Ocean literacy in European Oceanographic Agencies: EuroGOOS recomendations for the UN Decade of Ocean Science for Sustainable Development 2021-2030. EuroGOOS Policy Brief

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Efficacy of fatty acids dietary supplement in polyethylene glycol-induced mouse model of retinal degeneration

Current knowledge of the benefits of nutrition supplements for eye pathologies is based largely on the use of appropriate animal models, together with defined dietary supplementation. Here, C57BL6 mice were subretinally injected with polyethylene glycol (PEG)-400, an established model of retinal degeneration with a dry age-related macular degeneration (AMD)-like phenotype, an eye pathology that lacks treatment. In response to PEG-400, markers of the complement system, angiogenesis,inflammation,gliosis,andmacrophageinfiltrationwereupregulatedinbothretinasand retinal pigment epithelium (RPE)/choroids, whereas dietary supplementation with a mixture based on fatty acids counteracted their upregulation. Major effects include a reduction of inflammation, in both retinas and RPE/choroids, and an inhibition of macrophage infiltration in the choroid, yet not in the retina, suggesting a targeted action through the choroidal vasculature. Histological analysis revealed a thinning of the outer nuclear layer (ONL), together with dysregulation of the epithelium layer in response to PEG-400. In addition, immunohistofluorescence demonstrated Müller cell gliosis and macrophage infiltration into subretinal tissues supporting the molecular findings. Reduced ONL thickness,gliosis,andmacrophageinfiltrationwerecounteractedbythedietsupplement. The present data suggest that fatty acids may represent a useful form of diet supplementation to prevent or limit the progression of dry AMD

A self-filling microfluidic device for noninvasive and time-resolved single red blood cell experiments

Existing approaches to red blood cell (RBC) experiments on the single-cell level usually rely on chemical or physical manipulations that often cause difficulties with preserving the RBC's integrity in a controlled microenvironment. Here, we introduce a straightforward, self-filling microfluidic device that autonomously separates and isolates single RBCs directly from unprocessed human blood samples and confines them in diffusion-controlled microchambers by solely exploiting their unique intrinsic properties. We were able to study the photo-induced oxygenation cycle of single functional RBCs by Raman microscopy without the limitations typically observed in optical tweezers based methods. Using bright-field microscopy, our noninvasive approach further enabled the time-resolved analysis of RBC flickering during the reversible shape evolution from the discocyte to the echinocyte morphology. Due to its specialized geometry, our device is particularly suited for studying the temporal behavior of single RBCs under precise control of their environment that will provide important insights into the RBC's biomedical and biophysical properties

Understanding the Ultra-Rare Disease Autosomal Dominant Leukodystrophy: an Updated Review on Morpho-Functional Alterations Found in Experimental Models

Autosomal dominant leukodystrophy (ADLD) is an ultra-rare, slowly progressive, and fatal neurodegenerative disorder associated with the loss of white matter in the central nervous system (CNS). Several years after its first clinical description, ADLD was found to be caused by coding and non-coding variants in the LMNB1 gene that cause its overexpression in at least the brain of patients. LMNB1 encodes for Lamin B1, a protein of the nuclear lamina. Lamin B1 regulates many cellular processes such as DNA replication, chromatin organization, and senescence. However, its functions have not been fully characterized yet. Nevertheless, Lamin B1 together with the other lamins that constitute the nuclear lamina has firstly the key role of maintaining the nuclear structure. Being the nucleus a dynamic system subject to both biochemical and mechanical regulation, it is conceivable that changes to its structural homeostasis might translate into functional alterations. Under this light, this review aims at describing the pieces of evidence that to date have been obtained regarding the effects of LMNB1 overexpression on cellular morphology and functionality. Moreover, we suggest that further investigation on ADLD morpho-functional consequences is essential to better understand this complex disease and, possibly, other neurological disorders affecting CNS myelination

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators

Fluctuations of the total entropy production in stochastic systems

Fluctuations of the excess heat in an out of equilibrium steady state are experimentally investigated in two stochastic systems : an electric circuit with an imposed mean current and a harmonic oscillator driven out of equilibrium by a periodic torque. In these two linear systems, we study excess heat that represents the difference between the dissipated heat out of equilibrium and the dissipated heat at equilibrium. Fluctuation theorem holds for the excess heat in the two experimental systems for all observation times and for all fluctuation magnitudes.Comment: 6

RET PLCγ Phosphotyrosine Binding Domain Regulates Ca2+ Signaling and Neocortical Neuronal Migration

The receptor tyrosine kinase RET plays an essential role during embryogenesis in regulating cell proliferation, differentiation, and migration. Upon glial cell line-derived neurotrophic factor (GDNF) stimulation, RET can trigger multiple intracellular signaling pathways that in concert activate various downstream effectors. Here we report that the RET receptor induces calcium (Ca2+) signaling and regulates neocortical neuronal progenitor migration through the Phospholipase-C gamma (PLCγ) binding domain Tyr1015. This signaling cascade releases Ca2+ from the endoplasmic reticulum through the inositol 1,4,5-trisphosphate receptor and stimulates phosphorylation of ERK1/2 and CaMKII. A point mutation at Tyr1015 on RET or small interfering RNA gene silencing of PLCγ block the GDNF-induced signaling cascade. Delivery of the RET mutation to neuronal progenitors in the embryonic ventricular zone using in utero electroporation reveal that Tyr1015 is necessary for GDNF-stimulated migration of neurons to the cortical plate. These findings demonstrate a novel RET mediated signaling pathway that elevates cytosolic Ca2+ and modulates neuronal migration in the developing neocortex through the PLCγ binding domain Tyr1015

A nutritional approach to the prevention of cancer: from assessment to personalized intervention

Among lifestyle factors, nutrition is one of the most important determinants of health, and represents a pivotal element of cancer risk. Nonetheless, epidemiological evidences of the relationship between several cancers and specific foods and nutrients is still inadequate, and solid conclusions are missing. Indeed, caloric restriction without malnutrition is associated to cancer prevention. Food may be also the primary route of exposure to contaminants such as metals, persistent organic pollutants, and pesticides. Exposuredisease associations and the interplay with genetic susceptibility requires further studies on genetic variation, environment, lifestyle, and chronic disease in order to eliminate and reduce associated health risks, thus contributing to improve health outcomes for the population. A primary nutritional approach for Active and Healthy Ageing (AHA) has been developed by the Nutrition group of the European Innovation Partnership (EIP) on AHA. The working group on lifestyles of the Italian Ministry of Health has developed a comprehensive approach to adequate nutrition using a consensus methodology to collect and integrate the available evidences from the literature and from the Italian experiences at the regional level, to raise the interest of other experts and relevant stakeholders to outline and scale-up joint strategies for a primary nutritional approach to cancer prevention