CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription

The creation of translation-competent mRNA is dependent on RNA polymerase II transcripts being modified by addition of the 7-methylguanosine (m7G) cap. The factors that mediate splicing, nuclear export, and translation initiation are recruited to the transcript via the cap. The cap structure is formed by several activities and completed by RNMT (RNA guanine-7 methyltransferase), which catalyzes N7 methylation of the cap guanosine. We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. RNMT T77 phosphorylation results in elevated m7G cap methyltransferase activity at the beginning of G1 phase, coordinating mRNA capping with the burst of transcription that occurs following nuclear envelope reformation. RNMT T77 phosphorylation is required for the production of cohort of proteins, and inhibiting T77 phosphorylation reduces the cell proliferation rate

Juventudes rurais : Mapa de estudos recentes

Em 2005, o governo federal criou a Secretaria Nacional de Juventude com o propósito de coordenar políticas e ações voltadas para promover a participação econômica e social dos jovens. No âmbito das políticas de desenvolvimento rural e de geração de emprego e renda, várias ações estão sendo implementadas, envolvendo vários ministérios, entre os quais o Ministério do Desenvolvimento Agrário (MDA ) e o Ministério do Trabalho e Emprego. O Plano da Safra da Agricultura Familiar criou uma linha especial de crédito, o Pronaf Jovem; está em execução o Programa Nossa Primeira Terra, linha do Programa Nacional de Crédito Fundiário, ação que integra o II Plano Nacional de Reforma Agrária. Jovens estão sendo formados como agentes de desenvolvimento territorial, e no Programa Arca das Letras, os jovens atuam como agentes de leitura. Em parceria com a sociedade civil, foi criado o Consórcio Social da Juventude Rural, para oferecer formação e qualificação profissional aos jovens, associado à implantação de inovações tecnológicas. A presente publicação da Série NEAD Estudos articula-se com essas iniciativas e propõe-se a dar visibilidade às discussões presentes e apropriar-se do conhecimento produzido por um conjunto de estudos e pesquisas que focalizam a temática da juventude rural, buscando desvendar esse universo em suas múltiplas faces, contribuir para qualificar a participação social dos atores e para aprofundar a compreensão sobre a própria dinâmica do meio rural brasileiro

The silicon isotope composition of Ethmodiscus rexlaminated diatom mats from the tropical West Pacific: Implications for silicate cycling during the Last Glacial Maximum

The cause of massive blooms of Ethmodiscus rex laminated diatom mats (LDMs) in the eastern Philippine Sea (EPS) during the Last Glacial Maximum (LGM) remains uncertain. In order to better understand the mechanism of formation of E. rex LDMs from the perspective of dissolved silicon (DSi) utilization, we determined the silicon isotopic composition of single E. rex diatom frustules (δ30SiE. rex) from two sediment cores in the Parece Vela Basin of the EPS. In the study cores, δ30SiE. rex varies from −1.23‰ to −0.83‰ (average −1.04‰), a range that is atypical of marine diatom δ30Si and that corresponds to the lower limit of reported diatom δ30Si values of any age. A binary mixing model (upwelled silicon versus eolian silicon) accounting for silicon isotopic fractionation during DSi uptake by diatoms was constructed. The binary mixing model demonstrates that E. rex dominantly utilized DSi from eolian sources (i.e., Asian dust) with only minor contributions from upwelled seawater sources (i.e., advected from Subantarctic Mode Water, Antarctic Intermediate Water, or North Pacific Intermediate Water). E. rex utilized only ~24% of available DSi, indicating that surface waters of the EPS were eutrophic with respect to silicon during the LGM. Our results suggest that giant diatoms did not always use a buoyancy strategy to obtain nutrients from the deep nutrient pool, thus revising previously proposed models for the formation of E. rex LDMs

The Essential Nucleolar Yeast Protein Nop8p Controls the Exosome Function during 60S Ribosomal Subunit Maturation

The yeast nucleolar protein Nop8p has previously been shown to interact with Nip7p and to be required for 60S ribosomal subunit formation. Although depletion of Nop8p in yeast cells leads to premature degradation of rRNAs, the biochemical mechanism responsible for this phenotype is still not known. In this work, we show that the Nop8p amino-terminal region mediates interaction with the 5.8S rRNA, while its carboxyl-terminal portion interacts with Nip7p and can partially complement the growth defect of the conditional mutant strain Δnop8/GAL::NOP8. Interestingly, Nop8p mediates association of Nip7p to pre-ribosomal particles. Nop8p also interacts with the exosome subunit Rrp6p and inhibits the complex activity in vitro, suggesting that the decrease in 60S ribosomal subunit levels detected upon depletion of Nop8p may result from degradation of pre-rRNAs by the exosome. These results strongly indicate that Nop8p may control the exosome function during pre-rRNA processing

Salt Reduction Initiatives around the World – A Systematic Review of Progress towards the Global Target

Objective To quantify progress with the initiation of salt reduction strategies around the world in the context of the global target to reduce population salt intake by 30% by 2025. Methods A systematic review of the published and grey literature was supplemented by questionnaires sent to country program leaders. Core characteristics of strategies were extracted and categorised according to a pre-defined framework. Results A total of 75 countries now have a national salt reduction strategy, more than double the number reported in a similar review done in 2010. The majority of programs are multifaceted and include industry engagement to reformulate products (n = 61), establishment of sodium content targets for foods (39), consumer education (71), front-of-pack labelling schemes (31), taxation on high-salt foods (3) and interventions in public institutions (54). Legislative action related to salt reduction such as mandatory targets, front of pack labelling, food procurement policies and taxation have been implemented in 33 countries. 12 countries have reported reductions in population salt intake, 19 reduced salt content in foods and 6 improvements in consumer knowledge, attitudes or behaviours relating to salt. Conclusion The large and increasing number of countries with salt reduction strategies in place is encouraging although activity remains limited in low- and middle-income regions. The absence of a consistent approach to implementation highlights uncertainty about the elements most important to success. Rigorous evaluation of ongoing programs and initiation of salt reduction programs, particularly in low- and middle- income countries, will be vital to achieving the targeted 30% reduction in salt intake

Evidence for a Transport-Trap Mode of Drosophila melanogaster gurken mRNA Localization

The Drosophila melanogaster gurken gene encodes a TGF alpha-like signaling molecule that is secreted from the oocyte during two distinct stages of oogenesis to define the coordinate axes of the follicle cell epithelium that surrounds the oocyte and its 15 anterior nurse cells. Because the gurken receptor is expressed throughout the epithelium, axial patterning requires region-specific secretion of Gurken protein, which in turn requires subcellular localization of gurken transcripts. The first stage of Gurken signaling induces anteroposterior pattern in the epithelium and requires the transport of gurken transcripts from nurse cells into the oocyte. The second stage of Gurken signaling induces dorsovental polarity in the epithelium and requires localization of gurken transcripts to the oocyte's anterodorsal corner. Previous studies, relying predominantly on real-time imaging of injected transcripts, indicated that anterodorsal localization involves transport of gurken transcripts to the oocyte's anterior cortex followed by transport to the anterodorsal corner, and anchoring. Such studies further indicated that a single RNA sequence element, the GLS, mediates both transport steps by facilitating association of gurken transcripts with a cytoplasmic dynein motor complex. Finally, it was proposed that the GLS somehow steers the motor complex toward that subset of microtubules that are nucleated around the oocyte nucleus, permitting directed transport to the anterodorsal corner. Here, we re-investigate the role of the GLS using a transgenic fly assay system that includes use of the endogenous gurken promoter and biological rescue as well as RNA localization assays. In contrast to previous reports, our studies indicate that the GLS is sufficient for anterior localization only. Our data support a model in which anterodorsal localization is brought about by repeated rounds of anterior transport, accompanied by specific trapping at the anterodorsal cortex. Our data further indicate that trapping at the anterodorsal corner requires at least one as-yet-unidentified gurken RLE

D-Cbl Binding to Drk Leads to Dose-Dependent Down-Regulation of EGFR Signaling and Increases Receptor-Ligand Endocytosis

Proper control of Epidermal Growth Factor Receptor (EGFR) signaling is critical for normal development and regulated cell behaviors. Abnormal EGFR signaling is associated with tumorigenic process of various cancers. Complicated feedback networks control EGFR signaling through ligand production, and internalization-mediated destruction of ligand-receptor complexes. Previously, we found that two isoforms of D-Cbl, D-CblS and D-CblL, regulate EGFR signaling through distinct mechanisms. While D-CblL plays a crucial role in dose-dependent down-regulation of EGFR signaling, D-CblS acts in normal restriction of EGFR signaling and does not display dosage effect. Here, we determined the underlying molecular mechanism, and found that Drk facilitates the dose-dependent regulation of EGFR signaling through binding to the proline-rich motif of D-CblL, PR. Furthermore, the RING finger domain of D-CblL is essential for promoting endocytosis of the ligand-receptor complex. Interestingly, a fusion protein of the two essential domains of D-CblL, RING- PR, is sufficient to down-regulate EGFR signal in a dose-dependent manner by promoting internalization of the ligand, Gurken. Besides, RING-SH2Drk, a fusion protein of the RING finger domain of D-Cbl and the SH2 domain of Drk, also effectively down-regulates EGFR signaling in Drosophila follicle cells, and suppresses the effects of constitutively activated EGFR. The RING-SH2Drk suppresses EGFR signaling by promoting the endosomal trafficking of ligand-receptor complexes, suggesting that Drk plays a negative role in EGFR signaling by enhancing receptor endocytosis through cooperating with the RING domain of D-Cbl. Interfering the recruitment of signal transducer, Drk, to the receptor by the RING-SH2Drk might further reduces EGFR signaling. The fusion proteins we developed may provide alternative strategies for therapy of cancers caused by hyper-activation of EGFR signaling

Citizen culture and student coexistence from the use of research as a pedagogical strategy supported by Information and communication technologies

La integración al currículo de la investigación como estrategia pedagógica (IEP) y el uso de las tecnologías de la información y la comunicación (TIC), tiene como objetivo generar propuestas novedosas a partir de las cuales se propone impactar a la comunidad estudiantil en el desarrollo de la cultura ciudadana y el mejoramiento de la convivencia escolar. El propósito de la presente investigación es generar cultura ciudadana y convivencia estudiantil desde el uso de la IEP apoyada en las TIC. El estudio es de tipo cualitativo. La población estuvo conformada por 190 estudiantes de la Institución Educativa Agropecuaria Otilia Mena Álvarez. Para la recolección de datos se realizó un diagnóstico apoyado en las TIC de la cultura ciudadana y convivencia escolar en la institución. A partir de la investigación, como estrategia pedagógica se logró fomentar la reflexión crítica de los estudiantes frente a la problemática de convivencia escolar y cultura ciudadana resaltando la tolerancia y buenas relaciones personalesThe integration into the curriculum of research as a pedagogical strategy (IEP) and the use of information and communication technologies (ICT) generates novel proposals from which it is proposed to impact the student community in the development of citizen culture and the improvement of school coexistence. The purpose of this research is to generate citizen culture and student coexistence from the use of the IEP supported by ICT. The study is of a qualitative, proactive type. The population consisted of 190 students of the Otilia Mena Álvarez Agricultural Educational Institution. For data collection, a diagnosis was made based on the ICT of the citizen culture and school coexistence in the institution, and work tables and workshops of contextualized experiences were developed with students, teachers and parents. From the research, as a pedagogical strategy it was possible to foster the critical reflection of the students in the face of the problem of school coexistence and civic culture highlighting tolerance, good personal relationships and respect for individual difference

Role of Scrib and Dlg in anterior-posterior patterning of the follicular epithelium during Drosophila oogenesis

<p>Abstract</p> <p>Background</p> <p>Proper patterning of the follicle cell epithelium over the egg chamber is essential for the <it>Drosophila </it>egg development. Differentiation of the epithelium into several distinct cell types along the anterior-posterior axis requires coordinated activities of multiple signaling pathways. Previously, we reported that <it>lethal(2)giant larvae </it>(<it>lgl</it>), a <it>Drosophila </it>tumor suppressor gene, is required in the follicle cells for the posterior follicle cell (PFC) fate induction at mid-oogenesis. Here we explore the role of another two tumor suppressor genes, <it>scribble </it>(<it>scrib</it>) and <it>discs large </it>(<it>dlg</it>), in the epithelial patterning.</p> <p>Results</p> <p>We found that removal of <it>scrib </it>or <it>dlg </it>function from the follicle cells at posterior terminal of the egg chamber causes a complete loss of the PFC fate. Aberrant specification and differentiation of the PFCs in the mosaic clones can be ascribed to defects in coordinated activation of the EGFR, JAK and Notch signaling pathways in the multilayered cells. Meanwhile, the clonal analysis revealed that loss-of-function mutations in <it>scrib/dlg </it>at the anterior domains result in a partially penetrant phenotype of defective induction of the stretched and centripetal cell fate, whereas specification of the border cell fate can still occur in the most anterior region of the mutant clones. Further, we showed that <it>scrib </it>genetically interacts with <it>dlg </it>in regulating posterior patterning of the epithelium.</p> <p>Conclusion</p> <p>In this study we provide evidence that <it>scrib </it>and <it>dlg </it>function differentially in anterior and posterior patterning of the follicular epithelium at oogenesis. Further genetic analysis indicates that <it>scrib </it>and <it>dlg </it>act in a common pathway to regulate PFC fate induction. This study may open another window for elucidating role of <it>scrib/dlg </it>in controlling epithelial polarity and cell proliferation during development.</p