The mitochondrial uncoupling as a promising pharmacological target against cancer

Context: Mitochondria represent a key intracellular signalling hub that is emerging as important determinants of numerous aspects of cancer development and progression. In this sense, the organelle constitutes a promising target for the development of novel anticancer agents. Despite the negative history, mitochondrial uncoupling has recently proposed as a pharmacological target against cancer, but little is known about the mechanisms involved. Aims: To demonstrate the role of mitochondria in tumor formation and to describe how targeting of mitochondria uncoupling can be beneficial in the therapy of these diseases, which affect a large human population. Methods: The data for this systematic review were collected from three popular databases including PubMed, Google Scholar, and Scopus and included in the search terms the words “mitochondrial uncoupling” and “cancer”. The influence of mitochondrial uncoupling on cells physiology that could lead to cancer cells death, invasion and metastasis was critically appraised from relevant researches. The anticancer effects of small molecules mitochondrial uncouplers and their anticancer mechanisms were also discussed. The present dataset finally included 201 published articles. Results: It was found that the mitochondrial uncoupling-mediated responses possibly involved in the anti-cancer/anti-metastatic effects include Ca2+ homeostasis and bioenergetics disruption, mitochondrial membrane potential dissipation, reactive oxygen species generation, mitochondrial dynamics alteration, and gene expression modulation. Conclusions: Overall, this critical review suggests that mitochondrial uncoupling could be an interesting pharmacological target to be considered in the design and synthesis of novel anti-cancer compounds with optimal physic-chemical and biopharmaceutical properties and improved safety profiles

Fish Microbiome Modulation and Convenient Storage of Aquafeeds When Supplemented with Vitamin K1

Vitamin K (VK) is a fat-soluble vitamin necessary for fish metabolism and health. VK stability as dietary component during aquafeed storage and its potential effect on intestinal microbiome in fish have not yet been completely elucidated. The convenient storage conditions of aquafeeds when supplemented with phylloquinone (VK1), as well as its potential effects on the gut microbiota of Senegalese sole (Solea senegalensis) juveniles, have been explored. Experimental feeds were formulated to contain 0, 250 and 1250 mg kg−1 of VK1 and were stored at different temperatures (4, −20 or −80 ◦C). VK stability was superior at −20 ◦C for short-term (7 days) storage, while storing at −80 ◦C was best suited for long-term storage (up to 3 months). A comparison of bacterial communities from Senegalese sole fed diets containing 0 or 1250 mg kg−1 of VK1 showed that VK1 supplementation decreased the abundance of the Vibrio, Pseudoalteromonas, and Rhodobacterace families. All these microorganisms were previously associated with poor health status in aquatic organisms. These results contribute not only to a greater understanding of the physiological effects of vitamin K, particularly through fish intestinal microbiome, but also establish practical guidelines in the industry for proper aquafeed storage when supplemented with VK1

I feel you: the design and evaluation of a domotic affect-sensitive spoken conversational agent

We describe the work on infusion of emotion into a limited-task autonomous spoken conversational agent situated in the domestic environment, using a need-inspired task-independent emotion model (NEMO). In order to demonstrate the generation of affect through the use of the model, we describe the work of integrating it with a natural-language mixed-initiative HiFi-control spoken conversational agent (SCA). NEMO and the host system communicate externally, removing the need for the Dialog Manager to be modified, as is done in most existing dialog systems, in order to be adaptive. The first part of the paper concerns the integration between NEMO and the host agent. The second part summarizes the work on automatic affect prediction, namely, frustration and contentment, from dialog features, a non-conventional source, in the attempt of moving towards a more user-centric approach. The final part reports the evaluation results obtained from a user study, in which both versions of the agent (non-adaptive and emotionally-adaptive) were compared. The results provide substantial evidences with respect to the benefits of adding emotion in a spoken conversational agent, especially in mitigating users' frustrations and, ultimately, improving their satisfaction

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers var-ious events from the molecular to the tissue level, which in turn is given by the intrinsic character-istics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue, and clinical effects are difficult to predict, which determines the hetero-geneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to the persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms un-derlying virus–host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsy-chiatric disorders, and organ damage. The article concludes by discussing future directions for re-search and implications for the management and treatment of COVID-19 and long COVID

MicroRNAs overexpressed in Crohn's disease and their interactions with mechanisms of epigenetic regulation explain novel aspects of Crohn's disease pathogenesis

Background In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease. Methods We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database. Results We found 190 miRNAs with great abundance in patients with CD, of which 26 miRNAs regulate the gene expression of enzymes known to catalyze epigenetic modifications involved in essentials pathophysiological processes, such as chromatin architecture reorganization, immune response regulation including CD4+ T cells polarization, integrity of gut mucosa, gut microbiota composition and tumorigenesis. Conclusion The integrated analysis of miRNAs with a high relative abundance in patients with CD showed a combined and superimposed gene expression regulation of enzymes associated with relevant epigenetic mechanisms and that could explain, in part, the pathogenesis of CD

Conserving Ecosystem Diversity in the Tropical Andes

Documenting temporal trends in the extent of ecosystems is essential to monitoring their status but combining this information with the degree of protection helps us assess the effectiveness of societal actions for conserving ecosystem diversity and related ecosystem services. We demonstrated indicators in the Tropical Andes using both potential (pre-industrial) and recent (~2010) distribution maps of terrestrial ecosystem types. We measured long-term ecosystem loss, representation of ecosystem types within the current protected areas, quantifying the additional representation offered by protecting Key Biodiversity Areas. Six (4.8%) ecosystem types (i.e., measured as 126 distinct vegetation macrogroups) have lost >50% in extent across four Andean countries since pre-industrial times. For ecosystem type representation within protected areas, regarding the pre-industrial extent of each type, a total of 32 types (25%) had higher representation (>30%) than the post-2020 Convention on Biological Diversity (CBD) draft target in existing protected areas. Just 5 of 95 types (5.2%) within the montane Tropical Andes hotspot are currently represented with >30% within the protected areas. Thirty-nine types (31%) within these countries could cross the 30% CBD 2030 target with the addition of Key Biodiversity Areas. This indicator is based on the Essential Biodiversity Variables (EBV) and responds directly to the needs expressed by the users of these countries

Manejo actual de la otitis externa maligna. Una revisión sistemática.

INTRODUCTION: Malignant external otitis (OEM), or also called necrotizing external otitis, is a life-threatening infection, mainly affecting the external auditory canal, producing osteomyelitis of the temporal bone; extends to the base of the skull and surrounding tissue, causing sepsis; eventually compromising the cranial nerves and generating multisystemic. Objectives: To describe the current management of malignant external otitis. Specific objectives: 1) To determine the etiology of malignant external otitis. 2) To determine the complications of malignant external otitis. METHODS: A systematic review was performed according to the PRISMA 2020 guidelines with a search for scientific articles, with the term malignant external otitis. We recovered 40 articles corresponding to the last 5 years, obtained from databases such as Cochrane, academic Google, Medline, Mendeley, ScientDirect, IntechOpen. The risks of bias in the studies showed systematic differences due to the heterogeneity of the patients and the treatments between the groups. RESULTS: the management of malignant external otitis includes treatment with anti-pseudomonas antibiotics such as fluoroquinolones in combination with a beta-lactam and an antifungal such as amphotericin B, voriconazole, fluconazole, or echinocandin; in addition to treatment with surgical debridement of the ear canal and radical mastoidectomy, to avoid the risk of neurocranial sepsis, obtaining good results. DISCUSSION: Malignant external otitis is a pathology of rare occurrence that affects immune immunocompromised patients, whose morbidity and mortality is high, if not treated properly. Its main causal agents are: pseudomona aeruginosa, staphylococcus aureus, Candida spp, Aspergillus spp and Geotrichum. The importance of this research lies in optimizing care in the patient with OEM, making a timely clinical and imaging diagnosis, to provide an effective therapeutic alternative, based on broad-spectrum antibiotic therapy, antifungal treatment, and surgical treatment, to avoid complications.INTRODUCCIÓN: La otitis externa maligna (OEM), o también llamada otitis externa necrotizante, es una infección potencialmente mortal, que afecta principalmente al canal auditivo externo, produciendo osteomielitis del hueso temporal; se extiende hasta la base del cráneo y tejido circundante, provocando sepsis; llegando a comprometer los nervios craneales y generar afección multisistémica. Objetivos General: Describir el manejo actual de la otitis externa maligna. Objetivos específicos: 1) Determinar la etiología de la otitis externa maligna.  2) Determinar las complicaciones de la de la otitis externa maligna. MÉTODOS: se realizó una revisión sistemática según las guías PRISMA 2020 con búsqueda de artículos científicos, con el termino otitis externa maligna. Se recuperaron 40 artículos correspondientes a los últimos 5 años, obtenidos de bases de datos como Cochrane, Google académico, Medline, Mendeley, ScientDirect, IntechOpen. Los riesgos de sesgo en los estudios observaron diferencias sistemáticas por la heterogeneidad de los pacientes y los tratamientos entre los grupos.  RESULTADOS: el manejo de la otitis externa maligna incluye tratamiento con antibióticos anti pseudomona como las fluoroquinolonas en combinación con un betalactámico y un antifúngico como la anfotericina B, voriconazol, fluconazol o equinocandinas; además del tratamiento con desbridamiento quirúrgico del canal auditivo y mastoidectomía radical, para evitar el riesgo de sepsis neurocraneal, obteniéndose buenos resultados.  DISCUSIÓN: La otitis externa maligna, es una patología de rara ocurrencia que afecta a pacientes inmunocomprometidos, cuya morbimortalidad es alta, si no se trata adecuadamente. Sus principales agentes causales son: pseudomona aeruginosa, estafilococo aureus, Cándida spp, Aspergillus spp y Geotrichum. La importancia de esta investigación radica en optimizar la atención en el paciente con OEM, realizando un diagnóstico clínico e imagenológico oportuno, para brindar una alternativa terapéutica eficaz, basada en antibioticoterapia de amplio espectro, el tratamiento antifúngico, complementario al tratamiento quirúrgico, para evitar complicaciones

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Caracterización del Banco de La Concepción

Se integra información hidrográfica, geomorfológica, sedimentológica, biológica, sobre hábitats marinos y pesquera, para establecer las bases ecológicas necesarias para la protección y conservación del Banco de La ConcepciónEl proyecto INDEMARES ha permitido utilizar amplios medios económicos y personales para estudiar en detalle y desde múltiples perspectivas la zona del Banco de La Concepción. Se han aplicado metodologías para el estudio de la hidrografía, caracterizando la región, describiendo sus principales masas de agua y la hidrodinámica de las corrientes. También se ha abordado la geología de la zona, incluyendo levantamientos batimétricos, perfiles sísmicos, muestreos de sedimento y petrológicos, obteniendo modelos digitales del terreno, mapas de tipos de fondo, geomorfológicos. Se han caracterizado las comunidades bentopelágicas, demersales, epibentónicas y endobentónicas, prestando especial atención a aquellas que conforman o estructuran los hábitats sensibles cuyo inventariado y cartografía era objeto principal del proyecto. Los trabajos de identificación de hábitats se han realizado con muestreadores directos, pero también con muestreadores visuales, que han permitido hacer un mayor esfuerzo de muestreo sin aumentar el impacto sobre los fondos de la zona. Por otro lado se ha estudiado la huella pesquera de la zona por medio del análisis de los datos VMS y los cuadernos de pesca proporcionados por la SGP, además de una ardua labor a pie de puerto de entrevistas y encuestas. Toda la información ha sido gestionada y analizada por diferentes grupos de investigación de diferentes centros (Universidad de La Laguna, Instituto Universitario de Ciencias Políticas y Sociales, Universidad de Las Palmas de Gran Canaria, Instituto de Ciencias del Mar de Barcelona, Universidad de Barcelona, Centro de Investigaciones Medioambientales del Atlántico, Centro Oceanográfico de Santander y Centro Oceanográfico de Málaga del Instituto Español de Oceanografía, …), aunque el grueso de esta labor, además de la coordinación, se ha llevado a cabo en el Centro Oceanográfico de Canarias del Instituto Español de Oceanografía. Los resultados permiten tener un conocimiento profundo y multidisciplinar de la zona de estudio comparable a pocos proyectos de investigación marina en la macaronesia. El estudio oceanográfico, el geológico, y el de las comunidades biológicas, ha permitido la caracterización de los hábitats de la zona, y su cartografiado mediante el intenso muestreo y la aplicación de análisis de idoneidad de hábitats.INDEMARES Project made possible to bring together economic and staff resources to study in detail, and from multiple perspectives, the area of Banco de La Concepción. Methodologies have been applied to study hydrography, making a regional characterization, depicting main water masses, and current hydrodynamics. Geology has been tackled including bathymetric uplifting, seismic profiles, sediment and petrological sampling, obtaining digital terrain models, type of bottom maps, geomorphological maps, as an output. Benthopelagic, demersal, epibenthic and endobenthic communities have been characterized, paying special attention to sensitive habitats which inventory and mapping was the project’s main aim. Habitat identification has been made with direct and visual samplers, the latter making a major sampling effort possible without an increase of bottom impact. Moreover, fisheries footprint has been identified by Vessel Monitoring System data, together with logbooks from Secretaría General de Pesca (Fisheries Ministry), as well as a hard interviewing and surveying task at landing points. Information has been managed and analysed by different research groups from different Centres (Universidad de La Laguna, Instituto Universitario de Ciencias Políticas y Sociales, Universidad de Las Palmas de Gran Canaria, Instituto de Ciencias del Mar de Barcelona, Universidad de Barcelona, Centro de Investigaciones Medioambientales del Atlántico, Centro Oceanográfico de Santander y Centro Oceanográfico de Málaga del Instituto Español de Oceanografía), although the main body of the work, plus coordination, has been made by the Canary Islands Oceanographic Centre, from the Spanish Institute of Oceanography. Results let us have a multidisciplinary profound knowledge of the study zone, comparable to few other marine research projects off Macaronesia. The study about oceanography, geology and biologic communities has allowed the habitats characterization and mapping by means of intensive sampling and habitat suitability analysis.Instituto Español de Oceanografía, Comisión Europea Programa LIFE+, Fundación Biodiversida

Caracterización del Sur de Fuerteventura

Se integra información hidrográfica, geomorfológica, sedimentológica, biológica, sobre hábitats marinos y pesquera, para establecer las bases ecológicas necesarias para la protección y conservación del Sur de Fuerteventura (Montes de Amanay y El Banquete)El proyecto INDEMARES ha permitido utilizar amplios medios económicos y personales para estudiar en detalle y desde múltiples perspectivas la zona del Sur de Fuerteventura (montes de Amanay y El Banquete). Se han aplicado metodologías para el estudio de la hidrografía, caracterizando la región, describiendo sus principales masas de agua y la hidrodinámica de las corrientes. También se ha abordado la geología de la zona, incluyendo levantamientos batimétricos, perfiles sísmicos, muestreos de sedimento y petrológicos, obteniendo modelos digitales del terreno, mapas de tipos de fondo, geomorfológicos. Se han caracterizado las comunidades bentopelágicas, demersales, epibentónicas y endobentónicas, prestando especial atención a aquellas que conforman o estructuran los hábitats sensibles cuyo inventariado y cartografía era objeto principal del proyecto. Los trabajos de identificación de hábitats se han realizado con muestreadores directos, pero también con muestreadores visuales, que han permitido hacer un mayor esfuerzo de muestreo sin aumentar el impacto sobre los fondos de la zona. Por otro lado se ha estudiado la huella pesquera de la zona por medio del análisis de los datos VMS y los cuadernos de pesca proporcionados por la SGP, además de una ardua labor a pie de puerto de entrevistas y encuestas. Toda la información ha sido gestionada y analizada por diferentes grupos de investigación de diferentes centros (Universidad de La Laguna, Instituto Universitario de Ciencias Políticas y Sociales, Universidad de Las Palmas de Gran Canaria, Instituto de Ciencias del Mar de Barcelona, Universidad de Barcelona, Centro de Investigaciones Medioambientales del Atlántico, Centro Oceanográfico de Santander y Centro Oceanográfico de Málaga del Instituto Español de Oceanografía, …), aunque el grueso de esta labor, además de la coordinación, se ha llevado a cabo en el Centro Oceanográfico de Canarias del Instituto Español de Oceanografía. Los resultados permiten tener un conocimiento profundo y multidisciplinar de la zona de estudio comparable a pocos proyectos de investigación marina en la Macaronesia. El estudio oceanográfico, el geológico, y el de las comunidades biológicas, ha permitido la caracterización de los hábitats de la zona, y su cartografiado mediante el intenso muestreo y la aplicación de análisis de idoneidad de hábitats.Abstract: INDEMARES Project made possible to bring together economic and staff resources to study in detail, and from multiple perspectives, the area of South of Fuerteventura (Amanay and El Banquete Semounts). Methodologies have been applied to study hydrography, making a regional characterization, depicting main water masses, and current hydrodynamics. Geology has been tackled including bathymetric uplifting, seismic profiles, sediment and petrological sampling, obtaining digital terrain models, type of bottom maps, geomorphological maps, as an output. Benthopelagic, demersal, epibenthic and endobenthic communities have been characterized, paying special attention to sensitive habitats which inventory and mapping was the project’s main aim. Habitat identification has been made with direct and visual samplers, the latter making a major sampling effort possible without an increase of bottom impact. Moreover, fisheries footprint has been identified by Vessel Monitoring System data, together with logbooks from Secretaría General de Pesca (Fisheries Ministry), as well as a hard interviewing and surveying task at landing points. Information has been managed and analysed by different research groups from different Centres (Universidad de La Laguna, Instituto Universitario de Ciencias Políticas y Sociales, Universidad de Las Palmas de Gran Canaria, Instituto de Ciencias del Mar de Barcelona, Universidad de Barcelona, Centro de Investigaciones Medioambientales del Atlántico, Centro Oceanográfico de Santander y Centro Oceanográfico de Málaga del Instituto Español de Oceanografía), although the main body of the work, plus coordination, has been made by the Canary Islands Oceanographic Centre, from the Spanish Institute of Oceanography. Results let us have a multidisciplinary profound knowledge of the study zone, comparable to few other marine research projects off Macaronesia. The study about oceanography, geology and biologic communities has allowed the habitats characterization and mapping by means of intensive sampling and habitat suitability analysis.Instituto Español de Oceanografía, Comisión Europea Programa LIFE+, Fundación Biodiversida