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The aim of the research is to analyze companies’ demand of workforce with mathematical skills. The type of sample was not probabilistic by selfdetermination and 255 companies’ managers were surveyed. The data matrix was analyzed using exploratory factor analysis and the use of polychoric matrices. The results show that companies require their employees to know and remember mathematical operations that allow them to be fast and precise in their calculations; a better understanding of mathematics to improve their calculations in computer applications. They also need employees capable of performing calculations that allow them to solve complicated financial problems for better financial decision making.

The financial knowledge that young people have is fundamental to their financial decision making, to guarantee their future consumption and their well-being in retirement. The study focused on analyzing the knowledge that high school students have of income, money management, savings, investment, credit and spending, and comparing if there is a difference by gender. Data from 100 high school students from Boca del Río, Veracruz were obtained using test designed by Contreras-Rodríguez, et al. The analysis seeks to determine the structure of variables that explain the knowledge that Mexican high school students have of financial topics; in addition to verifying that the variables are correlated and that the data matrix is not an identity matrix. The results show that the instrument used has a relatively low Cronbach's alpha (0.597). It was verified that the data matrix did not constitute an identity matrix, which made the data analysis possible through factorial analysis with component extraction. The two extracted factors are explained by 67% of the total variance. The ANOVA tests and the values of the F statistic with gl and its significance (0.05), as well as the Levene statistic, showed that there is no gender difference. Based on the results, strengthening financial education of students is advisable to contribute to their future inclusion in the financial system.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system ageing. In this prospective cohort study, we describe a straightforward methodology for quantifying the effect of HIV on aging factors compared with other relevant conditions, such as MAFLD, by quantifying DNA methylation and telomere length. Fifty-seven samples in total, thirty-eight from HIV-infected and nineteen from HIV-uninfected participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. The results showed an increased association with these age-acceleration markers in individuals with HIV, who were also diagnosed with MAFLD. This highlights the importance of HIV infection and MAFLD conditions in the biological ageing process in PLWH, and the fact that these markers of ageing can be measured through DNA methylation and telomere length quantification. Thus, we propose including these quantifications in studies of comorbidities to better understand them and potentially prevent their effects in this population.

he aim of this research is to determine if there is a significant difference between the socio-demographic population groups in relation to financial literacy in Mexican adults, between 18 and 70 years old. It is assumed that there is a significant difference in financial literacy levels according to age, gender, educational level, residence, region, marital status, household position, economic dependents, work conditions, job position, income, material and financial wealth, and financial experience. The method is derived from the approaches of Lusardi and Mitchell (2011a), OECD (2018), OECD (2017) and Atkinson and Messy (2012). Data from the Mexican survey ENIF (2018) are used. The methodology and the use of microeconomic data provide originality on the research of financial literacy for Mexico. The results of the Probit econometric model show sociodemographic variables that help to predict the probability that Mexican adults will answer the financial literacy questions correctly and provide evidence on specific groups of the Mexican population that present significant differences in financial literacy. Particularly this refers to those with low educational level, women, the disabled, retirees, low-income people, those who are not included in the financial system, as well as those who lack training in financial education issues. The findings can be useful for the design of public policies on financial literacy, the basic financial knowledge that the population should acquire in order to make informed decisions.

Resumen Objetivos: El estudio pretende reconocer la existencia de agentes portadores y reproductores de prácticas y saberes populares en salud, sus dominios y dinámica en el espacio social. Georreferenciar sus dinámicas y establecer su relación con el Plan Básico de Ordenamiento Territorial. Metodología: Estudio cualitativo analítico, que conjuga la geografía crítica y la etnografía. Mediante el uso de técnicas de georreferenciación, -localización y espacialización-, con uso del software QGIS versión 3.6 Nossa. Y mediante el uso de técnicas de entrevistas a profundidad y observaciones documentadas, información que se ordenó y sistematizó por categorías, mediante la implementación del programa ATLAS.ti versión 9. Resultados: Se reconocieron más de 60 agentes y se localizaron 48. Se reconocen dos dominios del saber popular: el mágico religioso, expresado en sobanderos con secreto, y el curanderismo expresado en hierbateros, rezanderos y sobanderos. Se legitiman a través de su presencia en espacios sociales, en sus tres dimensiones: material, al portar una identidad y un dominio, que habitan con objetos; mental, el cual cargan de relaciones y simbolismos; y político, donde reproducen una cadena comercial vinculada a la zona de vocación comercial establecida por el PBOT del municipio. Conclusiones: Los agentes, sus prácticas y saberes se determinan y legitiman, a partir de actos de reproducción social, cultural y política en el territorio como espacio social, y en sus dimensiones, a partir de expresiones culturales, simbolismos y rituales, relaciones materiales a partir del intercambio con objetos y servicios, y su asiento político en las zonas de vocación territorial. Abstract Objectives: The study aims at recognizing the existence of agents carrying and reproducing popular practices and knowledge in health, their domains and dynamics in the social space and at geo-positioning their dynamics and establishing their relationship with the Basic Plan of Territorial Planning. Methodology: qualitative analytical study that combines critical geography through georeferencing techniques, -localization and spatialization-, using the QGIS Version 3.6 Nossa program, and ethnography through the use of in-depth interview techniques and observations, information that was organized and systematized by categories through the implementation of the ATLAS.ti version 9 program. Results: More than 60 agents were recognized and 48 were located. Two domains of popular knowledge were recognized: the Religious Magic, expressed in massage therapists (sobanderos) with secrecy, and folk medicine (Curanderismo) expressed in shamans, rezanderos and sobanderos. They are legitimized through their presence in social spaces in their 3 dimensions: material by carrying an identity and a domain inhabiting objects; mental which is loaded with relationships and symbolism; and political where they reproduce an overlapping and expanded commercial chain, linked to the area of commercial vocation delimited by the PBOT of the municipality. Conclusions: Agents, their practices and knowledge are determined and legitimized based on acts of social, cultural and political reproduction in the territory as a social space, and in their dimensions based on cultural expressions, symbolisms and rituals, material relationships from the exchange with objects and services and settled politically in the areas of territorial vocation. Resumo Objetivos: o estudo pretende reconhecer a existência de agentes portadores e reprodutores de práticas e saberes populares em saúde, seus domínios e dinâmica no espaço social. Georreferenciar suas dinâmicas e estabelecer sua relação com o Plano Básico de Ordenamento Territorial. Metodologia: estudo qualitativa analítico, que conjuga a geografia crítica e a etnografia. Através do uso de técnicas de georreferenciação, -localização e espacialização-, com uso do software QGIS versão 3.6 Nossa. E através do uso de técnicas de entrevistas a profundidade e observações documentadas, informação que se arrumou e sistematizou por categorias, através da execução do programa ATLAS.ti versão 9. Resultados: reconhecerem-se mais de 60 agentes e se localizaram 48. Reconhecem-se dois domínios do saber popular: o mágico religioso, expressado em sobanderos (pessoa que sana a través de massagens) com secreto, e o curandeirismo expressado em curandeiros, rezanderos (pessoa que sana a través da oração) e sobanderos. Legitimam-se através de sua presença em espaços sociais, em suas três dimensões: material, ao trazer uma identidade e um domínio, que habitam com objetos; mental, o qual carregam de relaciones e simbolismos; e político, onde reproduzem uma cadeia comercial vinculada à zona de vocação comercial estabelecida pelo PBOT do município. Conclusões: os agentes, suas práticas e saberes se determinam e legitimam, a partir de atos de reprodução social, cultural e política no território como espaço social, e em suas dimensões, a partir de expressões culturais, simbolismos e rituais, relações materiais a partir do intercâmbio com objetos e serviços, e sua posição política nas zonas de vocação territorial.

Engineered autonomous bioluminescence (EAB) offers many potential applications in Plant Synthetic Biology, notably asin vivoreporter system. Current EAB reporter configurations are limited for quantitative applications due to low dynamic range. We reconfigured theNeonothopanus nambifungal bioluminescence (NeoLuc) pathway to serve as a high-throughput and inexpensive reporter for quantitative analysis of gene expression. We showed that by configuring the first committed step in the pathway (HispS) as the transcriptional entry point instead of the fungal luciferase, the dynamic range of the output increased dramatically, equaling that of the FLuc/RLuc reporter, and outperforming it in high throughput capacity. Furthermore, the inclusion of an enhanced GFP as normalizer allowed transient ratiometric measurements inN. benthamiana. Fast and rich datasets generated by the NeoLuc/eGFP system enabled us to undertake the optimization of new challenging synthetic gene circuits, including a complex agrochemical/optogenetic dual input switch for tight control of engineered metabolic pathways.

Los foros virtuales se han convertido en una de las principales herramientas didácticas de los cursos en línea. En el presente artículo se presenta un análisis de algunas metodologías para valorar la pertinencia de éstos desde una perspectiva pedagógica; se retoman algunas investigaciones realizadas en la Universidad Veracruzana-México respecto a los principales resultados que se han obtenido para la generación de aprendizaje significativo, así como de metodologías de distintos autores que han aportado ideas para su comprensión. Por ello, se analizan distintos tipos de foros y se revisan sus principales áreas de oportunidad. Se enuncian propuestas de mejora, basadas en los beneficios que aporta la realidad virtual e intentando recuperar la condición humana. Partimos del supuesto que el uso de la tecnología es relevante en la medida en que existe el sustento didáctico que propicia la construcción de conocimiento a partir de los medios y las herramientas. Creemos que se continúa privilegiando la palabra como la principal vía de comunicación y se dejan de lado la imagen, el video, y entornos amigables que facilitan la convivencia en los escenarios virtuales y que pudieran favorecer a estudiantes que tienen diferentes estilos de aprendizaje.

Several studies have identified the main barriers and facilitators that breast cancer survivors experience in the return to work (RTW). The authors conducted a qualitative study using focus group discussions with a group of female non-metastatic breast cancer survivors (n = 6), a group of health professionals from different medical specialties (n = 8), and a third group of company managers mainly composed of human resources managers (n = 7). The study was carried out between March and December 2021 in Zaragoza (Spain). Transcripts were analyzed using inductive content analysis to identify work-related barriers and facilitators and coded by the research team. Barriers identified included physical and cognitive symptoms, psychosocial problems, lack of knowledge and coordination (health professional, patients, and managers), legal vacuum, physical change, time constraints, work characteristics (lower skilled jobs), unsupportive supervisors and coworkers, family problems and self-demand. Facilitators included family and work support, physical activity and rehabilitation, personalized attention, interdisciplinary collaboration, legal advice for workers, knowledge about breast cancer in companies, positive aspects of work, elaboration of protocols for RTW in women with breast cancer. RTW in working women with breast cancer requires a personalized and holistic view that includes the perspectives of patients, healthcare professionals and company managers.

Purpose: To identify organizational and technological reactions of companies in the Mexican states of Oaxaca and Veracruz with regards to the COVID-19 crisis. Methodological design: This is a quantitative and cross-sectional study. The information was collected in two phases: May and September, 2020. The survey was answered by 154 companies in the first phase and 178 in the second. The instruments were designed to collect information on the impact the pandemic had on companies’ operation: the measures adopted to survive the crisis, the government "support" they received, and the conditions for a possible return to the "new normal." The sample of 154 and 178 companies has statistical validity with a confidence level of 95% and a margin of error of 7.88% and 6%, in phase 1 and 2, respectively. Results: At the beginning of the pandemic, only a third of the companies from Veracruz, Boca del Río and Tuxtepec registered major affectations, unlike the border cities of the northern states of Mexico. Research limitations: Despite the design of an extensive promotion campaign, high rates of rejection could have affected the representativeness of the study. Findings: The results show that uncertainty resulting from the pandemic has generated new business opportunities for those companies capable of combining the internal adjustment of their costs and the search of new business models with greater use of digital technologies and higher inventory margins.

Students academic performance could be affected by excessive use of the smartphone. This study focuses on analyzing the level of cell phone addiction in engineering university students. It also seeks to determine if there is a difference by gender in this behavior. 306 engineering students from a Technological Institute in Veracruz, Mexico participated in the study. The instrument used to obtain data was SAS-SV (Smartphone addiction scale-short version) designed by [1]. In order to identify the set of indicators with the highest factor loadings, an exploratory factor analysis was carried out with extraction of components and orthogonal rotation with the Varimax method. To identify if there is a difference by gender, the t test is used to contrast the hypothesis about two independent population means. The findings demonstrated the extraction of two components, which differs from the one-dimensional model proposed by [1], and no difference was found between the groups of male and female students.

Anorexia nervosa (AN) typically emerges in adolescence. The cortico-striatal system (CSTS) and the default mode network (DMN) are brain circuits with a crucial development during this period. These circuits underlie cognitive functions that are impaired in AN, such as cognitive flexibility and inhibition, among others. Little is known about their involvement in adolescent AN and how weight and symptom improvement might modulate potential alterations in these circuits. Forty-seven adolescent females (30 AN, 17 healthy control) were clinically/neuropsychologically evaluated and scanned during a 3T-MRI resting-state session on two occasions, before and after a 6-month multidisciplinary treatment of the AN patients. Baseline and baseline-to-follow-up between-group differences in CSTS and DMN resting-state connectivity were evaluated, as well as their association with clinical/neuropsychological variables. Increased connectivity between the left dorsal putamen and the left precuneus was found in AN at baseline. At follow-up, body mass index and clinical symptoms had improved in the AN group. An interaction effect was found in the connectivity between the right dorsal caudate to right mid-anterior insular cortex, with lower baseline AN connectivity that improved at follow-up; this improvement was weakly associated with changes in neuropsychological (Stroop test) performance. These results support the presence of CSTS connectivity alterations in adolescents with AN, which improve with weight and symptom improvement. In addition, at the level of caudate-insula connectivity, they might be associated with inhibitory processing performance. Alterations in CSTS pathways might be involved in AN from the early stages of the disorder.

Background. People with HIV (PWH) exhibit a markedly increased risk of anal cancer, especially men who have sex with men (MSM), with specific microbiota signatures possibly contributing to greater human papillomavirus (HPV) oncogenic potential. Low specificity of the current screening strategy for detecting high-grade squamous intraepithelial lesions (HSIL) hinders anal cancer prevention. We investigated microbiome derivatives associated with HSIL in anal cytology samples. Methods. We recruited a discovery and a validation cohort at four clinical sites in Spain and Italy. Study participants were mostly MSM undergoing HSIL screening with high-resolution anoscopy and anal biopsies to confirm HSIL. We extracted the bacterial DNA, proteins, and metabolites from anal cytology samples, and we performed 16SrRNA gene sequencing, mass spectrometry, and targeted metabolite quantification. Results. We included 213 participants, 167 in the discovery cohort (70 with confirmed HSIL) and 46 in the validation cohort (25 with confirmed HSIL). While we did not find clear microbiome composition signatures associated with HSIL, the microbiome associated with HSIL overexpressed proteins involved in the production of succinyl-CoA and cobalamin, with levels consistently increased in subjects with HSIL in the discovery and validation cohorts. Combined measurement of succinyl-CoA and cobalamin overperformed anal cytology, improving sensitivity from 91.2% to 96.6%, specificity from 34.1% to 81.8%, positive predictive value from 48.1% to 77.8%, and negative predictive value from 85.3% to 97.3%. While anal cytology correctly classified only 59.9% of individuals, combined measurement of both metabolites improved the classification to 87.7%. This test overcame internal (adjusted AUC 0.877) and external validation. From 98 false-positive cytologic results, succinyl-CoA and cobalamin level measurement reclassified 49 (50%) to true negatives. Finally, we demonstrate greater in vitro production of succinyl-CoA and cobalamin in bacteria associated with HSIL or cancer vs. those presumably protective. Conclusions. Cobalamin and succinyl-CoA are overexpressed in the anal microbiome of patients with HSIL and show excellent diagnostic capacity. Their measurement overperforms anal cytology to screen for patients with HSIL. Hence, we discovered two powerful biomarkers for which detection methods can readily be established, that could improve the current strategy of anal cancer screening.

The buckling failure of reinforced concrete spherical shell structures under the effect of the horizontal component of earthquake is investigated using a finite element method over a wide range of shell configurations. For this effect, two different loading case scenarios are considered; first, the shell is analyzed under the effects of the vertical seismic component alone. Then, the model is reanalyzed under the same loading conditions plus the horizontal earthquake component, taking into account two different horizontal-to-vertical earthquake spectral ratios. It is concluded that including the horizontal component of earthquake can result in a reduction in the buckling capacity of this type of structure; the impact of which is highly influenced by the horizontal-to-vertical earthquake spectral ratio and the shell geometry. It is also observed that the formulation adopted by ACI slightly overestimates the buckling capacity of spherical shells especially when horizontal seismic effects are included.

Candidates for combined liver-kidney transplant frequently present pretransplant HLA sensitization in most cases related to elevated prior transfusion requirements. The urgency criterion and the evidence of the protective effect at the immunologic level of the liver graft open the possibility of carrying out the combined transplant in patients with an incompatible crossmatch. The single-center experience presented here describes the patient profile and kidney graft evolution observed in this highly sensitized group.Descriptive study of a series of 4 cases of patients with positive crossmatch results who received a simultaneous liver-kidney transplant at our center. Demographic characteristics and clinical information were collected and detailed.Before the transplant, 2 patients presented HLA class I antibodies and the other 2 showed both class I and II. The post-transplant crossmatch result was negative in 2 of the 4 patients. All received induction with Thymoglobulin. In the 2 patients in whom the crossmatch remained positive, treatment with plasmapheresis, intravenous immunoglobulins and rituximab was initiated, after which the crossmatch resulted negative. During follow-up, anti-HLA antibodies were monitored, with the presence of mainly class I antibodies with variable mean fluorescence intensity being detected in all but 1 patient. Renal graft function remained stable throughout the tracing without objectifying histologic signs of rejection during the first 6 months of evolution.In our experience, combined liver-kidney transplant in sensitized patients with an incompatible crossmatching test has presented satisfactory outcomes. Close clinical and analytical monitoring is essential.

The presence of archaeocyath-bearing clasts from Cenozoic tills and Cambrian Mount Wegener Formation reveal erosion of a hidden Cambrian carbonate platform in Shackleton Range, Antarctica. We provide microfacies, paleontological, diagenetic and tectonically induced fabric data from carbonate clasts which, in addition to available geochemical and geochronological data from Shackleton Range, allow the paleoenvironmental reconstruction of a lost CambrianSeries 2mixed siliciclastic–carbonate platform that was developed and eroded during the Ross orogeny. Carbonate production was dominated by non-skeletal grains in possibly restricted platform-interior and oolitic shoal complex settings, while open subtidal sub-environments (calcimicrobe carpets, calcimicrobe–archaeocyath patch reefs, muddy bottoms) were dominated by a diverse calcimicrobe assemblage and/or by secondary to accessory heterozoan assemblage (archaeocyaths and other sponges, chancelloriids, hyoliths, coralomorphs, trilobites, echinoderms). We describe a Botoman assemblage with 34 archaeocyathan species among 12 existing archaeocyathan genera. A new archaeocyath family Shackletoncyathidae is proposed. New species (Rotundocyathus glaciussp. nov.,Buggischicyathus microporusgen. et sp. nov.,Paragnaltacyathus hoeflei,Shackletoncyathus buggischigen. et. sp. nov.,Santelmocyathus santelmoigen. et sp. nov.,Wegenercyathus sexangulaegen. et sp. nov.) andTabulaconus kordaecoralomorph are reported from Antarctica for the first time. Archaeocyathan fauna share few species with contemporary fauna of South Australia (9) and even fewer with the Antarctic platforms of the Shackleton Limestone (2) or the Schneider Hills limestone (1). Similarity is greater with Antarctic allochthonous assemblages of Permo-Carboniferous tillites from Ellsworth Mountains (2), Cenozoic deposits from King George Island (4) or Weddell Sea (1). The Shackleton Range lost/hidden platform shows a distinct entity related with its tectonosedimentary evolution, in a possible back-arc basin on the Mozambique seaway during the E and W Gondwana amalgamation, which distinguishes it from those developed on the palaeo-Pacific margin of the E Antarctic craton.

The Child Obsessive-Compulsive Impact Scale (COIS-R) is a parent- and self-report measure of the impairment related to Obsessive-Compulsive Disorder (OCD) symptoms. Previous research has demonstrated the reliability and validity of the original version of the COIS-R; to date, however, the scale has not been validated for use in Spanish samples of pediatric OCD. The present study aimed to assess the psychometric properties of this in a clinical sample of pediatric OCD (n = 91). Analyses of internal consistency, convergent and divergent validity were conducted. For both the COIS-R report scales estimates similar to those in the original instrument were obtained for internal consistency, test-retest reliability, and convergent validity. Thus, the Spanish version of the COIS-R seems to retain sound psychometric properties of its original version; it appears to be a reliable instrument for the assessment of obsessive-compulsive impairment and the effects of treatment, and can be used in other cultural contexts.

SummaryPrevious work has demonstrated that plants can be used as production platforms for molecules used in health, medicine, and agriculture. Production has been exemplified in both stable transgenic plants and using transient expression strategies. In particular, species ofNicotianahave been engineered to produce a range of useful molecules, including insect sex pheromones, which are valued for species-specific control of agricultural pests. To date, most studies have relied on strong constitutive expression of all pathway genes. However, work in microbes has demonstrated that yields can be improved by controlling and balancing gene expression. Synthetic regulatory elements that provide control over the timing and levels of gene expression are therefore useful for maximizing yields from heterologous biosynthetic pathways. In this study, we demonstrate the use of pathway engineering and synthetic genetic elements for controlling the timing and levels of production of Lepidopteran sex pheromones inNicotiana benthamiana. We demonstrate that copper can be used as a low-cost molecule for tightly regulated inducible expression. Further, we show how construct architecture influences relative gene expression and, consequently, product yields in multigene constructs. We compare a number of synthetic orthogonal regulatory elements and demonstrate maximal yields from constructs in which expression is mediated by dCas9-based synthetic transcriptional activators. The approaches demonstrated here provide new insights into the heterologous reconstruction of metabolic pathways in plants.

We wish to thank the Spanish Directorate General of Traffic forallowing access to their database of traffic accidents with victims,and K. Shashok for improving the use of English in the manuscript., Objective: To estimate the number of collateral casualties associated with road users considered responsible for a road crash. Method: We analyzed the case series comprising all 790,435 road users involved in road crashes with victims in Spain from 2009 to 2013, recorded in a nationwide police-based registry. For each road user assumed to be responsible for a crash, we collected information relative to health outcomes in other people involved in it, and obtained the total number of collateral casualties per 100 road users considered responsible for the crash. We then estimated the strength of associations between sex, age and the number of collateral casualties generated by car drivers considered responsible for the crash, and calculated rate ratios and corresponding 95% confidence intervals. Results: Pedestrians responsible for crashes were associated with the lowest number of collateral casualties (13.1/100), whereas the highest number (153/100) was observed for bus drivers responsible for crashes. Car drivers were associated with 104.4/100 collateral casualties. The youngest and the oldest car drivers responsible for crashes were associated with 33% and 41% more deaths, respectively, than the 25-4 year old group. Male drivers were associated with 22% more collateral casualties than female drivers. Conclusions: Regardless of the type of road user who was responsible for a road crash, their active contribution to the crash led to an additional number of collateral casualties in other, non-responsible users. The number and severity of collateral casualties were related to the type of vehicle and the number of people involved. These results are potentially useful to support the need to promote safer driver practices among subgroups of high-risk drivers., Objetivo: Estimar el número de víctimas colaterales asociadas a los usuarios de las vías de tráfico respon-sables de una colisión. Método: Se estudió la serie de casos formada por los 790.435 usuarios de la vía implicados en accidentes de tráfico con víctimas en España, entre 2009 y 2013, recogidos en el Registro de Accidentes de Tráfico con Víctimas de la Dirección General de Tráfico. Para cada uno de los usuarios considerado responsable se recogió información sobre las consecuencias sanitarias para las otras personas implicadas en el mismo accidente, y se calculó el número total de víctimas colaterales por cada 100 usuarios responsables. A continuación se estimó la fuerza de asociación de la edad y el sexo de los conductores de turismo con el número de víctimas colaterales generadas por ellos, y se obtuvieron las correspondientes razones detasas y sus intervalos de confianza del 95%.Resultados: Los peatones responsables de atropellos se asociaron al menor número de víctimas colaterales (13,1/100), mientras que la cifra más alta de estas (153/100) se asoció a los conductores de autobús responsables del accidente. Los de turismo implicaron a 104,4/100. Los conductores de turismo más jóvenes (64 años) implicaron respectivamente un 33% y un41% más de víctimas colaterales que el grupo de 25-34 años. Los varones se asociaron a un 22% más de víctimas colaterales que las mujeres. Conclusiones: Independientemente del tipo de usuario responsable del accidente, su contribución activase asoció a un número adicional de víctimas colaterales, cuyas magnitud y gravedad dependieron sobre todo del tipo de vehículo conducido. Este trabajo puede ser útil para reforzar las actuaciones destinadas a prevenir la accidentalidad en los usuarios de alto riesgo.

Without question, changes in U.S. policies have impacts beyond its own borders. This work reports an analysis of how university students perceive Mexico’s economic problems and their sources. The perceptions of younger Mexicans about economic problems are important, especially since young people represent 31% of Mexico’s population. A survey developed by the National Survey GEA-ISA was administered to 200 students in May 2019. The results of this survey show that students believe that their family economy today is vulnerable and will not improve next year, and that the economic outlook last year was better than today. Results also indicate that improvements in macroeconomic variables alone are not enough to generate a perceived improvement in the Mexican economy.

Objective: Pneumococcal diseases including invasive pneumococcal disease (IPD), pneumonia, and acute otitis media (AOM) impose a substantial public health burden. This study performed a budget impa...

Phytopathogenic fungi can cause economic losses. The application of natural products from species of the genus Agave is an alternative for controlling these organisms. The present study aimed to determine the phytochemical profile of Agave angustifolia and A. cupreata extracts and to evaluate their antifungal activity against several species of phytopathogenic fungi. The aqueous extract from A. angustifolia and the acetonic extract from A. cupreata were studied. The phytochemical profile was determined by thin-layer chromatography. Mycelial growth inhibition and spore production were evaluated. Phytochemical screening revealed the presence of alkaloids, flavonoids, saponins, and triterpenes. The acetonic extract of A. cupreata inhibited 76, 60, and 59% of the mycelial growth of Lasiodiplodia viticola, Colletotrichum sp., and Epicoccum sorghinum, respectively, at 8 and 16 mg mL-1 (p?0.05), while spore production decreased by 92 and 86 % (p?0.001) for Fusarium subglutinans and Colletotrichum sp., respectively. The aqueous extract of A. angustifolia inhibited 40% of the mycelial growth of E. sorghinum at 16 mg mL-1 (p?0.05) and reduced the spore production of L. viticola by 35% (p?0.001). The results indicate that the extracts under study can be an alternative source of antifungal compounds.

The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant and its BA.X lineages, has rendered ineffective a number of previously FDA emergency use authorized SARS-CoV-2 neutralizing antibody therapies. Furthermore, those approved antibodies with neutralizing activity against Omicron BA.1 are reportedly ineffective against the subset of Omicron subvariants that contain a R346K substitution, BA.1.1, and the more recently emergent BA.2, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern.Following a campaign of antibody discovery based on the vaccination of Harbor H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167.STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against each of the tested Omicron subvariants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice.With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for intravenous or intranasal use in human clinical trials.Funded by CRIPT (no. 75N93021R00014), DARPA (HR0011-19-2-0020), and NCI Seronet (U54CA260560).

While changes in microbiome composition have been associated with HIV, the effect of diet and its potential impact on inflammation remains unclear. Methods: Twenty-seven people living with HIV (PWH) on antiretroviral therapy (ART) were studied. A comprehensive dietary analysis was performed and two types of dietary patterns were determined. We explored the associations of each dietary pattern with gut microbiota and plasma inflammatory biomarkers. Results: We appreciated two dietary patterns, Mediterranean-like (MEL) and one Western-like (WEL). Compared to participants with the WEL pattern, participants with MEL pattern showed higher abundance of Lachnospira (p-value = 0.02) and lower levels of the inflammatory biomarkers D-dimer (p-value = 0.050) and soluble TNF-alpha receptor 2 (sTNFR2) (p-value = 0.049). Men who have sex with men (MSM) with MEL pattern had lower abundance of Erysipelotrichaceae (p-value < 0.001) and lower levels of D-dimer (p-value = 0.026) than MSM with WEL pattern. Conclusion: MEL pattern favours Lachnospira abundance, and protects against Erysipelotrichaceae abundance and higher levels of the inflammatory biomarkers D-dimer and sTNFR2, precursors of inflammatory processes in HIV-infected patients. Our study contributes to understanding the determinants of a healthier diet and its connections with gut microbiota and inflammation.

El estudio consistió en desarrollar un modelo didáctico, innovador e inclusivo para el desarrollo de la educación en tecnología mediante la construcción de objetos tecnológicos en educación media, para responder a la pandemia de COVID 19. Teóricamente se sustentó en Morín (2006); Moreno, Tezón, Rivera, Durán, y Parra (2018); De Zubiria (2014), entre otros. Se adoptó el paradigma cualitativo, investigación interpretativa y social, la metodología se desarrolla a través de tres fases. Los informantes claves lo formaron 5 docentes del área de educación para el trabajo, se les aplicó entrevista no estructurada focalizada y registro de sesiones de trabajo. Se concluyó que la relevancia de concebir al docente como mediador del proceso para el desarrollo creativo y descubridor, es parte del desarrollo de la innovación. Se demostró la importancia de seguir aportando conocimiento para fortalecer en el desarrollo del pensamiento tecnológico en educación, además de la permanente formación en la búsqueda de las didácticas más idónea para la construcción de objetos tecnológicos.

Además de ser una forma de entretenimiento y ocio actual, los escape rooms han llamado la atención de los docentes en educación superior porque permiten al alumnado desarrollar diferentes habilidades y conectar los contenidos de las áreas para resolver distintas pruebas y llegar a un resultado de forma conjunta y colaborativa. De la misma forma, el aprendizaje-servicio abre la posibilidad de establecer vías de acción entre las universidades, la sociedad y el mercado laboral. En este artículo presentamos una experiencia de innovación educativa en la que alumnado de los grados en Educación Infantil y Primaria del Centro Universitario Sagrada Familia han diseñado breakouts digitales a partir de los contenidos y objetivos curriculares de las distintas unidades didácticas de segundo curso de educación primaria del colegio SAFA Andújar. Una vez terminados dichos breakouts educativos, se han enviado al centro para que el alumnado pudiera trabajar con ellos y enviar su feedback y el de la docente al alumnado universitario resultando en una experiencia muy rica para todos los agentes educativos implicados.

Despite the enormous efforts made to achieve effective tools that fight against Staphylococcus aureus, the results have not been successful. This failure may be due to the absence of truly representative experimental models. To overcome this deficiency, the present work describes and immunologically characterizes the infection for 28 days, in an experimental low-dose (300 colony-forming units) intradermal model of infection in rabbits, which reproduces the characteristic staphylococcal abscess. Surprisingly, when mutant strains in the genes involved in virulence (JΔagr, JΔcoaΔvwb, JΔhla, and JΔpsmα) were inoculated, no strong effect on the severity of lesions was observed, unlike other models that use high doses of bacteria. The inoculation of a human rabbitized (FdltBr) strain demonstrated its capacity to generate a similar inflammatory response to a wild-type rabbit strain and, therefore, validated this model for conducting these experimental studies with human strains. To conclude, this model proved reproducible and may be an option of choice to check both wild-type and mutant strains of different origins.

The main aim of this paper is to evaluate if there are significant statistical differences in ankle range of motion and stability between flamenco dancers and a control group of non-dancers. Injuries in dancers are generally associated with different factors, such as shoe characteristics, heel height and physical requirements. The ankle joint is the most susceptible when loads are not handled properly. This study involved 48 subjects divided into two groups of 24 (30.77 ± 13.379 years old). Clinical differences were observed, but not statistically significant in the left Anterior Drawer Test between both groups (p

BACKGROUND Fetal smallness affects 10% of pregnancies. These fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight (EFW) and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37-38 weeks. On the other hand, the classification using angiogenic factors (AF) seems to have a lower false positive rate. Here we present a protocol for the GRAFD trial, which compares the management of small fetuses at term using AF or Doppler. OBJECTIVE The primary objective is to demonstrate that classification based on AF is not inferior to EFW and Doppler to detect fetuses at risk of adverse perinatal outcomes. METHODS This is a multicentre, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1,030 singleton pregnancies with an EFW ≤10th percentile at 36+0 to 37+6 weeks will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF) ≥38 will be classified as fetal growth restriction (FGR), otherwise as small for gestational age (SGA). In both arms, FGR will be delivered at ≥37 weeks and SGA at ≥40 weeks. We will assess the differences between groups calculating the relative risks (RR) and their 95% confidence intervals. RESULTS The study is in the recruitment and data collection phase. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences by the end of 2022 or in early 2023. CONCLUSIONS The AF-based protocol may reduce the number of pregnancies with classified as FGR without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities. CLINICALTRIAL NCT04502823

A well-tolerated and cost-effective oral drug that blocks SARS-CoV-2 growth and dissemination would be a major advance in the global effort to reduce COVID-19 morbidity and mortality. Here, we show that the oral FDA-approved drug nitazoxanide (NTZ) significantly inhibits SARS-CoV-2 viral replication and infection in different primate and human cell models including stem cell-derived human alveolar epithelial type 2 cells. Furthermore, NTZ synergizes with remdesivir, and it broadly inhibits growth of SARS-CoV-2 variants B.1.351 (beta), P.1 (gamma), and B.1617.2 (delta) and viral syncytia formation driven by their spike proteins. Strikingly, oral NTZ treatment of Syrian hamsters significantly inhibits SARS-CoV-2-driven weight loss, inflammation, and viral dissemination and syncytia formation in the lungs. These studies show that NTZ is a novel host-directed therapeutic that broadly inhibits SARS-CoV-2 dissemination and pathogenesis in human and hamster physiological models, which supports further testing and optimization of NTZ-based therapy for SARS-CoV-2 infection alone and in combination with antiviral drugs. ispartof: bioRxiv ispartof: location:United States status: Published online

Fungal antifungal proteins (AFPs) have attracted attention as novel biofungicides. Their exploitation requires safe and cost-effective producing biofactories. Previously, Penicillium chrysogenum and Penicillium digitatum produced recombinant AFPs with the use of a P. chrysogenum-based expression system that consisted of the paf gene promoter, signal peptide (SP)-pro sequence and terminator. Here, the regulatory elements of the afpA gene encoding the highly produced PeAfpA from Penicillium expansum were developed as an expression system for AFP production through the FungalBraid platform. The afpA cassette was tested to produce PeAfpA and P. digitatum PdAfpB in P. chrysogenum and P. digitatum, and its efficiency was compared to that of the paf cassette. Recombinant PeAfpA production was only achieved using the afpA cassette, being P. chrysogenum a more efficient biofactory than P. digitatum. Conversely, P. chrysogenum only produced PdAfpB under the control of the paf cassette. In P. digitatum, both expression systems allowed PdAfpB production, with the paf cassette resulting in higher protein yields. Interestingly, these results did not correlate with the performance of both promoters in a luciferase reporter system. In conclusion, AFP production is a complex outcome that depends on the regulatory sequences driving afp expression, the fungal biofactory and the AFP sequence., This work was supported by grant RTI2018-101115B-C21 funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe”, PROMETEO/2018/066 from ‘Conselleria d’Educació’ (Generalitat Valenciana, Comunitat Valenciana, Spain) and by grant PCI2018-092893 funded by MCIN/AEI/ 10.13039/501100011033 and by “The European Union” (SUSPHIRE Project, ERACoBioTech; Horizon 2020 grant agreement No. 722361). EM and MGL were recipients of predoctoral grants FPU18/02019 and FPU19/02066 funded by MCIN/AEI/ 10.13039/501100011033 and by “ESF Investing in your future”.

The continual emergence of SARS-CoV-2 variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant, has rendered ineffective a number of previously EUA approved SARS-CoV-2 neutralizing antibody therapies. Furthermore, even those approved antibodies with neutralizing activity against Omicron are reportedly ineffective against the subset of Omicron variants that contain a R346K substitution, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. Following a campaign of antibody discovery based on the vaccination of Harbour H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of Spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167. STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against the Omicron and Omicron + R346K variants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice. With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for use in human clinical trials.

Background: The SARS -CoV -2 infection has had a major impact on kidney transplant patients. Our single -center experience aims to analyze the risk factors for affected patient hospitalization and predictors of worse clinical outcome on admission. Material and methods: A retrospective cohort study with kidney transplant patients with positive PCR for SARS -CoV -19 between March 16th 2020 and February 11th 2021 was conducted. Demographic characteristics and clinical and laboratory information on admission was collected and analyzed to assess risk factors related to patient hospitalization and disease evolution. Results: Seventy -six kidney transplant recipients diagnosed with COVID -19 were included and divided into hospitalized (n=48) and non- -hospitalized (n=28) patients. Two hospitalized patients were not taken into account for the analysis due to a lack of data, and the remaining patients were divided into mild -moderate (n=25) and severe pneumonia (n=21). Lasso and multivariate logistic regression demonstrated that age (OR 1.041, p=0.039) and hypertension (OR 4.177, p=0.040) were risk factors for hospitalization, while time after transplant (OR 0.993, p=0.029) decreases the probability of being hospitalized. Analyses also revealed that SpO2 ≤92% on admission (OR 8.954, p= 0.026) and overweight/obesity (OR 13.453, p= 0.001) were related to a worse evolution and severe pneumonia among hospitalized recipients. Seven patients died due to COVID -19 complications. Conclusion: Age and hypertension are risk factors for hospitalization among positive COVID -19 patients, while time after transplant decreases the probability of being hospitalized. Overweight/obesity and levels of SpO2 ≤92% on admission were the main risk factors that could help to predict the severity of COVID -19 disease in our series.

The current treatment for head and neck cancer involves radiotherapy, systemic therapy and surgery in a multidisciplinary approach. Unfortunately, cancer therapies can lead to local and systemic complications or side effects such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. Moreover, radiotherapy interruptions due to toxicity can impact negatively in local control and survival. The main purpose of this study was to analyze patient satisfaction of Ectoin solution use in radiotherapy or radiochemotherapy-induced oral mucositis.This is an institutional prospective analysis including 15 patients, conducted by two Spanish centers, between October 2019 and May 2020. Patients were treated with Ectoin solution during Radiotherapy and one month after the end of the treatment, three times per day. A seven-ítem Likert scale was used. We present our descriptive statistic regarding doctors and patients´s satisfaction.Our results suggest that Ectoin solution relieves mucositis and is well tolerated by patients.We observed a favorable repercussion in the oral mucositis management and suggest a potential benefit of treating it.

This paper develops a unique analysis of the impact of board gender diversity on environmental innovation, considering diverse factors that determine the influence of female directors. To that end, different methodological approaches are employed, including panel data analysis and quantile regression. A number of robustness tests are also considered. Using a sample composed of the firms listed on the FTSE-250, our results highlight that the one-size-fits-all approach proves to be inappropriate to understand the role of female directors. Particularly, our findings confirm that board gender diversity positively impacts environmental innovation, but only when there are at least three women in the boardroom, and only for firms with greater levels of environmental innovation. Moreover, the effect of board gender diversity is strengthened in the presence of CSR committees, but weakened in boards with larger size and longer tenure. Given the ever-increasing importance of environmental innovation and the ongoing debates surrounding gender diversity, our evidence has direct implications for firms when selecting board members, for regulators and professionals when refining their legislation and recommendations, and for academics when defining theoretical frameworks and methodological approaches.

BACKGROUND: SARS-CoV-2 infection has had a major impact on kidney transplant patients. Recent evidence suggests that solid organ transplant recipients who received mRNA vaccines reach low immunization rates. There are only few reports about the risk factors and severity of COVID-19 in these patients. Our single center experience describes the patient profile and disease evolution observed in this vulnerable group after inoculation. MATERIAL AND METHODS: Retrospective cohort study with kidney transplant patients who received a COVID-19 vaccine before testing positive for SARS-CoV-19 using polymerase chain reaction. Demographic characteristics and clinical information are described and compared with our previous series of patients who were infected before the initiation of the vaccination rollout. RESULTS: Sixteen kidney transplant recipients diagnosed with COVID-19 after being vaccinated were included and compared with our previous series of 76 unvaccinated patients who were positive for COVID-19. No differences were found among risk factors such as age, time after transplant, hypertension, and obesity between groups (P value > .05). After COVID-19 diagnosis among inoculated patients, 10 patients were hospitalized, and 4 of who met the criteria for admission to the intensive care unit. Three patients died of COVID-19 complications. Despite this, the incidence of infections has decreased after vaccination rollout (P value < .05). CONCLUSIONS: Patients' risk profiles remain constant among recipients who were positive for COVID-19 between waves. We did not find significant differences in hospitalization and severity rates in this reduced group of patients. However, the overall incidence in our kidney transplant population has decreased.

This study conducts a bibliometric analysis of research on sustainability committees. Specifically, our paper analyses the development of this field of research by identifying the most influential articles, authors, and relevant research themes, and highlighting potential future lines of research. Our sample is composed of the publications from the main collection of the Clarivate Analytics Web of Science database (WOS) for the period 1900–2021. Our findings stress the interdisciplinary nature of research about sustainability committees. In addition, our evidence emphasizes the need for more research to understand how firms respond to regulatory and societal pressures on sustainability matters. In addition, the network analysis highlights the main research themes and provides a basis for recognizing future research opportunities. Our paper is the first to perform a comprehensive bibliometric analysis for sustainability committees. Our evidence presents relevant implications for academics in the definition of their research projects.

Exposure to environmental pollutants has been associated with alteration on relative levels of mitochondrial DNA copy number (mtDNAcn). However, the results obtained from epidemiological studies are inconsistent. This meta-analysis aimed to evaluate whether environmental pollutant exposure can modify the relative levels of mtDNAcn in humans. We performed a literature search using PubMed, Scopus, and Web of Science databases. We selected and reviewed original articles performed in humans that analyzed the relationship between environmental pollutant exposure and the relative levels of mtDNAcn; the selection of the included studies was based on inclusion and exclusion criteria. Only twenty-two studies fulfilled our inclusion criteria. A total of 6011 study participants were included in this systematic review and meta-analysis. We grouped the included studies into four main categories according to the type of environmental pollutant: (1) heavy metals, (2) polycyclic aromatic hydrocarbons (PAHs), (3) particulate matter (PM), and (4) cigarette smoking. Inconclusive results were observed in all categories; the pooled analysis shows a marginal increase of relative levels of mtDNAcn in response to environmental pollutant exposure. The trial sequential analysis and rate confidence in body evidence showed the need to perform new studies. Therefore, a large-scale cohort and mechanistic studies in this area are required to probe the possible use of relative levels of mtDNAcn as biomarkers linked to environmental pollution exposure.

A western diet and increased intestinal permeability may contribute to systemic inflammation and the development of cardio-metabolic alterations. The aim of this study was to assess the relationship between diet, biomarkers of intestinal permeability, and chronic low-grade inflammation on the cardiometabolic profile. A cross-sectional study was carried out in 238 young subjects aged 18–29 years, divided into two groups: with

Despite of the scientific and human efforts to understand COVID-19, there are questions still unanswered. Variations in the metabolic reaction to SARS-CoV-2 infection could explain the striking differences in the susceptibility to infection and the risk of severe disease. Here, we used untargeted metabolomics to examine novel metabolic pathways related to SARS-CoV-2 susceptibility and COVID-19 clinical severity using capillary electrophoresis coupled to a time-of-flight mass spectrometer (CE-TOF-MS) in plasma samples. We included 27 patients with confirmed COVID-19 early after symptom onset who were prospectively followed and 29 healthcare workers heavily exposed to SARS-CoV-2 but with low susceptibility to infection (‘nonsusceptible’). We found that the metabolite profile was predictive of the study group. We identified a total of 55 metabolites as biomarkers of SARS-CoV-2 susceptibility or COVID-19 clinical severity. We report the discovery of new plasma biomarkers for COVID-19 that provide mechanistic explanations for the clinical consequences of SARS-CoV-2, including mitochondrial and liver dysfunction as a consequence of hypoxemia (citrulline, citrate, and BAIBA), energy production and amino acid catabolism (L-glycine, L-alanine, L-serine, L-proline, L-aspartic acid and L-histidine), endothelial dysfunction and thrombosis (citrulline, L-ADMA, 2-AB, and Neu5Ac), and we found interconnections between these pathways. In summary, in this first report of the metabolomic profile of individuals with severe COVID-19 and SARS-CoV-2 susceptibility by CE-MS, we define several metabolic pathways implicated in SARS-CoV-2 susceptibility and COVID-19 clinical progression that could be developed as biomarkers of COVID-19.

Background Variations in the ACE2 activity in saliva could explain the striking differences of susceptibility to infection and risk of severe disease. Methods We analyze the activity of ACE2 in saliva in different population groups across a wide age range and disease status during April to June 2020, before SARS-CoV-2 vaccine implementation, and we establish differences between infected people and participants considered resistant (highly exposed healthcare workers and children who cohabited with parents with COVID-19 without isolation and remain IgG negative). Results We included 74 adults, of which 47 (64%) were susceptible and 27 (36%) were resistant, and 79 children, of which 41 (52%) were susceptible and 38 (48%) were resistant. Resistant adults have significantly lower ACE2 activity in saliva than susceptible adults and non-significant higher values than susceptible and resistant children. ACE2 activity is similar in the susceptible and resistant pediatric population (p = 0.527). In contrast, we observe an increase in activity as the disease's severity increases among the adult population (mild disease vs. severe disease, 39 vs. 105 FU, p = 0.039; severe disease vs. resistant, 105 vs. 31 FU, p < 0.001). Conclusions using an enzymatic test, we show that ACE2 activity in saliva correlates with the susceptibility to SARS-Cov-2 infection and disease severity. Children and adults with low-susceptibility to SARS-Cov-2 infection showed the lowest ACE2 activity. These findings could inform future strategies to identify at-risk individuals., This work was supported by Instituto de Salud Carlos III (AC17/00019, PI18/00154, COV20/00349, ICI20/00058), CRUE-Supera COVID, cofinanced by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF), Merck, Sharp & Dohme Investigator Studies Program (code MISP# IIS 60257), Fondo Supera COVID-19 (2020-001), and SEIMC (becas SEIMC).

Preadipocytes are crucial for healthy adipose tissue expansion. Preadipocyte differentiation is altered in obese individuals, which has been proposed to contribute to obesity-associated metabolic disturbances. Here, we aimed at identifying the pathogenic processes underlying impaired adipocyte differentiation in obese individuals with insulin resistance (IR)/type 2 diabetes (T2D). We report that down-regulation of a key member of the major spliceosome, PRFP8/PRP8, as observed in IR/T2D preadipocytes from subcutaneous (SC) fat, prevented adipogenesis by altering both the expression and splicing patterns of adipogenic transcription factors and lipid droplet-related proteins, while adipocyte differentiation was restored upon recovery of PRFP8/PRP8 normal levels. Adipocyte differentiation was also compromised under conditions of endoplasmic reticulum (ER)-associated protein degradation (ERAD) hyperactivation, as occurs in SC and omental (OM) preadipocytes in IR/T2D obesity. Thus, targeting mRNA splicing and ER proteostasis in preadipocytes could improve adipose tissue function and thus contribute to metabolic health in obese individuals.

CRISPR-based programmable transcriptional activators (PTAs) are used in plants for rewiring gene networks. Better tuning of their activity in a time and dose-dependent manner should allow precise control of gene expression. Here, we report the optimization of a Copper Inducible system called CI-switch for conditional gene activation in Nicotiana benthamiana. In the presence of copper, the copper-responsive factor CUP2 undergoes a conformational change and binds a DNA motif named copper-binding site (CBS). In this study, we tested several activation domains fused to CUP2 and found that the non-viral Gal4 domain results in strong activation of a reporter gene equipped with a minimal promoter, offering advantages over previous designs. To connect copper regulation with downstream programable elements, several copper-dependent configurations of the strong dCasEV2.1 PTA were assayed, aiming at maximizing activation range, while minimizing undesired background expression. The best configuration involved a dual copper regulation of the two protein components of the PTA, namely dCas9:EDLL and MS2:VPR, and a constitutive RNA pol III-driven expression of the third component, a guide RNA with anchoring sites for the MS2 RNA-binding domain. With these optimizations in place, the CI/dCasEV2.1 system resulted in copper-dependent activation rates of 2,600-fold for the endogenous N. benthamiana DFR gene, with negligible expression in the absence of the trigger. The tight regulation of copper over CI/dCasEV2.1 makes this system ideal for the conditional production of plant-derived metabolites and recombinant proteins in the field.