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β-Amyloid is one of the main pathological hallmarks of Alzheimer’s disease and plays a major role in synaptic dysfunction. It has been demonstrated that β-amyloid can elicit aberrant excitatory activity in cortical-hippocampal networks, which is associated with behavioral abnormalities. However, the mechanism of the spreading of β-amyloid action within a specific circuitry has not been elucidated yet. We have previously demonstrated that the motion of microglia-derived large extracellular vesicles carrying β-amyloid, at the neuronal surface, is crucial for the initiation and propagation of synaptic dysfunction along the entorhinal-hippocampal circuit. Here, using chronic EEG recordings, we show that a single injection of extracellular vesicles carrying β-amyloid into the mouse entorhinal cortex could trigger alterations in the cortical and hippocampal activity that are reminiscent of those found in Alzheimer’s disease mouse models and human patients. The development of EEG abnormalities was associated with progressive memory impairment as assessed by an associative (object-place context recognition) and non-associative (object recognition) task. Importantly, when the motility of extracellular vesicles, carrying β-amyloid, was inhibited, the effect on network stability and memory function was significantly reduced. Our model proposes a new biological mechanism based on the extracellular vesicles mediated progression of β-amyloid pathology and offers the opportunity to test pharmacological treatments targeting the early stages of Alzheimer’s disease.

The nitric oxide (NO)/cGMP pathway has been extensively studied for its pivotal role in synaptic plasticity and memory processes, resulting in an increase of cAMP response element-binding (CREB) phosphorylation, and consequent synthesis of plasticity-related proteins. The NO/cGMP/CREB signaling is downregulated during aging and neurodegenerative disorders and is affected by Amyloid-β peptide (Aβ) and tau protein, whose increase and deposition is considered the key pathogenic event of Alzheimer's disease (AD). On the other hand, in physiological conditions, the crosstalk between the NO/cGMP/PKG/CREB pathway and Aβ ensures long-term potentiation and memory formation. This review summarizes the current knowledge on the interaction between the NO/cGMP/PKG/CREB pathway and Aβ in the healthy and diseased brain, offering a new perspective to shed light on AD pathophysiology. We will focus on the synaptic mechanisms underlying Aβ physiological interplay with cGMP pathway and how this balance is corrupted in AD, as high levels of Aβ interfere with NO production and cGMP molecular signaling leading to cognitive impairment. Finally, we will discuss results from preclinical and clinical studies proposing the increase of cGMP signaling as a therapeutic strategy in the treatment of AD.

CERN/NASA “Accelerating the Adoption of Open Science”, from July 10th-14th at CERN in Geneva, Switzerland https://indico.cern.ch/event/1254282/ 12 July 2023 (Day 3)Open-Source for Open Science Watch the recording of this contribution here:https://cds.cern.ch/record/2865009

Research hardware represents physical artifacts and may incorporate mechanical, electrical, and even software components. It is an inherent part of research, together with research data and research software. However, while the latter have been recognized as research outputs by funders and institutions (leading for example to the creation of novel career paths in academia), research hardware has not received much attention so far. There is also no specific publication pathway or specific repositories for hardware documentation. In 2022, the Open.Make project collected user stories about researchers' perspectives on hardware publication. They combined this knowledge with the work of the FAIR Principles for Research Hardware RDA interest group and experience in hardware engineering to propose a hardware publication system. In this workshop, this proposition was discussed with professionals in scholarly communication, institutions and political influencers. The goal was to create a roadmap for the creation of an ecosystem for the recognition of hardware as a research output, its quality control and therefore a publication system for research hardware engineers.

Executive summary “Open science hardware” (OSH) refers to any piece of hardware used for scientific research that can be obtained, assembled, used, studied, modified, shared, and sold by anyone. It includes standard lab equipment as well as auxiliary materials. This report explains how research institutions and science funders can better promote open science hardware. Researchers today are both developers and users of OSH. Their work is essential for users inside and outside academia, but they get no institutional support. Tech transfer offices are a natural contact point, but their IP-focused work pushes OSH out of their scope. Most OSH developers are early career researchers who find it impossible to make their work visible for promotion. Today there is a real risk of losing key personnel. --> What can institutions do TODAY: Legitimize & Nurture Institutions can immediately support OSH by incorporating it as a core component of open science strategies, by building institutional capabilities at TTOs or OSPOs for supporting practitioners, and by raising awareness through students’ and researchers training to incentivize OSH demand. --> What can institutions do NEXT: Standardize & Recognize A necessary follow up for an OSH strategy includes enforcing documentation standards for OSH, creating Research Hardware Engineer roles for OSH developers, and including OSH as a pathway in entrepreneurship training and business incubators. --> What can institutions do LONG TERM: Assess & Reinforce A long-term vision for establishing OSH demands developing criteria for assessing its broader social impact and incentivizing professionalization through minimal OSH preference in purchase policies. Timing is key: Enforcing standards can only happen once OSH work is recognized and incentivized, otherwise there is risk of generating “just another checklist”. Nurturing OSH business models will set the foundations for professionalizing OSH, necessary for implementing purchase preference policies. About the Report This document was written by Dr. Julieta Arancio as part of her postdoctoral work, based on the results of a real-time Delphi survey with OSH experts (see contributors in this record). Special thanks to Dr. Gwen Ottinger, who provided extremely valuable insights for turning various drafts into the final document, and to the experts who provided their valuable input for this study. Report and website design by SAYGRID. Access to the Real-Time Delphi platform was kindly provided by 4strat. Anonymized raw data can be accessed at 10.5281/zenodo.8074180. A full description of methods can be found in the pdf document., This work was supported by the Alfred P. Sloan Foundation, grant number 2020-14078.

Aim High alpine regions are threatened but understudied ecosystems that harbor diverse endemic species, making them an important biome for testing the role of environmental factors in driving functional trait-mediated community assembly processes. We tested the hypothesis that plant-soil feedbacks along a climatic and elevation gradient influence plant community assembly through shifts in habitat suitability, which drive plant functional, phylogenetic, and spectral diversity. Location In a high mountain system (2400-3500 m) of Región Metropolitana in the Chilean Andes (33°S, 70°W). Methods We surveyed vegetation and spectroscopic reflectance (400-2400 nm) to quantify taxonomic, phylogenetic, functional, and spectral diversity at five sites from 2400 m to 3500 m elevation. We characterized soil attributes and processes by measuring water content, carbon and nitrogen, and net nitrogen mineralization rates. Results At high elevation, colder temperatures reduced available soil nitrogen, while at warmer, lower elevations, soil moisture was lower. Metrics of taxonomic, functional, and spectral alpha diversity peaked at mid-elevations, while phylogenetic species richness was highest at low elevation. Leaf nitrogen increased with elevation at the community level and within individual species, consistent with global patterns of increasing leaf nitrogen with colder temperatures. Main conclusions The increase in leaf nitrogen, coupled with shifts in taxonomic and functional diversity associated with turnover in lineages, indicate that the ability to acquire and retain nitrogen in colder temperatures may be important in plant community assembly in this range. Such environmental filters have important implications for forecasting shifts in alpine plant communities under a warming climate.

Actas del 3er Congreso de Ciencia Abierta y Ciudadana, que incluye los resúmenes de las conferencias, las sesiones temáticas, los talleres y los pósters., Universidad Nacional de La Plata

Streptomyces coelicolor is a model organism for studying streptomycetes. This genus possesses relevant medical and economical roles, because it produces many biologically active metabolites of pharmaceutical interest, including the majority of commercialized antibiotics. In this bioinformatic study, the transcriptome of S. coelicolor has been analyzed to identify novel RNA species and quantify the expression of both annotated and novel transcripts in solid and liquid growth medium cultures at different times. The major characteristics disclosed in this study are: (i) the diffuse antisense transcription; (ii) the great abundance of transfer-messenger RNAs (tmRNA); (iii) the abundance of rnpB transcripts, paramount for the RNase-P complex; and (iv) the presence of abundant fragments derived from pre-ribosomal RNA leader sequences of unknown biological function. Overall, this study extends the catalogue of ncRNAs in S. coelicolor and suggests an important role of non-coding transcription in the regulation of biologically active molecule production.

Made available in DSpace on 2022-04-28T19:52:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-03-18 Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale. Department of Biology University of Toronto Mississauga ON Centre for Urban Environments University of Toronto Mississauga ON Department of Biology University of North Carolina, Chapel Hill Department of Biology University of Louisiana LA Department of Biology Queen's University ON Department of Biology Concordia University QC Department of Biological Sciences DePaul University Department of Biology DePauw University IN Department of Urban Design and Planning, University of Washington, Seattle, WA, USA Colegio de Ciencias Biológicas y Ambientales Universidad San Francisco de Quito USFQ Department of Genetics University of Georgia Department of Ecology and Genetics Evolutionary Biology Centre Uppsala University Field Science Center for Northern Biosphere Hokkaido University Natural History Museum Zoology University of New England NSW Programa de Pós-Graduação em Geografia da UFMT campus de Rondonópolis Department of Botany and Biodiversity Research Centre University of British Columbia Graduate Program in Genome Sciences and Technology Genome Sciences Centre University of British Columbia Department of Microbiology and Immunology University of British Columbia Red de Biología Evolutiva Instituto de Ecología A. C. School of the Environment Yale University CT Departamento de Ciencias Ecológicas Universidad de Chile, Facultad de Ciencias Instituto de Ecología y Biodiversidad Universidad de Chile Department of Biology Mount Allison University Red de Ecoetología Instituto de Ecología A. C. Department of Biology University of Ottawa ON Department of Zoology University of Cambridge Department of Biology, Washington University in St. Louis, St. Louis, MO, USA Department of Biology University of Miami FL Centro de Investigación en Recursos Naturales y Sustentabilidad (CIRENYS) Universidad Bernardo O'Higgins Department of Biology, University of La Verne, La Verne, CA, USA Département des sciences du bois et de la forêt Université Laval QC Evolution & Ecology Research Centre School of Biological Earth and Environmental Sciences UNSW Sydney NSW Department of Biology Ghent University Department of Biology Monmouth University West Long Branch Centre for Ecology Evolution and Environmental Changes Faculdade de Ciências Universidade de Lisboa Lisboa Department of Biology KU Leuven School of Agriculture and Environment Wildlife and Ecology group Massey University, Palmerston North Department of Biological Sciences University of Cape Town Institute of Landscape Ecology University of Münster Gosnell School of Life Sciences, Rochester Institute of Technology, Rochester, NY, USA Department of Biological Sciences University of Alberta AB Louis Calder Center and Department of Biological Sciences, Fordham University, Armonk, NY, USA Departamento de Ecología Tropical, Universidad Autónoma de Yucatán, Mérida, Yucatán, México School of Life Sciences University of Sussex Department of Ecology Environment and Plant Sciences Stockholm University iBIOTROP Instituto de Biodiversidad Tropical Universidad San Francisco de Quito Department of Biology, San Francisco State University, San Francisco, CA, USA Unidad de Recursos Naturales, Centro de Investigación Científica de Yucatán AC, Mérida, Yucatán, México School of Ecological and Environmental Sciences East China Normal University Shanghai Engineering Research Center of Sustainable Plant Innovation Centre for Ecosystem Science School of Biological Earth and Environmental Sciences UNSW Sydney NSW Department of Ecology and Evolutionary Biology University of Michigan MI Department of Biosciences Rice University TX IFEVA Universidad de Buenos Aires Facultad de Agronomía, CONICET Biology Department Saint Mary's University NS Department of Biological Sciences, Universidad de los Andes Department of Biology and Biochemistry University of Houston TX Université de Rennes Department of Zoology and Biodiversity Research Centre University of British Columbia Department of Environmental Studies Dordt University Sioux Center IA Department of Biology Minneapolis Community and Technical College MN Department of Natural Sciences Ecology and Environment Research Centre Manchester Metropolitan University Instituto de Investigaciones en Ecosistemas y Sustentabilidad UNAM Department of Botany School of Biology Aristotle University of Thessaloniki Faculty of Biological and Environmental Science Organismal & Evolutionary Biology Research Programme University of Helsinki Institute of Biodiversity Animal Health and Comparative Medicine University of Glasgow Department of Biology Hendrix College Department of Ecological Science Vrije Universiteit Amsterdam Departamento de Ciencias Biológicas y Agropecuarias Universidad Técnica Particular de Loja Departamento de Biologia Universidade Federal de Santa Maria (UFSM) Department of Plant Sciences School of Biology College of Science University of Tehran NTNU University Museum Norwegian University of Science and Technology Red de Estudios Moleculares Avanzados Instituto de Ecología A. C. School of Biological Sciences, University of Reading, Whiteknights Park, Reading, Berkshire, UK Department of Biology Northern Arizona University AZ Department of Biological Sciences MacEwan University AB Max Planck Institute for Plant Breeding Research Departamento de Ecología Evolutiva Instituto de Ecología Universidad Nacional Autónoma de México Max Planck Institute of Molecular Plant Physiology Potsdam-Golm BIO5 Institute University of Arizona AZ Alaska Center for Conservation Science University of Alaska Anchorage Tropical Diversity, Royal Botanical Garden of Edinburgh Département de biologie Université de Moncton Department of Biological Sciences University of Manitoba MB Departments of Microbiology & Statistics University of Manitoba MB Department of Biology University of New Brunswick Department of Biology Kalamazoo College MI BioProtection Research Centre Lincoln University Departamento de Ciencias Facultad de Artes Liberales Universidad Adolfo Ibáñez Department of Ecology Evolution Behaviour University of Minnesota MN Department of Biological Sciences Brock University Department of Environmental Toxicology, University of California, Davis, CA, USA ICB - University of Talca School of Molecular and Life Science Curtin University College of Science Health Engineering and Education Murdoch University, Murdoch School of Life and Environmental Sciences University of Sydney NSW School of Biological Sciences, Monash University, Melbourne, VIC, Australia Department of Biological Sciences Wayne State University MI Department of Biology Western Oregon University, OR School of Natural Resources and the Environment University of Arizona AZ Departamento de Ecología Humana, Cinvestav Mérida Departamento de Ciencias Biológicas y Departamento de Ecología y Biodiversidad Facultad de Ciencias de la Vida, Universidad Andrés Bello Institute of Ecology and Biodiversity (IEB) Department of Biology Lund University Department of Biology Norwegian University of Science and Technology Escuela Superiro de Desarrollo Sustentable Universidad Autónoma de Guerrero -CONACYT Clarkson Secondary School Peel District School Board ON Homelands Sr. Public School Peel District School Board ON Department of Biological Sciences University of Illinois at Chicago Dufferin-Peel Catholic District School Board, St. James Catholic Global Learning Centre Department of Biosciences University of Calgary AB Ecological Processes Branch U.S. Army ERDC-CERL Department of Biology, Oberlin College, Oberlin, OH, USA Escuela Nacional de Estudios Superiores Unidad Morelia UNAM Institute of Evolution and Ecology University of Tübingen Tübingen Department of Evolutionary Biology and Environmental Studies University of Zurich, Winterthurerstrasse Urban Wildlife Institute Department of Conservation and Science, Lincoln Park Zoo Departamento de Ecología Universidad Católica de la Santísima Concepción Department of Biological Sciences University of Denver CO Department of Biological Sciences Mississippi State University MS Department of Biology Center for Computational & Integrative Biology Rutgers University-Camden Kunming Institute of Botany Chinese Academy of Sciences Department of Chemistry & Biochemistry Laurentian University ON Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering College of Life Sciences Beijing Normal University School of BioSciences, University of Melbourne, Melbourne, VIC, Australia Posgrado en Ciencias Biológicas Universidad Nacional Autónoma de México Department of Biological Sciences, Auburn University, Auburn, AL, USA Department of Entomology and Nematology, University of California, Davis, CA, USA Department of Biology University of New Mexico NM Department of Biology University of Wisconsin - Eau Claire Agriculture Institute Iranian Research Organization for Science and Technology (IROST) Department of Biology Colby College ME Instituto de Biología Universidad de Antioquia Department of Biology University of Massachusetts Boston MA Agricultural Biology Colorado State University CO Departamento de Biología Vegetal y Ecología Facultad de Biología Universidad de Sevilla, Av. Reina Mercedes s/n Facultad de Estudios Interdisciplinarios Centro GEMA- Genómica Universidad Mayor Evolutionary Ecology Group Naturalis Biodiversity Center Department of Biology and Chemistry Nipissing University ON, North Bay Center for Ecological Research Kyoto University Bonanza Creek Long Term Ecological Research Program University of Alaska Fairbanks Department of Botany and Molecular Evolution Senckenberg Research Institute and Natural History Museum Frankfurt Departamento de Biodiversidade Instituto de Biociências Univ Estadual Paulista - UNESP Nelson Institute for Environmental Studies University of Wisconsin-Madison WI Department of Biology, California State University, Northridge, Los Angeles, CA, USA Department of Ecology Swedish University of Agricultural Sciences Facultad de Ciencias y Biotecnologia Universidad CES Department of Biology Hofstra University Faculty of Biosciences and Aquaculture Nord University, Bodø Division of Biological Sciences, University of California San Diego, San Diego, CA, USA Department of Biology University of Richmond VA Estación de Biodiversidad Tiputini Colegio de Ciencias Biológicas y Ambientales Universidad San Francisco de Quito USFQ Department of Biological Sciences Institute of Environment Florida International University FL Agronomy Department University of Almería Department of Biological Sciences and Center for Urban Ecology and Sustainability Butler University IN Department of Biological Sciences Louisiana State University LA Faculty of Biological Sciences, Goethe University Frankfurt Institute of Biology Leiden Leiden University Department of Biological and Environmental Science University of Jyväskylä Jyväskylä Department of Biology University of Louisville KY Organization for Programs on Environmental Science University of Tokyo CNRS AgroParisTech Ecologie Systématique et Evolution, Université Paris-Saclay Department of Biology, Providence College, Providence, RI, USA General Zoology Institute for Biology Martin Luther University Halle-Wittenberg International Arctic Research Center University of Alaska Fairbanks Science, Technology and Society Department, Rochester Institute of Technology, Rochester, NY, USA SLU Swedish Species Information Centre Swedish University of Agricultural Sciences Department of Biology Westfield State University MA Centre of New Technologies University of Warsaw Department of Biology, Stanford University, Stanford, CA, USA Plant Biology Department Michigan State University MI Biology Department Davidson College College of Horticulture and Forestry Sciences/ Hubei Engineering Technology Research Center for Forestry Information Huazhong Agricultural University School of Life Sciences Technical University of Munich School of Life Sciences Lanzhou University Institute of Ecology and Evolution University of Bern Department of Evolution Ecology and Behaviour University of Liverpool Departamento de Biodiversidade Instituto de Biociências Univ Estadual Paulista - UNESP

Open science hardware (OSH) is a term frequently used to refer to artifacts, but also to a practice, a discipline and a collective of people worldwide pushing for open access to the design of tools to produce scientific knowledge. The Global Open Science Hardware (GOSH) movement gathers actors from academia, education, the private sector and civil society advocating for OSH to be ubiquitous by 2025. This paper examines the GOSH movement’s emergence and main features through the lens of transitions theory and the grassroots innovation movements framework. GOSH is here described embedded in the context of the wider open hardware movement and analyzed in terms of framings that inform it, spaces opened up for action and strategies developed to open them. It is expected that this approach provides insights on niche development in the particular case of transitions towards more plural and democratic sociotechnical systems.

Changes in science funders’ mandates have resulted in advances in open access to data, software, and publications. Research capacity, however, is still unequally distributed worldwide, hindering the impact of these efforts. We argue that to achieve the Sustainable Development Goals (SDGs), open science policies must shift focus from products to processes and infrastructure, including access to open source scientific equipment. This article discusses how conventional, black box, proprietary approaches to science hardware reinforce inequalities in science and slow down innovation everywhere, while also representing a threat to research capacity strengthening efforts. We offer science funders three policy recommendations to promote open science hardware for research capacity strengthening: a) incorporating open hardware into existing open science mandates, b) incentivizing demand through technology transfer and procurement mechanisms, c) promoting the adoption of open hardware in national and regional service centers. We expect this agenda to foster capacity building towards enabling the more equitable and efficient science needed to achieve the SDGs.

La desigualdad territorial asociada a la localización de población y actividades, al acceso a infraestructuras y servicios, al empleo y a las condiciones materiales de vida, es una realidad histórica en América Latina. Este fenómeno acompañó las demandas de los sucesivos modelos de desarrollo y desde mediados del siglo xx se comenzó a reconocer en su total complejidad a la par de la instalación de gobiernos desarrollistas. Consecuentemente, se adoptaron diversas políticas públicas que no lograron incidir significativamente sobre esas desigualdades ni aten­der a sus consecuencias sociales. Ante la necesidad de reformular enfoques, optimizar recur­sos y sortear obstáculos en la concreción de las políticas públicas, este trabajo busca analizar críticamente las políticas en agenda de gobierno en Argentina a partir del cambio de gestión concretado a fines de 2019, identificando las limitaciones, logros y potencialidades de las po­líticas propuestas en Argentina, Brasil y México y sus efectos sobre la desigualdad territorial.

CNOT2 haploinsufficiency underlies a rare neurodevelopmental disorder named Intellectual Developmental disorder with NAsal speech, Dysmorphic Facies, and variable Skeletal anomalies (IDNADFS, OMIM 618608). The condition clinically overlaps with chromosome 12q15 deletion syndrome, suggesting a major contribution of CNOT2 haploinsufficiency to the latter. CNOT2 is a member of the CCR4-NOT complex, which is a master regulator of multiple cellular processes, including gene expression, RNA deadenylation, and protein ubiquitination. To date, less than 20 pathogenic 12q15 microdeletions encompassing CNOT2, together with a single truncating variant of the gene, and two large intragenic deletions have been reported. Due to the small number of affected subjects described so far, the clinical profile of IDNADFS has not been fully delineated. Here we report five unrelated individuals, three of which carrying de novo intragenic CNOT2 variants, one presenting with a multiexon intragenic deletion, and an additional case of 12q15 microdeletion syndrome. Finally, we assess the features of IDNADFS by reviewing published and present affected individuals and reevaluate the clinical phenotype of this neurodevelopmental disorder.

Jubaea chilensis (Molina) Baill., also named Chilean palm, is an endemic species found in the coastal area of Mediterranean sclerophyllous forest in Chile. It has a highly restricted and fragmented distribution along the coast, being under intense exploitation and anthropogenic impact. Based on 1038 SNP markers, we evaluated the genetic diversity and population structure among six J. chilensis natural groups encompassing 96% of the species distribution. We observed low levels of genetic diversity, a deficit of heterozygotes (mean HE = 0.024; HO = 0.014), and high levels of inbreeding (mean FIS = 0.424). The fixation index (FST) and Nei’s genetic distance pairwise comparisons indicated low to moderate structuring among populations. There was no evidence of isolation by distance (r = −0.214, p = 0.799). In the cluster analysis, we observed a closer relationship among Culimo, Cocalán, and Candelaria populations. Migration rates among populations were low, except for some populations with moderate values. The K value that best represented the spatial distribution of genetic diversity was ∆K = 3. Habitat fragmentation, deterioration of the sclerophyllous forest, lack of long-distance dispersers, and a natural regeneration deficit may have driven inbreeding and low levels of genetic diversity in the palm groves of J. chilensis. Although extant populations are not at imminent risk of extinction, the rate of inbreeding could increase and migration could decrease if the effects of climate change and human impact become more acute.

Simple Summary P-selectin glycoprotein ligand-1 (PSGL-1), coded by the SELPLG gene, is the major ligand of selectins and plays a pivotal role in tethering, rolling and extravasation of immune cells. PSGL-1 involvement in core molecular programs, such as SYK, PLCγ2, PI3Kγ or MAPK pathways, suggests additional functions beyond the modulation of cell trafficking. Recently, several studies identified a novel mechanism responsible for PSGL-1-mediated immune suppression in the tumor microenvironment and proved a novel concept of PSGL-1 as a critical checkpoint molecule for tumor immunotherapy. The immunotherapeutic approach has gained an ever-growing interest in the treatment of several hematological malignancies, and in particular, novel targets for immunotherapy are still highly sought-after in T-cell lymphomas. Based on our results obtained through gene expression profiling and immunohistochemical analysis, PSGL-1, already suggested as a potential target in multiple myeloma humoral immunotherapy, could be considered noteworthy among the candidates. Abstract Due to the high expression of P-selectin glycoprotein ligand-1 (PSGL-1) in lymphoproliferative disorders and in multiple myeloma, it has been considered as a potential target for humoral immunotherapy, as well as an immune checkpoint inhibitor in T-cells. By investigating the expression of SELPLG in 678 T- and B-cell samples by gene expression profiling (GEP), further supported by tissue microarray and immunohistochemical analysis, we identified anaplastic large T-cell lymphoma (ALCL) as constitutively expressing SELPLG at high levels. Moreover, GEP analysis in CD30+ ALCLs highlighted a positive correlation of SELPLG with TNFRSF8 (CD30-coding gene) and T-cell receptor (TCR)-signaling genes (LCK, LAT, SYK and JUN), suggesting that the common dysregulation of TCR expression in ALCLs may be bypassed by the involvement of PSGL-1 in T-cell activation and survival. Finally, we evaluated the effects elicited by in vitro treatment with two anti-PSGL-1 antibodies (KPL-1 and TB5) on the activation of the complement system and induction of apoptosis in human ALCL cell lines. In conclusion, our data demonstrated that PSGL-1 is specifically enriched in ALCLs, altering cell motility and viability due to its involvement in CD30 and TCR signaling, and it might be considered as a promising candidate for novel immunotherapeutic approaches in ALCLs.

Citrus limon (L.) Burm. F. is an important evergreen fruit crop whose rhizosphere and phyllosphere microbiota have been characterized, while seed microbiota is still unknown. Bacterial and fungal endophytes were isolated from C. limon surface-sterilized seeds. The isolated fungi—belonging to Aspergillus, Quambalaria and Bjerkandera genera—and bacteria—belonging to Staphylococcus genus—were characterized for indoleacetic acid production and phosphate solubilization. Next Generation Sequencing based approaches were then used to characterize the endophytic bacterial and fungal microbiota structures of surface-sterilized C. limon seeds and of shoots obtained under aseptic conditions from in vitro growing seedlings regenerated from surface-sterilized seeds. This analysis highlighted that Cutibacterium and Acinetobacter were the most abundant bacterial genera in both seeds and shoots, while Cladosporium and Debaryomyces were the most abundant fungal genera in seeds and shoots, respectively. The localization of bacterial endophytes in seed and shoot tissues was revealed by Fluorescence In Situ Hybridization coupled with Confocal Laser Scanning Microscopy revealing vascular bundle colonization. Thus, these results highlighted for the first time the structures of endophytic microbiota of C. limon seeds and the transmission to shoots, corroborating the idea of a vertical transmission of plant microbiota and suggesting its crucial role in seed germination and plant development.

l presente trabajo tiene por objetivo analizar el despliegue territorial de activi-dades clave de la economía extractiva intensiva en Argentina desde la década del 90 a la actualidad, comparando el cultivo de la soja en Charata y Villa Ángela (Provincia de Chaco), la minería a cielo abierto en Belén, Hualfín y Andalgalá (Provincia de Catamarca) y la extracción de hidrocarburos no convencionales en Añelo y Rincón de los Sauces (Provincia de Neuquén). Se indaga en la arti-culación de las actividades con su entorno regional y en la relación global-local. Como resultados se observaron diferentes desempeños vinculados a la generación de empleo y atracción de población, a las dinámicas económicas locales y a la generación de actividades complementarias, como a las políticas públicas que direccionaron su desarrollo. Este estudio permitió pensar, en función de ello, su comportamiento como enclaves regionales.

Background: The serine/threonine protein phosphatase, PP2A, is thought to play a central role in the molecular pathogenesis of Alzheimer’s disease (AD), and the activity and substrate specificity of PP2A is regulated, in part, through methylation and demethylation of its catalytic subunit. Previously, we found that transgenic overexpression of the PP2A methyltransferase, LCMT-1, or the PP2A methylesterase, PME-1, altered the sensitivity of mice to impairments caused by acute exposure to synthetic oligomeric amyloid-β (Aβ). Objective: Here we sought to test the possibility that these molecules also controlled sensitivity to impairments caused by chronically elevated levels of Aβ produced in vivo. Methods: To do this, we examined the effects of transgenic LCMT-1, or PME-1 overexpression on cognitive and electrophysiological impairments caused by chronic overexpression of mutant human APP in Tg2576 mice. Results: We found that LCMT-1 overexpression prevented impairments in short-term spatial memory and synaptic plasticity in Tg2576 mice, without altering APP expression or soluble Aβ levels. While the magnitude of the effects of PME-1 overexpression in Tg2576 mice was small and potentially confounded by the emergence of non-cognitive impairments, Tg2576 mice that overexpressed PME-1 showed a trend toward earlier onset and/or increased severity of cognitive and electrophysiological impairments. Conclusion: These data suggest that the PP2A methyltransferase, LCMT-1, and the PP2A methylesterase, PME-1, may participate in the molecular pathogenesis of AD by regulating sensitivity to the pathogenic effects of chronically elevated levels of Aβ.

Brain accumulation of soluble oligomers of the amyloid-β peptide (AβOs) has been implicated in synapse failure and memory impairment in Alzheimer’s disease. Here, we show that treatment with NUsc1, a single-chain variable fragment antibody (scFv) that selectively targets AβOs, prevents the inhibition of long-term potentiation in hippocampal slices and memory impairment induced by AβOs in mice. As a therapeutic approach for intracerebral antibody delivery, we developed an adeno-associated virus vector to drive neuronal expression of NUsc1 (AAV-NUsc1) within the brain. Transduction by AAV-NUsc1 induced NUsc1 expression and secretion in adult human brain slices, and inhibited AβO binding to neurons and AβO-induced loss of dendritic spine loss in primary rat hippocampal cultures. Treatment of mice with AAV-NUsc1 prevented memory impairment induced by AβOs and, importantly, reversed memory deficits in aged APPswe/PS1ΔE9 Alzheimer’s disease model mice. These results support the feasibility of gene-mediated immunotherapy using single-chain antibodies as a potential therapeutic approach in Alzheimer’s disease.

La plastica costituisce la componente più abbondante dei rifiuti in ambiente marino. Le plastiche in mare sono colonizzate da biofilm microbici, denominati plastisfera, che possono comprendere patogeni, specie algali tossiche e invasive e, potenzialmente, organismi in grado di biodeteriorare e degradare le plastiche (Zettler et al. 2013). Lo scopo di questo lavoro è studiare e confrontare le comunità microbiche che colonizzano plastiche biodegradabili e non biodegradabili in ambiente marino. Un esperimento di esposizione di film plastici in ambiente marino portuale è stato allestito per studiare la diversità della plastisfera di alcune plastiche biodegradabili (Mater Bi e PLA-acido polilattico) e non biodegradabili (PET-polietilene tereftalato e HDPE-polietilene ad alta densità). I film plastici sono stati immersi nel bacino La Cala di Palermo in due siti a 2 e 9 metri di profondità e prelevati dopo una esposizione di uno e tre mesi. La biomassa microbica reclutata sulle plastiche è stata stimata al termine dei due periodi di esposizione mediante quantizzazione del DNA totale estratto e conte vitali. La struttura del biofilm è stata osservata attraverso microscopia elettronica a scansione (SEM). La diversità della componente coltivabile dopo tre mesi di esposizione è stata studiata mediante isolamento su terreni di coltura per batteri marini eterotrofi e sequenziamento del gene 16SrRNA. La biodiversità della comunità microbica totale delle plastiche esposte nel sito a maggiore profondità, meno soggette all’influenza della luce solare, è stata analizzata dopo un mese di esposizione mediante analisi dello spaziatore intergenico ribosomale procariotico ITS (Automated Ribsomal Intergenic Spacer Analysis-ARISA) e analisi metagenomica 16SrRNA (Next Generation Sequencing) dopo tre mesi di esposizione. Le potenzialità degradative delle comunità microbiche sono state valutate con analisi gravimetrica. Dopo un’esposizione di 1 e 3 mesi in ambiente marino si osserva un’elevata capacità di colonizzazione microbica su tutti i tipi di plastica ed una tendenza della carica batterica ad aumentare nel tempo. L’osservazione al SEM rivela la presenza di diatomee, strutture filamentose e cellule batteriche sulla superficie delle plastiche. Le plastiche biodegradabili ospitano un maggior numero di batteri coltivabili ed una maggiore biomassa rispetto alle non biodegradabili2. Gli isolati ottenuti dopo tre mesi di esposizione sono stati affiliati ai generi Pseudoalteromonas e Vibrio. L’analisi fingerprinting ARISA sul DNA totale estratto dai biofilm mostra alta beta diversità tra le comunità microbiche di plastiche diverse già dopo un mese di esposizione e maggiori livelli di alfa diversità delle comunità associate al Mater Bi. L’analisi metagenomica condotta sul biofilm adeso a Mater Bi e HDPE (rappresentativi rispettivamente delle plastiche biodegradabili e non biodegradabili) dopo tre mesi di esposizione in mare rivela comunità microbiche in parte differenti e un arricchimento di potenziali patogeni, in particolare delle famiglie Vibrionaceae e Flavobacteriaceae. Sul Mater Bi (bioplastica a base di amido di mais e oli vegetali), che dopo tre mesi di esposizione in mare mostra una perdita di peso del 25% circa rispetto al peso iniziale (Catania et al. 2019), risulta particolarmente abbondante la famiglia Cellvibrionaceae, che comprende membri in grado di degradare polisaccaridi e carboidrati complessi, quali cellulosa, agar, chitina, amido e che potrebbe avere un ruolo nella degradazione del Mater Bi in ambiente marino. I risultati mostrano che tutte le plastiche sono colonizzate da un biofilm microbico che tende ad aumentare in complessità e biomassa nel tempo. Le analisi colturali e molecolari suggeriscono che la struttura del biofilm e la composizione delle comunità microbiche che lo costituiscono sono in parte influenzate dal tipo di substrato/polimero e dal tempo di esposizione e che si differenziano già dopo un mese di esposizione in ambiente marino. La componente coltivabile tuttavia mostra bassi livelli di diversità e non si differenzia tra le plastiche analizzate.

BACKGROUND: Although the widespread use of factor VIII/IX replacement therapy has significantly reduced the severity of arthropathy in persons with haemophilia (PWH), some develop degenerative joint changes, associated with significant pain. The aim of this survey was to investigate the management and perception of pain among Italian physicians who treat PWH. MATERIALS AND METHODS: Between September and October 2017, a questionnaire was distributed to 35 Italian haemophilia treatment centres (60 physicians). RESULTS: Fifty-three haemophilia specialists completed the survey. We found that there was good agreement (98.1%) on the need to investigate pain at each clinical visit, but there was heterogeneity in the opinions of haemophilia specialists with regards to the availability of validated guidelines (35.8%) and whether pain specialists should be a part of the comprehensive care team in daily clinical practice (58.5%). Haemophilia specialists also agreed pain should be evaluated using a rating scale validated in PWH (88.7%). Pain was mainly managed by the haemophilia specialists themselves, supported by a physiatrist and physiotherapist, while a pain specialist was only involved in 26.4% of cases. The combination of paracetamol with tramadol or codeine was the most common first-line treatment, while cyclo-oxygenase-2 inhibitors, non-steroidal anti-inflammatory drugs, and opioids were less commonly used. DISCUSSION: There are some unmet needs in Italy regarding pain management for PWH and the management of pain in these patients by haemophilia specialists. There is a lack of evidence-based guidelines for these specialists to use, as well as a reluctance to involve pain specialists. The lack of spontaneous reporting of pain by PWH, despite using pain relief, highlights the need for clinicians to actively ask patients about any pain they may be experiencing.

The natriuretic peptide (NP) system comprises of three ligands, the Atrial Natriuretic Peptide (ANP), Brain Natriuretic peptide (BNP) and C-type Natriuretic peptide (CNP), and three natriuretic peptide receptors, NPRA, NPRB and NPRC. Here we present a comprehensive study of the natriuretic peptide system in healthy murine and human submandibular salivary glands (SMGs). We show CNP is the dominant NP in mouse and human SMG and is expressed together with NP receptors in ducts, autonomic nerves and the microvasculature of the gland, suggesting CNP autocrine signalling may take place in some of these glandular structures. These data suggest the NP system may control salivary gland function during homeostasis through the regulation of electrolyte re-absorption, neural stimulation and/or blood vessel wall contraction/relaxation. We also show abnormal expression of NPRA in the stroma of a subset of human SMGs resected from patients diagnosed with oral squamous cell carcinoma (OSCC) of non-salivary gland origin. This finding warrants further research to investigate a possible correlation between early OSCC invasion and NPRA overexpression.

The present study is aimed to assess and characterize the structure of bacterial community in advanced activated sludge systems. In particular, activated sludge samples were collected from an Integrated Fixed-film Activated Sludge – Membrane Bioreactor pilot plant under a University of Cape Town configuration with in-series anaerobic (Noair)/anoxic (Anox)/aerobic (Oxy) reactors – and further analyzed. The achieved results – based on Next Generation Sequencing (NGS) of 16S rDNA amplicons – revealed that the bacterial biofilm (bf) communities on plastic carriers of Oxy and Anox reactors had a greater diversity compared to suspended (sp) bacterial flocs of Oxy, Anox and Noair. Indeed, the Shannon diversity indices of both biofilm communities were higher than those of suspended growth samples (Oxy-bf = 4.1 and Anox-bf = 4.2 vs. Oxy-sp = 3.4, Anox-sp = 3.5 and Noair-sp = 3.4). The most striking differences have been reported in Rhodobacteraceae being more abundant in biofilm specimens than in suspended biomass samples. The vast majority of the identified bacteria differs from those obtained by culture dependent method, thus suggesting that NGS-based method is really suitable to analyze the bacterial community composition, even in advanced systems for wastewater treatment.

International audience; The accumulation of soluble oligomers of the amyloid-β peptide (AβOs) in the brain has been implicated in synapse failure and memory impairment in Alzheimer's disease. Here, we initially show that treatment with NUsc1, a single-chain variable-fragment antibody (scFv) that selectively targets a subpopulation of AβOs and shows minimal reactivity to Aβ monomers and fibrils, prevents the inhibition of long-term potentiation in hippocampal slices and memory impairment induced by AβOs in mice. As a therapeutic approach for intracerebral antibody delivery, we developed an adeno-associated virus vector to drive neuronal expression of NUsc1 (AAV-NUsc1) within the brain. Transduction by AAV-NUsc1 induced NUsc1 expression and secretion in adult human brain slices and inhibited AβO binding to neurons and AβO-induced loss of dendritic spines in primary rat hippocampal cultures. Treatment of mice with AAV-NUsc1 prevented memory impairment induced by AβOs and, remarkably, reversed memory deficits in aged APPswe/PS1ΔE9 Alzheimer's disease model mice. These results support the feasibility of immunotherapy using viral vector-mediated gene delivery of NUsc1 or other AβO-specific single-chain antibodies as a potential therapeutic approach in Alzheimer's disease.

Several studies reported that astrocytes support neuronal communication by the release of gliotransmitters, including ATP and glutamate. Astrocytes also play a fundamental role in buffering extracellular glutamate in the synaptic cleft, thus limiting the risk of excitotoxicity in neurons. We previously demonstrated that extracellular tau oligomers (ex-oTau), by specifically targeting astrocytes, affect glutamate-dependent synaptic transmission via a reduction in gliotransmitter release. The aim of this work was to determine if ex-oTau also impair the ability of astrocytes to uptake extracellular glutamate, thus further contributing to ex-oTau-dependent neuronal dysfunction.Primary cultures of astrocytes and organotypic brain slices were exposed to ex-oTau (200 nM) for 1 h. Extracellular glutamate buffering by astrocytes was studied by: NaEx-oTau uploading in astrocytes significantly affected glutamate-transporter-1 expression and function, thus impinging on glutamate buffering activity. Ex-oTau also reduced Na-K-ATPase activity because of pump mislocalisation on the plasma membrane, with no significant changes in expression. This effect was independent of oTau internalisation and it caused NaEx-oTau exerted a complex action on astrocytes, at both intracellular and extracellular levels. The net effect was dysregulated glutamate signalling in terms of both release and uptake that relied on reduced expression of glutamate-transporter-1, altered function and localisation of NKA1A1, and NKA1A2. Consequently, Na

Alzheimer's disease (AD) is characterized by neurotoxic immuno-inflammation concomitant with cytotoxic oligomerization of amyloid beta (Aβ) and tau, culminating in concurrent, interdependent immunopathic and proteopathic pathogeneses.We performed a comprehensive series of in silico, in vitro, and in vivo studies explicitly evaluating the atomistic-molecular mechanisms of cytokine-mediated and Aβ-mediated neurotoxicities in AD. Next, 471 new chemical entities were designed and synthesized to probe the pathways identified by these molecular mechanism studies and to provide prototypic starting points in the development of small-molecule therapeutics for AD.In response to various stimuli (e.g., infection, trauma, ischemia, air pollution, depression), Aβ is released as an early responder immunopeptide triggering an innate immunity cascade in which Aβ exhibits both immunomodulatory and antimicrobial properties (whether bacteria are present, or not), resulting in a misdirected attack upon "self" neurons, arising from analogous electronegative surface topologies between neurons and bacteria, and rendering them similarly susceptible to membrane-penetrating attack by antimicrobial peptides (AMPs) such as Aβ. After this self-attack, the resulting necrotic (but not apoptotic) neuronal breakdown products diffuse to adjacent neurons eliciting further release of Aβ, leading to a chronic self-perpetuating autoimmune cycle. AD thus emerges as a brain-centric autoimmune disorder of innate immunity. Based upon the hypothesis that autoimmune processes are susceptible to endogenous regulatory processes, a subsequent comprehensive screening program of 1137 small molecules normally present in human brain identified tryptophan metabolism as a regulator of brain innate immunity and a source of potential endogenous anti-AD molecules capable of chemical modification into multi-site therapeutic modulators targeting AD's complex immunopathic-proteopathic pathogenesis. Conceptualizing AD as an autoimmune disease, identifying endogenous regulators of this autoimmunity, and designing small molecule drug-like analogues of these endogenous regulators represents a novel therapeutic approach for AD.

International audience

Cognitive impairment and dementia can negatively impact the nutritional capacities of older people. Malnutrition is common in hospitalized frail elderly people with cognitive impairment and negatively affects prognosis. Malnutrition worsens the quality of life and increases morbidity and mortality. This scoping review aimed to identify factors affecting the risk of malnutrition and preventive strategies in hospitalized patients with cognitive impairment, focusing on nursing interventions. The authors researched population, context, and concept in international databases of nursing interest. Full texts that met the inclusion criteria were selected and reviewed. The extracted data were subject to thematic analysis. A five-stage approach, already reported in the scientific literature, was utilized in the following scoping review. Of 638 articles yielded, 9 were included. Two focus areas were identified as follows: (1) prevalence and risk factors of malnutrition in older patients with cognitive decline; (2) nursing strategies used to enhance clinical outcomes. Nursing health interventions aim to recognize and reduce malnutrition risk, positively impacting this phenomenon. A multidisciplinary team is essential to meet the nutritional needs of these patients.

Radionuclides are unstable isotopes that mainly emit alpha (α), beta (β) or gamma (γ) radiation through radiation decay. Therefore, they are used in the biomedical field to label biomolecules or drugs for diagnostic imaging applications, such as positron emission tomography (PET) and/or single-photon emission computed tomography (SPECT). A growing field of research is the development of new radiopharmaceuticals for use in cancer treatments. Preclinical studies are the gold standard for translational research. Specifically, in vitro radiopharmaceutical studies are based on the use of radiopharmaceuticals directly on cells. To date, radiometric β- and γ-counters are the only tools able to assess a preclinical in vitro assay with the aim of estimating uptake, retention, and release parameters, including time- and dose-dependent cytotoxicity and kinetic parameters. This review has been designed for researchers, such as biologists and biotechnologists, who would like to approach the radiobiology field and conduct in vitro assays for cellular radioactivity evaluations using radiometric counters. To demonstrate the importance of in vitro radiopharmaceutical assays using radiometric counters with a view to radiogenomics, many studies based on 64Cu-, 68Ga-, 125I-, and 99mTc-labeled radiopharmaceuticals have been revised and summarized in this manuscript.

Presentación que fue parte de una charla organizada por la Asociación Argentina de Humanidades Digitales el día 19 de noviembre de 2021, en el marco de la Semana de la Ciencia y Tecnología.

Presentaci��n que fue parte de una charla organizada por la Asociaci��n Argentina de Humanidades Digitales el d��a 19 de noviembre de 2021, en el marco de la Semana de la Ciencia y Tecnolog��a.

Adaptation to acute and chronic stress and/or persistent stressors is a subject of wide interest in central nervous system disorders. In this context, stress is an effector of change in organismal homeostasis and the response is generated when the brain perceives a potential threat. Herein, we discuss a nuanced and granular view whereby a wide variety of genotoxic and environmental stressors, including aging, genetic risk factors, environmental exposures, and age- and lifestyle-related changes, act as direct insults to cellular, as opposed to organismal, homeostasis. These two concepts of how stressors impact the central nervous system are not mutually exclusive. We discuss how maladaptive stressor-induced changes in protein connectivity through epichaperomes, disease-associated pathologic scaffolds composed of tightly bound chaperones, co-chaperones, and other factors, impact intracellular protein functionality altering phenotypes, that in turn disrupt and remodel brain networks ranging from intercellular to brain connectome levels. We provide an evidence-based view on how these maladaptive changes ranging from stressor to phenotype provide unique precision medicine opportunities for diagnostic and therapeutic development, especially in the context of neurodegenerative disorders including Alzheimer's disease where treatment options are currently limited.

Andean uplift and the concomitant formation of the Diagonal Arid of South America is expected to have promoted species diversification through range expansions into this novel environment. We evaluate the evolution of Argylia, a genus belonging to the Bignoniaceae family whose oldest fossil record dates back to 49.4 Ma. Today, Argylia is distributed along the Andean Cordillera, from 15°S to 38.5°S and from sea level up to 4,000 m.a.s.l. We ask whether Argylia’s current distribution is a result of a range expansion along the Andes Cordillera (biological corridor) modulated by climatic niche conservatism, considering the timing of Andean uplift (30 Ma – 5 Ma). To answer this question, we reconstructed the phylogenetic relationships of Argylia species, estimated divergence times, estimated the realized climatic niche of the genus, reconstructed the ancestral climatic niche, evaluated its evolution, and finally, performed an ancestral range reconstruction. We found strong evidence for climatic niche conservatism for moisture variables, and an absence of niche conservatism for most of the temperature variables considered. Exceptions were temperature seasonality and winter temperature. Results imply that Argylia had the capacity to adapt to extreme temperature conditions associated with the Andean uplift and the new climatic corridor produced by uplift. Ancestral range reconstruction for the genus showed that Argylia first diversified in a region where subtropical conditions were already established, and that later episodes of diversification were coeval with the of Andean uplift. We detected a second climatic corridor along the coastal range of Chile-Peru, the coastal lomas, which allowed a northward range expansion of Argylia into the hyperarid Atacama Desert. Dating suggests the current distribution and diversity of Argylia would have been reached during the Late Neogene and Pleistocene.

On June 1st of 2021, members of the Gathering for Open Science Hardware (GOSH) community convened a virtual writing workshop for promoting Open Source Hardware (OScH) at the international policy level (you can read more about this workshops in a blog post here). Workshop participants included OScH practitioners and those with international policy backgrounds from across the globe. The resulting policy brief highlights the potential for innovation that OScH brings on the international level and how international organizations can best promote OScH practices. Key Messages 1. International organisations and governments can increase their innovation capacity towards the SDGs by adopting and promoting open hardware. 2. Open hardware can build innovation capacity in countries with low investments in science, technology and innovation, making these investments more efficient. 3. Open hardware enables new multi-stakeholder partnerships and collaborations between academia, civil society and the private sector, towards the SDGs. 4. Open hardware adoption makes science more transparent and participative, supporting global decentralised collaboration. 5. International organisations can promote open hardware expansion by incorporating open hardware (OH) in their strategies, aligning incentives and raising awareness through education and training. This work was made possible by support from the Alfred P. Sloan Foundation to Gathering for Open Science Hardware, Inc.

On April 21, 2021, the GOSH community convened a virtual workshop that brought together 17 participants, including previous Global GOSH events’ organisers plus a limited number of GOSH community members that have participated in these events. The goal of the workshop was to collaboratively build the foundations of a framework for future GOSH gatherings. After the session, a document containing the draft framework was shared in the GOSH Forum and open for comments, which were later incorporated into this final text. We want to thank all participants for their valuable contributions to this document. We also want to thank the members of the open science hardware community for their helpful comments and advice on the open draft of this framework. More information can be found at https://openhardware.science/gosh-community-events-framework/

With the development of offshore energies, producers are confronted with the thermal limiting point that the cable undergoes in a J-tube. This vertical conduit, accompanying the electrical connection from the bottom of the sea to the heights of wind or oil platforms, has the role of ensuring its mechanical protection against the environment (waves, winds). However, in the emerged section, the tube encloses the cable with air, causing a rise in temperature. In order to limit this overheating, the cable is oversized, resulting in an increase in the cross-section of the copper cores, and this for the entire offshore electrical network. The present thesis aims to provide an understanding of thermal phenomena, to deliver a method of cable rating, and to propose potential technical solutions. A numerical model was set up based on the thermal network. In order to validate this model, it was compared with the literature and temperature measurements carried out over a full year on a platform that is currently active. Moreover, in order to take into account 2D phenomena such as the temperature stratification of the air in the tube, an experimental setup resembling a J-tube was designed and constructed in the laboratory. Correlations of the natural convection have been drawn and numerical simulations have been performed using free software developed by EDF. The model was then improved, now capable of estimating local temperatures, and showing a thermal limiting point at 80% of height. A sensitivity analysis by Sobol indices was performed, and improvement solutions were then proposed thanks to this simple model.; Avec le développement des énergies offshore, les producteurs se heurtent à la contrainte thermique que subit le câble dans un Jtube. Ce conduit vertical, accompagnant la liaison électrique du fond de la mer vers les hauteurs des plateformes éoliennes ou pétrolières, a pour rôle d’assurer sa protection mécanique contre l’environnement (vagues, vents). Or, dans la section émergée, le tube enferme le câble avec de l’air, provoquant une montée en température de celui-ci. Afin de limiter cette surchauffe, le câble est surdimensionné, occasionnant ainsi une augmentation de la section des âmes en cuivre, et ce pour l’ensemble du réseau électrique en mer. Les travaux de cette thèse, ont pour but d’apporter une compréhension des phénomènes thermiques, de fournir une méthode de dimensionnement du câble, ainsi que de proposer de potentielles solutions techniques. Pour ce faire, un modèle numérique a été mis en place basé sur la méthode nodale. Afin d’en vérifier la validité, le modèle a été comparé d’une part avec la littérature, puis d’autre part avec des mesures de température effectuées durant une année complète sur une plateforme aujourd’hui en activité. De plus, dans le but de prendre en compte les phénomènes 2D comme la stratification de la température de l’air dans le tube, une maquette expérimentale reprenant par similitude un J-tube a été montée en laboratoire. Des corrélations de la convection naturelle en ont été tirées et des simulations numériques ont été réalisées à l’aide de logiciels libres développés par EDF. Le modèle a été alors amélioré, désormais capable d’estimer localement les températures, montrant notamment que les contraintes thermiques se situent à 80 % de la hauteur. Une analyse de sensibilité par indices de Sobol a été réalisée, et des pistes d’amélioration ont alors été proposées grâce à ce modèle simple.

Amyloid precursor protein (APP) is associated with both familial and sporadic forms of Alzheimer’s disease. Despite its importance, the role of APP family in neuronal function and survival remains unclear due to perinatal lethality exhibited by knockout mice lacking all three APP family members. Here we report that selective inactivation of APP family members in excitatory neurons of the postnatal forebrain results in neither cortical neurodegeneration nor increases in apoptosis and gliosis up to ~2 years of age. However, hippocampal synaptic plasticity, learning and memory are impaired in these mutant mice. Furthermore, hippocampal neurons lacking APP family exhibit hyperexcitability, as evidenced by increased neuronal spiking in response to depolarizing current injections, whereas blockade of Kv7 channels mimics and largely occludes the effects of APP family inactivation. These findings demonstrate that APP family is not required for neuronal survival, and suggest that APP family may regulate neuronal excitability through Kv7 channels.

BackgroundVitamin D is a hot topic in the scientific community. Its deficiency and the implications for the children’s health became increasingly discussed during the last 20 years. The main aim of this retrospective study was to determinate the prevalence of vitamin D metabolism disorders in a population of adopted children and their risk factors.MethodsWe gathered data from 2140 children observed in five different National Working Group for the Migrant Children of the Italian Society of Pediatrics centers, variously located in Italy. Serum 25-hydroxy (OH)-D concentration was used to determine every child’s vitamin D status, defined as severely deficient (serum 25-OH-D < 10 ng/ml), moderately deficient (serum 25-OH-D {≥10 ng/ml U < 20 ng/ml}), mildly deficient (serum 25-OH-D {≥20 ng/ml U < 30 ng/ml}) and normal (serum 25-OH-D ≥ 30 ng/ml).ResultsMean value of serum 25-OH-D was 22.7 ng/ml (SD ± 12.1). Vitamin D status was deemed as normal in 483 (22.6%) children, mildly deficient in 718 (33.6%) children, moderately deficient in 730 (34.1%) children and severely deficient in 209 (9.8%) children.ConclusionsA very high percentage of migrant children is affected by hypovitaminosis D, with a strong association with age, geographic origin, season of blood sample collection and time spent in Italy after the arrival. This finding highlights the need for corrective measures. However, these measures cannot be applied without increasing the access of migrant populations to healthcare services.

Repetitive sequences represent about half of the human genome. They are actively transcribed and play a role during development and in epigenetic regulation. The altered activity of repetitive sequences can lead to genomic instability and they can contribute to the establishment or the progression of degenerative diseases and cancer transformation. In this work, we analyzed the expression profiles of DNA repetitive sequences in the breast cancer specimens of the HMUCC cohort. Satellite expression is generally upregulated in breast cancers, with specific families upregulated per histotype: in HER2-enriched cancers, they are the human satellite II (HSATII), in luminal A and B, they are part of the ALR family and in triple-negative, they are part of SAR and GSAT families, together with a perturbation in the transcription from endogenous retroviruses and their LTR sequences. We report that the background expression of repetitive sequences in healthy tissues of cancer patients differs from the tissues of non-cancerous controls. To conclude, peculiar patterns of expression of repetitive sequences are reported in each specimen, especially in the case of transcripts arising from satellite repeats.