Ecological Aspects and Conservation of Wild Grapevine Populations in the S.W. of the Iberian Peninsula

Populations of wild grapevine, Vitis vinifera L. subsp. sylvestris (Gmelin) Hegi, were discovered in S.W. of the Iberian Peninsula over the last years. Location, ecological aspects, sanitary characteristics, including the ELISA test to detect specific virus attack, are described. In vitro propagation and conservation are also considered. The paper also contains a global description of female and male individuals. This material could be used to start breeding programs of cultivated varieties and also to restore riverbank forests, which constitute one of the worst preserved ecosystems in the area

Deterministic and probabilistic dietary exposure assessment to deoxynivalenol in Spain and the Catalonian region

Deoxynivalenol (DON) remains one of the most concerning mycotoxins produced by the Fusarium genus due to the wide occurrence in highly consumed cereal-based food and its associ-ated toxicological effects. Previous studies conducted in Spain and other European countries suggested that some vulnerable groups such as children could be exceeding the tolerable daily intakes. Thus, the aim of this study was to conduct a comprehensive and updated dietary expo-sure assessment study in Spain, with a specific analysis in the region of Catalonia. Cereal-based food samples collected during 2019 were analysed using liquid chromatography coupled to tan-dem mass spectrometry for multi-mycotoxin detection including DON and its main metabolites and derivatives. Consumption data were gathered from the nation-wide food surveys ENALIA and ENALIA2 conducted in Spain, and a specific survey conducted in Catalonia. The data were combined using deterministic and semi-parametric probabilistic methods. The results showed that DON was widely present in cereal-based food highly consumed in Spain and the Catalonia region. Exposure to DON among the adult population was globally low; however, among in-fants aged 3-9 years, it resulted in the median of 192 ng/kg body weight/day and the 95th per-centiles of 604 ng/kg body weight/day, that would exceed the most conservative safety threshold for infants. Bread and pasta were the main contributing foodstuffs to the global exposure to DON, even among infants; thus, those foods should be considered a priority for food control or to develop strategies to reduce the exposure. In any case, further toxicological and epidemiolog-ical studies are required in order to refine the safety thresholds accounting for the sensitivity of the infant population.This research was funded by the Catalan Agency of Food Safety (ACSA) (SA-2019-391) and the Agency for Management of University and Research Grants (AGAUR) with a doctoral fellowship (2021 FI_B 00129; 2022 FI_B1 00033)

Novel chimeric proteins mimicking SARS-CoV-2 spike epitopes with broad inhibitory activity.

SARS-CoV-2 spike (S) protein mediates virus attachment to the cells and fusion between viral and cell membranes. Membrane fusion is driven by mutual interaction between the highly conserved heptad-repeat regions 1 and 2 (HR1 and HR2) of the S2 subunit of the spike. For this reason, these S2 regions are interesting therapeutic targets for COVID-19. Although HR1 and HR2 have been described as transiently exposed during the fusion process, no significant antibody responses against these S2 regions have been reported. Here we designed chimeric proteins that imitate highly stable HR1 helical trimers and strongly bind to HR2. The proteins have broad inhibitory activity against WT B.1 and BA.1 viruses. Sera from COVID-19 convalescent donors showed significant levels of reactive antibodies (IgG and IgA) against the HR1 mimetic proteins, whereas these antibody responses were absent in sera from uninfected donors. Moreover, both inhibitory activity and antigenicity of the proteins correlate positively with their structural stability but not with the number of amino acid changes in their HR1 sequences, indicating a conformational and conserved nature of the involved epitopes. Our results reveal previously undetected spike epitopes that may guide the design of new robust COVID-19 vaccines and therapies.This work was supported by grants CV20.26565 from the Consejería de Economía y Conocimiento, Junta de Andalucía (Spain), PID2019.107515RB.C21 from the Spanish State Research Agency (SRA/10.13039/501100011033), and co-funded by ERDF/ESF, “A way to make Europe”/“Investing in your future. The work performed in C.M.’s laboratory was supported by grants from ANRS (Agence Nationale de Recherches sur le SIDA et les h´epatites virales), the Investissements d’Avenir program managed by the ANR under reference ANR-10-LABX-77 and EHVA (No. 681032, Horizon 2020). Work in S.B.’s laboratory was supported by grants from the Agence Nationale de la Recherche (ANR) (ANR-11-LABX-0070_TRANSPLANTEX), the INSERM (UMR_S1109), the Institut Universitaire de France (IUF), all the University of Strasbourg (IDEX UNISTRA), the European Regional Development Fund (European Union) INTERREG V program (project no. 3.2 TRIDIAG) and MSD-Avenir grant AUTOGEN

INFLUÊNCIA DO GÊNERO, NÍVEL EDUCACIONAL E PRÁTICA DESPORTIVA DOS PAIS NOS HÁBITOS ESPORTIVOS DAS CRIANÇAS EM IDADE ESCOLAR

The importance of parents in the physical activity of their children during adolescence has been previously established, but few studies have determined which are the most important variables. This study analyzes the influence of gender stereotypes, educational level, and the level of parents’ sports practice on their children’s practice. The sample included 965 adolescents and 1,599 parents from the Region of Murcia. The results showed differences in the sports practice of the adolescents when considering the educational level of their mothers, the physical activity carried out by the fathers on male children, the frequency of practice of the mothers for female children and gender stereotypes of the mothers. It found that gender stereotypes and parents’ educational level influenced adolescents’ sports practice.La importancia de los padres en la actividad física de sus hijos durante la adolescencia ha sido constatada previamente, pero pocos estudios han establecido cuáles son las variables más determinantes. El objetivo del presente estudio fue analizar las diferencias en la práctica deportiva de los adolescentes según el nivel educativo, el nivel de práctica deportiva y los estereotipos de género de sus progenitores. La muestra estuvo compuesta por 965 adolescentes y 1599 progenitores de la Región de Murcia. Los resultados mostraron diferencias en la práctica deportiva de los adolescentes al considerar el nivel educativo de las madres, la actividad física realizada por los padres para los varones, la frecuencia de práctica de las madres para las mujeres y los estereotipos de género de las madres. Como conclusiones, señalar que los estereotipos de género y el nivel educativo de los progenitores influyeron en la práctica deportiva de los adolescentes.  A importância dos pais na atividade física dos seus filhos durante a adolescência foi previamente afirmada, mas poucos estudos determinaram quais são as variáveis mais determinantes. O objetivo do presente estudo foi analisar a influência dos estereótipos de gênero, o nível educacional e o nível de prática desportiva dos pais sobre a prática desportiva dos seus filhos. A amostra foi composta por 965 adolescentes e 1599 pais da Região de Múrcia. Os resultados mostraram diferenças na prática desportiva dos adolescentes ao considerar o nível educacional das mães, a atividade física realizada pelos pais para os homens, a frequência da prática das mães para as mulheres e os estereótipos de gênero das mães. Como conclusões, é de notar que os estereótipos de gênero e o nível de educação dos pais influenciaram a prática do desporto pelos adolescentes.

Rational engineering of a human GFP-like protein scaffold for humanized targeted nanomedicines

Green fluorescent protein (GFP) is a widely used scaffold for protein-based targeted nanomedicines because of its high biocompatibility, biological neutrality and outstanding structural stability. However, being immunogenicity a major concern in the development of drug carriers, the use of exogenous proteins such as GFP in clinics might be inadequate. Here we report a human nidogen-derived protein (HSNBT), rationally designed to mimic the structural and functional properties of GFP as a scaffold for nanomedicine. For that, a GFP-like β-barrel, containing the G2 domain of the human nidogen, has been rationally engineered to obtain a biologically neutral protein that self-assembles as 10nm-nanoparticles. This scaffold is the basis of a humanized nanoconjugate, where GFP, from the well-characterized protein T22-GFP-H6, has been substituted by the nidogen-derived GFP-like HSNBT protein. The resulting construct T22-HSNBT-H6, is a humanized CXCR4-targeted nanoparticle that selectively delivers conjugated genotoxic Floxuridine into cancer CXCR4+ cells. Indeed, the administration of T22-HSNBT-H6-FdU in a CXCR4-overexpressing colorectal cancer mouse model results in an even more efficient selective antitumoral effect than that shown by its GFP-counterpart, in absence of systemic toxicity. Therefore, the newly developed GFP-like protein scaffold appears as an ideal candidate for the development of humanized protein nanomaterials and successfully supports the tumor-targeted nanoscale drug T22-HSNBT-H6-FdU.Patricia Álamo and Juan Cedano contributed equally to this work. The authors are indebted to Agencia Estatal de Investigación (AEI) and to Fondo Europeo de Desarrollo Regional (FEDER) (grant BIO2016-76063-R, AEI/FEDER, UE), to AGAUR (2017SGR-229) and CIBER-BBN (project NANOPROTHER), granted to AV, to CIBER-BBN (project NANOSCAPE and NANOLINK) and ISCIII (PI20/00400 co-funding FEDER) granted to UU, to ISCIII (PI15/00272 co-founding FEDER) granted to EV and to ISCIII (PIE15/00028 and PI18/00650, co-funding FEDER) and AGAUR (2017 SGR 865 GRC) granted to RM. We are also indebted to CERCA programme (Generalitat de Catalunya) and to the Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) that is an initiative funded by the VI National R&D&I Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III, with assistance from the European Regional Development Fund. We also appreciate the support from the COST-Action Nano2Clinics. Protein production has been partially performed by the ICTS “NANBIOSIS”, more specifically by the Protein Production Platform of CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN)/ IBB, at the UAB sePBioEs scientific-technical service (http://www.nanbiosis.es/portfolio/u1-protein-production-platform-ppp/), and the nanoparticle size analysis by the Biomaterial Processing and Nanostructuring Unit. Synthesis of thiolated oligo-FdU was performed by the ICTS NANBIOSIS Oligonucleotide Synthesis Platform (CIBER-BBN). The in vivo work was performed by the ICTS NANBIOSIS of the CIBER-BBN Nanotoxicology Unit (http://www.nanbiosis.es/portfolio/u18-nanotoxicology-unit/). We are indebted to Servei de Microscopia from UAB for their excellent confocal and electronic microscopy services. We are also indebted to Servei de Cultius Celulars i Anticossos (SCAC) form UAB for their excellent cell culture and flow cytometry facilities and especially to Fran Cortes for his excellent technical support. We are thankful to Dra. Marta Taulés from CCiT-UB for her help in SPR experiments and analysis. We are also thankful to Luis Carlos Navas from Institut d'Investigacions biomèdiques Sant Pau (IIB Sant Pau) for his technical support in immunohistochemistry experiments. UU and LMCD were supported by Miguel Servet (CP19/00028) and PFIS (FI19/00148) contracts respectively from ISCIII co-funded by European Social Fund (ESF investing in your future). NS was supported by a pre-doctoral fellowship from the Government of Navarra and LAC was supported by AECC Scientific Foundation grant postdoctoral fellow. AV received an ICREA ACADEMIA award.Peer reviewe

Engineering secretory amyloids for remote and highly selective destruction of metastatic foci

Altres ajuts: to EU COST Action CA 17140Functional amyloids produced in bacteria as nanoscale inclusion bodies are intriguing but poorly explored protein materials with wide therapeutic potential. Since they release functional polypeptides under physiological conditions, these materials can be potentially tailored as mimetic of secretory granules for slow systemic delivery of smart protein drugs. To explore this possibility, bacterial inclusion bodies formed by a self-assembled, tumor-targeted Pseudomonas exotoxin (PE24) are administered subcutaneously in mouse models of human metastatic colorectal cancer, for sustained secretion of tumor-targeted therapeutic nanoparticles. These proteins are functionalized with a peptidic ligand of CXCR4, a chemokine receptor overexpressed in metastatic cancer stem cells that confers high selective cytotoxicity in vitro and in vivo. In the mouse models of human colorectal cancer, time-deferred anticancer activity is detected after the subcutaneous deposition of 500 µg of PE24-based amyloids, which promotes a dramatic arrest of tumor growth in the absence of side toxicity. In addition, long-term prevention of lymphatic, hematogenous, and peritoneal metastases is achieved. These results reveal the biomedical potential and versatility of bacterial inclusion bodies as novel tunable secretory materials usable in delivery, and they also instruct how therapeutic proteins, even with high functional and structural complexity, can be packaged in this convenient format

Dietary diversity and nutritional adequacy among an older Spanish population with metabolic syndrome in the PREDIMED-Plus study: a cross-sectional analysis

Dietary guidelines emphasize the importance of a varied diet to provide an adequate nutrient intake. However, an older age is often associated with consumption of monotonous diets that can be nutritionally inadequate, increasing the risk for the development or progression of diet-related chronic diseases, such as metabolic syndrome (MetS). To assess the association between dietary diversity (DD) and nutrient intake adequacy and to identify demographic variables associated with DD, we cross-sectionally analyzed baseline data from the PREDIMED-Plus trial: 6587 Spanish adults aged 55-75 years, with overweight/obesity who also had MetS. An energy-adjusted dietary diversity score (DDS) was calculated using a 143-item validated semi-quantitative food frequency questionnaire (FFQ). Nutrient inadequacy was defined as an intake below 2/3 of the dietary reference intake (DRI) forat least four of 17 nutrients proposed by the Institute of Medicine (IOM). Logistic regression models were used to evaluate the association between DDS and the risk of nutritionally inadequate intakes. In the higher DDS quartile there were more women and less current smokers. Compared with subjects in the highest DDS quartile, those in the lowest DDS quartile had a higher risk of inadequate nutrient intake: odds ratio (OR) = 28.56 (95% confidence interval (CI) 20.80-39.21). When we estimated food varietyfor each of the food groups, participants in the lowest quartile had a higher risk of inadequate nutrient intake for the groups of vegetables, OR = 14.03 (95% CI 10.55-18.65), fruits OR = 11.62 (95% CI 6.81-19.81), dairy products OR = 6.54 (95% CI 4.64-9.22) and protein foods OR = 6.60 (95% CI 1.96-22.24). As DDS decreased, the risk of inadequate nutrients intake rose. Given the impact of nutrient intake adequacy on the prevention of non-communicable diseases, health policies should focus on the promotion of a healthy varied diet, specifically promoting the intake of vegetables and fruit among population groups with lower DDS such as men, smokers or widow(er)s