Developmental Role and Regulation of cortex, a Meiosis-Specific Anaphase-Promoting Complex/Cyclosome Activator

During oogenesis in metazoans, the meiotic divisions must be coordinated with development of the oocyte to ensure successful fertilization and subsequent embryogenesis. The ways in which the mitotic machinery is specialized for meiosis are not fully understood. cortex, which encodes a putative female meiosis-specific anaphase-promoting complex/cyclosome (APC/C) activator, is required for proper meiosis in Drosophila. We demonstrate that CORT physically associates with core subunits of the APC/C in ovaries. APC/CCORT targets Cyclin A for degradation prior to the metaphase I arrest, while Cyclins B and B3 are not targeted until after egg activation. We investigate the regulation of CORT and find that CORT protein is specifically expressed during the meiotic divisions in the oocyte. Polyadenylation of cort mRNA is correlated with appearance of CORT protein at oocyte maturation, while deadenylation of cort mRNA occurs in the early embryo. CORT protein is targeted for degradation by the APC/C following egg activation, and this degradation is dependent on an intact D-box in the C terminus of CORT. Our studies reveal the mechanism for developmental regulation of an APC/C activator and suggest it is one strategy for control of the female meiotic cell cycle in a multicellular organism

Upstream-binding factor is sequestered into herpes simplex virus type 1 replication compartments

Previous reports have shown that adenovirus recruits nucleolar protein upstream-binding factor (UBF) into adenovirus DNA replication centres. Here, we report that despite having a different mode of viral DNA replication, herpes simplex virus type 1 (HSV-1) also recruits UBF into viral DNA replication centres. Moreover, as with adenovirus, enhanced green fluorescent protein-tagged fusion proteins of UBF inhibit viral DNA replication. We propose that UBF is recruited to the replication compartments to aid replication of HSV-1 DNA. In addition, this is a further example of the role of nucleolar components in viral life cycle

Adapting an Evidence-Based Intervention Targeting HIV-Infected Prisoners in Malaysia

HIV-infected prisoners in Malaysia represent a critical target population for secondary HIV risk reduction interventions and care. We report on the process and outcome of our formative research aimed at systematically selecting and adapting an EBI designed to reduce secondary HIV risk and improve adherence to antiretroviral therapy among soon-to-be-released HIV-infected prisoners. Our formative work involved a critical examination of established EBIs and associated published reports complemented by data elicited through structured interviews and focus groups with key stakeholders, members of the target population, and their family members. Based on all information, we adapted the Holistic Health Recovery Program targeting people living with HIV (HHRP+), an EBI, to consist of eight 2-hour sessions that cover a range of specified topics so that participants may individually apply intervention content as needed to accommodate their particular substance abuse, HIV risk, and antiretroviral adherence issues. This study provides a complete example of the process of selecting and adapting an EBI—taking into account both empirical evidence and input from target organization stakeholders and target population members and their families—for use in real world prison settings where high-risk populations are concentrated

Energy supply of countryside based on geothermal deposit

Meiosis is a specialized eukaryotic cell division that generates haploid gametes required for sexual reproduction. During meiosis, homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover (CO). Meiotic CO frequency varies along the physical length of chromosomes and is determined by hierarchical mechanisms, including epigenetic organization, for example methylation of the DNA and histones. Here we investigate the role of DNA methylation in determining patterns of CO frequency along Arabidopsis thaliana chromosomes. In A. thaliana the pericentromeric regions are repetitive, densely DNA methylated, and suppressed for both RNA polymerase-II transcription and CO frequency. DNA hypomethylated methyltransferase1 (met1) mutants show transcriptional reactivation of repetitive sequences in the pericentromeres, which we demonstrate is coupled to extensive remodeling of CO frequency. We observe elevated centromere-proximal COs in met1, coincident with pericentromeric decreases and distal increases. Importantly, total numbers of CO events are similar between wild type and met1, suggesting a role for interference and homeostasis in CO remodeling. To understand recombination distributions at a finer scale we generated CO frequency maps close to the telomere of chromosome 3 in wild type and demonstrate an elevated recombination topology in met1. Using a pollen-typing strategy we have identified an intergenic nucleosome-free CO hotspot 3a, and we demonstrate that it undergoes increased recombination activity in met1. We hypothesize that modulation of 3a activity is caused by CO remodeling driven by elevated centromeric COs. These data demonstrate how regional epigenetic organization can pattern recombination frequency along eukaryotic chromosomes

Caspase-11 Activation in Response to Bacterial Secretion Systems That Access the Host Cytosol

Inflammasome activation is important for antimicrobial defense because it induces cell death and regulates the secretion of IL-1 family cytokines, which play a critical role in inflammatory responses. The inflammasome activates caspase-1 to process and secrete IL-1β. However, the mechanisms governing IL-1α release are less clear. Recently, a non-canonical inflammasome was described that activates caspase-11 and mediates pyroptosis and release of IL-1α and IL-1β. Caspase-11 activation in response to Gram-negative bacteria requires Toll-like receptor 4 (TLR4) and TIR-domain-containing adaptor-inducing interferon-β (TRIF)-dependent interferon production. Whether additional bacterial signals trigger caspase-11 activation is unknown. Many bacterial pathogens use specialized secretion systems to translocate effector proteins into the cytosol of host cells. These secretion systems can also deliver flagellin into the cytosol, which triggers caspase-1 activation and pyroptosis. However, even in the absence of flagellin, these secretion systems induce inflammasome activation and the release of IL-1α and IL-1β, but the inflammasome pathways that mediate this response are unclear. We observe rapid IL-1α and IL-1β release and cell death in response to the type IV or type III secretion systems of Legionella pneumophila and Yersinia pseudotuberculosis. Unlike IL-1β, IL-1α secretion does not require caspase-1. Instead, caspase-11 activation is required for both IL-1α secretion and cell death in response to the activity of these secretion systems. Interestingly, whereas caspase-11 promotes IL-1β release in response to the type IV secretion system through the NLRP3/ASC inflammasome, caspase-11-dependent release of IL-1α is independent of both the NAIP5/NLRC4 and NLRP3/ASC inflammasomes as well as TRIF and type I interferon signaling. Furthermore, we find both overlapping and non-redundant roles for IL-1α and IL-1β in mediating neutrophil recruitment and bacterial clearance in response to pulmonary infection by L. pneumophila. Our findings demonstrate that virulent, but not avirulent, bacteria trigger a rapid caspase-11-dependent innate immune response important for host defense

Violent video games and morality: a meta-ethical approach

This paper considers what it is about violent video games that leads one reasonably minded person to declare "That is immoral" while another denies it. Three interpretations of video game content a re discussed: reductionist, narrow, and broad. It is argued that a broad interpretation is required for a moral objection to be justified. It is further argued that understanding the meaning of moral utterances – like "x is immoral" – is important to an understanding of why there is a lack of moral consensus when it comes to the content of violent video games. Constructive ecumenical expressivism is presented as a means of explaining what it is that we are doing when we make moral pronouncements and why, when it comes to video game content, differing moral attitudes abound. Constructive ecumenical expressivism is also presented as a means of illuminating what would be required for moral consensus to be achieved

Locus-Specific Ribosomal RNA Gene Silencing in Nucleolar Dominance

The silencing of one parental set of rRNA genes in a genetic hybrid is an epigenetic phenomenon known as nucleolar dominance. We showed previously that silencing is restricted to the nucleolus organizer regions (NORs), the loci where rRNA genes are tandemly arrayed, and does not spread to or from neighboring protein-coding genes. One hypothesis is that nucleolar dominance is the net result of hundreds of silencing events acting one rRNA gene at a time. A prediction of this hypothesis is that rRNA gene silencing should occur independent of chromosomal location. An alternative hypothesis is that the regulatory unit in nucleolar dominance is the NOR, rather than each individual rRNA gene, in which case NOR localization may be essential for rRNA gene silencing. To test these alternative hypotheses, we examined the fates of rRNA transgenes integrated at ectopic locations. The transgenes were accurately transcribed in all independent transgenic Arabidopsis thaliana lines tested, indicating that NOR localization is not required for rRNA gene expression. Upon crossing the transgenic A. thaliana lines as ovule parents with A. lyrata to form F1 hybrids, a new system for the study of nucleolar dominance, the endogenous rRNA genes located within the A. thaliana NORs are silenced. However, rRNA transgenes escaped silencing in multiple independent hybrids. Collectively, our data suggest that rRNA gene activation can occur in a gene-autonomous fashion, independent of chromosomal location, whereas rRNA gene silencing in nucleolar dominance is locus-dependent

The U.S. Arctic Observing Viewer: A Web-Mapping Application for Enhancing Environmental Observation of the Changing Arctic

Although much progress has been made with various Arctic Observing efforts, assessing that progress can be difficult. What data collection efforts are established or underway? Where? By whom? To help meet the strategic needs of programs such as the U.S. Study of Environmental Arctic Change (SEARCH), the Arctic Observing Network (AON), Sustaining Arctic Observing Networks (SAON) and related initiatives, an update has been released for the Arctic Observing Viewer (AOV; http://ArcticObservingViewer.org). This web mapping application and information system has begun to compile the who, what, where, and when for thousands of data collection sites (such as boreholes, ship tracks, buoys, towers, sampling stations, sensor networks, vegetation sites, stream gauges, and observatories) wherever marine, terrestrial, or atmospheric data are collected. Contributing partners for this collaborative resource include the U.S. NSF, ACADIS, ADIwg, AOOS, a2dc, AON, ARMAP, BAID, CAFF, IASOA, INTERACT, and others. While focusing on U.S. activities, the AOV welcomes information exchange with international groups for mutual benefit. Users can visualize, navigate, select, search, draw, print, and more. AOV is founded on principles of interoperability, with open metadata and web service standards, so that agencies and organizations can use AOV tools and services for their own purposes. In this way, AOV will reinforce and complement other distributed yet interoperable cyber-resources and will help science planners, funding agencies, researchers, data specialists, and others to assess status, identify overlap, fill gaps, optimize sampling design, refine network performance, clarify directions, access data, coordinate logistics, collaborate, and more in order to meet Arctic Observing goals.Malgré les progrès réalisés dans le cadre de nombreux efforts d’observation de l’Arctique, les progrès peuvent être difficiles à évaluer. Quelles initiatives de collecte de données sont en cours ou sont établies? À quel endroit? Et qui gère ces initiatives? Pour aider à répondre aux besoins stratégiques de programmes comme ceux de l’organisme américain Study of Environmental Arctic Change (SEARCH), du réseau Arctic Observing Network (AON), des réseaux Sustaining Arctic Observing Networks (SAON) et d’autres programmes connexes, on a procédé à la mise à jour de l’Arctic Observing Viewer (AOV; http://ArcticObservingViewer.org). Ce système d’information jumelé à une application de mappage sur le Web a amorcé la compilation des coordonnées et des renseignements se rapportant à des milliers de sites de collecte de données (comme les trous de forage, les trajets de navires, les bouées, les tours, les stations d’échantillonnage, les réseaux de capteurs, les sites de végétation, les fluviomètres et les observatoires) où des données marines, terrestres ou atmosphériques sont prélevées. Parmi les partenaires qui collaborent à cette ressource, notons U.S. NSF, ACADIS, ADIwg, AOOS, a2dc, AON, ARMAP, BAID, CAFF, IASOA, INTERACT et d’autres encore. Bien que l’AOV se concentre sur les activités américaines, il accepte l’échange d’information avec des groupes internationaux lorsqu’il existe des avantages mutuels. Les utilisateurs peuvent visualiser les données, naviguer dans le système, faire des sélections et des recherches, dessiner, imprimer et ainsi de suite. L’AOV fonctionne moyennant des principes d’interopérabilité, avec des métadonnées ouvertes et des normes de service sur le Web afin que les organismes et les organisations puissent utiliser les outils et les services de l’AOV pour leurs propres fins. De cette façon, l’AOV sera en mesure de consolider et de compléter d’autres cyberressources à la fois réparties et interopérables, en plus d’aider les planificateurs de la science, les bailleurs de fonds, les chercheurs, les spécialistes des données et d’autres encore à évaluer les statuts, à repérer les dédoublements, à combler les écarts, à optimiser les plans d’échantillonnage, à raffiner le rendement des réseaux, à clarifier les consignes, à accéder aux données, à coordonner la logistique, à collaborer et ainsi de suite afin de répondre aux objectifs d’observation de l’Arctique