Ectopic application of the repressive histone modification H3K9me2 establishes post-zygotic reproductive isolation in Arabidopsis thaliana

Hybrid seed lethality as a consequence of interspecies or interploidy hybridizations is a major mechanism of reproductive isolation in plants. This mechanism is manifested in the endosperm, a dosage-sensitive tissue supporting embryo growth. Deregulated expression of imprinted genes such as ADMETOS (ADM) underpin the interploidy hybridization barrier in Arabidopsis thaliana; however, the mechanisms of their action remained unknown. In this study, we show that ADM interacts with the AT hook domain protein AHL10 and the SET domain-containing SU (VAR) 3-9 homolog SUVH9 and ectopically recruits the heterochromatic mark H3K9me2 to AT-rich transposable elements (TEs), causing deregulated expression of neighboring genes. Several hybrid incompatibility genes identified in Drosophila encode for dosage-sensitive heterochromatin-interacting proteins, which has led to the suggestion that hybrid incompatibilities evolve as a consequence of interspecies divergence of selfish DNA elements and their regulation. Our data show that imbalance of dosage-sensitive chromatin regulators underpins the barrier to interploidy hybridization in Arabidopsis, suggesting that reproductive isolation as a consequence of epigenetic regulation of TEs is a conserved feature in animals and plants

Sofosbuvir, Velpatasvir, and Voxilaprevir for Treatment of Recurrent Hepatitis C Virus Infection After Liver Transplantation.

There are limited data on direct-acting antiviral (DAA) treatment options for previously treated patients with recurrent genotype 3 (GT3) hepatitis C virus (HCV) after liver transplantation. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is currently approved for treatment of HCV in patients with prior treatment with DAAs. We report the first published experience using SOF/VEL/VOX after liver transplantation for a DAA-experienced patient with severe hepatitis due to early recurrent GT3 HCV. The patient was treated with SOF/VEL/VOX that was extended to a total duration of 16 weeks and was intensified with ribavirin (RBV) starting at week 8 due to persistent viremia during treatment. Sustained virologic response at 12 weeks (SVR12) after treatment completion was achieved. SOF/VEL/VOX was well tolerated, and immediate drug-drug interaction (DDI) with tacrolimus (TAC) was not evident. Due to improvement in liver metabolic function with increasing TAC clearance, TAC dose adjustment was required throughout the treatment course

Molecular phenotyping of the pal1 and pal2 mutants of Arabidopsis thaliana reveals far-reaching consequences on phenylpropanoid, amino acid, and carbohydrate metabolism

The first enzyme of the phenylpropanoid pathway, Phe ammonia-lyase (PAL), is encoded by four genes in Arabidopsis thaliana. Whereas PAL function is well established in various plants, an insight into the functional significance of individual gene family members is lacking. We show that in the absence of clear phenotypic alterations in the Arabidopsis pall and pal2 single mutants and with limited phenotypic alterations in the pall pal2 double mutant, significant modifications occur in the transcriptome and metabolome of the pal mutants. The disruption of PAL led to transcriptomic adaptation of components of the phenylpropanoid biosynthesis, carbohydrate metabolism, and amino acid metabolism, revealing complex interactions at the level of gene expression between these pathways. Corresponding biochemical changes included a decrease in the three major flavonol glycosides, glycosylated vanillic acid, scopolin, and two novel feruloyl malates coupled to coniferyl alcohol. Moreover, Phe overaccumulated in the double mutant, and the levels of many other amino acids were significantly imbalanced. The lignin content was significantly reduced, and the syringyl/guaiacyl ratio of lignin monomers had increased. Together, from the molecular phenotype, common and specific functions of PAL1 and PAL2 are delineated, and PAL1 is qualified as being more important for the generation of phenylpropanoids

Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines.

Bluetongue virus (BTV) is endemic in many parts of the world, often causing severe hemorrhagic disease in livestock. To date, at least 27 different serotypes have been recognized. Vaccination against all serotypes is necessary to protect susceptible animals and to prevent onward spread of the virus by insect vectors. In our previous studies, we generated replication-deficient (disabled infectious single-cycle [DISC]) virus strains for a number of serotypes and reported preliminary data on their protective efficacy in animals. In this report, to advance the DISC vaccines to the marketplace, we investigated different parameters of these DISC vaccines. First, we demonstrated the genetic stabilities of these vaccine strains and also the complementing cell line. Subsequently, the optimal storage conditions of vaccines, including additives, temperature, and desiccation, were determined and their protective efficacies in animals confirmed. Furthermore, to test if mixtures of different vaccine strains could be tolerated, we tested cocktails of DISC vaccines in combinations of three or six different serotypes in sheep and cattle, the two natural hosts of BTV. Groups of sheep vaccinated with a cocktail of six different vaccines were completely protected from challenge with individual virulent serotypes, both in early challenge and after 5 months of challenge without any clinical disease. There was no interference in protection between the different vaccines. Protection was also achieved in cattle with a mixture of three vaccine strains, albeit at a lesser level than in sheep. Our data support and validate the suitability of these virus strains as the next-generation vaccines for BTV. IMPORTANCE: Bluetongue (BT) is a debilitating and in many cases lethal disease that affects ruminants of economic importance. Classical vaccines that afford protection against bluetongue virus, the etiological agent, are not free from secondary and undesirable effects. A surge in new approaches to produce highly attenuated, safer vaccines was evident after the development of the BTV reverse-genetics system that allows the introduction of targeted mutations in the virus genome. We targeted an essential gene to develop disabled virus strains as vaccine candidates. The results presented in this report further substantiate our previous evidence and support the suitability of these virus strains as the next-generation BTV vaccines

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Departamentos de Bolívar, Magdalena, Antioquia y el territorio de Chile

En este trabajo se analiza cómo el conflicto armado en Colombia ha afectado a la población rural, donde las comunidades son vulnerables por estar invisibilizadas por el mismo Estado, quienes no han prestado la suficiente atención a la población que se encuentra en medio de esta guerra que se ha vivido durante décadas en varios lugares del territorio colombiano. La violencia ha generado gran impacto en todo el mundo, violencia que ha causado pérdida humanas, afectaciones físicas, emocionales y psicológicas; causada por factores como pobreza, desigualdad social, indiferencia, exclusión, maltrato psicológico y social, falta de tolerancia y respeto por el otro, ha llevado a que se generen conflictos que han tenido una dimensión social tan exorbitante, que solo ha dejado dolor y sufrimiento en las víctimas, aquellas que han perdido sus derechos, su dignidad, su patrimonio y en algunos casos su libertad de pensamiento y de expresión. Se analizará el relato de Camilo un joven víctima del conflicto armado en Colombia, específicamente del pacifico colombiano, quien ha sufrido por amenazas y hechos violentos que han dejado en él y su familia un impacto psicosocial que lo llevaron a escapar del Chocó para no perder su vida. Se resalta la resiliencia de este joven que a pesar de sufrir tantas adversidades lucha día a día por su comunidad, quien desea ver su territorio libre, con mejores oportunidades y con protección de los derechos hacia su comunidad. Asimismo, se expondrán las diferentes problemáticas psicosociales por las que pasa la comunidad del caso Peñas Coloradas, quienes son estigmatizados por una falsa creencia de ser colaboradores y cómplices de la guerrilla, por estar en medio del conflicto armado y olvidados por el gobierno Colombiano. Al igual se presentarán las estrategias psicosociales para abordar este caso. Finalmente el informe termina con la foto voz y narrativa realizada en el paso 3 del diplomado, donde se refleja la realidad de diferentes comunidades que han mantenido algún tipo de violencia la cual ha permeado y dañado a estas comunidades, de igual forma se muestra una mirada transformadora que evoca una realidad de reconstrucción del tejido social. Palabras clave: conflicto armado, víctimas, resiliencia, impacto psicosocial.In this work, It analyzes how the armed conflict in Colombia has affected the rural population, where the communities are vulnerable because they are made invisible by the State itself, who have not paid enough attention to the population that is in the middle of this war that has been lived for decades in various parts of the Colombian territory. The Violence has generated great impact throughout the world, violence that has caused human loss, physical, emotional and psychological damage; caused by factors such as poverty, social inequality, indifference, exclusion, psychological and social abuse, lack of tolerance and respect for the other, It has led to the generation of conflicts that have had such an exorbitant social dimension, which has only left pain and suffering in the victims, those who have lost their rights, their dignity, their heritage and in some cases their freedom of thought and expression. The story of Camilo, a young victim of the armed conflict in Colombia, specifically from the Colombian Pacific, will be analyzed, who has suffered from threats and violent acts that have left a psychosocial impact on him and his family that led him to escape from Choco in order not to lose his life. The resilience of this young man is highlighted, who despite suffering so many adversities, fights every day for his community, who wants to see his territory free, with better opportunities and with protection of the rights towards his community. In this Word Will be exposed the different psychosocial problems that the community of the Peñas Coloradas, who are stigmatized by a false belief of being collaborators and accomplices of the guerrillas because they are in the middle of the armed conflict and are forgotten by the Colombian government. Likewise, psychosocial strategies will be presented to address this case. Finally, the report ends with the photo voice and narrative made in step 3 of the diplomat, which reflects the reality of different communities that have sustained some type of violence which has permeated and damaged these communities, in the same way, a transforming look is shown that evokes a reality of reconstruction of the social fabric. Keywords: armed conflict, victims, psychosocial impact, resilienc

How a Small Modification of the Corona-Forming Block Redirects the Self-Assembly of Crystalline-Coil Block Copolymers in Solution

In this study, we examine how the self-assembly of crystalline-coil block copolymers in solution can be influenced by small changes in the chemical structure of the corona-forming block. Three samples of poly­(ferrocenyldimethylsilane)-<i>block</i>-poly­(2-vinylpyridine) that form long fiber-like micelles uniform in width in 2-propanol, were treated with methyl iodide to convert a small fraction (0.1% to 6%) of the pyridines to methylpyridinium groups. When these partially quaternized samples (PFS-<i>b</i>-P2VP^Q) were subjected to the same self-assembly protocol, very different structures were obtained. For PFS₃₆-<i>b</i>-P2VP₅₀₂^Q, the presence of positive charges led to the formation of much shorter rod-like micelles. In contrast, for PFS₁₇-<i>b</i>-P2VP₁₇₀^Q and PFS₃₀-<i>b</i>-P2VP₃₀₀^Q, complex platelet structures were obtained. We explain the complexity of these structures in terms of a distribution of compositions, in which the polymer chains with the highest extent of methylation are the least soluble in 2-PrOH and the first to associate, leading to two-dimensional aggregates. The less quaternized polymer chains remaining in solution have a stronger tendency to form elongated fiber-like micelles that grow from the ends of the initially formed planar structures. In this way, we show that small extents of chemical modification of the corona forming chains can modify the self-assembly process and that simple one-pot protocols can lead to diverse hierarchical structures

Lightweight asynchronous scheduling in heterogeneous reconfigurable systems

The trend for heterogeneous embedded systems is the integration of accelerators and general-purpose CPU cores on the same die. In these integrated architectures, like the Zynq UltraScale+ board (CPU+FPGA) that we target in this work, hardware support for shared memory and low-overhead synchronization between the accelerator and the CPU cores make the case for exploring strategies that exploit a tight collaboration between the CPUs and the accelerator. In this paper we propose a novel lightweight scheduling strategy, FastFit, targeted to FPGA accelerators, and a new scheduler based on it, named MultiFastFit, which asynchronously tackles heterogeneous systems comprised of a variety of CPU cores and FPGA IPs. Our strategy significantly reduces the overhead to automatically compute the near-optimal chunksizes when compared to a previous state-of-the-art auto-tuned approach, which makes our approach more suitable for fine-grained applications. Additionally, our scheduler MultiFastFit has been designed to enable the efficient co-execution of work among compute devices in such a way that all the devices are busy while minimizing the load unbalance. Our approaches have been evaluated using four benchmarks carefully tuned for the low-power UltraScale+ platform. Our experiments demonstrate that the FastFit strategy always finds the near-optimal FPGA chunksize for any device configuration at a reasonable cost, even for fine-grained and irregular applications, and that heterogeneous CPU+FPGA co-executions that exploit all the compute devices are usually faster and more energy efficient than the CPU-only and FPGA-only executions. We have also compared MultiFastFit with other state-of-the-art scheduling strategies, finding that it outperforms other auto-tuned approach up to 2x and it achieves similar results to manually-tuned schedulers without requiring an offline search of the ideal CPU-FPGA partition or FPGA chunk granularity.This work was partially supported by the Spanish projects PID2019-105396RB-I00, UMA18-FEDERJA-108, and UK EPSRC projects ENEAC (EP/N002539/1), HOPWARE (EP/V040863/1) and RS MINET (INF\R2\192044). Funding for open access charge: Universidad de Málaga / CBUA

Functional characterization of the Arabidopsis transcription factor bZIP29 reveals its role in leaf and root development

Plant bZIP group I transcription factors have been reported mainly for their role during vascular development and osmosensory responses. Interestingly, bZIP29 has been identified in a cell cycle interactome, indicating additional functions of bZIP29 in plant development. Here, bZIP29 was functionally characterized to study its role during plant development. It is not present in vascular tissue but is specifically expressed in proliferative tissues. Genome-wide mapping of bZIP29 target genes confirmed its role in stress and osmosensory responses, but also identified specific binding to several core cell cycle genes and to genes involved in cell wall organization. bZIP29 protein complex analyses validated interaction with other bZIP group I members and provided insight into regulatory mechanisms acting on bZIP dimers. In agreement with bZIP29 expression in proliferative tissues and with its binding to promoters of cell cycle regulators, dominant-negative repression of bZIP29 altered the cell number in leaves and in the root meristem. A transcriptome analysis on the root meristem, however, indicated that bZIP29 might regulate cell number through control of cell wall organization. Finally, ectopic dominant-negative repression of bZIP29 and redundant factors led to a seedling-lethal phenotype, pointing to essential roles for bZIP group I factors early in plant development