Infection causes childhood leukemia

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- Editorial.Peer Reviewe

Genetically engineered mouse models of human B-cell precursor leukemias

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License.B-cell precursor acute lymphoblastic leukemias (pB-ALLs) are the most frequent type of malignancies of the childhood, and also affect an important proportion of adult patients. In spite of their apparent homogeneity, pB-ALL comprises a group of diseases very different both clinically and pathologically, and with very diverse outcomes as a consequence of their biology, and underlying molecular alterations. Their understanding (as a prerequisite for their cure) will require a sustained multidisciplinary effort from professionals coming from many different fields. Among all the available tools for pB-ALL research, the use of animal models stands, as of today, as the most powerful approach, not only for the understanding of the origin and evolution of the disease, but also for the development of new therapies. In this review we go over the most relevant (historically, technically or biologically) genetically engineered mouse models (GEMMs) of human pB-ALLs that have been generated over the last 20 years. Our final aim is to outline the most relevant guidelines that should be followed to generate an “ideal” animal model that could become a standard for the study of human pB-ALL leukemia, and which could be shared among research groups and drug development companies in order to unify criteria for studies like drug testing, analysis of the influence of environmental risk factors, or studying the role of both low-penetrance mutations and cancer susceptibility alterations.This work was supported by the German “Bundesamt fur Strah-lenschutz (BfS)” pilot project on childhood leukemia no. 3612S70029. JH has been supported by the German Children’s Cancer Foundation and from the “Forschungskommission” of the medical faculty of the Heinrich Heine University and the “Strategischer Forschungsfond” of the Heinrich-Heine-University. AB has been supported by the German Children’s Cancer Foundation and the Federal Ministry of Education and Research, Bonn, Germany. Research in ISG group is partially supported by FEDER and by MICINN (SAF2012-32810), by NIH grant (R01 CA109335-04A1), by Junta de Castilla y León (BIO/SA06/13) and by the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Program). ISG lab is a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program. Research at CC’s lab was partially supported by FEDER, Fondo de Investigaciones Sanitarias (PI13/00160), CSIC P.I.E., Junta de Castilla y León, and from an institutional grant from the Fundación Ramón Areces.Peer Reviewe

Revisión sistemática de las intervenciones para el abandono del hábito tabáquico en el último año

21 p.Introducción: El tabaco es actualmente la principal causa de muerte evitable en el mundo. El tabaco mata a 8 millones de personas cada año (7 millones de fumadores activos y más de un millón de no fumadores afectados por humo de fuente ajena). La esperanza de vida de los fumadores es de aproximadamente 10 años menor que la de los no fumadores. Los niños y adolescentes que utilizan cigarrillos electrónicos, tienen al menos el doble de probabilidades de fumar cigarrillos a lo largo de su vida. En el día Mundial del tabaco en 2022, la OMS recuerda que el tabaco mata cada año a más de 8 millones de personas y destruye nuestro medio ambiente, perjudicando aún más la salud de las personas debido al cultivo, la fabricación, la distribución, el consumo y la eliminación de los productos de tabaco. El tabaco es una droga estimulante del sistema nervioso central. Uno de sus componentes, la nicotina, posee una enorme capacidad adictiva, y es la causa por la que su consumo produce dependencia. Los tratamientos disponibles actualmente para la deshabituación tabáquica son: la terapia sustitutiva de nicotina, el bupropión y la vareniclina, los cigarrillos electrónicos, las intervenciones de cesación tabáquica basadas en telefonía móvil, las terapia cognitivo conductual para dejar de fumar y el coaching y el mindfulness Objetivo: Analizar los diferentes programas de deshabituación tabáquica publicados durante el año 2022. Metodología: Se realizó una revisión sistemática de artículos científicos consultando las bases de datos Pubmed y Cochranre , con un rango de fechas desde enero a diciembre de 2022, en los idiomas español e inglés. No se hicieron restricciones respecto al tipo de estudio. Se revisaron los abstracts y en los casos necesarios los artículos completos, teniéndose en cuenta finalmente todos los artículos que incluían programas de deshabituación tabáquica y eliminando el resto. Resultados: De los 65 ensayos clínicos analizados, el 33,84% corresponden a ensayos sobre aplicaciones móviles para dejar de fumar.Un 20% establece los tratamientos farmacológicos con bupropión y vareniclina. El 18,46% se relaciona con tratamientos cognitivos conductuales, un 6,15% aborda las terapias de reemplazo con nicotina, cigarrillo electrónico, y por último el 4,61% apuestan por los procesos de coaching y mindfulness. Conclusiones: Las principales plataformas de tecnologías utilizadas en los estudios analizados fueron las aplicaciones móviles (app), las páginas webs y el asesoramiento telefónico. El uso de app como principal recurso coincide con el aumento exponencial de teléfonos inteligentes. Tras la revisión de los estudios publicados en el último año, concluimos que los móviles son una herramienta imprescindible en el tratamiento del tabaquismo.Introduction: Tobacco is currently the main preventable cause of death in the world. Tobacco kills 8 million people each year (7 million active smokers and more than one million non-smokers affected by secondhand smoke). The life expectancy of smokers is approximately 10 years less than that of non-smokers. Children and adolescents who use e-cigarettes are at least twice as likely to smoke cigarettes in their lifetime. On World Tobacco Day in 2022, the WHO recalls that tobacco kills more than 8 million people each year and destroys our environment, further harming people's health due to cultivation, manufacturing, distribution, consumption and elimination of tobacco products. Tobacco is a central nervous system stimulant drug. One of its components, nicotine, has an enormous addictive capacity, and is the reason why its consumption produces dependency. The treatments currently available for smoking cessation are: nicotine replacement therapy, bupropion and varenicline, e-cigarettes, mobile phone-based smoking cessation interventions, cognitive behavioural therapy for smoking cessation, and coaching and mindfulness. Objective: Analyse the different smoking cessation programs published during the year 2022. Methodology: A systematic review of scientific articles was carried out by consulting the Pubmed and Cochrane databases, with a range of dates from January to December 2022, in Spanish and English. No restrictions were made regarding the type of study. The abstracts and, where necessary, the complete articles were reviewed, finally taking into account all the articles that included smoking cessation programs and eliminating the rest. Results: Of the 65 clinical trials analysed, 33.84%, correspond to trials on mobile applications to quit smoking. 20% establish pharmacological treatments with bupropion and varenicline. 18.46% are related to cognitive behavioural treatments, 6.15% address nicotine replacement therapies, electronic cigarettes and finally 4.61 % opt for coaching and mindfulness processes. Conclusions: The main technology platforms used in the studies analysed were mobile applications (app), web pages and telephone advice. The use of the app as the main resource coincides with the exponential increase in smartphones. After reviewing the studies published in the last year, we conclude that mobile phones are an essential tool in the treatment of smoking

Towards a Mechanistic Model of Tau-Mediated Pathology in Tauopathies: What Can We Learn from Cell-Based In Vitro Assays?

Tauopathies are a group of neurodegenerative diseases characterized by the hyperphosphorylation and deposition of tau proteins in the brain. In Alzheimer's disease, and other related tauopathies, the pattern of tau deposition follows a stereotypical progression between anatomically connected brain regions. Increasing evidence suggests that tau behaves in a prion-like manner, and that seeding and spreading of pathological tau drive progressive neurodegeneration. Although several advances have been made in recent years, the exact cellular and molecular mechanisms involved remain largely unknown. Since there are no effective therapies for any tauopathy, there is a growing need for reliable experimental models that would provide us with better knowledge and understanding of their etiology and identify novel molecular targets. In this review, we will summarize the development of cellular models for modeling tau pathology. We will discuss their different applications and contributions to our current understanding of the prion-like nature of pathological tau

Cobertura vacunal antigripal durante la COVID, en un entorno laboral

12 p.La pandemia de la enfermedad por coronavirus, puede llegar a los máximos niveles de gravedad, al simultanearse con la gripe anual estacional, para intentar paliar los efectos que estas dos enfermedades pudieran ocasionar, es imprescindible centrarse en la campaña de vacunación frente a la gripe de la temporada 2020-2021, iniciándola precozmente, con una planificación exhaustiva, disponiendo de los recursos materiales necesarios y procurando realizarla en el más corto espacio de tiempo.The coronavirus disease pandemic can reach the highest levels of severity, when combined with the annual seasonal flu, to try to relieve the effects that these two diseases could cause. It is essential to focus on the vaccination campaign against influenza in the 2020-2021 season, starting it early, with exhaustive planning, having the necessary material resources and trying to carry it out in the shortest space of time

Capacity for seeding and spreading of argyrophilic grain disease in a wild-type murine model; comparisons with primary age-related tauopathy

Argyrophilic grain disease (AGD) is a common 4R-tauopathy, causing or contributing to cognitive impairment in the elderly. AGD is characterized neuropathologically by pre-tangles in neurons, dendritic swellings called grains, threads, thorn-shaped astrocytes, and coiled bodies in oligodendrocytes in the limbic system. AGD has a characteristic pattern progressively involving the entorhinal cortex, amygdala, hippocampus, dentate gyrus, presubiculum, subiculum, hypothalamic nuclei, temporal cortex, and neocortex and brainstem, thus suggesting that argyrophilic grain pathology is a natural model of tau propagation. One series of WT mice was unilaterally inoculated in the hippocampus with sarkosyl-insoluble and sarkosyl-soluble fractions from 'pure' AGD at the age of 3 or 7/12 months and killed 3 or 7 months later. Abnormal hyper-phosphorylated tau deposits were found in ipsilateral hippocampal neurons, grains (dots) in the hippocampus, and threads, dots and coiled bodies in the fimbria, as well as the ipsilateral and contralateral corpus callosum. The extension of lesions was wider in animals surviving 7 months compared with those surviving 3 months. Astrocytic inclusions were not observed at any time. Tau deposits were mainly composed of 4Rtau, but also 3Rtau. For comparative purposes, another series of WT mice was inoculated with sarkosyl-insoluble fractions from primary age-related tauopathy (PART), a pure neuronal neurofibrillary tangle 3Rtau + 4Rtau tauopathy involving the deep temporal cortex and limbic system. Abnormal hyper-phosphorylated tau deposits were found in neurons in the ipsilateral hippocampus, coiled bodies and threads in the fimbria, and the ipsilateral and contralateral corpus callosum, which extended with time along the anterior-posterior axis and distant regions such as hypothalamic nuclei and nuclei of the septum when comparing mice surviving 7 months with mice surviving 3 months. Astrocytic inclusions were not observed. Tau deposits were mainly composed of 4Rtau and 3Rtau. These results show the capacity for seeding and spreading of AGD tau and PART tau in the brain of WT mouse, and suggest that characteristics of host tau, in addition to those of inoculated tau, are key to identifying commonalities and differences between human tauopathies and corresponding murine models

Natural Variation in the VELVET Gene bcvel1 Affects Virulence and Light-Dependent Differentiation in Botrytis cinerea

Botrytis cinerea is an aggressive plant pathogen causing gray mold disease on various plant species. In this study, we identified the genetic origin for significantly differing phenotypes of the two sequenced B. cinerea isolates, B05.10 and T4, with regard to light-dependent differentiation, oxalic acid (OA) formation and virulence. By conducting a map-based cloning approach we identified a single nucleotide polymorphism (SNP) in an open reading frame encoding a VELVET gene (bcvel1). The SNP in isolate T4 results in a truncated protein that is predominantly found in the cytosol in contrast to the fulllength protein of isolate B05.10 that accumulates in the nuclei. Deletion of the full-length gene in B05.10 resulted in the T4 phenotype, namely light-independent conidiation, loss of sclerotial development and oxalic acid production, and reduced virulence on several host plants. These findings indicate that the identified SNP represents a loss-of-function mutation of bcvel1. In accordance, the expression of the B05.10 copy in T4 rescued the wild-type/B05.10 phenotype. BcVEL1 is crucial for full virulence as deletion mutants are significantly hampered in killing and decomposing plant tissues. However, the production of the two best known secondary metabolites, the phytotoxins botcinic acid and botrydial, are not affected by the deletion of bcvel1 indicating that other factors are responsible for reduced virulence. Genome-wide expression analyses of B05.10- and Dbcvel1-infected plant material revealed a number of genes differentially expressed in the mutant: while several protease- encoding genes are under-expressed in Dbcvel1 compared to the wild type, the group of over-expressed genes is enriched for genes encoding sugar, amino acid and ammonium transporters and glycoside hydrolases reflecting the response of Dbcvel1 mutants to nutrient starvation conditions

Development of a novel electrochemical coagulant dosing unit for water treatment

The design of new approaches that help to decrease both the environmental impact of industrial activities and the cost of existing water treatment technologies is becoming a key aspect of research. In the present work, an efficient and easy-to-use electrochemical device designed to dose iron coagulants is presented. The proposed device (the Electrochemically-assisted Coagulant – production & dosing Unit, ECU) exhibits an efficient performance in the dosing of coagulants regardless of the ionic conductivity of the water matrixes tested (within the range 100 to 1000 µS cm−1), covering a wide range of potential real surface waters. The behaviour of the ECU device was compared to that of a conventional chemical dosing of iron, and showed better pH (pH ≈ 8 for ECU but < 4 for equivalent chemical dosing) and conductivity (decrease for ECU but increase up to 60% for equivalent chemical dosing) control. Moreover, the ECU unit produced a noticeable amount of Fe2+ ions, due to the limited access of atmospheric oxygen inside the device. The device developed overcomes traditional chemical iron dosing and could be potentially applied in uses different from electrocoagulation, as it is the case of Fenton-related technologies

Pre-disinfection columns to improve the performance of the direct electro-disinfection of highly faecal-polluted surface water

This work presents the design and evaluation of a new concept of pre-disinfection treatment that is especially suited for highly polluted surface water and is based on the combination of coagulation-flocculation, lamellar sedimentation and filtration into a single-column unit, in which the interconnection between treatments is an important part of the overall process. The new system, the so-called PREDICO (PRE-DIsinfection Column) system, was built with low-cost consumables from hardware stores (in order to promote in-house construction of the system in poor countries) and was tested with a mixture of 20% raw wastewater and 80% surface water (in order to simulate an extremely bad situation). The results confirmed that the PREDICO system helps to avoid fouling in later electro-disinfection processes and attains a remarkable degree of disinfection (3–4 log units), which supplements the removal of pathogens attained by the electrolytic cell (more than 4 log units). The most important sizing parameters for the PREDICO system are the surface loading rate (SLR) and the hydraulic residence time (HRT); SLR values under 20 cm min−1 and HRT values over 13.6 min in the PREDICO system are suitable to warrant efficient performance of the system