<b>Publicacions de projectes de recerca finançats per la UE</b>

URI permanent per a aquesta col·leccióhttps://diposit.ub.edu/handle/2445/15202

Publicacions resultants de projectes de recerca finançats per la Unió Europea, recollides en el Projecte OpenAIRE (Open Access Infraestructure for Research in Europe) que promou l'accés obert a Europa.

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Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis
(Frontiers Media, 2022-09-06) Micó, Víctor; San Cristobal, Rodrigo; Martín, Roberto; Martínez-González, Miguel Ángel, 1957-; Salas Salvadó, Jordi; Corella Piquer, Dolores; Fitó Colomer, Montserrat; Alonso Gómez, Ángel M.; Wärnberg, Julia; Vioque, Jesús; Romaguera, Dora; López Miranda, José; Estruch Riba, Ramon; Tinahones, Francisco J.; Lapetra, José; Serra Majem, Lluís; Bueno Cavanillas, Aurora; Tur, Josep A.; Martín Sánchez, Vicente; Pintó Sala, Xavier; Delgado Rodríguez, Miguel; Matía Martín, Pilar; Vidal i Cortada, Josep; Vázquez, Clotilde; García Arellano, Ana; Pertusa Martinez, Salvador; Chaplin, Alice; García Ríos, Antonio; Muñoz Bravo, Carlos; Schröder, Helmut, 1958-; Babio, Nancy; Sorlí, José V.; Gonzalez, Jose I.; Martinez Urbistondo, Diego; Toledo Atucha, Estefanía; Bullón, Vanessa; Ruiz Canela, Miguel; Portillo, María Puy; Macías González, Manuel; Perez Diaz del Campo, Nuria; García Gavilán, Jesús; Daimiel, Lidia; Martínez, J. Alfredo, 1957-
Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient ' s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients.
Extensive antimicrobial resistance mobilization via Multicopy Plasmid Encapsidation mediated by temperate phages
(Oxford University Press, 2020-07-28) Rodríguez-Rubio, Lorena; Serna, Carlos; Ares-Arroyo, Manuel; Matamoros, Bosco R.; Delgado-Blas, Jose F.; Montero, Natalia; Bernabe-Balas, Cristina; Wedel, Emilia F.; Mendez, Irene S.; Muniesa Pérez, Ma. Teresa; Gonzalez-Zorn, Bruno
Objectives: To investigate the relevance of multicopy plasmids in antimicrobial resistance and assess their mobilization mediated by phage particles Methods: Several databases with complete sequences of plasmids and annotated genes were analysed. The 16S methyltransferase gene armA conferring high-level aminoglycoside resistance was used as a marker in eight different plasmids, from different incompatibility groups, and with differing sizes and plasmid copy numbers. All plasmids were transformed into Escherichia coli bearing one of four different lysogenic phages. Upon induction, encapsidation of armA in phage particles was evaluated using qRT-PCR and Southern blotting. Results: Multicopy plasmids carry a vast set of emerging clinically important antimicrobial resistance genes. However, 60% of these plasmids do not bear mobility (MOB) genes. When carried on these multicopy plasmids, mobilization of a marker gene armA into phage capsids was up to 10000 times more frequent than when it was encoded by a large plasmid with a low copy number. Conclusions: Multicopy plasmids and phages, two major mobile genetic elements (MGE) in bacteria, represent a novel high-efficiency transmission route of antimicrobial resistance genes that deserves further investigation.
Advanced characterization of multicaloric materials in pulsed magnetic fields.
(American Institute of Physics (AIP), 2020-05-11) Gottschall, T; Bykov, E.; Garcia Capdevila, Xavier; Beckmann, B.; Taublel, A.; Pfeuffer, L.; Gutfleisch, O.; Mañosa, Lluís; Planes Vila, Antoni; Skourski, Y.; Wonitza, J.
The multicaloric effect is described by a temperature or entropy change of a material triggered by external stimuli applied or removed simultaneously or sequentially. The prerequisite for this is a material exhibiting multiple ferroic states. However, direct measurements of the effect are rarely reported. Now, for this reason, we built a measurement device allowing to determine the adiabatic temperature change in pulsed magnetic fields and, simultaneously, under the influence of a uniaxial load. We selected the all-𝑑-metal Heusler alloy Ni-Mn-Ti-Co for our first test because of its enhanced mechanical properties and enormous magneto- and elastocaloric effects. Ni-Mn-Ti-Co was exposed to pulsed magnetic fields up to 10 T and uniaxial stresses up to 80 MPa, and the corresponding adiabatic temperature changes were measured. With our new experimental tool, we are able to better understand multicaloric materials and determine their cross-coupling responses to different stimuli.
Mapping the relationship between total and functional antibodies conjugated to nanoparticles with spectrally-resolved direct stochastic optical reconstruction microscopy (SR-dSTORM)
(2022-09-13) Archontakis, Emmanouil; Woythe, Laura; Hoof, Bas van; Albertazzi, Lorenzo
Antibody-functionalized nanoparticles (NPs) have shown numerous benefits in drug delivery and biosensing, improving the specificity of cell targeting and analyte detection, respectively. However, one of the main challenges is the lack of control over antibody orientation on the NP surface. Popular and easy conjugation strategies, such as carbodiimide-based conjugations, lead to a random orientation of antibodies on the NPs, compromising ligand functionality and contributing to undesired biological effects and reduced target recognition. While new methods for more controlled NP functionalization have been proposed, there is a lack of techniques that can elucidate the orientation of the antibodies at the single-particle level to determine the conjugation outcome and, therefore, the NPs' potential in selective targeting. Here, spectrally-resolved direct stochastic optical reconstruction microscopy (SR-dSTORM), an optical super-resolution technique, is introduced to quantify the relationship between total and functional NP conjugated cetuximab antibodies at the single-particle level. An evident single-particle heterogeneity in total and functional cetuximab is observed, leading to particles with different functional : total ratios. Additionally, the results indicate that the functional : total ratio of cetuximab highly depends on the conjugated cetuximab concentration. Overall, SR-dSTORM represents a direct approach for the NP structure-functionality relationship quantification, providing a platform to improve antibody-conjugated NPs characterization and facilitating their rational design.
On Simulating the Propagation and Countermeasures of Hate Speech in Social Networks
(MDPI, 2021-12-16) Maite Lopez-Sanchez; Arthur Müller
Hate speech expresses prejudice and discrimination based on actual or perceived innate characteristics such as gender, race, religion, ethnicity, colour, national origin, disability or sexual orientation. Research has proven that the amount of hateful messages increases inevitably on online social media. Although hate propagators constitute a tiny minority with less than 1% participants they create an unproportionally high amount of hate motivated content. Thus, if not countered properly, hate speech can propagate through the whole society. In this paper we apply agent-based modelling to reproduce how the hate speech phenomenon spreads within social networks. We reuse insights from the research literature to construct and validate a baseline model for the propagation of hate speech. From this, three countermeasures are modelled and simulated to investigate their effectiveness in containing the spread of hatred: Education, deferring hateful content, and cyber activism. Our simulations suggest that: (1) Education consititutes a very successful countermeasure, but it is long term and still cannot eliminate hatred completely; (2) Deferring hateful content has a similar although lower positive effect than education, and it has the advantage of being a short-term countermeasure; (3) In our simulations, extreme cyber activism against hatred shows the poorest performance as a countermeasure, since it seems to increase the likelihood of resulting in highly polarised societies.
Plasmodium falciparum Apicomplexan-Specific Glucosamine-6-Phosphate N-Acetyltransferase Is Key for Amino Sugar Metabolism and Asexual Blood Stage Development.
(American Society for Microbiology, 2020-10-20) Chi, Jordi; Cova, Marta; Rivas, Matilde de las; Medina, Ana; Borges, Rafael Junqueir; Leivar, Pablo; Planas i Anzano, Antoni; Usón Finkenzeller, Isabel; Hurtado Guerrero, Ramón; Izquierdo, Luis
--- - i: - N - N - O - N - Plasmodium falciparum - Cryptosporidium parvum - P. falciparum - N - N - P. falciparum - C. parvum b: - IMPORTANCE content: - UDP- - "-acetylglucosamine (UDP-GlcNAc), the main product of the hexosamine biosynthetic pathway, is an important metabolite in protozoan parasites since its sugar moiety is incorporated into glycosylphosphatidylinositol (GPI) glycolipids and " - "- and " - "-linked glycans. Apicomplexan parasites have a hexosamine pathway comparable to other eukaryotic organisms, with the exception of the glucosamine-phosphate " - "-acetyltransferase (GNA1) enzymatic step that has an independent evolutionary origin and significant differences from nonapicomplexan GNA1s. By using conditional genetic engineering, we demonstrate the requirement of GNA1 for the generation of a pool of UDP-GlcNAc and for the development of intraerythrocytic asexual " - " parasites. Furthermore, we present the 1.95\xE2\x80\x89\xC3\x85 resolution structure of the GNA1 ortholog from " - ", an apicomplexan parasite which is a leading cause of diarrhea in developing countries, as a surrogate for " - " GNA1. The in-depth analysis of the crystal shows the presence of specific residues relevant for GNA1 enzymatic activity that are further investigated by the creation of site-specific mutants. The experiments reveal distinct features in apicomplexan GNA1 enzymes that could be exploitable for the generation of selective inhibitors against these parasites, by targeting the hexosamine pathway. This work underscores the potential of apicomplexan GNA1 as a drug target against malaria." - " Apicomplexan parasites cause a major burden on global health and economy. The absence of treatments, the emergence of resistances against available therapies, and the parasite's ability to manipulate host cells and evade immune systems highlight the urgent need to characterize new drug targets to treat infections caused by these parasites. We demonstrate that glucosamine-6-phosphate " - -acetyltransferase (GNA1), required for the biosynthesis of UDP- - "-acetylglucosamine (UDP-GlcNAc), is essential for " - " asexual blood stage development and that the disruption of the gene encoding this enzyme quickly causes the death of the parasite within a life cycle. The high-resolution crystal structure of the GNA1 ortholog from the apicomplexan parasite " - ", used here as a surrogate, highlights significant differences from human GNA1. These divergences can be exploited for the design of specific inhibitors against the malaria parasite."
Free boundary regularity for almost every solution to the Signorini problem
(Springer Verlag, 2021-02-11) Fernandez-Real, Xavier; Ros, Xavier
We investigate the regularity of the free boundary for the Signorini problem in $\mathbb{R}^{n+1}$. It is known that regular points are $(n-1)$-dimensional and $C^{\infty}$. However, even for $C^{\infty}$ obstacles $\varphi$, the set of non-regular (or degenerate) points could be very large-e.g. with infinite $\mathcal{H}^{n-1}$ measure. The only two assumptions under which a nice structure result for degenerate points has been established are when $\varphi$ is analytic, and when $\Delta \varphi<0$. However, even in these cases, the set of degenerate points is in general $(n-1)$-dimensional-as large as the set of regular points. In this work, we show for the first time that, 'usually', the set of degenerate points is small. Namely, we prove that, given any $C^{\infty}$ obstacle, for almost every solution the nonregular part of the free boundary is at most $(n-2)$-dimensional. This is the first result in this direction for the Signorini problem. Furthermore, we prove analogous results for the obstacle problem for the fractional Laplacian $(-\Delta)^s$, and for the parabolic Signorini problem. In the parabolic Signorini problem, our main result establishes that the non-regular part of the free boundary is $\left(n-1-\alpha_{\circ}\right)$-dimensional for almost all times $t$, for some $\alpha_{\circ}>0$. Finally, we construct some new examples of free boundaries with degenerate points.
Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue
(Elsevier B.V., 2022-08-01) González Franquesa, Alba; Gama-Perez, Pau; Kulis, Marta; Szczepanowska, K.; Dahdah, Norma; Moreno-Gomez, Sonia; Latorre Pellicer, Ana; Fernández Ruiz, Rebeca; Aguilar-Mogas, Antoni; Hoffman, Anne; Monelli, Erika; Samino Gené, Sara; Miró-Blanch, Joan; Oemer, Gregor; Duran, Xavier; Sanchez-Rebordelo, Estrella; Schneeberger, Marc; Obach, Merce; Montane, Joel; Castellano, Giancarlo; Chapaprieta, Vicente; Sun, Wenfei; Navarro, Lourdes; Prieto, Ignacio; Castaño, Carlos; Novials, Anna; Gomis, Ramon, 1946-; Monsalve, Maria; Claret i Carles, Marc; Graupera i Garcia-Milà, Mariona; Soria, Guadalupe; Wolfrum, Christian; Vendrell, Joan; Fernández-Veledo, Sonia; Enriquez, Jose Antonio; Carracedo Álvarez, Ángel; Perales Losa, Carlos; Nogueiras, Rubén; Herrero, Laura; Trifunovic, Aleksandra; Keller, Markus A; Yanes, Oscar; Sales-Pardo, Marta; Guimerà, Roger; Blüher, Matthias; Martín-Subero, José Ignacio; Garcia Roves, Pablo M.
Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, proteomic, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most obesity and overnutrition-related pathological features were successfully reverted, we observed a high degree of metabolic dysfunction in visceral white adipose tissue, characterized by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and an apparent global healthy phenotype, obesity triggered a cascade of events in visceral adipose tissue progressing from mitochondrial metabolic and proteostatic alterations to widespread cellular stress, which compromises its biosynthetic and recycling capacity. In humans, weight loss after bariatric surgery showed a transcriptional signature in visceral adipose tissue similar to our mouse model of obesity reversion. Overall, our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in visceral adipose tissue.
Tumor microenvironment gene expression profiles associated to complete pathological response and disease progression in resectable NSCLC patients treated with neoadjuvant chemoimmunotherapy
(BMJ, 2022-09-01) Casarrubios, Marta; Provencio, Mariano; Nadal, Ernest; Insa, Amelia; Del Rosario García Campelo, María; Lázaro Quintela, Martín; Dómine, Manuel; Majem, Margarita; Rodriguez Abreu, Delvys; Martinez Marti, Alex; De Castro Carpeño, Javier; Cobo, Manuel; López Vivanco, Guillermo; Del Barco, Edel; Bernabé, Reyes; Viñolas, Nuria; Barneto Aranda, Isidoro; Massuti, Bartomeu; Sierra Rodero, Belén; Martinez Toledo, Cristina; Fernández Miranda, Ismael; Serna Blanco, Roberto; Romero, Atocha; Calvo, Virginia; Cruz Bermúdez, Alberto
Background Neoadjuvant chemoimmunotherapy for non-small cell lung cancer (NSCLC) has improved pathological responses and survival rates compared with chemotherapy alone, leading to Food and Drug Administration (FDA) approval of nivolumab plus chemotherapy for resectable stage IB-IIIA NSCLC (AJCC 7th edition) without ALK or EGFR alterations. Unfortunately, a considerable percentage of tumors do not completely respond to therapy, which has been associated with early disease progression. So far, it is impossible to predict these events due to lack of knowledge. In this study, we characterized the gene expression profile of tumor samples to identify new biomarkers and mechanisms behind tumor responses to neoadjuvant chemoimmunotherapy and disease recurrence after surgery. Methods Tumor bulk RNA sequencing was performed in 16 pretreatment and 36 post-treatment tissue samples from 41 patients with resectable stage IIIA NSCLC treated with neoadjuvant chemoimmunotherapy from NADIM trial. A panel targeting 395 genes related to immunological processes was used. Tumors were classified as complete pathological response (CPR) and non-CPR, based on the total absence of viable tumor cells in tumor bed and lymph nodes tested at surgery. Differential-expressed genes between groups and pathway enrichment analysis were assessed using DESeq2 and gene set enrichment analysis. CIBERSORTx was used to estimate the proportions of immune cell subtypes. Results CPR tumors had a stronger pre-established immune infiltrate at baseline than non-CPR, characterized by higher levels of IFNG, GZMB, NKG7, and M1 macrophages, all with a significant area under the receiver operating characteristic curve (ROC) >0.9 for CPR prediction. A greater effect of neoadjuvant therapy was also seen in CPR tumors with a reduction of tumor markers and IFN gamma signaling after treatment. Additionally, the higher expression of several genes, including AKT1, BST2, OAS3, or CD8B; or higher dendritic cells and neutrophils proportions in post-treatment non-CPR samples, were associated with relapse after surgery. Also, high pretreatment PD-L1 and tumor mutational burden levels influenced the post-treatment immune landscape with the downregulation of proliferation markers and type I interferon signaling molecules in surgery samples. Conclusions Our results reinforce the differences between CPR and non-CPR responses, describing possible response and relapse immune mechanisms, opening the possibility of therapy personalization of immunotherapy-based regimens in the neoadjuvant setting of NSCLC.
BioExcel Building Blocks Workflows (BioBB-Wfs), an integrated web-based plartform for biomolecular simulations.
(Oxford University Press, 2022-05-02) Bayarri, Genís; Andrio, Pau; Hospital Gasch, Adam; Orozco López, Modesto; Gelpi Buchaca, Josep Lluís
We present BioExcel Building Blocks Workflows, a web-based graphical user interface (GUI) offering access to a collection of transversal pre-configured biomolecular simulation workflows assembled with the BioExcel Building Blocks library. Available workflows include Molecular Dynamics setup, protein-ligand docking, trajectory analyses and small molecule parameterization. Workflows can be launched in the platform or downloaded to be run in the users' own premises. Remote launching of long executions to user's available High-Performance computers is possible, only requiring configuration of the appropriate access credentials. The web-based graphical user interface offers a high level of interactivity, with integration with the NGL viewer to visualize and check 3D structures, MDsrv to visualize trajectories, and Plotly to explore 2D plots. The server requires no login but is recommended to store the users' projects and manage sensitive information such as remote credentials. Private projects can be made public and shared with colleagues with a simple URL. The tool will help biomolecular simulation users with the most common and repetitive processes by means of a very intuitive and interactive graphical user interface. The server is accessible at https://mmb.irbbarcelona.org/biobb-wfs.
Xeno-free bioengineered human skeletal muscle tissue using human platelet lysate-based hydrogels
(2022-08-30) Fernández Garibay, Xiomara; Gomez Florit, Manuel; Domingues, Rui M. A.; Gomes, Manuela E.; Fernández Costa, Juan M.; Ramón Azcón, Javier
Bioengineered human skeletal muscle tissues have emerged in the last years as new in vitro systems for disease modeling. These bioartificial muscles are classically fabricated by encapsulating human myogenic precursor cells in a hydrogel scaffold that resembles the extracellular matrix. However, most of these hydrogels are derived from xenogenic sources, and the culture media is supplemented with animal serum, which could interfere in drug testing assays. On the contrary, xeno-free biomaterials and culture conditions in tissue engineering offer increased relevance for developing human disease models. In this work, we used human platelet lysate-based nanocomposite hydrogels (HUgel) as scaffolds for human skeletal muscle tissue engineering. These hydrogels consist of human platelet lysate reinforced with cellulose nanocrystals (a-CNC) that allow tunable mechanical, structural, and biochemical properties for the 3D culture of stem cells. Here, we developed hydrogel casting platforms to encapsulate human muscle satellite stem cells in HUgel. The a-CNC content was modulated to enhance matrix remodeling, uniaxial tension, and self-organization of the cells, resulting in the formation of highly aligned, long myotubes expressing sarcomeric proteins. Moreover, the bioengineered human muscles were subjected to electrical stimulation, and the exerted contractile forces were measured in a non-invasive manner. Overall, our results demonstrated that the bioengineered human skeletal muscles could be built in xeno-free cell culture platforms to assess tissue functionality, which is promising for drug development applications.
Impulsivity is longitudinally associated with healthy and unhealthy dietary patterns in individuals with overweight or obesity and metabolic syndrome within the framework of the PREDIMED-Plus trial
(BioMed Central, 2022-12-01) Gómez Martínez, Carlos; Babio, Nancy; Julvez, Jordi; Nishi, Stephanie K.; Fernández Aranda, Fernando; Martínez-González, Miguel Ángel, 1957-; Cuenca Royo, Aida; Fernández, Rebeca; Jiménez-Murcia, Susana; de la Torre, Rafael; Pintó Sala, Xavier; Bloemendaal, Mirjam; Fitó Colomer, Montserrat; Corella Piquer, Dolores; Arias, Alejandro; Salas Salvadó, Jordi
Background: Few studies have analyzed the associations between impulsivity and dietary patterns. Some of them have shown a cross-sectional inverse relationship between impulsivity and healthy diet scores, whereas others reported a positive association with unhealthy dietary assessments. We aimed to examine longitudinal associations of impulsivity trait with adherence to healthy and unhealthy dietary patterns in older participants at high risk of cardiovascular disease over 3 years of follow-up. Methods: A 3-year prospective cohort analysis within the PREDIMED-Plus-Cognition study conducted in 4 PREDIMED-Plus study centers was performed. The PREDIMED-Plus study aimed to test the beneficial effect of a lifestyle intervention on the primary prevention of cardiovascular disease. The participants with overweight or obesity and metabolic syndrome included in the present study (n = 462; mean age of 65.3 years; 51.5% female) completed both the UPPS-P Impulsive Behavior Scale (range: 0-236 points) and the 143-item Food Frequency Questionnaire at baseline, 1-year and 3-years of follow-up. Ten diet scores assessing healthy and unhealthy dietary patterns were evaluated. Linear mixed models were performed adjusting by several confounders to study the longitudinal associations between impulsivity trait and adherence to dietary pattern scores over 3 years of follow-up (also assessing interactions by sex, age, and intervention group). Results: Impulsivity were negatively associated with adherence to the Healthy Plant-Based [β = -0.92 (95%CI -1.67, -0.16)], Mediterranean [β = -0.43 (95%CI -0.79, -0.07)], Energy-Restricted Mediterranean [β = -0.76 (95%CI -1.16, -0.37)], Alternative Healthy Eating Index [β = -0.88 (95%CI -1.52, -0.23)], Portfolio [β = -0.57 (95%CI -0.91, -0.22)], and DASH [β = -0.50 (95%CI -0.79, -0.22)] diet scores over 3 years of follow-up, whereas impulsivity was positively related with adherence to the unhealthy Western diet [β = 1.59 (95%CI 0.59, 2.58)] over time. An interaction by intervention group was found, with those participants in the intervention group with high impulsivity levels having lower adherence to several healthy dietary patterns. Conclusions: Heightened impulsivity was longitudinally associated with lower adherence to healthy dietary patterns and higher adherence to the Western diet over 3 years of follow-up. Furthermore, nutritional intervention programs should consider impulsivity as a relevant factor for the intervention success.
Mycotoxin Exposure and Renal Cell Carcinoma Risk: An Association Study in the EPIC European Cohort
(MDPI AG, 2022-08-30) Claeys, Liesel; De Saeger, Sarah; Scelo, Ghislaine; Biessy, Carine; Casagrande, Corinne; Nicolas, Geneviève; Korenjak, Michael; Fervers, Beatrice; Heath, Alicia K.; Krogh, Vittorio; Luján Barroso, Leila; Castilla, Jesús; Ljungberg, Börje; Rodriguez Barranco, Miguel; Ericson, Ulrika; Santiuste, Carmen; Catalano, Alberto; Overvad, Kim; Brustad, Magritt; Gunter, Marc J.; Zavadil, Jiri; De Boevre, Marthe; Huybrechts, Inge
Background: Mycotoxins have been suggested to contribute to a spectrum of adverse health effects in humans, including at low concentrations. The recognition of these food contaminants being carcinogenic, as co-occurring rather than as singularly present, has emerged from recent research. The aim of this study was to assess the potential associations of single and multiple mycotoxin exposures with renal cell carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Food questionnaire data from the EPIC cohort were matched to mycotoxin food occurrence data compiled by the European Food Safety Authority (EFSA) from European Member States to assess long-term dietary mycotoxin exposures, and to associate these with the risk of renal cell carcinoma (RCC, n = 911 cases) in 450,112 EPIC participants. Potential confounding factors were taken into account. Analyses were conducted using Cox's proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) with mycotoxin exposures expressed as mu g/kg body weight/day. Results: Demographic characteristics differed between the RCC cases and non-cases for body mass index, age, alcohol intake at recruitment, and other dietary factors. In addition, the mycotoxin exposure distributions showed that a large proportion of the EPIC population was exposed to some of the main mycotoxins present in European foods such as deoxynivalenol (DON) and derivatives, fumonisins, Fusarium toxins, Alternaria toxins, and total mycotoxins. Nevertheless, no statistically significant associations were observed between the studied mycotoxins and mycotoxin groups, and the risk of RCC development. Conclusions: These results show an absence of statistically significant associations between long-term dietary mycotoxin exposures and RCC risk. However, these results need to be validated in other cohorts and preferably using repeated dietary exposure measurements. In addition, more occurrence data of, e.g., citrinin and fumonisins in different food commodities and countries in the EFSA database are a prerequisite to establish a greater degree of certainty.
Whole-brain dynamics differentiate among cisgender and transgender individuals
(Wiley, 2022-05-18) Uribe, Carme; Escrichs, Anira; de Filippi, Eleonora; Sanz Perl, Yonatan; Junqué i Plaja, Carme, 1955-; Gomez Gil, Esther; Kringelbach, Morten L.; Guillamon, Antonio; Deco, Gustavo
How the brain represents gender identity is largely unknown, but some neural differences have recently been discovered. We used an intrinsic ignition framework to investigate whether there are gender differences in the propagation of neural activity across the whole-brain and within resting-state networks. Studying 29 trans men and 17 trans women with gender incongruence, 22 cis women, and 19 cis men, we computed the capability of a given brain area in space to propagate activity to other areas (mean-ignition), and the variability across time for each brain area (node-metastability). We found that both measurements differentiated all groups across the whole brain. At the network level, we found that compared to the other groups, cis men showed higher mean-ignition of the dorsal attention network and node-metastability of the dorsal and ventral attention, executive control, and temporal parietal networks. We also found higher mean-ignition values in cis men than in cis women within the executive control network, but higher mean-ignition in cis women than cis men and trans men for the default mode. Node-metastability was higher in cis men than cis women in the somatomotor network, while both mean-ignition and node-metastability were higher for cis men than trans men in the limbic network. Finally, we computed correlations between these measurements and a body image satisfaction score. Trans men's dissatisfaction as well as cis men's and cis women's satisfaction toward their own body image were distinctively associated with specific networks in each group. Overall, the study of the whole-brain network dynamical complexity discriminates gender identity groups, functional dynamic approaches could help disentangle the complex nature of the gender dimension in the brain.
Comparing human and chimpanzee temporal lobe neuroanatomy reveals modifications to human language hubs beyond the frontotemporal arcuate fasciculus
(National Academy of Sciences, 2022-07-05) Sierpowska, Joanna; Bryant, Katherine L.; Janssen, Nikki; Blazquez Freches, Guilherme; Römkens, Manon; Mangnus, Margot; Mars, Rogier B.; Piai, Vitória
The biological foundation for the language-ready brain in the human lineage remains a debated subject. In humans, the arcuate fasciculus (AF) white matter and the posterior portions of the middle temporal gyrus are crucial for language. Compared with other primates, the human AF has been shown to dramatically extend into the posterior temporal lobe, which forms the basis of a number of models of the structural connectivity basis of language. Recent advances in both language research and comparative neuroimaging invite a reassessment of the anatomical differences in language streams between humans and our closest relatives. Here, we show that posterior temporal connectivity via the AF in humans compared with chimpanzees is expanded in terms of its connectivity not just to the ventral frontal cortex but also to the parietal cortex. At the same time, posterior temporal regions connect more strongly to the ventral white matter in chimpanzees as opposed to humans. This pattern is present in both brain hemispheres. Additionally, we show that the anterior temporal lobe harbors a combination of connections present in both species through the inferior fronto-occipital fascicle and human-unique expansions through the uncinate and middle and inferior longitudinal fascicles. These findings elucidate structural changes that are unique to humans and may underlie the anatomical foundations for full-fledged language capacity.
Mechanical strain stimulates COPII‐dependent secretory trafficking via Rac1
(2022-08-08) Phuyal, Santosh; Djaerff, Elena; Le Roux, Anabel-Lise; Baker, Martin J.; Fankhauser, Daniela; Mahdizadeh, Sayyed Jalil; Reiterer, Veronika; Parizadeh, Amirabbas; Felder, Edward; Kahlhofer, Jennifer C.; Teis, David; Kazanietz, Marcelo G.; Geley, Stephan; Eriksson, Leif A.; Roca-Cusachs Soulere, Pere; Farhan, Hesso
Associations Between the Modified Food Standard Agency Nutrient Profiling System Dietary Index and Cardiovascular Risk Factors in an Elderly Population
(Frontiers Media SA, 2022-07-14) Khoury, Nadine; Gómez Donoso, Clara; Martínez, María Ángeles; Martínez-González, Miguel Ángel, 1957-; Corella Piquer, Dolores; Fitó Colomer, Montserrat; Martínez, J. Alfredo, 1957-; Alonso Gómez, Ángel M.; Wärnberg, Julia; Vioque, Jesús; Romaguera, Dora; León Acuña, Ana; Tinahones, Francisco J.; Santos Lozano, Jose Manuel; Serra Majem, Lluís; Massó Guijarro, Paloma; Tur, Josep A.; Martín Sánchez, Vicente; Pintó Sala, Xavier; Delgado Rodríguez, Miguel, 1958-; Matía Martín, Pilar; Vidal i Cortada, Josep; Vázquez Martínez, C.; Daimiel, Lidia; Ros Rahola, Emilio; Bes Rastrollo, Maira; Barragan, Rocio; Castañer, Olga; Torres Peña, Jose D.; Notario Barandiaran, Leyre; Muñoz Bravo, Carlos; Abete, Itziar; Prohens, Lara; Cano Ibáñez, Naomi; Tojal Sierra, Lucas; Fernández García, José C.; Sayon Orea, Carmen; Pascual, Maria; Sorlí, José V.; Zomeño Fajardo, María Dolores; Peña Orihuela, Patricia J.; Signes Pastor, Antonio J.; Basterra Gortari, F. Javier; Schröeder, Helmut; Salas Salvadó, Jordi; Babio, Nancy
Background: Helping consumers to improve the nutritional quality of their diet is a key public health action to prevent cardiovascular diseases (CVDs). The modified version of the Food Standard Agency Nutrient Profiling System Dietary Index (FSAm-NPS DI) underpinning the Nutri-Score front-of-pack label has been used in public health strategies to address the deleterious consequences of poor diets. This study aimed to assess the association between the FSAm-NPS DI and some CVD risk factors including body mass index (BMI), waist circumference, plasma glucose levels, triglyceride levels, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and diastolic and systolic blood pressure. Materials and Methods: Dietary intake was assessed at baseline and after 1 year of follow-up using a 143-item validated semi-quantitative food-frequency questionnaire. Dietary indices based on FSAm-NPS applied at an individual level were computed to characterize the diet quality of 5,921 participants aged 55-75 years with overweight/obesity and metabolic syndrome from the PREDIMED-plus cohort. Associations between the FSAm-NPS DI and CVD risk factors were assessed using linear regression models. Results: Compared to participants with a higher nutritional quality of diet (measured by a lower FSAm-NPS DI at baseline or a decrease in FSAm-NPS DI after 1 year), those participants with a lower nutritional quality of diet (higher FSAm-NPS DI or an increase in score) showed a significant increase in the levels of plasma glucose, triglycerides, diastolic blood pressure, BMI, and waist circumference (beta coefficient [95% confidence interval]; P for trend) (1.67 [0.43, 2.90]; <0.001; 6.27 [2.46, 10.09]; <0.001; 0.56 [0.08, 1.05]; 0.001; 0.51 [0.41, 0.60]; <0.001; 1.19 [0.89, 1.50]; <0.001, respectively). No significant associations in relation to changes in HDL and LDL-cholesterol nor with systolic blood pressure were shown. Conclusion: This prospective cohort study suggests that the consumption of food items with a higher FSAm-NPS DI is associated with increased levels of several major risk factors for CVD including adiposity, fasting plasma glucose, triglycerides, and diastolic blood pressure. However, results must be cautiously interpreted because no significant prospective associations were identified for critical CVD risk factors, such as HDL and LDL-cholesterol, and systolic blood pressure.
A cryopreservation method for bioengineered 3D cell culture models
(2022-07-01) Herrero Gómez, Alba; Azagra, Marc; Marco Rius, Irene
Technologies to cryogenically preserve (a.k.a. cryopreserve) living tissue, cell lines and primary cells have matured greatly for both clinicians and researchers since their first demonstration in the 1950s and are widely used in storage and transport applications. Currently, however, there remains an absence of viable cryopreservation and thawing methods for bioengineered, three-dimensional (3D) cell models, including patients' samples. As a first step towards addressing this gap, we demonstrate a viable protocol for spheroid cryopreservation and survival based on a 3D carboxymethyl cellulose scaffold and precise conditions for freezing and thawing. The protocol is tested using hepatocytes, for which the scaffold provides both the 3D structure for cells to self-arrange into spheroids and to support cells during freezing for optimal post-thaw viability. Cell viability after thawing is improved compared to conventional pellet models where cells settle under gravity to form a pseudo-tissue before freezing. The technique may advance cryobiology and other applications that demand high-integrity transport of pre-assembled 3D models (from cell lines and in future cells from patients) between facilities, for example between medical practice, research and testing facilities.
Unparalleled selectivity and electronic structure of heterometallic [LnLn'Ln] molecules as 3-qubit quantum gates
(Royal Society of Chemistry, 2022-04-14) Maniaki, Diamantoula; Garay-Ruiz, Diego; Barrios Moreno, Leoní Alejandra; Martins, Daniel O.T.A.; Aguilà Avilés, David; Tuna, Floriana; Reta Mañeru, Daniel; Roubeau, Olivier; Bo, Carles; Aromí Bedmar, Guillem
Heterometallic lanthanide [LnLn′] coordination complexes that are accessible thermodynamically are very scarce because the metals of this series have very similar chemical behaviour. Trinuclear systems of this category have not been reported. A coordination chemistry scaffold has been shown to produce molecules of type [LnLn′Ln] of high purity, i.e. exhibiting high metal distribution ability, based on their differences in ionic radius. Through a detailed analysis of density functional theory (DFT) based calculations, we discern the energy contributions that lead to the unparalleled chemical selectivity of this molecular system. Some of the previously reported examples are compared here with the newly prepared member of this exotic list, [Er2Pr(LA)2(LB)2(py)(H2O)2](NO3) (1) (H2LA and H2LB are two β-diketone ligands). A magnetic analysis extracted from magnetization and calorimetry determinations identifies the necessary attributes for it to act as an addressable, conditional multiqubit spin-based quantum gate. Complementary ab initio calculations confirm the feasibility of these complexes as composite quantum gates, since they present well-isolated ground states with highly anisotropic and distinct g-tensors. The electronic structure of 1 has also been analyzed by EPR. Pulsed experiments have allowed the establishment of the quantum coherence of the transitions within the relevant spin states, as well as the feasibility of a coherent control of these states via nutation experiments.
Donor-Acceptor Stenhouse Adduct Displaying Reversible Photoswitching in Water and Neuronal Activity
(2022-08-17) Castagna, Rossella; Maleeva, Galyna; Pirovano, Deborah; Matera, Carlo; Gorostiza Langa, Pablo Ignacio
The interest in the photochromism and functional applications of donor-acceptor Stenhouse adducts (DASAs) soared in recent years owing to their outstanding advantages and flexible design. However, their low solubility and irreversible conversion in aqueous solutions hampered exploring DASAs for biology and medicine. It is notably unknown whether the barbiturate electron acceptor group retains the pharmacological activity of drugs such as phenobarbital, which targets γ-aminobutyric acid (GABA)-type A receptors (GABAARs) in the brain. Here, we have developed the model compound DASA-barbital based on a scaffold of red-switching second-generation DASAs, and we demonstrate that it is active in GABAARs and alters the neuronal firing rate in a physiological medium at neutral pH. DASA-barbital can also be reversibly photoswitched in acidic aqueous solutions using cyclodextrin, an approved ingredient of drug formulations. These findings clarify the path toward the biological applications of DASAs and to exploit the versatility displayed in polymers and materials science.

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