Enhanced expression of the voltage-dependent anion channel 1 (VDAC1) in Alzheimer's disease transgenic mice: an insight into the pathogenic effects of amyloid-β

The mitochondrial voltage-dependent anion channel 1 (VDAC1) is involved in the release of apoptotic proteins with possible relevance in Alzheimer's disease (AD) neuropathology. Through proteomic analysis followed by Western blotting and immunohistochemical techniques, we have found that VDAC1 is overexpressed in the hippocampus from amyloidogenic AD transgenic mice models. VDAC1 was also overexpressed in postmortem brain tissue from AD patients at an advanced stage of the disease. Interestingly, amyloid-β (Aβ) soluble oligomers were able to induce upregulation of VDAC1 in a human neuroblastoma cell line, further supporting a correlation between Aβ levels and VDAC1 expression. In hippocampal extracts from transgenic mice, a significant increase was observed in the levels of VDAC1 phosphorylated at an epitope that is susceptible to phosphorylation by glycogen synthase kinase-3β, whose activity was also increased. The levels of hexokinase I (HXKI), which interacts with VDAC1 and affects its function, were decreased in mitochondrial samples from AD models. Since phospho-VDAC and reduced HXKI levels favors a VDAC1 conformational state more prone to the release proapoptotic factors, regulation of the function of this channel may be a promising therapeutic approach to combat AD

Status and trends of the fish community in the Flemish Cap (NAFO Div. 3M) bioregion

This report summarizes fish community trends for the Flemish Cap (NAFO Div. 3M) based on European Union summer trawl research vessel surveys between 1988 and 2018. Species were classified into eight functional groups and trends were described using biomass indices, biomass and abundance anomalies, and fish size (Biomass/Abundance Ratio) anomalies. In 2003, a replacement of the research vessel allowed extending the depth coverage of the survey from 700m to 1400m. The vessel change had an impact on survey catchability, so to account for it conversion factors were applied. Considering the change in depth coverage, trends were examined for 1988-2018 with data up to 700m, and for 2004-2018 with data up to 1400m. Fish community trends were similar between the two datasets, but the analyses including deeper waters showed a comparatively higher levels of benthivores, reflecting the changes in community structure with depth. Generally speaking, trends in average fish size as tracked by the Biomass/Abundance Ratio appeared driven by recruitment, where general declines in abundance and absences of good recruitments got reflected in increases of this ratio. Biomass of plankpiscivores (mostly Sebastes sp.) experienced a sharp increase in the early 2000s but then returned to levels comparable to the 1990s. Piscivores biomass showed a strong decline in the early 1990s due to the collapse of cod but has since shown signs of recovery. Shellfish, driven by northern shrimp, saw a sustained increase in biomass from the early 1990s until 2002, when started a decline that has persisted until 2018. The biomass of large benthivores decline in the late 1990s and remains low to this date

Advances in the Assessment of Habitat Fragmentation and Protection in the NAFO Regulatory Area

NAFO has used kernel density analyses to identify VMEs dominated by large-sized sponges, sea pens, small and large gorgonian corals, erect bryozoans, sea squirts (Boltenia ovifera), and black corals. That analysis generates polygons of significant concentrations of biomass for each VME indicator which are spread across the spatial domain of the NAFO fishing footprint. There is potential for bottom contact fishing to induce changes in both the amount and configuration of habitat (e.g., decreased polygon size, increased polygon isolation, and increased edge area) through direct and indirect impacts, and it is unknown to what degree such changes may already have taken place given the long fishing history of the area. In the Report of the 13th Meeting of the NAFO Scientific Council Working Group on Ecosystem Science and Assessment (WGE-ESA), preliminary work on assessing and monitoring habitat fragmentation was presented. Here we continue that work by recalculating the indices after removing connections that are not identified through particle tracking models. We have reanalyzed the nearest neighbour distances and PX, a proximity index, for the VME polygons noted above, and for the new closed areas that will come into effect 1 January 2022. We show that PX when applied to the new closures appears sensitive to their spatial configuration which bodes will for the ability of this index to identify habitat fragmentation in the future, brought about through fishing activities and/or natural disturbances.Versión del edito

Report of the Scientific Council Meeting 01 -15 June 2017

Council met at the Sobey Building, Saint Mary’s University, Halifax, NS, Canada, during 01 – 15 June 2017, to consider the various matters in its Agenda. Representatives attended from Canada, Denmark (in respect of Faroe Islands and Greenland), the European Union (France, Germany (via WebEx), Portugal, Spain, the United Kingdom and the European Commission), Japan, the Russian Federation and the United States of America. Observers from the Ecology Action Centre and Dalhousie University were also present. The Executive Secretary, Scientific Council Coordinator and other members of the Secretariat were in attendance. The Executive Committee met prior to the opening session of the Council to discuss the provisional agenda and plan of work. The Council was called to order at 1000 hours on 01 June 2017. The provisional agenda was adopted with modification. The Scientific Council Coordinator was appointed the rapporteur. The Council was informed that the meeting was quorate and authorization had been received by the Executive Secretary for proxy votes from the European Union, Denmark (in respect of Faroe Islands and Greenland), Iceland, Japan, Republic of Korea, and Norway. The opening session was adjourned at 1200 hours on 01 June 2017. Several sessions were held throughout the course of the meeting to deal with specific items on the agenda. The Council considered adopted the STACFEN report on 8 June 2017, and the STACPUB, STACFIS and STACREC reports on 15 June 2017. The concluding session was called to order at 0830 hours on 15 June 2017. The Council considered and adopted the report the Scientific Council Report of this meeting of 01 -15 June 2017. The Chair received approval to leave the report in draft form for about two weeks to allow for minor editing and proof-reading on the usual strict understanding there would be no substantive changes. The meeting was adjourned at 1430 hours on 15 June 2017. The Reports of the Standing Committees as adopted by the Council are appended as follows: Appendix I - Report of the Standing Committee on Fisheries Environment (STACFEN), Appendix II - Report of Standing Committee on Publications (STACPUB), Appendix III - Report of Standing Committee on Research Coordination (STACREC), and Appendix IV - Report of Standing Committee on Fisheries Science (STACFIS). The Agenda, List of Research (SCR) and Summary (SCS) Documents, and List of Representatives, Advisers and Experts, are given in Appendix V-VII. The Council’s considerations on the Standing Committee Reports, and other matters addressed by the Council follow in Sections II-XV

A Case Study of available methodology for the identification of Vulnerable Ecosystems/Habitats in bottom deep-sea fisheries: Possibilities to apply this method in the NAFO Regulatory Area in order to select Marine Protected Areas

Information is critical to Ecosystem Approach and to research about Vulnerable Marine Ecosystems/Habitats (VME/Hs), fishing impacts on habitats and ad-hoc management measures are high-priority. Therefore, this paper presents the ECOVUL/ARPA Interdisciplinary Approach, a case study of methodology for the identification of VME/Hs in order to advise on conservation measures such as marine protected areas (MPAs). By means of an interactive process involving Conventional Fisheries Science, Geomorphology, Sedimentology and Benthic Ecology, the methodology developed under the ECOVUL/ARPA project, has been useful in order to contribute to define practical criteria to the identification of VME/Hs, to improve the knowledge about VME/Hs distribution and the adverse impacts of bottom trawl fisheries and to produce high quality advice on habitat protection. Applying an interdisciplinary approach, the project identified the deep-water bottom trawl fishery footprint on the Hatton Bank Western slope (NEAFC Regulatory Area), mapped the main fishing grounds and related seabed habitats and studied the interactions between fishing and cold-water corals. This approach was used to suggest, with high level of precision, the spatial limits of an area closed to bottom fishing, as an essential conservation measure to protect the cold-water corals in the framework of the Ecosystem Approach to Fisheries management. We present here the methods used, the main results obtained and discuss on the utility of this approach and the possibilities to apply it in the NAFO Regulatory Area, with the aim to advise on measures for reducing the interactions of bottom fishing with sensitive high-seas habitats and to contribute to implement the UNGA recommendations about habitat conservation

Kernel Density Surface Modelling as a Means to Identify Significant Concentrations of Vulnerable Marine Ecosystem Indicators

The United Nations General Assembly Resolution 61/105, concerning sustainable fisheries in the marine ecosystem, calls for the protection of vulnerable marine ecosystems (VME) from destructive fishing practices. Subsequently, the Food and Agriculture Organization (FAO) produced guidelines for identification of VME indicator species/taxa to assist in the implementation of the resolution, but recommended the development of case-specific operational definitions for their application. We applied kernel density estimation (KDE) to research vessel trawl survey data from inside the fishing footprint of the Northwest Atlantic Fisheries Organization (NAFO) Regulatory Area in the high seas of the northwest Atlantic to create biomass density surfaces for four VME indicator taxa: large-sized sponges, sea pens, small and large gorgonian corals. These VME indicator taxa were identified previously by NAFO using the fragility, life history characteristics and structural complexity criteria presented by FAO, along with an evaluation of their recovery trajectories. KDE, a non-parametric neighbour-based smoothing function, has been used previously in ecology to identify hotspots, that is, areas of relatively high biomass/abundance. We present a novel approach of examining relative changes in area under polygons created from encircling successive biomass categories on the KDE surface to identify ‘‘significant concentrations’’ of biomass, which we equate to VMEs. This allows identification of the VMEs from the broader distribution of the species in the study area. We provide independent assessments of the VMEs so identified using underwater images, benthic sampling with other gear types (dredges, cores), and/or published species distribution models of probability of occurrence, as available. For each VME indicator taxon we provide a brief review of their ecological function which will be important in future assessments of significant adverse impact on these habitats here and elsewhere.Versión del editor4,411

Overexpression of wild-type human APP in mice causes cognitive déficits and pathological features unrelated to Abeta levels

Transgenic mice expressing mutant human amyloid precursor protein (APP) develop an age-dependent amyloid pathology and memory deficits, but no overt neuronal loss. Here, in mice overexpressing wild-type human APP (hAPPwt) we found an early memory impairment, particularly in the water maze and to a lesser extent in the object recognition task, but β-amyloid peptide (Aβ42) was barely detectable in the hippocampus. In these mice, hAPP processing was basically non-amyloidogenic, with high levels of APP carboxy-terminal fragments, C83 and APP intracellular domain. A tau pathology with an early increase in the levels of phosphorylated tau in the hippocampus, a likely consequence of enhanced ERK1/2 activation, was also observed. Furthermore, these mice presented a loss of synapse-associated proteins: PSD95, AMPA and NMDA receptor subunits and phosphorylated CaMKII. Importantly, signs of neurodegeneration were found in the hippocampal CA1 subfield and in the entorhinal cortex that were associated to a marked loss of MAP2 immunoreactivity. Conversely, in mice expressing mutant hAPP, high levels of Aβ42 were found in the hippocampus, but no signs of neurodegeneration were apparent. The results support the notion of Aβ- independent pathogenic pathways in Alzheimer's disease

Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease

Abstract. Synapse loss occurs early in Alzheimer’s disease (AD) and is considered the best pathological correlate of cognitive decline. Ephrins and Eph receptors are involved in regulation of excitatory neurotransmission and play a role in cytoskeleton remodeling. We asked whether alterations in Eph receptors could underlie cognitive impairment in an AD mouse model overexpressing human amyloid-β protein precursor (hAβPP) with familial mutations (hAβPPswe-ind mice). We found that EphA4 and EphB2 receptors were reduced in the hippocampus before the development of impaired object recognition and spatial memory. Similar results were obtained in another line of transgenic AβPP mice, Tg2576. A reduction in Eph receptor levels was also found in postmortem hippocampal tissue from patients with incipient AD. At the time of onset of memory decline in hAβPPswe-ind mice, no change in surface expression of AMPA or NMDA receptor subunits was apparent, but we found changes in Eph-receptor downstream signaling, in particular a decrease in membrane-associated phospho-cofilin levels that may cause cytoskeletal changes and disrupted synaptic activity. Consistent with this finding, Eph receptor activation in cell culture increased phospho-cofilin levels. The results suggest that alterations in Eph receptors may play a role in synaptic dysfunction in the hippocampus leading to cognitive impairment in a model of AD

Preliminary study of the variations on the spatio-temporal distribution of a potentially exploitable species (Patagonotothen spp.) in the southwest Atlantic, using GIS techniques

The genus Patagonotothen is the most common Nototheniid on the Patagonian Shelf and slope and is part of the by-catch species in the bottom trawl fisheries. This paper presents preliminary results from the EC CRAFT project “Promoting higher added value to a finfish species rejected to sea”, aiming to develop the research and the technology necessary to promote higher added value to fishing activity by taking profit from a finfish species (Rockcod, Patagonotothen spp.) not known to consumers and currently discarded by the EU fishing fleet operating in the South West Atlantic in order to supply the EU seafood industry with a good quality raw material for human food manufacturing. Historical fishery data series (26 168 commercial hauls of which 12 745 were positive), including effort, catches and discards, as well as biological and environmental information, from 1988 onwards was used to describe and quantify patterns and spatio-temporal changes in the rockcod fishery. These data was collected by scientific observers on board commercial vessels.GIS analysis was carried out in order to study the seasonal geographical changes in the distribution of abundance, SST and densities calculated from CPUE. Fishery and environmental data as well as SST data derived from the NOAA Advanced Very High Resolution Radiometer (AVHRR), were analysed in order to find monthly variations in spatial and depth distribution of Patagonotothen spp. Preliminary results demonstrated that, within areas of occurrence, there are significant correlations between fish abundance (CPUE), the oceanographic conditions of the area (SST gradients) and depth in certain months

Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology

Clinical studies suggest that agonists at peroxisome proliferator-activated receptor gamma (PPARγ) may exert beneficial effects in patients with mild-to-moderate Alzheimer's disease (AD), but the mechanism for the potential therapeutic interest of this class of drugs has not yet been elucidated. Here, in mice overexpressing mutant human amyloid precursor protein, we found that chronic treatment with rosiglitazone, a high-affinity agonist at PPARγ, facilitated β-amyloid peptide (Aβ) clearance. Rosiglitazone not only reduced Aβ burden in the brain but, importantly, almost completely removed the abundant amyloid plaques observed in the hippocampus and entorhinal cortex of 13-month-old transgenic mice. In the hippocampus, neuropil threads containing phosphorylated tau, probably corresponding to dystrophic neurites, were also decreased by the drug. Rosiglitazone switched on the activated microglial phenotype, promoting its phagocytic ability, reducing the expression of proinflammatory markers and inducing factors for alternative differentiation. The decreased amyloid pathology may account for the reduction of p-tau-containing neuropil threads and for the rescue of impaired recognition and spatial memory in the transgenic mice. This study provides further insights into the mechanisms for the beneficial effect of rosiglitazone in AD patients