Euskal adjektibozko adberbioak aztergai

Lan honetan, adjektibozko adberbioen jokabide sintaktiko eta semantikoa izango dut aztergai. Adjektibozko adberbioak deritzet inolako morfemaren laguntzarik gabe, adberbio gisa ageri diren adjektiboei. Euskara ez da, jakina, halakoak dituen hizkuntza bakarra. Gaztelaniaz eta ingelesez ere lekukotzen dira, beste hizkuntza batzuen artean. Gaztelaniaz oro har adberbios adjetivales deitu izan dira eta ingelesez, adjectival adverbs. Lan honetan, Fábregas eta Alexeyenko-ren (2016) lana baliatuko dut adjektibozko adberbioek gaztelaniaz eta ingelesez nola jokatzen duten ikusteko eta euren azterbidea euskarara ekartzeko. Gaztelaniaz eta ingelesez, Fabregas eta Alexeyenko-k (2016) -mente atzizkidun moduzko adberbioekin eta bigarren mailako predikatuekin konparatzen dituzte adjektibozko adberbioak. Azaleko antzekotasunak egon arren, desberdintasun semantiko eta sintaktikoek iradokitzen dute adjektibozko adberbioak beste zerbait direla. Fábregas eta Alexeyenkoren (2016) arabera, adjektibozko adberbioak determinatzaile sintagmak (DetS) dira; moduzko adberbioak, aldiz, preposizio sintagmak (PrepS). Alabaina, ez dira nolanahiko DetSak, izaera berezikoak baino. Izan ere, izen nuludun DetSak dira, Det burua ere hutsik izan behar dutenak. Kokapen sintaktikoari dagokionez, aditzaren osagarri gunean kokatzen dute DetS hori eta horrek zenbait jokabide azaltzeko balioko du. Bestalde, euskaraz moduzko adberbioen eta adjektibozko adberbioen artean ez dago ia alderik. Horregatik, biak ala biak kategoria berean kokatzea proposatuko dut nik lan honetan. Batik bat jokabide sintaktikoak erakusten du euskal adjektibozko adberbioa ez dela osagarri bat, adjuntu bat baizik. Izan ere, perpausean kokaleku desberdinetan eta aditzetik urrun agertzeko aukeratu dute eta ez dituzte aditzaren osagarriak izan daitezkeen sintagmak oztopatzen. Jokabide sintaktiko hauek azaltzeko modurik onena euskaraz adjektibozko adberbioak postposizio sintagmak (PostS) direla proposatzea ematen du: - ki atzizki nuludun PostS, Post burua eta Det burua ere nuluak dituen sintagma bat. Fábregas eta Alexeyenkorekin (2016) bat etorriz, -ki atzizkidun moduzko adberbioak PostSak dira euskaraz ere. Moduzko adberbio hauek, adjektibozko adberbioek ez bezala, eratorpenezko atzizkia agerikoa dute. Eta hori da diferentzia 3 bakarra, izan ere, hauek ere Post eta Det buruak nulu izatea behar dute. Proposamen honen alde esan beharra dago moduzko adberbio bezala PostS arrunt ugari erabiltzen ditugula

Correction: Ordoñez, et al.; DNA methylation of enhancer elements in myeloid neoplasms: think outside the promoters? Cancers 2019, 11, 1424

The authors would like to make a correction to their published pape

DNA methylation of enhancer elements in myeloid neoplasms: think outside the promoters?

Gene regulation through DNA methylation is a well described phenomenon that has a prominent role in physiological and pathological cell-states. This epigenetic modification is usually grouped in regions denominated CpG islands, which frequently co-localize with gene promoters, silencing the transcription of those genes. Recent genome-wide DNA methylation studies have challenged this paradigm, demonstrating that DNA methylation of regulatory regions outside promoters is able to influence cell-type specific gene expression programs under physiologic or pathologic conditions. Coupling genome-wide DNA methylation assays with histone mark annotation has allowed for the identification of specific epigenomic changes that affect enhancer regulatory regions, revealing an additional layer of complexity to the epigenetic regulation of gene expression. In this review, we summarize the novel evidence for the molecular and biological regulation of DNA methylation in enhancer regions and the dynamism of these changes contributing to the fine-tuning of gene expression. We also analyze the contribution of enhancer DNA methylation on the expression of relevant genes in acute myeloid leukemia and chronic myeloproliferative neoplasms. The characterization of the aberrant enhancer DNA methylation provides not only a novel pathogenic mechanism for different tumors but also highlights novel potential therapeutic targets for myeloid derived neoplasms

HDAC inhibitors in acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological malignancy characterized by uncontrolled proliferation, differentiation arrest, and accumulation of immature myeloid progenitors. Although clinical advances in AML have been made, especially in young patients, long-term disease-free survival remains poor, making this disease an unmet therapeutic challenge. Epigenetic alterations and mutations in epigenetic regulators contribute to the pathogenesis of AML, supporting the rationale for the use of epigenetic drugs in patients with AML. While hypomethylating agents have already been approved in AML, the use of other epigenetic inhibitors, such as histone deacetylases (HDAC) inhibitors (HDACi), is under clinical development. HDACi such as Panobinostat, Vorinostat, and Tricostatin A have been shown to promote cell death, autophagy, apoptosis, or growth arrest in preclinical AML models, yet these inhibitors do not seem to be effective as monotherapies, but rather in combination with other drugs. In this review, we discuss the rationale for the use of different HDACi in patients with AML, the results of preclinical studies, and the results obtained in clinical trials. Although so far the results with HDACi in clinical trials in AML have been modest, there are some encouraging data from treatment with the HDACi Pracinostat in combination with DNA demethylating agents

KAF: Kyoto Annotation Framework

This document presents the current draft of KAF: Kyoto Annotation Framework to be used within the KYOTO project. KAF aims to provide a reference format for the representation of semantic annotations

In-silico gene essentiality analysis of polyamine biosynthesis reveals APRT as a potential target in cancer

Constraint-based modeling for genome-scale metabolic networks has emerged in the last years as a promising approach to elucidate drug targets in cancer. Beyond the canonical biosynthetic routes to produce biomass, it is of key importance to focus on metabolic routes that sustain the proliferative capacity through the regulation of other biological means in order to improve in-silico gene essentiality analyses. Polyamines are polycations with central roles in cancer cell proliferation, through the regulation of transcription and translation among other things, but are typically neglected in in silico cancer metabolic models. In this study, we analysed essential genes for the biosynthesis of polyamines. Our analysis corroborates the importance of previously known regulators of the pathway, such as Adenosylmethionine Decarboxylase 1 (AMD1) and uncovers novel enzymes predicted to be relevant for polyamine homeostasis. We focused on Adenine phosphoribosyltransferase (APRT) and demonstrated the detrimental consequence of APRT gene silencing on diferent leukaemia cell lines. Our results highlight the importance of revisiting the metabolic models used for in-silico gene essentiality analyses in order to maximize the potential for drug target identifcation in cance