The Effect of the Environmental Temperature on the Adaptation to Host in the Zoonotic Pathogen Vibrio vulnificus

Vibrio vulnificus is a zoonotic pathogen that lives in temperate, tropical and subtropical aquatic ecosystems whose geographical distribution is expanding due to global warming. The species is genetically variable and only the strains that belong to the zoonotic clonal-complex can cause vibriosis in both humans and fish (being its main host the eel). Interestingly, the severity of the vibriosis in the eel and the human depends largely on the water temperature (highly virulent at 28°C, avirulent at 20°C or below) and on the iron content in the blood, respectively. The objective of this work was to unravel the role of temperature in the adaptation to the host through a transcriptomic and phenotypic approach. To this end, we obtained the transcriptome of a zoonotic strain grown in a minimum medium (CM9) at 20, 25, 28, and 37°C, and confirmed the transcriptomic results by RT-qPCR and phenotypic tests. In addition, we compared the temperature stimulon with those previously obtained for iron and serum (from eel and human, respectively). Our results suggest that warm temperatures activate adaptive traits that would prepare the bacteria for host colonization (metabolism, motility, chemotaxis, and the protease activity) and fish septicemia (iron-uptake from transferrin and production of O -antigen of high molecular weight) in a generalized manner, while environmental iron controls the expression of a host-adapted virulent phenotype (toxins and the production of a protective envelope). Finally, our results confirm that beyond the effect of temperature on the V. vulnificus distribution in the environment, it also has an effect on the infectious capability of this pathogen that must be taken into account to predict the real risk of V. vulnificus infection caused by global warming

Desarrollo de bioherramientas para la remediación de agua y suelos contaminados con cobre

Motivación: La contaminación por cobre es uno de los principales problemas mediambientales en Andalucía. Diversos estudios señalan el estuario conjunto de los ríos Tinto y Odiel como uno de los ecosistemas más contaminados del mundo (Sáinz et al., 2004). El objetivo de este trabajo es diseñar bioherramientas útiles para la descontaminación de suelos y aguas residuales contaminadas con cobre. Métodos: Se ha caracterizado un operón copABCD de resistencia a cobre de la cepa Pseudomonas sp. Az13 , aislada de la rizosfera de leguminosas que crecían de forma espontánea en la zona de Aznalcóllar afectada por el vertido tóxico de 1998 (Dary et al., 2010). Diversos genes de dicho operón se han transferido a rizobios y a plantas, con el propósito de aumentar su resistencia y/o capacidad de acumulación de Cu. Resultados: Con el objetivo de mejorar la respuesta de la simbiosis Sinorhizobium medicae-Medicago truncatula en suelos contaminados con Cu (lo que permitiría su enriquecimiento en nitrógeno), se obtuvo una cepa de S. medicae modificada genéticamente que expresaba parte del operón resistencia a Cu (genes copAB). Las plantas inoculadas con esta bacteria tienen parámetros de crecimiento y nodulación similares en sustratos contaminados con 300 µM de Cu y sin contaminar. El microsimbionte obtenido por ingeniería genética parece dirigir la acumulación de Cu de forma preferente al nódulo. Por otro lado, el gen copC (cuyo producto es capaz de unir dos átomos de Cu) se introdujo en plantas de Arabidopsis thaliana y en raíces pilosas de tabaco. En plantas transgénicas que expresaban dicho gen se incrementó hasta 5 veces su capacidad de acumulación de Cu, si bien su tolerancia al metal disminuía (Rodríguez-Llorente et al., 2012). Por su parte, las raíces transgénicas que expresan el mismo gen se han mostrado como el sistema vivo capaz de acumular los niveles de Cu más altos descritos hasta la fecha, alcanzando valores de 30.000 ppm, sin mostrar síntomas aparentes de toxicidad. Conclusiones: La cepa de S. medicae que expresa los genes copAB tiene un gran potencial como herramienta para la fitoestabilización de Cu utilizando plantas del género Medicago. La expresión de copC tanto en plantas como en raíces permite aumentar su capacidad de acumulación de Cu, haciendo esta herramienta útil en biorremediación de suelos y aguas contaminadas por Cu

(16) Psyche: A mesosiderite-like asteroid?

Asteroid (16) Psyche is the target of the NASA Psyche mission. It is considered one of the few main-belt bodies that could be an exposed proto-planetary metallic core and that would thus be related to iron meteorites. Such an association is however challenged by both its near- and mid-infrared spectral properties and the reported estimates of its density. Here, we aim to refine the density of (16) Psyche to set further constraints on its bulk composition and determine its potential meteoritic analog. We observed (16) Psyche with ESO VLT/SPHERE/ZIMPOL as part of our large program (ID 199.C-0074). We used the high angular resolution of these observations to refine Psyche's three-dimensional (3D) shape model and subsequently its density when combined with the most recent mass estimates. In addition, we searched for potential companions around the asteroid. We derived a bulk density of 3.99\,$\pm$\,0.26\,g$\cdot$cm$^{-3}$ for Psyche. While such density is incompatible at the 3-sigma level with any iron meteorites ($\sim$7.8\,g$\cdot$cm$^{-3}$), it appears fully consistent with that of stony-iron meteorites such as mesosiderites (density $\sim$4.25\,$\cdot$cm$^{-3}$). In addition, we found no satellite in our images and set an upper limit on the diameter of any non-detected satellite of 1460\,$\pm$\,200}\,m at 150\,km from Psyche (0.2\%\,$\times$\,R$_{Hill}$, the Hill radius) and 800\,$\pm$\,200\,m at 2,000\,km (3\%\,$\times$\,$R_{Hill}$). Considering that the visible and near-infrared spectral properties of mesosiderites are similar to those of Psyche, there is merit to a long-published initial hypothesis that Psyche could be a plausible candidate parent body for mesosiderites.Comment: 16 page

Conocimientos, actitudes y prácticas de alimentación saludable e índice de masa corporal en adolescentes peruanos: Un estudio transversal

Introduction: Overweight and obesity constitute one of the main health concerns in adolescents. Having a sufficient level of knowledge represents an option to reduce risks. The objective of the study was to evaluate the correlation between knowledge, attitudes and practices and body mass index (BMI) in Peruvian adolescents. Material and methods: A non-experimental cross-sectional study was carried out in 242 adolescents aged 11 to 18 years. To determine knowledge, attitudes and practices on healthy eating, a questionnaire was developed according to the criteria proposed by the Food and Agriculture Organization of the United Nations (FAO). In addition, the body mass index for age (BMI/Age) was calculated according to the recommendations of the World Health Organization (WHO). Data analysis was done using IBM SPSS version 24 statistical software.Results: The proportion of women who demonstrated a high level of knowledge, favorable attitudes and adequate practices, was higher in relation to men (76.5% vs. 75.0%), (75.5% vs. 70.7%) and 72.5% vs. 67.9%, respectively. However, there were no significant differences (p> 0.05). The proportion of men who were overweight and obese was 25.7% and 12.1%, respectively. Finally, a statistically significant positive correlation was found between BMI / Age with the level of knowledge, attitudes and practices about healthy eating in adolescents (ρ = 0.137, p = 0.033), (ρ = 0.160, p = 0.013) and (ρ = 0.133, p = 0.039), respectively.Conclusions: The findings suggest that adolescents, especially boys, should be the focus of integrated nutritional intervention programs, with the purpose of reducing the prevalence of overweight and obesity.Introducción: El sobrepeso y la obesidad constituyen una de las principales preocupaciones sanitarias en los adolescentes. Tener los conocimientos suficientes, representa una opción para disminuir los riesgos. El objetivo del estudio fue evaluar la correlación entre conocimientos, actitudes y prácticas e índice de masa corporal (IMC) en adolescentes peruanos.Material y métodos: Se realizó un estudio no experimental de tipo transversal en 242 adolescentes de edades comprendidas entre 11 a 18 años. Para determinar los conocimientos, actitudes y prácticas sobre alimentación saludable, se desarrolló un cuestionario según los criterios propuestos por la Organización de las Naciones Unidas para la Agricultura y Alimentación (FAO, por sus siglas en inglés). Además, se calculó el índice de masa corporal para la edad (IMC/Edad) de acuerdo con las recomendaciones de la Organización Mundial de Salud (OMS). El análisis de los datos se hizo mediante el software estadístico IBM SPSS versión 24. Resultados:La proporción de mujeres que demostraron conocimientos altos, actitudes favorables y prácticas adecuadas, fue superior en relación con los varones (76,5 % vs. 75,0%), (75,5% vs. 70,7%) y 72,5% vs. 67,9%, respectivamente. Sin embargo, no hubo diferencias significativas (p>0,05). La proporción de varones que presentaron sobrepeso y obesidad fue 25,7% y 12,1%, respectivamente. Finalmente, se encontró correlación positiva estadísticamente significativa entre el IMC/Edad con los conocimiento, actitudes y prácticas acerca de alimentación saludable en los adolescentes (ρ=0,137; p=0,033), (ρ=0,160; p=0,013) y (ρ=0,133; p=0,039), respectivamente.Conclusiones: Los hallazgos sugieren que los adolescentes, especialmente los varones, deben ser el foco de programas de intervención nutricional integrados, con el propósito de disminuir la prevalencia de sobrepeso y obesidad

Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation

Several psychiatric, neurologic and neurodegenerative disorders present increased brain ventricles volume, being hydrocephalus the disease with the major manifestation of ventriculomegaly caused by the accumulation of high amounts of cerebrospinal fluid (CSF). The molecules and pathomechanisms underlying cerebral ventricular enlargement are widely unknown. Kinase D interacting substrate of 220 kDa (KIDINS220) gene has been recently associated with schizophrenia and with a novel syndrome characterized by spastic paraplegia, intellectual disability, nystagmus and obesity (SINO syndrome), diseases frequently occurring with ventriculomegaly. Here we show that Kidins220, a transmembrane protein effector of various key neuronal signalling pathways, is a critical regulator of CSF homeostasis. We observe that both KIDINS220 and the water channel aquaporin-4 (AQP4) are markedly downregulated at the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. We also find that Kidins220 deficient mice develop ventriculomegaly accompanied by water dyshomeostasis and loss of AQP4 in the brain ventricular ependymal layer and astrocytes. Kidins220 is a known cargo of the SNX27-retromer, a complex that redirects endocytosed plasma membrane proteins (cargos) back to the cell surface, thus avoiding their targeting to lysosomes for degradation. Mechanistically, we show that AQP4 is a novel cargo of the SNX27-retromer and that Kidins220 deficiency promotes a striking and unexpected downregulation of the SNX27-retromer that results in AQP4 lysosomal degradation. Accordingly, SNX27 silencing decreases AQP4 levels in wild-type astrocytes whereas SNX27 overexpression restores AQP4 content in Kidins220 deficient astrocytes. Together our data suggest that the KIDINS220-SNX27-retromer-AQP4 pathway is involved in human ventriculomegaly and open novel therapeutic perspectives

Mesenchymal Stromal Cell-Based Therapies as Promising Treatments for Muscle Regeneration After Snakebite Envenoming

Snakebite envenoming is a global neglected disease with an incidence of up to 2.7 million new cases every year. Although antivenoms are so-far the most effective treatment to reverse the acute systemic effects induced by snakebite envenoming, they have a limited therapeutic potential, being unable to completely neutralize the local venom effects. Local damage, such as dermonecrosis and myonecrosis, can lead to permanent sequelae with physical, social, and psychological implications. The strong inflammatory process induced by snake venoms is associated with poor tissue regeneration, in particular the lack of or reduced skeletal muscle regeneration. Mesenchymal stromal cells (MSCs)-based therapies have shown both anti-inflammatory and pro-regenerative properties. We postulate that using allogeneic MSCs or their cell-free products can induce skeletal muscle regeneration in snakebite victims, improving all the three steps of the skeletal muscle regeneration process, mainly by anti-inflammatory activity, paracrine effects, neovascularization induction, and inhibition of tissue damage, instrumental for microenvironment remodeling and regeneration. Since snakebite envenoming occurs mainly in areas with poor healthcare, we enlist the principles and potential of MSCs-based therapies and discuss regulatory issues, good manufacturing practices, transportation, storage, and related-procedures that could allow the administration of these therapies, looking forward to a safe and cost-effective treatment for a so far unsolved and neglected health problem.The authors are supported by the University Pablo de Olavide (Sevilla), the University Miguel Hernández (Elche, Alicante), National University Toribio Rodriguez de Mendoza (Chachapoyas, Peru) Grants: Contrato N° 09-2019-FONDECYT-BM-INC.INV to JRT, JDRF 2-SRA-2019-837-S-B and AVI-GVA COVID-19-68 to BS, Fundación Andaluza de I+D and Al-Andalus Biopharma Project (FAID-2018-1). The authors CC-O, CG-D, and TCSA were supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq) (Process: 406163/2018-9), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil - CAPES (Program COFECUB Process: 88881.191812/2018-01) and by Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil (FAPEMIG)

El almacenamiento en el conjunto amurallado Xllangchic An (Ex palacio Uhle), complejo arqueológico Chan Chan, Trujillo, Perú

El sector de depósitos en el conjunto amurallado Xllangchic An (Ex palacio Uhle), Chan Chan, está compuesto por patios, plazas, audiencias, depósitos y vías de circulación, que en su conjunto crean un contexto de almacenamiento. Apartir de este rasgo surge algunas interrogantes: ¿Qué bienes se almacenaban?, ¿Cómo eran los depósitos?, ¿Cuáles fueron las necesidades que originaron el almacenamiento? El almacenamiento de bienes es una actividad realizada desde tiempos muy tempranos y para el Intermedio Tardío no es una excepción; siendo la geografía, el medio ambiente y la carga cultural factores transcendentales en las maneras de realizar esta actividad, de tal forma que en este conjunto amurallado temprano se estima que sus características particulares lo podrían diferenciar de otros sitios prehispánicos.The sector deposits in the walled complex Xllangchic An (ex Uhle palace), is composed of various structures (patios, plazas, hearings, deposits and roads) that when intertwine creates a context storage; but from this trait some ques tions are arise: What goods were stored?, Who controlled the storage?, How were the deposits?, How was the managed this sector?, What was the purpose of this activity? The storage of goods is an activity realized since very early periods and the late intermediate is not the exception, but the geography, environment and cultural load plays a transcendental role in the ways of realized this same activity, so in this early walled complex is estimated to record particular characteristics that differ it from other pre-Hispanic sites

A multi-stakeholder multicriteria decision analysis for the reimbursement of orphan drugs (FinMHU-MCDA study)

Background: Patient access to orphan medicinal products (OMPs) is limited and varies between countries, reimbursement decisions on OMPs are complex, and there is a need for more transparent processes to know which criteria should be considered to inform these decisions. This study aimed to determine the most relevant criteria for the reimbursement of OMPs in Spain, from a multi-stakeholder perspective, and using multicriteria decision analysis (MCDA). Methods: An MCDA was developed in 3 phases and included 28 stakeholders closely related to the field of rare diseases (6 physicians, 5 hospital pharmacists, 7 health economists, 4 patient representatives and 6 members from national and regional health authorities). Initially [phase A], a bibliographic review was conducted to identify the potential reimbursement criteria. Then, a reduced advisory board (8 members) proposed, selected, and defined the final list of criteria that could be relevant for reimbursement. A discrete choice experiment (DCE) [phase B] was developed to determine the relevance and relative importance weight of such criteria according to the stakeholders’ preferences by choosing between pairs of hypothetical financing scenarios. A multinomial logit model was fitted to analyze the DCE responses. Finally [phase C], the advisory board review the results using a deliberative process. Results: Thirteen criteria were selected, related to 4 dimensions: patient population, disease, treatment, and economic evaluation. Nine criteria were deemed relevant for decision-making and associated with a higher relative importance: Health-related quality of life (HRQL) (23.53%), treatment efficacy (14.64%), availability of treatment alternatives (13.51%), disease severity (12.62%), avoided costs (11.21%), age of target population (7.75%), safety (seriousness of adverse events) (4.72%), quality of evidence (3.82%) and size of target population (3.12%). The remaining criteria had a < 3% relative importance: economic burden of disease (2.50%), cost of treatment (1.73%), cost-effectiveness (0.83%) and safety (frequency of adverse events) (0.03%). Conclusion: The reimbursement of OMPs in Spain should be determined by its effect on patient’s HRQL, the extent of its therapeutic benefit from efficacy and the availability of other therapeutic options. Furthermore, the severity of the rare disease should also influence the decision along with the potential of the treatment to avoid associated costs