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Abstract During the last decade, Latin America has witnessed an unprecedented massive current of migration flows. This migration crisis has been well documented by the local and international press. This article focuses on the reporting of the internal migration crisis in Latin America, particularly how the media has negatively framed migrants. The main objective focuses on understanding how Latin American newspapers have covered the internal migration flows? And what kind of frames promote a negative image towards migrants? As final outcomes will show, it is possible to observe how local newspapers have promoted an adverse vision towards migrants based on traditional stereotypes and prejudices.

Based on data from the Global Cancer Statistics 2022, lung cancer stands as the most lethal cancer worldwide, with age-adjusted incidence and mortality rates of 23.6 and 16.9 per 100,000 people, respectively. Despite significant strides in precision oncology driven by large-scale international research consortia, there remains a critical need to deepen our understanding of the genomic landscape across diverse racial and ethnic groups. To address this challenge, we performed comprehensive in silico analyses and data mining to identify pathogenic variants in genes that drive lung cancer. We subsequently calculated the allele frequencies and assessed the deleteriousness of these oncogenic variants among populations such as African, Amish, Ashkenazi Jewish, East and South Asian, Finnish and non-Finnish European, Latino, and Middle Eastern. Our analysis examined 117,707 variants within 86 lung cancer-associated genes across 75,109 human genomes, uncovering 8042 variants that are known or predicted to be pathogenic. We prioritized variants based on their allele frequencies and deleterious scores, and identified those with potential significance for response to anti-cancer therapies through in silico drug simulations, current clinical pharmacogenomic guidelines, and ongoing late-stage clinical trials targeting lung cancer-driving proteins. In conclusion, it is crucial to unite global efforts to create public health policies that emphasize prevention strategies and ensure access to clinical trials, pharmacogenomic testing, and cancer research for these groups in developed nations.

Resumen: Las variaciones de los vasos que surgen del arco aórtico son numerosas1, reportándose según la literatura consultada entre el 6 al 49% en diversos países. La mayoría de las variantes son descritas como asintomáticas. No obstante, algunas se han asociado con síntomas significativos y problemas quirúrgicos serios, causados por efectos de la compresión o presión que ejercen esas variantes sobre la tráquea o el esófago2. Presentamos el caso de una variante que no encontramos descripción previa en la literatura la cual fue un hallazgo transquirúrgico durante una corrección de un paciente neonato con diagnóstico de coartación aortica. Abstract: The variations of the vessels that arise from the aortic arch are numerous, reported according to the literature consulted between 6 to 49% in various countries. Most variants are described as asymptomatic. However, some have been associated with significant symptoms and serious surgical problems, caused by the effects of compression or pressure that these variants exert on the trachea or esophagus. We present the case of a variant that we found no previous description in the literature, which was a trans surgical finding during a correction of a neonatal patient with a diagnosis of aortic coarctation.

AbstractCell division cycle 7 kinase (CDC7) has been found overexpressed in many cancer cell lines being also one of the kinases involved in the nuclear protein TDP-43 phosphorylation in vivo. Thus, inhibitors of CDC7 are emerging drug candidates for the treatment of oncological and neurodegenerative unmet diseases. All the known CDC7 inhibitors are ATP-competitives, lacking of selectivity enough for success in clinical trials. As allosteric sites are less conserved among kinase proteins, discovery of allosteric modulators of CDC7 is a great challenge and opportunity in this field.Using different computational approaches, we have here identified new druggable cavities on the human CDC7 structure and subsequently selective CDC7 inhibitors with allosteric modulation mainly targeting the pockets where the interaction between this kinase and its activator DBF4 takes place.

The SARS coronavirus 2 (SARS-CoV-2) epidemic remains globally active. The emergence of new variants of interest and variants of concern (VoCs), which are potentially more vaccine-resistant and less sensitive to existing treatments, is evident due to their high prevalence. The prospective spread of such variants and other coronaviruses with epidemic potential demands preparedness that can be met by developing fast-track workflows to find new candidates that target viral proteins with a clear in vitro and in vivo phenotype. Mpro (or 3CLpro) is directly involved in the viral replication cycle and the production and function of viral polyproteins, which makes it an ideal target. The biological relevance of Mpro is highly conserved among betacoronaviruses like HCoV-OC43 and SARS-CoV-2, which makes the identification of new chemical scaffolds targeting them a good starting point for designing broad-spectrum antivirals. We report an optimized methodology based on orthogonal cell-free assays to identify small molecules that inhibit the binding pockets of both SARS-CoV-2-Mpro and HCoV-OC43-Mpro; this blockade correlates with antiviral activities in HCoV-OC43 cellular models. By using such a fast-tracking approach against the Open Global Health Library (Merck KGaA), we have found evidence of the antiviral activity of compound OGHL98. In silico studies dissecting intermolecular interactions between OGHL98 and both proteases and comprising docking and molecular dynamics simulations (MDSs) concluded that the binding mode was primarily governed by conserved H-bonds with their C-terminal amino acids and that the rational design of OGHL98 has potential against VoCs proteases resistant to current therapeutics.

Mango (Mangifera indica) is a fruit highly consumed for its flavor and nutrient content. The mango peel is rich in compounds with biological functionality, such as antioxidant activity among others. The influence of microwave-assisted extraction variables on total phenol compounds (TPC) and antioxidant activity (TEAC) of natural extracts obtained from mango peel var. Tommy and Sugar were studied using a response surface methodology (RSM) and Artificial Neural Networks (ANN). TPC of mango peel extract var. Tommy was significantly influenced by time extraction (X1), solvent/plant ratio (X2) and concentration of ethanol (X3) and while mango peel extract var. Sugar was influenced by X2. TEAC by ABTS was significantly influenced by X3. Maximum of TPC (121.3 mg GAE / g of extract) and TEAC (1185.9 μmol Trolox/g extract) for mango peel extract var. Tommy were obtained at X1=23.9s, X2=12.6mL/gand X3=63.2%, and for mango peel extract var. Sugar, the maximum content of TPC (224.86 mg GAE/g extract) and TEAC (2117.7 μmol Trolox/g extract) were obtained at X1=40s, X2=10mL/g and X3=74.9%. The ANN model presented a higher predictive capacity than the RSM (RANN2>RRSM2,RMSEANN

Resumen: Introducción y objetivos: A medida que la supervivencia de los niños con cardiopatía congénita intervenidos de cirugía cardiaca ha aumentado significativamente, la necesidad de seguimiento en términos de calidad de vida relacionada con la salud se ha vuelto cada vez más importante. En este estudio, describimos la calidad de vida relacionada con la salud en niños con cardiopatía congénita con y sin reparación quirúrgica. Métodos: Estudio descriptivo. Aplicamos el cuestionario Pediatric Quality of Life Inventory (PedsQLTM) en 271 pacientes con edades de 2 a 17 años, de los que acudieron a consulta de cardiología tanto en protocolo prequirúrgico como posquirúrgico. La calidad de vida relacionada con la salud se expresó como puntaje total (100 más alto) y se proporcionó como medianas y porcentajes de 10 a 100. Resultados: Incluimos a 271 pacientes de 2 a 17 años, el 94,8% con un corazón biventricular. La cirugía cardiaca se realizó en el 67,8%. Los principales factores que afectaron de forma negativa en la calidad de vida fueron la fisiología univentricular, la presencia de cortocircuito residual, requerir otra cirugía, el manejo con polifármacos y el acceso quirúrgico por esternotomía media. Conclusión: Los pacientes con cardiopatías congénitas no solo presentan su enfermedad principal, sino que también experimentan una calidad de vida que puede afectarse por factores sociales, educativos y emocionales. La evaluación de la calidad de vida de la salud debe ser parte integral en la evaluación de estos pacientes. Abstract: Introduction and objectives: As the survival of children with congenital heart disease who have undergone cardiac surgery has increased significantly, the need for follow-up in terms of health related quality of life has become increasingly important. In this study, we sought to describe the health related quality of life in children with congenital heart disease with and without surgical repair. Methods: We applied the Pediatric Quality of Life Inventory (PedsQLTM) questionary in 271 patients aged 2 to 17 years, of the patients who attended the cardiology clinic both pre surgery and postsurgery. Health related quality of life was expressed as a total score (highest 100) and provided as medians and percentages from 10 to 100. Results: We included 271 patients from 2 to 17 years old, 94.8% had a biventricular heart. Cardiac surgery was performed in 67.8% The main factor that negatively affected quality of life were univentricular physiology, the presence of residual shunt, requiring another surgery, management with polidrugs, and surgical access through median sternotomy. Conclusion: Patients with congenital heart disease nor only suffer from their main disease, but also experience a quality of life that can be affected by social, educational and emotional factors. The assessment of quality of life by health professionals should be an integral part of the evaluation of these patients.

Epigenetic modifications, characterized by changes in gene expression without altering the DNA sequence, play a crucial role in the development and progression of cancer by significantly influencing gene activity and cellular function. This insight has led to the development of a novel class of therapeutic agents, known as epigenetic drugs. These drugs, including histone deacetylase inhibitors, histone acetyltransferase inhibitors, histone methyltransferase inhibitors, and DNA methyltransferase inhibitors, aim to modulate gene expression to curb cancer growth by uniquely altering the epigenetic landscape of cancer cells. Ongoing research and clinical trials are rigorously evaluating the efficacy of these drugs, particularly their ability to improve therapeutic outcomes when used in combination with other treatments. Such combination therapies may more effectively target cancer and potentially overcome the challenge of drug resistance, a significant hurdle in cancer therapy. Additionally, the importance of nutrition, inflammation control, and circadian rhythm regulation in modulating drug responses has been increasingly recognized, highlighting their role as critical modifiers of the epigenetic landscape and thereby influencing the effectiveness of pharmacological interventions and patient outcomes. Epigenetic drugs represent a paradigm shift in cancer treatment, offering targeted therapies that promise a more precise approach to treating a wide spectrum of tumors, potentially with fewer side effects compared to traditional chemotherapy. This progress marks a step towards more personalized and precise interventions, leveraging the unique epigenetic profiles of individual tumors to optimize treatment strategies.

Abstract Circadian rhythms (CRs) are fundamental biological processes that significantly impact human well-being. Disruption of these rhythms can trigger insufficient neurocognitive development, insomnia, mental disorders, cardiovascular diseases, metabolic dysfunctions, and cancer. The field of chronobiology has increased our understanding of how rhythm disturbances contribute to cancer pathogenesis, and how circadian timing influences the efficacy of cancer treatments. As the circadian clock steadily gains recognition as an emerging factor in tumorigenesis, a thorough and comprehensive multi-omics analysis of CR genes/proteins has never been performed. To shed light on this, we performed, for the first time, an integrated data analysis encompassing genomic/transcriptomic alterations across 32 cancer types (n = 10,918 tumors) taken from the PanCancer Atlas, unfavorable prognostic protein analysis, protein–protein interactomics, and shortest distance score pathways to cancer hallmark phenotypes. This data mining strategy allowed us to unravel 31 essential CR-related proteins involved in the signaling crossroad between circadian rhythms and cancer. In the context of drugging the clock, we identified pharmacogenomic clinical annotations and drugs currently in late phase clinical trials that could be considered as potential cancer therapeutic strategies. These findings highlight the diverse roles of CR-related genes/proteins in the realm of cancer research and therapy.

α-glucosidase, a pharmacological target for type 2 diabetes mellitus (T2DM), is present in the intestinal brush border membrane and catalyzes the hydrolysis of sugar linkages during carbohydrate digestion. Since α-glucosidase inhibitors (AGIs) modulate intestinal metabolism, they may influence oxidative stress and glycolysis inhibition, potentially addressing intestinal dysfunction associated with T2DM. Herein, we report on a study of an ortho-carbonyl substituted hydroquinone series, whose members differ only in the number and position of methyl groups on a common scaffold, on radical-scavenging activities (ORAC assay) and correlate them with some parameters obtained by density functional theory (DFT) analysis. These compounds’ effect on enzymatic activity, their molecular modeling on α-glucosidase, and their impact on the mitochondrial respiration and glycolysis of the intestinal Caco-2 cell line were evaluated. Three groups of compounds, according their effects on the Caco-2 cells metabolism, were characterized: group A (compounds 2, 3, 5, 8, 9, and 10) reduces the glycolysis, group B (compounds 1 and 6) reduces the basal mitochondrial oxygen consumption rate (OCR) and increases the extracellular acidification rate (ECAR), suggesting that it induces a metabolic remodeling toward glycolysis, and group C (compounds 4 and 7) increases the glycolysis lacking effect on OCR. Compounds 5 and 10 were more potent as α-glucosidase inhibitors (AGIs) than acarbose, a well-known AGI with clinical use. Moreover, compound 5 was an OCR/ECAR inhibitor, and compound 10 was a dual agent, increasing the proton leak-driven OCR and inhibiting the maximal electron transport flux. Additionally, menadione-induced ROS production was prevented by compound 5 in Caco-2 cells. These results reveal that slight structural variations in a hydroquinone scaffold led to diverse antioxidant capability, α-glucosidase inhibition, and the regulation of mitochondrial bioenergetics in Caco-2 cells, which may be useful in the design of new drugs for T2DM and metabolic syndrome.

Astrocytes play a pivotal role in maintaining brain homeostasis. Recent research has highlighted the significance of palmitic acid (PA) in triggering pro-inflammatory pathways contributing to neurotoxicity. Furthermore, Genomic-scale metabolic models and control theory have revealed that metabolic switches (MSs) are metabolic pathway regulators by potentially exacerbating neurotoxicity, thereby offering promising therapeutic targets. Herein, we characterized these enzymatic MSs in silico as potential therapeutic targets, employing protein–protein and drug–protein interaction networks alongside structural characterization techniques. Our findings indicate that five MSs (P00558, P04406, Q08426, P09110, and O76062) were functionally linked to nervous system drug targets and may be indirectly regulated by specific neurological drugs, some of which exhibit polypharmacological potential (e.g., Trifluperidol, Trifluoperazine, Disulfiram, and Haloperidol). Furthermore, four MSs (P00558, P04406, Q08426, and P09110) feature ligand-binding or allosteric cavities with druggable potential. Our results advocate for a focused exploration of P00558 (phosphoglycerate kinase 1), P04406 (glyceraldehyde-3-phosphate dehydrogenase), Q08426 (peroxisomal bifunctional enzyme, enoyl-CoA hydratase, and 3-hydroxyacyl CoA dehydrogenase), P09110 (peroxisomal 3-ketoacyl-CoA thiolase), and O76062 (Delta(14)-sterol reductase) as promising targets for the development or repurposing of pharmacological compounds, which could have the potential to modulate lipotoxic-altered metabolic pathways, offering new avenues for the treatment of related human diseases such as neurological diseases.

Context: Valeriana pavonii Poepp. & Endl. (Caprifoliaceae), is a plant used in traditional medicine as a tranquilizer in Colombia. Valerian extracts have been widely used since ancient times for their sedative and anxiolytic properties; however, the way its active metabolites, including iridoids, interact on their respective targets is not fully understood. Aims: To isolate and identificate active iridoid esters from V. pavonii. Perform in vitro inhibition assays and computational analyses to study their possible interaction on the benzodiazepine site of the GABAA receptor. Methods: Two compounds were obtained from dichloromethane and petroleum ether fractions of V. pavonii, respectively, by chromatographic techniques. The structural elucidation was performed by NMR and spectroscopic analyses. In vitro inhibition assays of the binding of 3H-flunitrazepam (3H-FNZ) for the benzodiazepine binding site of the GABAA receptor (BDZ-bs of the GABAA receptor) were carried out. Results: Two iridoid esters, hydrine-type valepotriates (compounds 1 and 2), were reported for the first time in V. pavonii. Both iridoids, 1 and 2, inhibited the binding of 3H-FNZ on the BDZ-bs of the GABAA receptor (40% at 300 µM). Docking studies and MMGBSA calculations revealed that these compounds exhibited molecular interactions with crucial residues of the benzodiazepine site, similar to those observed for drugs like flunitrazepam, diazepam, and flumazenil. Conclusions: These findings contribute to understanding the in vivo activity of extracts of Valeriana pavonni on the central nervous system, which showed promising effects, especially as anticonvulsants, sedative-hypnotics, and antidepressants, through the modulation of the GABAergic system by hydrine-type valepotriates and its derivatives.

Chemoinformatics is an independent inter-discipline with a broad impact in drug design and discovery, medicinal chemistry, biochemistry, analytical and organic chemistry, natural products, and several other areas in chemistry. Through collaborations, scientific exchanges, and participation in international research networks, Latin American scientists have contributed to the development of this subject. The aim of this perspective is to discuss the status and progress of the chemoinformatic discipline in Latin America. We team up to provide an author´s perspective on the topics that have been investigated and published over the past twelve years, collaborations between Latin America researchers and others worldwide, contributions to open-access chemoinformatic tools such as web servers, and educational-related resources and events, such as scientific conferences. We conclude that linking and fostering collaboration within each nation as well as among other Latin American nations and globally is made possible by open science and the democratization of science. We also outline strategic actions that can boost the development and practice of chemoinformatic in the region and enhance the interaction between Latin American countries and the rest of the world.

Resumen: Presentamos el caso de un paciente escolar, derivado por la presencia de dolor torácico recurrente, que fue valorado por nuestro servicio donde se diagnosticó cor triatriatum, siendo una enfermedad sumamente rara, con una frecuencia del 0,1 al 0,4% de todas las cardiopatías congénitas. Se caracteriza por una membrana fibromuscular que divide la cámara de la aurícula izquierda en 2: una posterior, proximal a la entrada de las venas pulmonares, y otra anterior, que contiene el apéndice auricular y la válvula mitral. Clínicamente puede presentarse como arritmias cardiacas o como una enfermedad obstructiva grave en el periodo neonatal, dependiendo del grado de integridad de la membrana. En este caso se realizó la corrección quirúrgica del defecto, siendo exitosa. Actualmente el paciente se encuentra asintomático y continúa en seguimiento. Abstract: We present the case of a school patient, referred due to the presence of recurrent chest pain, who was evaluated by our service where cor triatriatum was diagnosed, being an extremely rare pathology with a frequency of 0.1 to 0.4% of all congenital heart diseases, characterized by a fibromuscular membrane that divides the left atrium chamber into 2, one posterior, proximal to the entrance of the pulmonary veins, and the other anterior, which contains the atrial appendage and the mitral valve. Clinically it can present as cardiac arrhythmias or as a severe obstructive pathology in the neonatal period, depending on the degree of integrity of the membrane. In this case, the surgical correction of the defect was performed, being successful. The patient is currently asymptomatic and continues to be monitored.

Abstract The variability of suicidal thoughts and other clinical factors during follow-up has emerged as a promising phenotype to identify vulnerable patients through Ecological Momentary Assessment (EMA). In this study, we aimed to (1) identify clusters of clinical variability, and (2) examine the features associated with high variability. We studied a set of 275 adult patients treated for a suicidal crisis in the outpatient and emergency psychiatric departments of five clinical centers across Spain and France. Data included a total of 48,489 answers to 32 EMA questions, as well as baseline and follow-up validated data from clinical assessments. A Gaussian Mixture Model (GMM) was used to cluster the patients according to EMA variability during follow-up along six clinical domains. We then used a random forest algorithm to identify the clinical features that can be used to predict the level of variability. The GMM confirmed that suicidal patients are best clustered in two groups with EMA data: low- and high-variability. The high-variability group showed more instability in all dimensions, particularly in social withdrawal, sleep measures, wish to live, and social support. Both clusters were separated by ten clinical features (AUC = 0.74), including depressive symptoms, cognitive instability, the intensity and frequency of passive suicidal ideation, and the occurrence of clinical events, such as suicide attempts or emergency visits during follow-up. Initiatives to follow up suicidal patients with ecological measures should take into account the existence of a high variability cluster, which could be identified before the follow-up begins.

In an experimental investigation, the development of sonic crystal noise barriers (SCNBs) is undertaken to address the issue of train brake noise (TBN), focusing on the use of local resonances in scatterers of sonic crystals. Recent research has shown that the inclusion of cavity resonators in the crystal scatterers allows for the modification of their insulating properties. In those works, it has been demonstrated that this interaction can be used to build highly insulating structures. The study proposes an SCNB design that includes a resonant cavity specifically to mitigate TBN and validates this design through experimental measures. The experiments confirm the enhanced sound insulation capabilities of SCNBs, compare them to the conventional noise barriers ones and demonstrate the applicability and effectiveness of the proposed design in real-world scenarios.

Traumatic brain injury (TBI) is a pathology of great social impact, affecting millions of people worldwide. Despite the scientific advances to improve the management of TBI in recent years, we still do not have a specific treatment that controls the inflammatory process after mechanical trauma. The discovery and implementation of new treatments is a long and expensive process, making the repurpose of approved drugs for other pathologies a clinical interest. Tibolone is a drug in use for the treatment of symptoms associated with menopause and has been shown to have a broad spectrum of actions by regulating estrogen, androgen and progesterone receptors, whose activation exerts potent anti-inflammatory and antioxidant effects. In the present study, we aimed to investigate the therapeutic potential of the tibolone metabolites 3α-Hydroxytibolone, 3β-Hydroxytibolone, and Δ4-Tibolone as a possible therapy in TBI using network pharmacology and network topology analysis. Our results demonstrate that the estrogenic component mediated by the α and β metabolites can regulate synaptic transmission and cell metabolism, while the Δ metabolite may be involved in modulating the post-TBI inflammatory process. We identified several molecular targets, including KDR, ESR2, AR, NR3C1, PPARD, and PPARA, which are known to play critical roles in the pathogenesis of TBI. Tibolone metabolites were predicted to regulate the expression of key genes involved in oxidative stress, inflammation, and apoptosis. Overall, the repurposing of tibolone as a neuroprotective treatment for TBI holds promise for future clinical trials. However, further studies are needed to confirm its efficacy and safety in TBI patients.

Este trabajo se enfoca en los flujos comunicativos relacionados con el COVID-19 generados en América Latina por usuarios de Facebook durante el primer semestre del 2020. El objetivo principal es analizar la información compartida con relación a tres principales categorías: (a) las acciones gubernamentales relacionadas con la seguridad y salud pública, (b) las reacciones de la sociedad ante la situación de emergencia, y (c) la visión del futuro post pandémico. La metodología empleada en este trabajo es el análisis de contenido, desde la cual se analizó el corpus de estudio, para identificar y generar categorías sobre los temas abordados en los flujos de información. Se trabajaron tablas de distribución de frecuencias para ponderar los pesos de difusión de cada categoría temática. Los resultados aportan, desde un nivel exploratorio, evidencias sobre el impacto de las redes sociales en el contexto pandémico, no solo de manera positiva, sino también generando incertidumbre, protestas y represión mediante la propagación de noticias falsas y teorías conspirativas.

Abstract Human intrusions into undisturbed wildlife areas greatly contribute to the emergence of infectious diseases. To minimize the impacts of novel emerging infectious diseases (EIDs) on human health, a comprehensive understanding of the microbial species that reside within wildlife species is required. The Gulf of California (GoC) is an example of an undisturbed ecosystem. However, in recent decades, anthropogenic activities within the GoC have increased. Zalophus californianus has been proposed as the main sentinel species in the GoC; hence, an assessment of sea lion bacterial microbiota may reveal hidden risks for human health. We evaluated the presence of potential human pathogenic bacterial species from the gastrointestinal (GI) tracts of wild sea lions through a metabarcoding approach. To comprehensively evaluate this bacterial consortium, we considered the genetic information of six hypervariable regions of 16S rRNA. Potential human pathogenic bacteria were identified down to the species level by integrating the RDP and Pplacer classifier outputs. The combined genetic information from all analyzed regions suggests the presence of at least 44 human pathogenic bacterial species, including Shigella dysenteriae and Bacillus anthracis. Therefore, the risks of EIDs from this area should be not underestimated.

La cirugía para la enfermedad obstructiva del tracto de salida del ventrículo izquierdo con enfermedad de la válvula aórtica e hipoplasia del anillo aórtico continúa siendo un reto. Se han descrito diversas técnicas quirúrgicas para la ampliación del anillo aórtico, de las cuales el procedimiento de Konno-Rastan es una opción atractiva; sin embargo, no es muy frecuente realizarla debido a su alto grado de dificultad. Se presenta el caso de una paciente femenina, de 15 años de edad, con diagnóstico de estenosis valvular aórtica grave e hipoplasia del anillo aórtico, a quien se le realizó ampliación del anillo aórtico con técnica de Konno-Rastan y reemplazo valvular aórtico.

Antimicrobial peptides have been developed based on plant-derived molecular scaffolds for the treatment of infectious diseases. Chenopodin is an abundant seed storage protein in quinoa, an Andean plant with high nutritional and therapeutic properties. Here, we used computer- and physicochemical-based strategies and designed four peptides derived from the primary structure of Chenopodin. Two peptides reproduce natural fragments of 14 amino acids from Chenopodin, named Chen1 and Chen2, and two engineered peptides of the same length were designed based on the Chen1 sequence. The two amino acids of Chen1 containing amide side chains were replaced by arginine (ChenR) or tryptophan (ChenW) to generate engineered cationic and hydrophobic peptides. The evaluation of these 14-mer peptides on Staphylococcus aureus and Escherichia coli showed that Chen1 does not have antibacterial activity up to 512 µM against these strains, while other peptides exhibited antibacterial effects at lower concentrations. The chemical substitutions of glutamine and asparagine by amino acids with cationic or aromatic side chains significantly favoured their antibacterial effects. These peptides did not show significant hemolytic activity. The fluorescence microscopy analysis highlighted the membranolytic nature of Chenopodin-derived peptides. Using molecular dynamic simulations, we found that a pore is formed when multiple peptides are assembled in the membrane. Whereas, some of them form secondary structures when interacting with the membrane, allowing water translocations during the simulations. Finally, Chen2 and ChenR significantly reduced SARS-CoV-2 infection. These findings demonstrate that Chenopodin is a highly useful template for the design, engineering, and manufacturing of non-toxic, antibacterial, and antiviral peptides.

This work proposes the design of β-keto esters as antibacterial compounds. The design was based on the structure of the autoinducer of bacterial quorum sensing, N-(3-oxo-hexanoyl)-l-homoserine lactone (3-oxo-C6-HSL). Eight β-keto ester analogues were synthesised with good yields and were spectroscopically characterised, showing that the compounds were only present in their β-keto ester tautomer form. We carried out a computational analysis of the reactivity and ADME (absorption, distribution, metabolism, and excretion) properties of the compounds as well as molecular docking and molecular dynamics calculations with the LasR and LuxS quorum-sensing (QS) proteins, which are involved in bacterial resistance to antibiotics. The results show that all the compounds exhibit reliable ADME properties and that only compound 7 can present electrophile toxicity. The theoretical reactivity study shows that compounds 6 and 8 present a differential local reactivity regarding the rest of the series. Compound 8 presents the most promising potential in terms of its ability to interact with the LasR and LuxS QS proteins efficiently according to its molecular docking and molecular dynamics calculations. An initial in vitro antimicrobial screening was performed against the human pathogenic bacteria Pseudomonas aeruginosa and Staphylococcus aureus as well as the phytopathogenic bacteria Pseudomonas syringae and Agrobacterium tumefaciens. Compounds 6 and 8 exhibit the most promising results in the in vitro antimicrobial screening against the panel of bacteria studied.

Resumen: Introducción y objetivos: En los pacientes que presentan anomalías en las válvulas cardiacas la cirugía que se prefiere siempre es la plastia; sin embargo, existen casos en los cuales el reemplazo valvular es la única opción. El objetivo de este estudio es valorar los resultados a corto y largo plazo de pacientes pediátricos que requirieron reemplazo valvular.Material y métodos Previo consentimiento informado firmado por los padres o el tutor legal, se ingresaron los datos de los pacientes menores de 18 años de edad que fueron sometidos a reemplazo valvular entre 2012 y 2020,. Resultados: Se ingresaron 13 pacientes, de los cuales el 84,6% corresponden al género masculino, la media de edad fue de 9 años, el peso medio fue de 29 kg, la válvula más afectada fue la mitral, con el 61,5%, seguida de la aórtica, con el 23,1%. En el 61,5% la presentación corresponde a la doble lesión valvular. En cuanto a la etiología, la más frecuente fue la congénita, con el 84,6%; la prótesis más utilizada fue la St. Jude Medical® número 23, la media de tiempo de circulación extracorpórea fue de 115 min y el de pinzamiento aórtico fue de 75 min; el promedio de seguimiento fue 23 meses. Conclusiones: El reemplazo valvular en la etapa pediátrica siempre es un procedimiento que se intenta postergar el mayor tiempo posible; sin embargo, no es factible en muchas ocasiones y conlleva un alto riesgo tanto quirúrgico como de complicaciones. En nuestra experiencia, los resultados son satisfactorios; sin embargo, nuestra muestra son pacientes mayores de 5 años. Abstract: Introduction and objectives: In paediatric patients with heart valve abnormalities plasty is always preferred; however, there are cases in which valve replacement is the only option. The objective of this study is to assess the short- and long-term results of paediatric patients who required valve replacement. Material and methods: With prior informed consent signed by the patient's parents or legal guardian, the data of patients under 18 years of age who underwent valve replacement were entered from the period between 2012 and 2020. Results: Thirteen patients were admitted of whom 84.6% were male, the mean age was 9 years, the mean weight was 29 kg, the most affected valve was the mitral valve in 61.5%, followed by the aortic valve at 23.1%. In 61.5% presentation was a double valve lesion. In terms of the aetiology; the most frequent aetiology was congenital in 84.6%; the most widely used prosthesis was St. Jude Medical® number 23. The mean time for extracorporeal surgery was 115 min and the mean time for aortic clamping was 75 min. Follow-up was 23 months. Conclusions: valve replacement in the paediatric stage is always a procedure that we should attempt to postpone as long as possible, as it carries a high risk both in surgery and in complications, however this is often not feasible. Although our sample is not in children under 5 years of age, the results are good.

Biodegradable magnesium alloys are promising candidates for temporary fracture fixation devices in orthopedics; nevertheless, its fast degradation rate at the initial stage after implantation remains as one of the main challenges to be resolved. ZrO2-based coatings to reduce the degradation rate of the Mg-implants are an attractive solution since they show high biocompatibility and stability. In this work, the degradation, cytotoxicity, and antibacterial performance of ZrO2 thin films deposited by magnetron sputtering on a Mg-Zn-Ca alloy was evaluated. Short-term degradation of ZrO2-coated and uncoated samples was assessed considering electrochemical techniques and H2 evolution (gas chromatography). Additionally, long term degradation was assessed by mass-loss measurements. The results showed that a 380 nm ZrO2 coating reduces the degradation rate and H2 evolution of the alloy during the initial 3 days after immersion but allows the degradation of the bare alloy for the long-term. The ZrO2 coating does not compromise the biocompatibility of the alloy and permits better cell adhesion and proliferation of mesenchymal stem cells directly on its surface, in comparison to the bare alloy. Finally, the ZrO2 coating prevents the adhesion and biofilm formation of S. aureus.

The coronavirus disease 2019 pandemic accelerated drug/vaccine development processes, integrating scientists all over the globe to create therapeutic alternatives against this virus. In this work, we have collected information regarding proteins from SARS-CoV-2 and humans and how these proteins interact. We have also collected information from public databases on protein–drug interactions. We represent this data as networks that allow us to gain insights into protein–protein interactions between both organisms. With the collected data, we have obtained statistical metrics of the networks. This data analysis has allowed us to find relevant information on which proteins and drugs are the most relevant from the network pharmacology perspective. This method not only allows us to focus on viral proteins as the main targets for COVID-19 but also reveals that some human proteins could be also important in drug repurposing campaigns. As a result of the analysis of the SARS-CoV-2–human interactome, we have identified some old drugs, such as disulfiram, auranofin, gefitinib, suloctidil, and bromhexine as potential therapies for the treatment of COVID-19 deciphering their potential complex mechanism of action.

El odio se ha convertido en un elemento clave en el discurso de los políticos populistas para apoyar su agenda. Tal es el caso del presidente mexicano, López Obrador (AMLO), quien ha utilizado medios de comunicación oficiales y redes sociales para acosar a sus críticos y a la oposición política. Un elemento distintivo en su estrategia mediática es “La Mañanera”, una conferencia matutina en la que se informa sobre la agenda presidencial, sin embargo, este espacio ha servido también para exculpar a sus familiares y militantes de su partido, así como para criticar a periodistas, organizaciones sociales, opositores y, desde el segundo semestre de 2021, a la clase media mexicana. El propósito de este artículo es emplear el corpus teórico del Enfoque Discursivo-Histórico (DHA) para estudiar la construcción discursiva de la “clase media” en Las Mañaneras de López Obrador, cómo AMLO usa el resentimiento social para atacar a sus críticos y cuáles son los principales elementos retóricos empleados contra la clase media. Los resultados finales mostrarán la capacidad de los gobiernos populistas de utilizar estereotipos tradicionales, el resentimiento colectivo y una interpretación parcial de la historia nacional para acosar a los disidentes y lograr altos niveles de aprobación pública.

The flavonoid izalpinin was isolated from the aerial parts of Chromolaena leivensis. Its structural determination was carried out using MS and NMR spectroscopic techniques (1H, 13C). This compound was evaluated for its anti-inflammatory effect in a rat model on λ-carrageenan-induced plantar edema. Paw inflammation was measured at one-hour intervals for seven hours following the administration of λ-carrageenan. Serum creatine kinase (CK) levels were evaluated, obtaining statistically significant results with the treatments at doses of 10 mg/kg (* p < 0.01) and 20 mg/kg (** p < 0.005). The anti-inflammatory effect of the compound was evaluated by using plethysmography, and the results showed significant differences at the three concentrations (10 mg/kg, 20 mg/kg, 40 mg/kg) in the first and third hours after treatment. * p < 0.05; ** p < 0.001; **** p < 0.0001 vs. the negative control group treated with vehicle (DMSO). Lastly, molecular docking analyses reveal that izalpinin has a strong binding affinity with five target proteins involved in the inflammatory process. The analysis using molecular dynamics allowed demonstrating that the ligand–protein complexes present acceptable stability, with RMSD values within the allowed range.

Helmholtz resonators (HRs) have the advantage of extending and improving their insulating capacity when used as scatterers in noise barriers made of periodic media, such as sonic crystals (SCs). However, the interaction between multiple Bragg scattering and local resonance phenomena can increase or decrease the insulation of the barrier depending on its design. In the present work, we numerically investigate the factors that determine how such interferences occur and the specific conditions to increase the insertion loss of sonic crystal noise barriers (SCNBs) made of cylindrical scatterers with HRs. Two factors are crucial for the variation of the isolation of the barrier in the Bragg-bandgap (Bragg-BG): the orientation of the resonator mouth with respect to the incident wave, and the resonance frequency of the resonator with respect to the central frequency of the Bragg-BG. Based on this phenomenon, we propose a sonic crystal noise barrier consisting of scatterers with two Helmholtz resonators. The insertion loss of the structure is determined numerically and shows an increase of 20 dB at the BG compared to a conventional barrier with cylindrical scatterers.

The evolution of some fetal growth indices and arterial blood flow parameters in the umbilical cord of the embryos and fetuses of primiparous pregnant goats of Murciano-Granadina breed were analyzed by ultrasonography. Weekly ultrasonographic sessions took place from 18- to 125-days post-breeding. Fetal measures were carried out by ultrasound B-mode. This mode was used to take a series of measurements in the embryo/fetus throughout pregnancy: crown-rump length (CRL, from 24-days post-mating -dpm- to 61 dpm), trunk diameter (TD, 24–34 dpm), biparietal diameter (BPD, 28–125 dpm) and eye orbit diameter (EOD, 75–125 dpm). Spectral Doppler was used to study blood flow from umbilical artery. Different blood flow parameters were obtained as follows: Arterial Pulse, Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), Mean Velocity (MV), Systolic velocity/Diastolic velocity Ratio (S/D), Pulsatility Index (PI) and Resistance Index (RI). In this study, the umbilical cord was first noticed between 32- and 35-days post-breeding. However, these umbilical arterial blood flow parameters were not conclusive (positive S/D ratios and RI < 1) until 65–80 days of pregnancy. The explanation to these results could be that vascular development related to umbilical arteries elasticity and diameter is not good enough in early pregnancy. Therefore, these vessels have already acquired their appropriate characteristics in order to allow blood flow parameters and Doppler index measures from only 2.5 months of pregnancy. This is the first time that a detailed study of fetal growth indices and umbilical artery flow rates in fetuses from Murciano-Granadina goats has been performed throughout virtually the entire duration of gestation. In conclusion, the evolution of the fetal growth indices in this breed has determined that the umbilical artery velocimetric parameters (PSV, EDV, MV) increase significantly and the AP, S/D, PI and RI indices decrease significantly throughout the analyzed pregnancy period.

Tubulin is a well-validated target for herbicides, fungicides, anti-parasitic, and anti-tumor drugs. Many of the non-cancer tubulin drugs bind to its colchicine site but no colchicine-site anticancer drug is available. The colchicine site is composed of three interconnected sub-pockets that fit their ligands and modify others’ preference, making the design of molecular hybrids (that bind to more than one sub-pocket) a difficult task. Taking advantage of the more than eighty published X-ray structures of tubulin in complex with ligands bound to the colchicine site, we generated an ensemble of pharmacophore representations that flexibly sample the interactional space between the ligands and target. We searched the ZINC database for scaffolds able to fit several of the subpockets, such as tetrazoles, sulfonamides and diarylmethanes, selected roughly ~8000 compounds with favorable predicted properties. A Flexi-pharma virtual screening, based on ensemble pharmacophore, was performed by two different methodologies. Combining the scaffolds that best fit the ensemble pharmacophore-representation, we designed a new family of ligands, resulting in a novel tubulin modulator. We synthesized tetrazole 5 and tested it as a tubulin inhibitor in vitro. In good agreement with the design principles, it demonstrated micromolar activity against in vitro tubulin polymerization and nanomolar anti-proliferative effect against human epithelioid carcinoma HeLa cells through microtubule disruption, as shown by immunofluorescence confocal microscopy. The integrative methodology succedes in the design of new scaffolds for flexible proteins with structural coupling between pockets, thus expanding the way in which computational methods can be used as significant tools in the drug design process.

The multiple ecological crisis that we are facing forces us to ponder the transition toward sustainable agricultural systems. Two key uncertainties need to be unveiled in addressing this problem; first, we need to identify the general features of alternative models that make them sustainable, and second, we need to explore how to build them from the (flawed) existing systems. In this work we explore these two questions using an ethnoecological and theoretical approach. In the exploration of alternative models, we evaluate an ancestral farming system, the conuco, characterized by, (i) the use of the ecological succession to constantly renew its properties, (ii) the increase of its biodiversity over time (in the horizontal and vertical components), and (iii) the self-regulation of the associated populations. Next, we characterize the topology of ecological networks of agroecosystems along the transition from a monoculture to a conuco-like agroecological system. We use topologies obtained from field information of conventional and agroecological systems as starting and arrival points. To model the dynamics of the systems and numerically simulate the transitions, we use a model based on Generalized Lotka-Volterra equations, where all types of population interactions are represented, with outcomes based on a density-dependent conditionality. The results highlight the relevance of increasing the connectance and diminishing the degree centrality of the conventional systems networks to promote their sustainability. Finally, we propose that the transitions between the monoculture and the agroecological systems could be figuratively interpreted as a cusp catastrophe, where the two systems are understood as alternative stable states and the path from one to the other cannot be reverted by just reversing the values of the control parameter. That is, once a system is in either of these states there is a tendency to stay and a resistance to move away from it. This implies that in the process of transition from a monoculture to a multi-diverse system, it is prudent not to despair if there are no immediate improvements in the performance of the system because once a certain point is reached, the system may experience an abrupt improvement.

Neurodegenerative diseases (NDD) have been of great interest to scientists for a long time due to their multifactorial character. Among these pathologies, Alzheimer’s disease (AD) is of special relevance, and despite the existence of approved drugs for its treatment, there is still no efficient pharmacological therapy to stop, slow, or repair neurodegeneration. Existing drugs have certain disadvantages, such as lack of efficacy and side effects. Therefore, there is a real need to discover new drugs that can deal with this problem. However, as AD is multifactorial in nature with so many physiological pathways involved, the most effective approach to modulate more than one of them in a relevant manner and without undesirable consequences is through polypharmacology. In this field, there has been significant progress in recent years in terms of pharmacoinformatics tools that allow the discovery of bioactive molecules with polypharmacological profiles without the need to spend a long time and excessive resources on complex experimental designs, making the drug design and development pipeline more efficient. In this review, we present from different perspectives how pharmacoinformatics tools can be useful when drug design programs are designed to tackle complex diseases such as AD, highlighting essential concepts, showing the relevance of artificial intelligence and new trends, as well as different databases and software with their main results, emphasizing the importance of coupling wet and dry approaches in drug design and development processes.

In the present work, we propose the development of a novel carrier that does not need organic solvents for its preparation and with the potential for the intravenous delivery of lipophilic and hydrophilic drugs. Named lipomics, this is a mixed colloid of micelles incorporated within a liposome. This system was designed through ternary diagrams and characterized by physicochemical techniques to determine the particle size, zeta potential, shape, morphology, and stability properties. The lipomics were subjected to electron microscopy (SEM, TEM, and STEM) to evaluate their physical size and morphology. Finally, pharmacokinetic studies were performed by radiolabeling the lipomics with Technetium-99m chelated with BMEDA to evaluate the in vivo biodistribution through techniques of molecular imaging (microSPECT/CT) in rats. Radiolabeling efficiency was used to compare the encapsulation efficiency of the hydrophilic and lipophilic molecules in lipomics and liposomes. According to the results, lipomics are potentially carriers of lipophilic and hydrophilic drugs.

Excessive accumulation and release of fatty acids (FAs) in adipose and non-adipose tissue are characteristic of obesity and are associated with the leading causes of death worldwide. Chronic exposure to high concentrations of FAs such as palmitic acid (pal) is a risk factor for developing different neurodegenerative diseases (NDs) through several mechanisms. In the brain, astrocytic dysregulation plays an essential role in detrimental processes like metabolic inflammatory state, oxidative stress, endoplasmic reticulum stress, and autophagy impairment. Evidence shows that tibolone, a synthetic steroid, induces neuroprotective effects, but its molecular mechanisms upon exposure to pal remain largely unknown. Due to the capacity of identifying changes in the whole data-set of proteins and their interaction allowing a deeper understanding, we used a proteomic approach on normal human astrocytes under supraphysiological levels of pal as a model to induce cytotoxicity, finding changes of expression in proteins related to translation, transport, autophagy, and apoptosis. Additionally, tibolone pre-treatment showed protective effects by restoring those same pal-altered processes and increasing the expression of proteins from cell survival processes. Interestingly, ARF3 and IPO7 were identified as relevant proteins, presenting a high weight in the protein-protein interaction network and significant differences in expression levels. These proteins are related to transport and translation processes, and their expression was restored by tibolone. This work suggests that the damage caused by pal in astrocytes simultaneously involves different mechanisms that the tibolone can partially revert, making tibolone interesting for further research to understand how to modulate these damages.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Its treatment includes antiarrhythmic drugs (AADs) to modulate the function of cardiac ion channels. However, AADs have been limited by proarrhythmic effects, non-cardiovascular toxicities as well as often modest antiarrhythmic efficacy. Theoretical models showed that a combined blockade of Nav1.5 (and its current, INa) and Kv1.5 (and its current, IKur) ion channels yield a synergistic anti-arrhythmic effect without alterations in ventricles. We focused on Kv1.5 and Nav1.5 to search for structural similarities in their binding site (BS) for flecainide (a common blocker and widely prescribed AAD) as a first step for prospective rational multi-target directed ligand (MTDL) design strategies. We present a computational workflow for a flecainide BS comparison in a flecainide-Kv1.5 docking model and a solved structure of the flecainide-Nav1.5 complex. The workflow includes docking, molecular dynamics, BS characterization and pattern matching. We identified a common structural pattern in flecainide BS for these channels. The latter belongs to the central cavity and consists of a hydrophobic patch and a polar region, involving residues from the S6 helix and P-loop. Since the rational MTDL design for AF is still incipient, our findings could advance multi-target atrial-selective strategies for AF treatment.

The microstructural characteristics of biodegradable Mg alloys determine their performance and appropriateness for orthopedic fixation applications. In this work, the effect of the annealing treatment of a Mg-0.7Zn-0.6Ca (ZX11) alloy on the mechanical integrity, corrosive behavior, and biocompatibility-osteoinduction was studied considering two annealing temperatures, 350 and 450 °C. The microstructure showed a recrystallized structure, with a lower number of precipitates, grain size, and stronger basal texture for the ZX11-350 condition than the ZX11-450. The characteristics mentioned above induce a higher long-term degradation rate for the ZX11-450 than the ZX11-350 on days 7th and 15th of immersion. In consequence, the mechanical integrity changes within this period. The increased degradation rate of the ZX11-450 condition reduces 40% the elongation at failure, in contrast with the 16% reduction for the ZX11-350 condition. After that period, the mechanical integrity remained unchanged. No cytotoxic effects were observed for both treatments and significant differentiation of mesenchymal stem cells into the osteoblast phenotype was observed.

Vibrio parahaemolyticus non-toxigenic strains are responsible for about 10% of acute gastroenteritis associated with this species, suggesting they harbor unique virulence factors. Zonula occludens toxin (Zot), firstly described in Vibrio cholerae, is a secreted toxin that increases intestinal permeability. Recently, we identified Zot-encoding genes in the genomes of highly cytotoxic Chilean V. parahaemolyticus strains, including the non-toxigenic clinical strain PMC53.7. To gain insights into a possible role of Zot in V. parahaemolyticus, we analyzed whether it could be responsible for cytotoxicity. However, we observed a barely positive correlation between Caco-2 cell membrane damage and Zot mRNA expression during PMC53.7 infection and non-cytotoxicity induction in response to purified PMC53.7-Zot. Unusually, we observed a particular actin disturbance on cells infected with PMC53.7. Based on this observation, we decided to compare the sequence of PMC53.7-Zot with Zot of human pathogenic species such as V. cholerae, Campylobacter concisus, Neisseria meningitidis, and other V. parahaemolyticus strains, using computational tools. The PMC53.7-Zot was compared with other toxins and identified as an endotoxin with conserved motifs in the N-terminus and a variable C-terminal region and without FCIGRL peptide. Notably, the C-terminal diversity among Zots meant that not all of them could be identified as toxins. Structurally, PMC53.7-Zot was modeled as a transmembrane protein. Our results suggested that it has partial 3D structure similarity with V. cholerae-Zot. Probably, the PMC53.7-Zot would affect the actin cytoskeletal, but, in the absence of FCIGRL, the mechanisms of actions must be elucidated.

Background/ObjectiveAdult Lower Secondary Education is an education program for basic qualifications for the labor market. Our study aimed to compare lifetime mental health problems between current Adult Lower Secondary Education students and higher Vocational Education students, as the former constitutes a highly distinct and understudied group.MethodsFindings were based on a cross-sectional self-report survey. Lifetime relative odds of occurrence of mental disorders [i.e., psychiatric disorders typically diagnosed in adults, learning difficulties or deficit hyperactivity disorder (ADHD)] were compared between Adult Lower Secondary Education students (n = 134) and Vocational Education students (n = 149).ResultsWhile the frequency of mental health problems was high in both groups, psychiatric disorders typically diagnosed in adults were more common in Adult Lower Secondary Education students than among other students. Vocational Education students reported higher rates of ADHD.ConclusionThere is a need for additional psychological resources for Adult Lower Secondary Education students, an educational level that is the last path for many to acquire a basic degree.

Frankenstein is not an exclusive character belonging to the realm of the Gothic narrative, but a vivid element that has evolved and adapted to diverse social contexts and geographies. Mary Shelley's work has endured the passing of time and now is a symbol of the popular culture. In this paper, I look to understand Mary Shelley's Frankenstein influence on people’s attitudes regarding technology and science, particularly artificial intelligence and robots. How the negative visions and fears about the misuse of science to break traditional moral and religious boundaries are still present in popular culture. Fieldwork will be focused on reviewing several Latin American newspapers and magazine articles in Spanish and Portuguese published on the Internet. As final outcomes will show, Mary Shelley’s Frankenstein still continues influencing people’s imagination about science and technology, even in technically less developed regions.

In 2019, about 4 million Venezuelans have left the country looking for a better landscape for them and their families. Thousands, even entire families, have arrived in Mexico, trying to regularize their situation and to stay permanently in the country. The purpose of this work is to analyze how the media portrays the Venezuelan migration in Mexico, and in what way this coverage influences people’s judgements about migration. Particularly to understand what kinds of arguments are used to justify hostility and xenophobic opinions. Data collection focuses on a textual analysis of online news generated by Mexican and international media. Final outcomes will show how the media serves to preserve a particular coverage based on traditional prejudiced stereotypes that serve to set a hostile ambient towards migrants and to justify violations to their human rights.

La presente investigación busca abordar la problemática sobre la normativa que rige la actividad de menores de edad youtubers. Particularmente la forma en que se ha desarrollado esta situación en México en los últimos años. La razón de escoger este país tiene que ver con el hecho de que es uno de los mercados más importantes en el consumo de medios digitales en América Latina. Centrada en la metodología de estudio de caso, este trabajo busca dar cuenta de tres principales objetivos: a) entender los potenciales riesgos a los que se exponen quiénes son youtubers menores de edad, b) analizar el caso de México: el mercado de consumo de medios, particularmente entre menores de edad, así como su marco regulatorio. Y c) ¿Qué propuestas existen actualmente para fortalecer este vacío legal y cómo pudieran adecuarse al caso mexicano? El análisis y las conclusiones en este trabajo demostrarán cómo la actividad de los menores creadores representa un nuevo campo de acción, de ahí que las normativas tienen que modernizarse para poder proteger estas nuevas formas de producción y consumo de contenidos.

Glucosinolate transporters (GTRs) are part of the nitrate/peptide transporter (NPF) family, members of which also transport specialized secondary metabolites as substrates. Glucosinolates are defense compounds derived from amino acids. We selected 4-methylthiobutyl (4MTB) and indol-3-ylmethyl (I3M) glucosinolates to study how GTR1 from Arabidopsis thaliana transports these substrates in computational simulation approaches. The designed pipeline reported here includes massive docking of 4MTB and I3M in an ensemble of GTR1 conformations (in both inward and outward conformations) extracted from molecular dynamics simulations, followed by clustered and substrate–protein interactions profiling. The identified key residues were mutated, and their role in substrate transport was tested. We were able to identify key residues that integrate a major binding site of these substrates, which is critical for transport activity. In silico approaches employed here represent a breakthrough in the plant transportomics field, as the identification of key residues usually takes a long time if performed from a purely wet-lab experimental perspective. The inclusion of structural bioinformatics in the analyses of plant transporters significantly speeds up the knowledge-gaining process and optimizes valuable time and resources.

Los estudios en historia de la cartografía —es decir, el análisis de los procesos creativos y del papel jugado por los mapas en la historia del mundo—, así como la cartografía histórica —o sea, la elaboración y utilización de mapas como herramienta adaptada al análisis histórico—, se han renovado, ampliado y consolidado significativamente en las últimas décadas, tanto en Colombia como en el ámbito internacional. Con abordajes diversos, estas tendencias han permitido repensar los procesos de construcción del espacio y revisar las historias territoriales establecidas en diferentes escalas, al mismo tiempo que han propiciado una resignificación y revalorización del patrimonio cartográfico, abriendo, de esta forma, nuevas perspectivas, caminos de investigación y posibilidades fecundas de entrecruzamientos entre la historia y la geografía.

Després de la crisi econòmica mundial de 2008, milers d’espanyols es van veure obligats a abandonar el país a la recerca de millors condicions en altres indrets del món. Alguns es van establir en països europeus, com Anglaterra o Alemanya, mentre que altres van creuar l’Atlàntic cap al «Nou Món». Alguns immigrants, majoritàriament joves, van arribar a Mèxic buscant feina o millors condicions econòmiques. En aquestes circumstàncies, les plataformes de xarxes socials han tingut una gran importància estratègica, i no solament per als espanyols que ja vivien a Mèxic i que volien mantenir-se en contacte amb els seus familiars i amics, i la seva cultura a Espanya. Aquestes plataformes també són una eina de gran valor per a les persones que pensen viatjar al país llatinoamericà i necessiten informació relacionada amb aspectes econòmics, migratoris i de seguretat. Aquest treball vol entendre com les plataformes de xarxes socials serveixen tant per a resoldre problemes de la vida quotidiana com per a fomentar la cohesió i permetre la creació de comunitats entre els espanyols que viuen a l’estranger.

Los metabolitos secundarios son señales importantes en la interacción planta-microrganismos; sin embargo, los datos que corroboran el rol de los flavonoides como señales entre plantas y la simbiosis micorrízica arbuscular son limitados y aún recientes. Este estudio tiene por objetivo evaluar el efecto de flavonoides presentes en exudados radiculares de Allium porrum L., Nicotiana gluaca y Brassica oleracea var. Itálica, en la germinación de esporas y establecimiento de colonización radicular de Diversispora trimulares. Se detectaron miricetina y canferol en exudados de A. porrum, con un contenido total de flavonoides de 23,80µg g-1, de raíz seca; quercetina, en N. glauca, con 23,35µg g-1 y crisina, en B. oleracea, con 14,71µg g-1. Quercetina estimuló la germinación y la vitalidad de esporas (24%, 40%), a diferencia de crisina, que presentó un efecto inhibitorio (4%, 20%). A. porrum y N. glauca incrementaron la germinación de esporas (54%, 56%) y porcentaje de colonización de micorriza arbuscular (72%, 75%). Los resultados de la investigación mostraron una evidencia sólida del efecto de los flavonoides como moléculas estimulantes en los procesos de germinación de esporas y colonización de micorriza arbuscular.