “cattle firefighting”, a popular concept often discussed in some academic circles, cannot be validated because cattle numbers are unrelated to aboveground phytomass. Gross primary productivity further invalidated the “cattle herbivory” hypothesis because GPP was found to be strongly correlated with cattle density but not with the spatial distribution of fires. Fires throughout the Pantanal are currently aggravated by the presence of livestock and result from a combination of extreme weather events and outdated agricultural practices