HUWE1 E3 ligase promotes PINK1/PARKINindependent mitophagy by regulating AMBRA1 activation via IKKa

The selective removal of undesired or damaged mitochondria by autophagy, known as mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion, neurodegeneration and ageing. The pro-autophagic molecule AMBRA1 (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKα are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Mitochondrial control of cell death induced by hyperosmotic stress

HeLa and HCT116 cells respond differentially to sorbitol, an osmolyte able to induce hypertonic stress. In these models, sorbitol promoted the phenotypic manifestations of early apoptosis followed by complete loss of viability in a time-, dose-, and cell type-specific fashion, by eliciting distinct yet partially overlapping molecular pathways. In HCT116 but not in HeLa cells, sorbitol caused the mitochondrial release of the caspase-independent death effector AIF, whereas in both cell lines cytochrome c was retained in mitochondria. Despite cytochrome c retention, HeLa cells exhibited the progressive activation of caspase-3, presumably due to the prior activation of caspase-8. Accordingly, caspase inhibition prevented sorbitol-induced killing in HeLa, but only partially in HCT116 cells. Both the knock-out of Bax in HCT116 cells and the knock-down of Bax in A549 cells by RNA interference reduced the AIF release and/or the mitochondrial alterations. While the knock-down of Bcl-2/Bcl-XL sensitized to sorbitol-induced killing, overexpression of a Bcl-2 variant that specifically localizes to mitochondria (but not of the wild-type nor of a endoplasmic reticulum-targeted form) strongly inhibited sorbitol effects. Thus, hyperosmotic stress kills cells by triggering different molecular pathways, which converge at mitochondria where pro- and anti-apoptotic members of the Bcl-2 family exert their control

Customization, extension and reuse of outdated hydrogeological software

Each scientist is specialized in his or her field of research and in the tools that he or she uses during the research in a specified site. Thus, he or she is the most suitable person for improving the tools by overcoming their limitations to realize faster and higher quality analysis. However, most scientists are not software developers. Hence, it is necessary to provide them with an easy approach that enables non-software developers to improve and customize their tools. This paper presents an approach for easily improving and customizing any hydrogeological software. It is the result of experiences with updating several interdisciplinary case studies. The main insights of this approachhave been demonstrated using four examples: MIX (FORTRAN-based), BrineMIX (C++-based), EasyQuim and EasyBal (both spreadsheet-based). The improved software has been proven to be a better tool for enhanced analysis by substantially reducing the computation time and the tedious processing of the input and output data files

Caracterización “In situ” de genotipos silvestres y cultivados de mora Rubus Spp en el municipio de Pasto

Sixty five individuals of blackberry (Rubus spp), located in nine places in the municipality of Pasto, were morphologically characterized in situ. The evaluated samples corresponded to the species: Rubus urticifolius, R. glaucus, R bogotensis, R. macrocarpus, R. niveus, R. robustus and a material that its taxonomic classification was not possible. The 20% of genotypes were located in the place of Buesaquillo, there was greater diversity of genus, followed by the places of Encano and Obonuco with a 12.31%, respectively. The Principal Component Analysis (PCA) and the Multiple Correspondence Analysis (MCA) allowed characterize samples and form groups by means of the method of hierarchical classification. Atotal of three factors helped explain the 79.96% of the variability expressed by qualitative variables, the first factor that explains 40.03% of the variability was the most important. The classification analysis conforms three groups, and characteristics with more contribution to the variability were the corolla color, stem pubescent, fruit form, shape leaflet and form of stipules. The PCA, the first three components explained the 71.16% of the total variation, was formed five groups; in the first group, the genotypes have important variables as the number of infructescenses per cluster and number of clusters per stem. The fourth an fiveth groups presented the greater weight and size infructescences of the populationSecaracterizaron“insitu”morfológicamente65individuosdemora(Rubusspp) localizadosen nueve corregimientos del municipio de Pasto. Las muestras evaluadas correspondierona las especies: Rubus urticifolius, R. glaucus, R. bogotensis, R. macrocarpus, R. niveus,R. robustus y un material que no fue posible su clasificación taxonómica. El 20% de losgenotipos se localizaron en el corregimiento de Buesaquillo, observándose una mayordiversidad del género, seguido por los corregimientos del Encano y Obonuco con un12.31%, respectivamente. ElAnálisis de CorrespondenciasMúltiples (ACM) y elAnálisisde Componentes Principales (ACP) permitieron caracterizar las muestras y formar gruposmediante el método de clasificación jerárquica. En el ACM, un total de tres factorespermitieron explicar el 79.96% de la variabilidad expresada por las variables cualitativas;sobresalió el primer factor que explica el 40.03% de la variabilidad. El análisis declasificación conformó tres grupos, y las características con mayor aporte a la variabilidadfueron color de corola, pubescencia de tallo, forma de infrutescencia, forma de tallo yforma de estípulas. En el ACP, los tres primeros componentes explicaron el 71.16% de lavariación total, conformándose cinco grupos; sobresalió el primero por presentar mayornúmero de infrutescencias por racimo y mayor número de racimos por tallo. Los gruposcuatro y cinco presentaron las infrutescencias de mayor peso y tamaño. 

Joining participatory approach and spatially-based modelling tools for groundwater resource management.

Although a lot of science has been produced on Water Resource Management (WRM) in the Information and Communication Technology (ICT) sector, WRM is still poorly addressed via scientific means. Some reasons for this may be: the underrated importance given to this topic at political and decision-making level; the low-capacity of the research environment to transfer results; and missing numerical modelling capacities at agencies and governing authorities. ICT may provide tools for water planning and management, as discussed within the ICT4WATER cluster initiative. Among these, GIS-integrated numerical modeling is a robust method to represent hydrological systems and to provide answers to problems of protection of groundwater resources. Because these tools require a high level of knowledge pertaining to various disciplines, they are often disregarded as complex “tricky games” providing unrealistic results. This is a barrier to the uptake of technologies for water management. To overcome this issue, the application of ICT tools has been combined with an innovative participatory approach, and large capacity building activities, in the framework of the H2020 FREEWAT project (FREE and open source software tools for WATer resource management; www.freewat.eu). The major result of the project consists in an open source and public domain, QGIS-integrated modeling platform for promoting WRM. FREEWAT capabilities have been demonstrated at 14 case studies in EU and non-EU Countries, where the effectiveness of few measures foreseen in River Basin Management Plans for achieving good status of water bodies was tested. At each case study, a Focus Group (FG) participated by local stakeholders (e.g., river basin authorities, research institutions, environmental protection agencies, environmental associations) was formed and seven meetings were organized. During these meetings, the objective of each case study, the methodology to be adopted, including definition of the conceptual model and of data needed, were discussed. The FG also took decisions on scenarios to be simulated for testing the feasibility of the foreseen measures. FGs aimed at demonstrating that WRM may be performed with open source and public domain software and participants’ perception on using ICT tools for WRM was discussed. Some of the implemented models are now being used for operational purposes: Vrbansky plato (Slovenia), where FREEWAT is used to monitor remediation of heating oil spillage and the water supply company intends to maintain and use developed groundwater flow model for managed groundwater recharge with induced riverbank filtration; the Bremerhaven case study (Germany), where the local water authority intends to use the developed groundwater flow model for predictions; the Scarlino-Follonica case study (Italy), where the model will be used by the regional authority to manage private groundwater remediation projects in a large industrial contaminated site; the Gozo case study (Malta), where the model is being developed to support the assessment of good groundwater quantitative status as part of the implementation of the Water Framework Directive

Clozapine Augments Delta, Theta, and Right Frontal EEG Alpha Power in Schizophrenic Patients

Objective. To explore the Quantitative EEG (QEEG) effects of established clozapine therapy regimes compared to those of previous ineffective antipsychotic regimes among 64 chronic (DSM-IV) schizophrenic patients. Methods. Data from 20 EEG channels referenced to linked ears were collected before and during maintenance clozapine therapy (mean duration 1.4 years). Absolute power was calculated in six frequency bands: delta (0.4–3.6 Hz), theta (4.2–7.8 Hz), alpha (8.2–11.8 Hz), beta1 (12.2–15.8 Hz), beta2 (16.2–19.8 Hz), and beta3 (20.2–23.8 Hz). Results. Clozapine augments power globally in the delta and theta bands, but this effect is more pronounced over frontal areas. Beta3 power was reduced. Alpha showed a frontal increase, more pronounced in the right, coupled with a posterior decrease with no net change in overall power. Conclusion. The demonstration of a significant clozapine-induced alpha topographic shift frontally and to the right is a novel discovery that may serve to encourage further investigations of subcortical structures in attempts to better understand the diverse aetiologies and optimal treatments of the schizophrenias.</jats:p

Prácticas sostenibles para la conservación de suelos en sistemas productivos ganaderos de trópico alto

Livestock in Colombia is carried out in large areas, in 2022 about 633.841 farms and 29.301.392 animals were reported. Traditional systems with low technology generate a negative impact on soils, affecting physical and chemical conditions. Therefore, it is important to implement management alternatives that guarantee sustainability and profitability. Through an alliance between FAO and AGROSAVIA, the effect of the three systems was evaluated during two periods of time: silvopastoral with an arrangement in a strip-grazing pasture (SPS), silvopastoral with grasslands renewal (GRS), and traditional grazing on grasslands (TS), on physical and chemical properties of the soil. A split-plot experimental design was used, a two-way multivariate analysis of variance (two-way MANOVA) was applied (productive system and sampling time), and an analysis of variance (ANOVA) with a 5% Tukey\u27s test. Using the ArcGIS® Pro 2.9.0 (ESRI®) software, the results of the previously georeferenced samplings were interpolated, using the inverse distance weighting technique (IDW) and the Moran\u27s Index, to verify the type of distribution of the variables influenced by the factors. The MANOVA indicated that individual factors had a significant effect on electrical conductivity (EC), Na, and P, and interaction of factors on Fe, Cu, Mn, particle density (PD), and moisture retention (MR). On the other hand, through the ANOVA, significant differences were identified, registering higher EC, P, MR, and lower PD in SPS, higher content of Fe and Mn in GRS and Cu in TS.La ganadería bovina en Colombia se lleva a cabo en grandes extensiones, en 2022 se reportaron cerca de 633.841 predios y 29.301.392 animales. Los sistemas tradicionales con baja implementación tecnológica generan un impacto negativo sobre los suelos, afectando sus propiedades físicas y químicas. Por lo tanto, es importante implementar alternativas de manejo que garanticen sostenibilidad y rentabilidad. En este sentido, mediante una alianza entre FAO y AGROSAVIA, se evaluó durante dos periodos de tiempo el efecto de tres sistemas: silvopastoril en arreglo en franjas de pastoreo (SSP), silvopastoril con renovación de praderas (SRP) y tradicional con praderas de pastoreo (ST), sobre las propiedades físicas y químicas del suelo. Se utilizó un diseño experimental de parcelas divididas, se aplicó un análisis de varianza multivariado (MANOVA) de dos vías (sistema productivo y tiempo de muestreo) y un análisis de varianza (ANOVA) con prueba Tukey al 5%. Mediante el software ArcGIS® Pro 2.9.0 (ESRI®), se interpolaron los resultados de los muestreos previamente georreferenciados, utilizando la técnica de distancia inversa ponderada (IDW) e Índice de Moran, para verificar el tipo de distribución de las variables influenciadas por los factores. El MANOVA indicó que los factores individuales incidieron significativamente sobre conductividad eléctrica (CE), Na y P, e interacción de factores sobre Fe, Cu, Mn, densidad real (DR) y retención de humedad (RH). Por su parte, mediante el ANOVA se identificaron diferencias significativas, registrándose mayor CE, P, RH y menor DR en SSP; mayor contenido de Fe y Mn en SRP y Cu en ST

Psychometric assessment and nursing intervention in fear of COVID-19. Project Crimea

Ramírez-Coronel, A.A., Martínez-Suárez, P.C., Pogyo-Morocho, G.L., Estrella-González, M.Á., Mesa-Cano, I.C., Minchala-Urgilés, R.E., Yambay-Bautista, X.R., Torres-Criollo, L.M., González-Pando, D., Sepulveda-Aravena, J., Romero-Sacoto, L.A., González-León, F.M., Ochoa-Yumbla, C.C., Latacela, G.A., Abad-Martínez, N.I