Understanding HAT1: A Comprehensive Review of Noncanonical Roles and Connection with Disease

Histone acetylation plays a vital role in organizing chromatin, regulating gene expression and controlling the cell cycle. The first histone acetyltransferase to be identified was histone acetyltransferase 1 (HAT1), but it remains one of the least understood acetyltransferases. HAT1 catalyzes the acetylation of newly synthesized H4 and, to a lesser extent, H2A in the cytoplasm. However, 20 min after assembly, histones lose acetylation marks. Moreover, new noncanonical functions have been described for HAT1, revealing its complexity and complicating the understanding of its functions. Recently discovered roles include facilitating the translocation of the H3H4 dimer into the nucleus, increasing the stability of the DNA replication fork, replication-coupled chromatin assembly, coordination of histone production, DNA damage repair, telomeric silencing, epigenetic regulation of nuclear lamina-associated heterochromatin, regulation of the NF-kappa B response, succinyl transferase activity and mitochondrial protein acetylation. In addition, the functions and expression levels of HAT1 have been linked to many diseases, such as many types of cancer, viral infections (hepatitis B virus, human immunodeficiency virus and viperin synthesis) and inflammatory diseases (chronic obstructive pulmonary disease, atherosclerosis and ischemic stroke). The collective data reveal that HAT1 is a promising therapeutic target, and novel therapeutic approaches, such as RNA interference and the use of aptamers, bisubstrate inhibitors and small-molecule inhibitors, are being evaluated at the preclinical level

Estudio de la expresión de EGFL7 (Epidermal growth factor-like domain-containing protein 7) en la pared venosa de pacientes con enfermedad venosa crónica

La enfermedad venosa crónica (EVC) se trata de una amplia variedad de anomalías del sistema venoso de gran prevalencia en nuestra sociedad. Frecuentemente, se manifiesta en las extremidades inferiores en forma de vena varicosa (VV), cursando como una situación de hipertensión venosa ambulatoria que se agrava conforme progresa la enfermedad. Cada vez más estudios evidencian la importancia de los cambios moleculares y de la matriz extracelular en la fisiopatogenia de la EVC. EGFL-7 (Epidermal growth factor-like domain-containing protein 7) es un componente de gran importancia en el desarrollo y patología del sistema vascular, aunque su papel en la EVC todavía no ha sido esclarecido. Así, el objetivo del presente trabajo es analizar la expresión génica y proteica de EGFL7 en la pared venosa de pacientes con EVC (n=35) y sanos (n=27), mediante la realización de RT-qPCR e immunohistoquímica, respectivamente. Nuestros resultados muestran como existe una disminución en la expresión de EGFL-7 en pacientes con EVC en comparación con las venas de individuos sanos. En su conjunto, nuestro trabajo apoya el papel de EGFL7 en la pérdida de la homeostasis vascular asociada a la EVC. Futuros estudios son necesarios para profundizar en las implicaciones de estos cambios en el tejido venoso patológico, así como el desarrollo de posibles estrategias dirigidas a esta diana.Chronic venous disease (CVD) is a wide variety of anomalies of the venous system that are highly prevalent in our society. Frequently, it manifests in the lower extremities in the form of varicose veins(VV), presenting as a situation of ambulatory venous hypertension that worsens as the disease progresses. More and more studies show the importance of molecular changes and of the extracellular matrix in the pathophysiology of CVD. EGFL-7 (Epidermal growth factor-like domain-containing protein 7) is a component of great importance in the development and pathology of the vascular system, although its role in CVD has not yet been clarified. Thus, the objective of this study is to analyze the gene and proteinexpression of EGFL7 in the venous wall of patients with CVD (n=35) and healthy patients (n=27), by performing RT-qPCR and immunohistochemistry, respectively. Our results show how there is a decrease in the expression of EGFL-7 in patients with CVD compared to the veins of healthy individuals. As a whole, our work supports the role of EGFL7 in the loss of vascular homeostasis associated with CVD. Future studies are necessary to delve into the implications of these changes in the pathological venous tissue, as well as the development of possible strategies aimed at this target

Database of spatial distribution of non indigenous species in Spanish marine waters

Research in marine Spanish waters are focused on several actions to achieve an effectively management on protected areas, with the active participation of the stakeholders and research as basic tools for decision-making. Among these actions, there is one about the knowledge and control on NIS. One of its objectives is the creation of NIS factsheets, which are going to be added to the National Marine Biodiversity Geographical System (GIS) providing complementary information about taxonomic classification, common names, taxonomic synonyms, species illustrations, identification morphological characters, habitat in the native and introduced regions, biological and ecological traits, GenBank DNA sequences, world distribution, first record and evolution in the introduced areas, likely pathways of introduction, effects in the habitats and interaction with native species, and potential management measures to apply. The database will also provide data for (1) the European online platforms, (2) the environmental assessment for the Descriptor 2 (D2-NIS) of the EU Marine Strategy Framework Directive (MSFD), as well as (3) supporting decisions made by stakeholders. It is the result of extensive collaboration among scientist, manager’s and citizen science in the Spanish North-Atlantic, South-Atlantic, Gibraltar Strait-Alboran, Levantine-Balearic and Canary Islands marine divisions, providing an updated overview of the spatial distribution of relevant extended and invasive NIS of recent and established NIS introduced by maritime transport and aquaculture pathways, as well as on cryptogenic or native species in expansion due to the climatic water warming trend

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Effect of cysteamine on cytosolic somatostatin binding-sites in rabbit duodenal mucosa

Administration of cysteamine in rabbits elicited a rapid depletion of both duodenal mucosa and plasma somatostatin. A significant reduction was observed within 5 min, returning toward control values by 150 min. The depletion of somatostatin was associated with an increase in the binding capacity and a decrease in the affinity of both high- and low-affinity binding sites present in cytosol of duodenal mucosa. Incubation of cytosolic fraction from control rabbits with 1 mM cysteamine did not modify somatostatin binding. Furthermore, addition of cysteamine at the time of binding assay did not affect the integrity of 125I-Tyr11-somatostatin. It is concluded that in vivo administration of cysteamine to rabbits depletes both duodenal mucosa and plasma somatostatin and leads to up-regulation of duodenal somatostatin binding sites

El Substrato del receptor de Insulina-4 está sobreexpresado en el cáncer colorrectal y promueve la activación del ciclo celular a través de la vía Rb/E2F

El substrato del receptor de insulina 4 (IRS-4) es una proteína adaptadora muy poco estudiada y la hipótesis que relaciona su función con el desarrollo tumoral cada vez gana más fuerza. Los estudios se llevaron a cabo in vitro (línea celular de cáncer de colon RKO) e in vivo, utilizando biopsias humanas de cáncer colorrectal (n=20) y tejido normal adyacente (n=20). El tratamiento con dosis fisiológicas de IGF-1 produjo una translocación subcelular de IRS-4 desde el citoplasma hacia el núcleo en células RKO. La sobreexpresión de IRS-4 en dichas células dio lugar a un aumento de la proteína fosforilada del retinoblastoma (pRb Ser 809/811 y pRb Ser 705), así como de la expresión de E2F, ciclina E y ciclina D1, comparado con las células control. Algunos de estos cambios fueron parcialmente revertidos al tratar las células con wortmanina. En cuanto a los estudios realizados en las muestras de pacientes con CCR se observó mediante fraccionamiento subcelular una clara sobreexpresión de IRS-4 en el citoplasma, membrana y núcleo, mientras que los niveles de proteína fueron prácticamente indetectables en los tres compartimentos del tejido normal. Estudios inmunohistoquímicos mostraron una tinción nuclear positiva de IRS-4 en el 74% de las células tumorales. La sobreexpresión de IRS-4 en las muestras de pacientes con CCR se correlacionó positivamente y de forma significativa con el incremento de proteínas importantes del ciclo celular como ciclina D1 (r = 0.6662), Rb (r = 0.7779), pRb serina 809/811 (r = 0.6864), pRb serina 705 (r = 0.6261) y E2F1 (r = 0.8702). Nuestros resultados sugieren que el IRS-4 promueve la activación del ciclo celular a través de la activación de la vía Rb/E2F y podría servir como una diana farmacológica dada su sobreexpresión en el tejido tumoral y sus niveles apenas detectables en el tejido norma

Dendrimers and dendritic materials: From laboratory to medical practice in infectious diseases

Infectious diseases are one of the main global public health risks, predominantly caused by viruses, bacteria, fungi, and parasites. The control of infections is founded on three main pillars: prevention, treatment, and diagnosis. However, the appearance of microbial resistance has challenged traditional strategies and demands new approaches. Dendrimers are a type of polymeric nanoparticles whose nanometric size, multivalency, biocompatibility, and structural perfection offer boundlesspossibilities in multiple biomedical applications. This review provides the reader a general overview about the uses of dendrimers and dendritic materials in the treatment, prevention, and diagnosis of highly prevalent infectious diseases, and their advantages compared to traditional approaches. Examples of dendrimers as antimicrobial agents per se, as nanocarriers of antimicrobial drugs, as well as their uses in gene transfection, in vaccines or as contrast agents in imaging assays are presented.Despite the need to address some challenges in order to be used in the clinic, dendritic materials appear as an innovative tool with a brilliant future ahead in the clinical management of infectiousdiseases and many other health issues

The Mediterranean fishery management: A call for shifting the current paradigm from duplication to synergy

Independence of science and best available science are fundamental pillars of the UN-FAO code of conduct for responsible fisheries and are also applied to the European Union (EU) Common Fishery Policy (CFP), with the overarching objective being the sustainable exploitation of the fisheries resources. CFP is developed by DG MARE, the department of the European Commission responsible for EU policy on maritime affairs and fisheries, which has the Scientific, Technical and Economic Committee for Fisheries (STECF) as consultant body. In the Mediterranean and Black Sea, the General Fisheries Commission for the Mediterranean (FAO-GFCM), with its own Scientific Advisory Committee on Fisheries (GFCM-SAC), plays a critical role in fisheries governance, having the authority to adopt binding recommendations for fisheries conservation and management. During the last years, advice on the status of the main stocks in the Mediterranean and Black Sea has been provided both by GFCM-SAC and EU-STECF, often without a clear coordination and a lack of shared rules and practices. This has led in the past to: i) duplications of the advice on the status of the stocks thus adding confusion in the management process and, ii) a continuous managers’ interference in the scientific process by DG MARE officials hindering its transparency and independence. Thus, it is imperative that this stalemate is rapidly resolved and that the free role of science in Mediterranean fisheries assessment and management is urgently restored to assure the sustainable exploitation of Mediterranean marine resources in the future

El parque de Yuncos como espacio educativo y recreativo

Resumen basado en el del proyecto. Premiado en la convocatoria: Premios para proyectos de innovación concluidos durante el curso 2006-2007, en los centros educativos no universitarios sostenidos con fondos públicos de la Comunidad Autónoma de Castilla-La Mancha (Orden 30-01-2008, de la Consejería de Educación y Ciencia de la Junta de Comunidades de Castilla-La Mancha. Resolución de 15-05-2009, de la Viceconsejería de Educación)El proyecto desarrolla una serie de actividades de enseñanza y aprendizaje en el campo de la educación ambiental basadas en el principio de la investigación recreativa. Las actividades se realizan en un parque municipal. Programadas por profesores del Instituto y del Colegio Público, en colaboración con el Ayuntamiento del municipio, dirigidas a alumnos de Primaria, e impartidas por alumnos de Secundaria, que intervienen como monitores. Los objetivos básicos que se persiguen son: mejorar la comunicación educativa entre centros de Primaria y de Secundaria, mediante el diseño compartido de actividades de enseñanza y aprendizaje, integrando conocimientos, planteamientos y experiencias docentes diferentes. Se persigue así una cooperación real y eficaz entre un Colegio y un Instituto de un mismo municipio, a partir de la colaboración en tareas comunes. Colaboración, a la que se suma el Ayuntamiento, facilitando aspectos logísticos y espacios necesarios para llevar a cabo las actividades programadas. En segundo lugar, incorporar al alumnado de secundaria en el proceso educativo como docente, impartiendo y adaptando actividades dirigidas a alumnos de niveles inferiores, como estrategia para lograr aprendizajes significativos y funcionales. El tercer objetivo es abordar la educación ambiental, explorando actividades con metodologías educativas basadas en el principio de la investigación recreativa con el objetivo de favorecer la adquisición de valores y conductas de respeto al medio ambiente. La metodología de trabajo se basa en el principio educativo de aprender a aprender, favoreciendo estrategias de aprendizaje a través del descubrimiento y de la interacción y facilitando la consecución de aprendizajes funcionales. La organización de las tareas se plantea a partir de un aprendizaje en grupos, que favorece las relaciones entre iguales y la superación de conflictos mediante el diálogo y la cooperación.Castilla La ManchaConsejería de Educación, Ciencia y Cultura. Viceconsejería de Educación y Cultura. Servicio de Documentación; Bulevar del Río Alberche, s. n. - 1 Planta; 45071 Toledo; Tel. +34925286045; Fax +34925247410; [email protected]