Fission Yeast Mitotic Regulator DSK1 is an SR Protein-Specific Kinase

Intricate interplay may exist between pre-mRNA splicing and the cell division cycle, and fission yeast Dsk1 appears to play a role in such a connection. Previous genetic analyses have implicated Dsk1 in the regulation of chromosome segregation at the metaphase/anaphase transition. Yet, its protein sequence suggests that Dsk1 may function as a kinase specific for SR proteins, a family of pre-mRNA splicing factors containing arginine-serine repeats. Using an in vitro system with purified components, we showed that Dsk1 phosphorylated human and yeast SR proteins with high specificity. The Dsk1-phosphorylated SF2/ASF protein was recognized strongly by a monoclonal antibody (mAb104) known to bind the in vivo phosphoepitope shared by SR proteins, indicating that the phosphorylation sites resided in the RS domain. Moreover, the fission yeast U2AF65 homolog, Prp2/Mis11 protein, was phosphorylated more efficiently by Dsk1 than by a human SR protein-specific kinase, SRPK1. Thus, these in vitro results suggest that Dsk1 is a fission yeast SR protein-specific kinase, and Prp2/Mis11 is likely an in vivo target for Dsk1. Together with previous genetic data, the studies support the notion that Dsk1 may play a role in coordinating pre-mRNA splicing and the cell division cycle

Extracellular matrix remodeling following myocardial infarction influences the therapeutic potential of mesenchymal stem cells

INTRODUCTION: Although stem cell therapy is a promising treatment for myocardial infarction, the minimal functional improvements observed clinically limit its widespread application. A need exists to maximize the therapeutic potential of these stem cells by first understanding what factors within the infarct microenvironment affect their ability to regenerate the necrotic tissue. In this study, we assessed both differentiation capacity and paracrine signaling as a function of extracellular matrix remodeling after myocardial infarction. METHODS: Mechanical and compositional changes to the decellularized infarcted myocardium were characterized to understand how the extracellular environment, specifically, was altered as a function of time after coronary artery ligation in Sprague–Dawley rats. These alterations were first modeled in a polyacrylamide gel system to understand how the variables of composition and stiffness drive mesenchymal stem cell differentiation towards a cardiac lineage. Finally, the paracrine secretome was characterized as a function of matrix remodeling through gene and protein expression and conditioned media studies. RESULTS: The decellularized infarct tissue revealed significant alterations in both the mechanical and compositional properties of the ECM with remodeling following infarction. This altered microenvironment dynamically regulates the potential for early cardiac differentiation. Whereas Nkx2.5 expression is limited in the presence of chronic remodeled matrix of increased stiffness, GATA4 expression is enhanced. In addition, the remodeled matrix promotes the expression of several proangiogenic, prosurvival, antifibrotic, and immunomodulatory growth factors. In particular, an increase in HGF and SDF1 expression and secretion by mesenchymal stem cells can rescue oxidatively stressed cardiomyocytes in vitro. CONCLUSIONS: This study demonstrated that decellularization of diseased tissue allows for the exclusive analysis of the remodeled matrix and its ability to influence significantly the cellular phenotype. Characterization of cell fate as a function of myocardial remodeling following infarction is critical in developing the ideal strategy for cell implantation to maximize tissue regeneration and to ultimately reduce the prevalence and severity of heart failure

Biochemical and Genetic Conservation of Fission Yeast DSK1 and Human SRPK1

Arginine/serine-rich (RS) domain-containing proteins and their phosphorylation by specific protein kinases constitute control circuits to regulate pre-mRNA splicing and coordinate splicing with transcription in mammalian cells. We present here the finding that similar SR networks exist in Schizosaccharomyces pombe. We previously showed that Dsk1 protein, originally described as a mitotic regulator, displays high activity in phosphorylating S. pombe Prp2 protein (spU2AF59), a homologue of human U2AF65. We now demonstrate that Dsk1 also phosphorylates two recently identified fission yeast proteins with RS repeats, Srp1 and Srp2, in vitro. The phosphorylated proteins bear the same phosphoepitope found in mammalian SR proteins. Consistent with its substrate specificity, Dsk1 forms kinase-competent complexes with those proteins. Furthermore, dsk1+ gene determines the phenotype of prp2+ overexpression, providing in vivo evidence that Prp2 is a target for Dsk1. The dsk1-null mutant strain became severely sick with the additional deletion of a related kinase gene. Significantly, human SR protein-specific kinase 1 (SRPK1) complements the growth defect of the double-deletion mutant. In conjunction with the resemblance of dsk1+ and SRPK1 in sequence homology, biochemical properties, and overexpression phenotypes, the complementation result indicates that SRPK1 is a functional homologue of Dsk1. Collectively, our studies illustrate the conserved SR networks in S. pombe consisting of RS domain-containing proteins and SR protein-specific kinases and thus establish the importance of the networks in eucaryotic organisms

Policy Advocacy Training for Women Victims of Violence in Maros Regency

Cases of violence against women in Maros Regency are quite high. For example, in 2016, according to Department of Women Empowerment and Child Protection (DP3A) data, there were 68 cases and 21 police data cases. Likewise, divorce data in the Religious Courts are more caused by domestic violence. Of course, this social problem must be immediately addressed through local government policies. However, in fact, no policy specifically regulates the handling of this problem. Therefore, community service in the form of policy advocacy training for village women victims of violence needs to be carried out. This advocacy training was attended by 25 participants from various villages. Participants were provided with policy advocacy materials covering (1) government policies and programs on the protection of women; (2) the concept and practice of policy advocacy; (3) issues of violence and protection of women; (4) technical public speaking and lobby strategy, and (5) public opinion and press release materials. The results of the training evaluation resulted in an increase in knowledge and skills for participants after following the entire set of materials provided. Recommendations for activities are suggested to immediately take more concrete action in the form of policy advocacy to encourage the issuance of the Regional Regulation (Perda) of Maros Regency concerning Protection of Women from Violenc

Recent advances in Apertium, a free/open-source rule-based machine translation platform for low-resource languages

This paper presents an overview of Apertium, a free and open-source rule-based machine translation platform. Translation in Apertium happens through a pipeline of modular tools, and the platform continues to be improved as more language pairs are added. Several advances have been implemented since the last publication, including some new optional modules: a module that allows rules to process recursive structures at the structural transfer stage, a module that deals with contiguous and discontiguous multi-word expressions, and a module that resolves anaphora to aid translation. Also highlighted is the hybridisation of Apertium through statistical modules that augment the pipeline, and statistical methods that augment existing modules. This includes morphological disambiguation, weighted structural transfer, and lexical selection modules that learn from limited data. The paper also discusses how a platform like Apertium can be a critical part of access to language technology for so-called low-resource languages, which might be ignored or deemed unapproachable by popular corpus-based translation technologies. Finally, the paper presents some of the released and unreleased language pairs, concluding with a brief look at some supplementary Apertium tools that prove valuable to users as well as language developers. All Apertium-related code, including language data, is free/open-source and available at https://github.com/apertium