Short and long-term regulation of autophagy

Autophagy is a conserved catabolic pathway triggered by stress conditions in which portions of the cytoplasm, damage organelles, misfolded proteins and intracellular bacteria are delivered and degraded in the lysosome/vacuoles. Thus, an efficient induction and completion of the process is required to ensure a proper homeostasis of the cell. Autophagy has been considered a cytoplasmic event where the role of the nucleus on the regulation of this pathway was underestimated. However, recent findings elicited the role of histone modifying enzymes on the transcriptional regulation of autophagy-related (ATG) genes. In line with those results, we focused on the role of the two histone modifying enzymes regulating the histone 3 lysine 36 (H3K36) trimethylation, Rph1/KDM4A and Set2/SETD2, on the regulation of autophagy. In paper I, we investigated the function of the histone demethylase, Rph1/KDM4 as a negative regulator of autophagy, whereas in paper II we uncovered the role of the histone methyltransferase, Set2/SETD2, as a positive transcriptional regulator of ATG genes, as the impact on the differential expression of ATG14 splice isoforms that results on the inhibition of the autophagosome-lysosome fusion. Moreover, in paper III, we identify that SETD2 inactivating mutations on clear cell renal cell carcinomas (ccRCC) lead to an aberrant ATG12-containing complexes and accumulation of free ATG12, which is associated with a differential expression of ATG12 isoforms and reduced autophagic flux. Whereas the previous studies report the involvement of histone modifying enzymes and on the short-term regulation of autophagy, we also aimed to decipher the epigenetic mechanism responsible for the long-lasting effects of autophagy. In paper IV, we found that short autophagy stimulus is associated with an upregulation of de novo DNA methyltransferase 3A (DNMT3A) responsible of an increase of DNA methylation on selected ATG genes. Eventually, this epigenetic memory involves a persistent decrease of baseline autophagy. Moreover, in paper V, we uncovered the mechanism upstream on the regulation of DNMT3A expression by ULK3-mediated phosphorylation and activation of GLI1. Overall, these insights bring light on novel mechanisms and signaling pathways controlling short and long-term transcriptional regulation of autophagy by histone modifying enzymes, alternative splicing and DNA methylation

Residual effect of natural and synthetic zinc chelates on zinc in a soil solution of a waterlogged acidic soil. Evolution of the pH and redox potential.

Zinc chelates have been widely used to correct deficiencies in this micronutrient in different soil types and under different moisture conditions. The aging of the metal in soil could cause a change in its availability. Over time the most labile forms of Zn could decrease in activity and extractability and change to more stable forms. Various soil parameters, such as redox conditions, time, soil type and moisture conditions, affect the aging process and modify the solubility of the metal. In general, redox conditions influence pH and also the chemical forms dissolved in the soil solution. Soil pH also affects Zn solubility; at high pH values, most of the Zn is present in forms that are not bioavailable to plants. The objective of this study was to determine the changes in Zn over time in a soil solution in a waterlogged acidic soil to which synthetic and natural chelates were applie

IPSC differentiation into ependymal progenitors to treat ventricular damage during hydrocephalus

Introduction: During both obstructive congenital hydrocephalus and post-hemorrhagic hydrocephalus additional pathological events are intimately associated with their ethiology: a) a detrimental inflammatory response; b) severe damage of the underlying periventricular nervous tissue, including white matter, and c). Therapeutic approaches have been directed to overcome a) and b), however recovery of damaged neuroepithelium/ependyma is, in our present, an important therapeutic gap. Methods: Human and mouse induced pluripotent stem cells (iPSC) have been artificially differented into ependymal progenitors. Intracerebroventricular (ICV) injections of iPCS are performed ex vivo and in vivo in the damaged ventricular wall. Their integration and differentiation has been studied by immunohistochemistry and histopathological analysis. Results: Mice and human ependymal progenitors are able to integrate and differentiate into ependyma in damaged ventricular wall. Stage of ependymal differentiation by the time of the injection defined different degrees of integration. Conclusions: IPSC appear to be a good ependymal progenitor source with no ethical controversy associated.RyC 2014-16980 Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Concrete Swelling in Existing Dams

Several chemical reactions are able to produce swelling of concrete for decades after its initial curing, a problem that affects a considerable number of concrete dams around the world. Principia has had several contracts to study this problem in recent years, which have required reviewing the state-of-the-art, adopting appropriate mathematical descriptions, programming them into user routines in Abaqus, determining model parameters on the basis of some parts of the dams’ monitored histories, ensuring reliability using some other parts, and finally predicting the future evolution of the dams and their safety margins. The paper describes some of the above experience, including the programming of sophisticated non-isotropic swelling models, that must be compatible with cracking and other nonlinearities involved in concrete behaviour. The applications concentrate on two specific cases, an archgravity dam and a double-curvature arch dam, both with a long history of concrete swelling and which, interestingly, entailed different degrees of success in the modelling effort

Carex elata All. ssp elata, new for Algarve in the lower Guadiana basin

Carex elata All. ssp elata novedad para el Algarve en la cuenca del rio Guadian

In-memory application-level checkpoint-based migration for MPI programs

This is a post-peer-review, pre-copyedit version of an article published in Journal of Supercomputing. The final authenticated version is available online at: https://doi.org/10.1007/s11227-014-1120-2[Abstract] Process migration provides many benefits for parallel environments including dynamic load balancing, data access locality or fault tolerance. This paper describes an in-memory application-level checkpoint-based migration solution for MPI codes that uses the Hierarchical Data Format 5 (HDF5) to write the checkpoint files. The main features of the proposed solution are transparency for the user, achieved through the use of CPPC (ComPiler for Portable Checkpointing); portability, as the application-level approach makes the solution adequate for any MPI implementation and operating system, and the use of the HDF5 file format enables the restart on different architectures; and high performance, by saving the checkpoint files to memory instead of to disk through the use of the HDF5 in-memory files. Experimental results prove that the in-memory approach reduces significantly the I/O cost of the migration process.Ministerio de Ciencia e Innovación; TIN2010-16735Galicia. Consellería de Economía e Industria; 10PXIB105180P

Failure Avoidance in MPI Applications Using an Application-Level Approach

[Abstract] Execution times of large-scale computational science and engineering parallel applications are usually longer than the mean-time-between-failures. For this reason, hardware failures must be tolerated by the applications to ensure that not all computation done is lost on machine failures. Checkpointing and rollback recovery is one of the most popular techniques to provide fault tolerance support to parallel applications. However, when a failure occurs, most checkpointing mechanisms require a complete restart of the parallel application from the last checkpoint. New advances in the prediction of hardware failures have led to the development of proactive process migration approaches, where tasks are migrated in a preventive way when node failures are anticipated, avoiding the restart of the whole application. The work presented in this paper extends an application-level checkpointing framework to proactively migrate message passing interface (MPI) processes when impending failures are notified, without having to restart the entire application. The main features of the proposed solution are: low overhead in failure-free executions, avoiding the checkpoint dumping associated to rolling back strategies; low overhead at migration time, by means of the design of a light and asynchronous protocol to achieve a consistent global state; transparency for the user, thanks to the use of a compiler tool and a runtime library and portability, as it is not locked into a particular architecture, operating system or MPI implementation.Ministerio de Ciencia e Innovación; TIN2010-16735Galicia. Consellería de Economía e Industria; 10PXIB105180P

Reducing the overhead of an MPI application-level migration approach

[Abstract] Process migration provides many benefits for parallel environments including dynamic load balance, data access locality, or fault tolerance. This work proposes a solution that reduces the memory and I/O overhead in an application-level checkpoint-based migration approach. The proposal splits the checkpoint files in order to overlap the writing of the state in the terminating processes with the read and restarting operation in the newly spawned processes. It has been tested using the MPI NAS Parallel Benchmarks, showing encouraging results, both in terms of memory consumption and I/O migration times.Ministerio de Economía y Competitividad; TIN2013-42148-PGalicia. Consellería de Cultura, Educación e Ordenación Universitaria; GRC2013/05

Aportes de las prácticas educativas implementadas por madres líderes al reconocimiento de sujetos sociales

El presente artículo, es resultado del trabajo investigativo desarrollado con madres líderes del Programa Más Familias en Acción- Medellín Solidaria, pertenecientes a la comuna 13- San Javier de la ciudad de Medellín. El cual, tuvo por objetivo realizar un acercamiento a los significados construidos por éstas frente a su rol y como lo anterior contribuye a la superación de la pobreza extrema, posibilitando así, la generación de reflexiones que permitieran consolidar y afianzar cada vez más el acompañamiento que se viene realizando con cada una de ellas. Lo anterior, permitió identificar como el liderazgo construido por las mujeres está relacionado con su capacidad para creer, dirigirse, auto-liderarse y ser agentes de su propio desarrollo. Simultáneamente, estos aspectos, les permiten ir confluyendo procesos organizativos y comunitarios en sus territorios, buscando transmitir y transformar desde las necesidades evidenciadas en sus propios hogares, pero también desde el interés por construir maneras de encuentro alrededor de espacios que son comunes y de descubrir potencialidades en dicho camino

Aplicación práctica de un assesment center

Tesis (Maestría en Ciencias de la Administración con Especialidad en Relaciones Industriales) UANLUANLhttp://www.uanl.mx