Multi-Criteria Decision Analysis as a tool to extract fishing footprints and estimate fishing pressure: application to small scale coastal fisheries and implications for management in the context of the Maritime Spatial Planning Directive

In the context of the Maritime Spatial Planning Directive and with the intention of contributing to the implementation of a future maritime spatial plan, it was decided to analyze data from the small scale coastal fisheries sector of Greece and estimate the actual extent of its activities, which is largely unknown to date. To this end we identified the most influential components affecting coastal fishing: fishing capacity, bathymetry, distance from coast, Sea Surface Chlorophyll (Chl-a) concentration, legislation, marine traffic activity, trawlers and purse seiners fishing effort and no-take zones. By means of Multi-Criteria Decision Analysis (MCDA) conducted through a stepwise procedure, the potential fishing footprint with the corresponding fishing intensity was derived. The method provides an innovative and cost-effective way to assess the impact of the, notoriously hard to assess, coastal fleet. It was further considered how the inclusion of all relevant anthropogenic activities (besides fishing) could provide the background needed to plan future marine activities in the framework of Marine Spatial Planning (MSP) and form the basis for a more realistic management approach

On planar polynomial vector fields with elementary first integrals

© 2019 Elsevier Inc. We show that under rather general conditions a polynomial differential system having an elementary first integral already must admit a Darboux first integral, and we explicitly characterize the vector fields in this class. We also investigate some exceptional cases, i.e. equations admitting an elementary first integral but not a Darboux first integral. In particular we provide a rather detailed discussion of exceptional elementary first integrals built from algebraic functions of prime degree

On the absence of analytic integrability of the Bianchi Class B cosmological models

El títol de la versió pre-print de l'article és: Analytic integrability of the Bianchi Class B cosmological modelBianchi models are cosmological models that describe space-times which are foliated by homogeneous hypersurfaces of constant time and are divided into two classes, Class A and Class B. There are many studies about the integrability of Class A. Here we study the integrability of Class B. For the homogeneous cosmological models of Class B, Einstein's system of differential equations reduces to a dynamical system of dimension seven according to Bogoyavlensky's approach. We show that in order to study the integrability of such systems it is sufficient to deal with homogeneous polynomial differential systems of dimension six. Concretely, Bianchi V is the simplest model and can be written as a homogeneous polynomial differential system of degree 2. Bianchi IV is dealt as a homogeneous polynomial differential system of degree 3 and the rest of the models, Bianchis III, V I and V II are of degree 5. Due to the fact that all Bianchi class B models have been reduced to homogeneous polynomial differential systems, the study of their analytic integrability reduces to analyze their homogeneous polynomial first integrals. We show that Bianchi model V admits polynomial first integral, and we prove that the corresponding homogeneous polynomial differential systems that represent models Bianchi IV , III, V I and V II do not admit polynomial first integrals

SARS-CoV-2/ACE2 Interaction Suppresses IRAK-M Expression and Promotes Pro-Inflammatory Cytokine Production in Macrophages

The major cause of death in SARS-CoV-2 infected patients is due to de-regulation of the innate immune system and development of cytokine storm. SARS-CoV-2 infects multiple cell types in the lung, including macrophages, by engagement of its spike (S) protein on angiotensin converting enzyme 2 (ACE2) receptor. ACE2 receptor initiates signals in macrophages that modulate their activation, including production of cytokines and chemokines. IL-1R-associated kinase (IRAK)-M is a central regulator of inflammatory responses regulating the magnitude of TLR responsiveness. Aim of the work was to investigate whether SARS-CoV-2 S protein-initiated signals modulate pro-inflammatory cytokine production in macrophages. For this purpose, we treated PMA-differentiated THP-1 human macrophages with SARS-CoV-2 S protein and measured the induction of inflammatory mediators including IL6, TNFα, IL8, CXCL5, and MIP1a. The results showed that SARS-CoV-2 S protein induced IL6, MIP1a and TNFα mRNA expression, while it had no effect on IL8 and CXCL5 mRNA levels. We further examined whether SARS-CoV-2 S protein altered the responsiveness of macrophages to TLR signals. Treatment of LPS-activated macrophages with SARS-CoV-2 S protein augmented IL6 and MIP1a mRNA, an effect that was evident at the protein level only for IL6. Similarly, treatment of PAM3csk4 stimulated macrophages with SARS-CoV-2 S protein resulted in increased mRNA of IL6, while TNFα and MIP1a were unaffected. The results were confirmed in primary human peripheral monocytic cells (PBMCs) and isolated CD14+ monocytes. Macrophage responsiveness to TLR ligands is regulated by IRAK-M, an inactive IRAK kinase isoform. Indeed, we found that SARS-CoV-2 S protein suppressed IRAK-M mRNA and protein expression both in THP1 macrophages and primary human PBMCs and CD14+ monocytes. Engagement of SARS-CoV-2 S protein with ACE2 results in internalization of ACE2 and suppression of its activity. Activation of ACE2 has been previously shown to induce anti-inflammatory responses in macrophages. Treatment of macrophages with the ACE2 activator DIZE suppressed the pro-inflammatory action of SARS-CoV-2. Our results demonstrated that SARS-CoV-2/ACE2 interaction rendered macrophages hyper-responsive to TLR signals, suppressed IRAK-M and promoted pro-inflammatory cytokine expression. Thus, activation of ACE2 may be a potential anti-inflammatory therapeutic strategy to eliminate the development of cytokine storm observed in COVID-19 patients

Cyclin-dependent kinase 9 as a potential target for anti-TNF resistant inflammatory bowel disease

BACKGROUND AND AIMS: Resistance to single cytokine blockade, namely anti-TNF therapy, is a growing concern for patients with inflammatory bowel disease (IBD). The transcription factor T-bet is a critical regulator of intestinal homeostasis, is genetically linked to mucosal inflammation and controls the expression of multiples genes such as the pro-inflammatory cytokines IFN-γ and TNF. Inhibiting T-bet may therefore offer a more attractive prospect for treating IBD but remains challenging to target therapeutically. In this study, we evaluate the effect of targeting the transactivation function of T-bet using inhibitors of P-TEFb (CDK9-cyclin T), a transcriptional elongation factor downstream of T-bet. METHODS: Using an adaptive immune-mediated colitis model, human colonic lymphocytes from IBD patients and multiple large clinical datasets, we investigate the effect of CDK9 inhibitors on cytokine production and gene expression in colonic CD4+ T cells and link these genetic modules to clinical response in patients with IBD. RESULTS: Systemic CDK9 inhibition led to histological improvement of immune-mediated colitis and was associated with targeted suppression of colonic CD4+ T cell-derived IFN-γ and IL-17A. In colonic lymphocytes from IBD patients, CDK9 inhibition potently repressed genes responsible for pro-inflammatory signalling, and in particular genes regulated by T-bet. Remarkably, CDK9 inhibition targeted genes that were highly expressed in anti-TNF resistant IBD and that predicted non-response to anti-TNF therapy. CONCLUSION: Collectively, our findings reveal CDK9 as a potential target for anti-TNF resistant IBD, which has the potential for rapid translation to the clinic

Indicator-based assessment of marine biological diversity-lessons from 10 case studies across the European seas

The Marine Strategy Framework Directive requires the environmental status of European marine waters to be assessed using biodiversity as 1 out of 11 descriptors, but the complexity of marine biodiversity and its large span across latitudinal and salinity gradients have been a challenge to the scientific community aiming to produce approaches for integrating information from a broad range of indicators. The Nested Environmental status Assessment Tool (NEAT), developed for the integrated assessment of the status of marine waters, was applied to 10 marine ecosystems to test its applicability and compare biodiversity assessments across the four European regional seas. We evaluate the assessment results as well as the assessment designs of the 10 cases, and how the assessment design, particularly the choices made regarding the area and indicator selection, affected the results. The results show that only 2 out of the 10 case study areas show more than 50% probability of being in good status in respect of biodiversity. No strong pattern among the ecosystem components across the case study areas could be detected, but marine mammals, birds, and benthic vegetation indicators tended to indicate poor status while zooplankton indicators indicated good status when included into the assessment. The analysis shows that the assessment design, including the selection of indicators, their target values, geographical resolution and habitats to be assessed, has potentially a high impact on the result, and the assessment structure needs to be understood in order to make an informed assessment. Moreover, recommendations are provided for the best practice of using NEAT for marine status assessments

An objective framework to test the quality of candidate indicators of good environmental status

This is the final version. Available from the publisher via the DOI in this record.Large efforts are on-going within the EU to prepare the Marine Strategy Framework Directive's (MSFD) assessment of the environmental status of the European seas. This assessment will only be as good as the indicators chosen to monitor the 11 descriptors of good environmental status (GEnS). An objective and transparent framework to determine whether chosen indicators actually support the aims of this policy is, however, not yet in place. Such frameworks are needed to ensure that the limited resources available to this assessment optimize the likelihood of achieving GEnS within collaborating states. Here, we developed a hypothesis-based protocol to evaluate whether candidate indicators meet quality criteria explicit to the MSFD, which the assessment community aspires to. Eight quality criteria are distilled from existing initiatives, and a testing and scoring protocol for each of them is presented. We exemplify its application in three worked examples, covering indicators for three GEnS descriptors (1, 5, and 6), various habitat components (seaweeds, seagrasses, benthic macrofauna, and plankton), and assessment regions (Danish, Lithuanian, and UK waters). We argue that this framework provides a necessary, transparent and standardized structure to support the comparison of candidate indicators, and the decision-making process leading to indicator selection. Its application could help identify potential limitations in currently available candidate metrics and, in such cases, help focus the development of more adequate indicators. Use of such standardized approaches will facilitate the sharing of knowledge gained across the MSFD parties despite context-specificity across assessment regions, and support the evidence-based management of European seas.European Union: 7th Framework ProgrammeNatural Environment Research Council (NERC)UK Department for Environment, Food and Rural Affair

An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery.

Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs