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Optimizing oncolytic virus design:a“Swiss army knife”approach to create a systemically delivered therapeutic

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1791-1792页

作者： carolina S.Ilkow John Cameron Bell Ottawa Hospital Research Institute 501 Smyth RoadOttawaONK1H 8L6Canada

In a recent paper published in nature Biotechnology,Chen et al.1 describe a multiplex oncolytic virus platform that coupled with adoptive T cell therapy could solve the problem of repeat,systemic delivery of virus based therapeutics.It is widely accepted that multi-targeted therapeutic approaches attacking several facets of cancer biology are necessary to effectively deal with the tumor heterogeneity that exists within and between patients.

关键词： therapeutic al. targeted

Commercialization of disruptive innovations:Literature review and proposal for a process framework

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International Journal of Innovation Studies 2021年第3期5卷 127-144页

作者： Javier nieto Cubero Saheed Adebayo Gbadegeshin carolina consolación Design Processes Research Group EINACentre Universitari de Disseny I ArtUniversitat Autonoma De Barcelona08017BarcelonaSpain Department of Management and Entrepreneurship Turku School of EconomicsUniversity of Turku20014TurkuFinland Department of Management ETSEBCUniversitat Politecnica De Catalunya08034BarcelonaSpain

The challenges of disruptive innovations have gained significant attention from both academics and practitioners,commercialization being one of the most critical phases.At the same time,however,it is the less studied area of disruptive innovation.Therefore,this article examined scholarly papers on the commercialization of disruptive innovations through a multidisciplinary systematic literature review.It resulted in the analysis of 64 high-quality peer-reviewed academic articles.The analysis highlighted the commercialization models and main constructs that are affecting the commercialization process:market orientation,market learning,user’s involvement,market configuration,adoption networks and stakeholders,and innovation transference.The study evidences how commercialization has evolved from a later stage in innovation to influence even the early phases of innovation,characterized in turn by exploration,learning and ecosystem creation activities.Additionally,the analysis led to a proposition that established an integrated commercialization model for high uncertainty innovations.The model has three phases:1)Concept/value proposition validation,2)Business model validation&Market creation,and 3)Creating sales in the majority market.Lastly,the article contributes to a better understanding of commercialization processes in high uncertainty innovations,bridging also the academic-practitioner divide.

关键词： Disruptive innovation Radical innovation Emerging technologies Commercialization process Market creation Scale-up Lean start-up

Gustatory responsiveness in Vespula germanica workers:exploring the interplay between sensory perception and task specialization

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Insect Science 2024年第2期31卷 587-598页

作者： Analia Mattiacci carolina Mengoni Gonalons MaitéMasciocchi Juan C.Corley Grupo de Ecologia de Poblaciones de Insectos IFAB(CONICETINTA EEA Bariloche)BarilocheArgentina Departamento de Ecologia Centro Regional Universitario BarilocheUniversidad Nacional Del ComahueBarilocheArgentina Departamento de Biodiversidad y Biologia Experimental Facultad de Ciencias Exactas y NaturalesUniversidad de Buenos AiresBuenos AiresArgentina

Workers'task specialization and division of labor are critical features of social insects'ecological success.It has been proposed that the division of labor relies on response threshold models:individuals varying their sensitivity(and responsiveness)to biologically relevant stimuli and performing a specific task when a stimulus exceeds an internal threshold.In this work,we study carbohydrate and protein responsiveness and their relation to worker task specialization in Vespula germanica,an invasive social wasp.The sucrose and peptone responsiveness of two different subcastes,preforagers and foragers,was determined by stimulating the antenna of the wasps with increasing concentrations of the solution and quantifying whether each concentration elicited a licking response.We studied responsiveness in five different ways:(1)response threshold,(2)concentration 50(concentration to which at least 50%of wasps responded),(3)maximum response,(4)mean scores and(5)median scores.Our results suggest that V germanica foragers are more sensitive to sucrose(lower thresholds)than preforager workers.However,we found no differences for peptone thresholds(i.e.,a protein resource).nonetheless,this is the first study to investigate response thresholds for protein resources.The intercaste variation in sucrose responsiveness shown in our work contributes to the existing knowledge about response threshold theory as a mechanism for task specialization observed in V germanica.

关键词： carbohydrates responsiveness division of labor protein responsiveness response thresholds models social insect yellow jacket

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： carolina Aguado Sara Badesso JoséMartínez-Hernández Alejandro Martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-Martínez Mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resil

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

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World Journal of Hepatology 2024年第5期16卷 832-842页

作者： Elisa carolina Lange Pabulo Henrique Rampelotto Larisse Longo Laura Bainy Rodrigues de Freitas carolina Uribe-Cruz Mario Reis Alvares-da-Silva Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Bioinformatics and Biostatistics Core Facility Universidade Federal do Rio Grande do SulPorto Alegre 91501-970Brazil Graduate Program in Biological Sciences:Pharmacology and Therapeutics Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007RSBrazil Conselho nacional de Desenvolvimento Científico e Tecnológico(CnPq)researcher Brasília 71605-001Brazil

BACKGROUnD Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.METHODS Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were collected.Following fecal DnA extraction,the V4 region of the 16S rRnA gene was amplified followed by sequencing in an Ion S5™system.RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides distasonis.The functional prediction provided two different metabolic profiles between MASLD and LOLA.The 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis.The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.COnCLUSIOn Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.

关键词： Animal model Gut microbiota Metabolic-associated steatotic liver disease Metabolic prediction Ornithine aspartate

Review of the Cretaceous avian diversity of Antarctica:a changing scenario for the evolution of early neornithine birds

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Advances in Polar Science 2024年第1期35卷 1-13页

作者： carolina ACOSTA HOSPITALECHE Facundo IRAZOQUI Paula BOnA Ariana PAULInA-CARABAJAL División Paleontología de Vertebrados Museo de La PlataFacultad de Ciencias Naturales y MuseoUniversidad Nacional de La PlataPaseo del Bosque s/nLa Plata B1900FWAArgentina Consejo nacional de Investigaciones Científicas y Técnicas(COnICET) Buenos Aires C1425FQBArgentina División Paleontología Vertebrados Museo de La Plata-Anexo ⅡFacultad de Ciencias Naturales y MuseoUniversidad Nacional de La PlataCalles 122 y 60La Plata B1900FWAArgentina Instituto de Investigaciones en Biodiversidad y Medioambiente(InIBIOMA) Consejo Nacional de Investigaciones Científicas y Técnicas-Universidad Nacional del ComahueSan Carlos de Bariloche R8400GAMArgentina

The worldwide record of Cretaceous neornithes and neornithine-like birds is both controversial and poorly understood.However,in recent years,the Antarctic continent has yielded a substantial number of Maastrichtian avian specimens,contributing significantly to our understanding of the early evolution of this group.Simultaneously,the keen interest and collaborative efforts of various paleornithologists have resulted in a wealth of knowledge,which we have thoroughly reviewed,updated,and discussed in the context of recent discoveries.

关键词： Maastrichtian Antarctic Peninsula Vega Island Seymour(Marambio)Island neornithes birds

Increasing dietary fiber intake for type 2 diabetes mellitus management: A systematic review

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World Journal of Diabetes 2024年第5期15卷 1001-1010页

作者： Douglas nitzke Juliana Czermainski carolina Rosa Chaline Coghetto Sabrina Alves Fernandes Randhall B Carteri Department of nutrition Centro Universitário CESUCACachoeirinha 94935-630Brazil Department of Hepatology Universidade Federal de Ciências da Saúde de Porto AlegrePorto Alegre 90430-080Brazil Postgraduate Program in Hepatology Universidade Federal de Ciências da Saúde de Porto AlegrePorto Alegre 90050-170Brazil Postgraduate Program in Hepatology Federal University of Health Sciences of Porto Alegre(UFCSPA)Porto Alegre 90050-170Brazil

BACKGROUnD Type 2 diabetes is a chronic,non-communicable disease with a substantial global impact,affecting a significant number of individuals.Its etiology is closely tied to imbalanced dietary practices and sedentary lifestyles.Conversely,increasing die-tary fiber(DF)intake has consistently demonstrated health benefits in numerous studies,including improvements in glycemic control and weight management.AIM To investigate the efficacy of DF interventions in the management of type 2 diabetes mellitus(T2DM).METHODS A systematic literature review was conducted to explore the association between DF intake and the management of T2DM.Following the inclusion and exclusion criteria,a total of 26 studies were included in this review.RESULTS The main strategies implied to increased DF intake were:High DF diet plus acarbose(2 studies);DF supplements(14 studies);and high DF diets(10 studies).Overall,most studies indicated that increased DF intake resulted in im-provements in glycemic control and weight management in T2DM patients.COnCLUSIOn DF represents a valuable strategy in the treatment of type 2 diabetes,improving health outcomes.DF intake offers the potential to improve quality of life and reduce complications and mortality associated with diabetes.Likewise,through supplements or enriched foods,DF contributes significantly to the control of several markers such as HbA1c,blood glucose,triglycerides,low-density lipoprotein,and body weight.

关键词： Type 2 diabetes mellitus Soluble fibers Insoluble fibers Probiotics Blood glucose nutrition

Hypothalamic circuits and aging:keeping the circadian clock updated

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neural Regeneration Research 2024年第9期19卷 1919-1928页

作者： Rosa Vázquez-Lizarraga Lucia Mendoza-Viveros carolina Cid-Castro Sareni Ruiz-Montoya Erick Carreño-Vázquez Ricardo Orozco-Solis Instituto nacional de Medicina Genómica(InMEGEn) México CityMéxico Centro de Investigacíon sobre el Envejecimiento Centro de Investigacíon y de Estudios Avanzados(CIE-CINVESTAV)México CityMéxico Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México UNAMMéxico CityMéxico

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

关键词： aging astrocytes cellular stress responses circadian clock hypothalamus intranasal drug administration metabolic control nutrient sensor SIRT1 sleep homeostasis

Prevalence and ecological factors affecting the distribution of plant-parasitic nematodes in Prunus groves in Spain

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Journal of Integrative Agriculture 2024年第2期23卷 566-589页

作者： Ilenia Clavero-Camacho Antonio Archidona-Yuste carolina Cantalapiedra-navarrete Pablo Castillo Juan Emilio Palomares-Rius Institute for Sustainable Agriculture(IAS) Spanish National Research Council(CSIC)Córdoba 14004Spain Andalusian Institute of Agricultural and Fisheries Research and Training(IFAPA) Centro Alameda del ObispoCórdoba 14004Spain

A wide survey was conducted to study plant-parasitic nematodes(PPns)associated with Prunus groves in Spain.This research aimed to determine the prevalence and distribution of PPns in Prunus groves,as well as the influence of explanatory variables describing soil,climate and agricultural management in structuring the variation of PPns community composition.A total of 218 sampling sites were surveyed and 84 PPn species belonging to 32 genera were identified based of an integrative taxonomic approach.PPn species considered as potential limiting factors in Prunus production,such as Meloidogyne arenaria,M.incognita,M.javanica,Pratylenchus penetrans and P.vulnus,were identified in this survey.Seven soil physico-chemical(C,Mg,n,na,OM,P,pH and clay,loamy sand and sandy loam texture classes),four climate(Bio04,Bio05,Bio13 and Bio14)and four agricultural management variables(grove-use history less than 10 years,irrigation,apricot seedling rootstock,and Montclar rootstock)were identified as the most influential variables driving spatial patterns of PPns communities.In particular,younger plantations showed higher values for species richness and diversity indices than groves cultivated for more than 20 years with Prunus spp.Our study increases the knowledge of the distribution and prevalence of PPns associated with Prunus rhizosphere,as well as on the influence of explanatory variables driving the spatial structure PPns communities,which has important implications for the successful design of sustainable management strategies in the future in this agricultural system.

关键词： nematodes Meloidogyne Pratylenchus Paratylenchus rootstock distribution soil grove-use almond peach