Nucleolar Localization of HIV-1 Rev Is Required, Yet Insufficient for Production of Infectious Viral Particles.

Combination antiretroviral therapy fails in complete suppression of HIV-1 due to drug resistance and persistent latency. Novel therapeutic intervention requires knowledge of intracellular pathways responsible for viral replication, specifically those untargeted by antiretroviral drugs. An understudied phenomenon is the nucleolar localization of Rev phosphoprotein, which completes nucleocytoplasmic transport of unspliced/partially spliced HIV mRNA through multimerization with intronic cis-acting targets-the Rev-response element (RRE). Rev contains a nucleolar localization signal (NoLS) comprising the COOH terminus of the arginine-rich motif for accumulation within nucleoli-speculated as the interaction ground for Rev with cellular proteins mediating mRNA-independent nuclear export and splicing. Functionality of Rev nucleolar access during HIV-1 production and infection was investigated in the context of deletion and single-point mutations within Rev-NoLS. Mutations induced upon Rev-NoLS are hypothesized to inactivate the HIV-1 infectious cycle. HIV-1HXB2 replication ceased with Rev mutations lacking nucleolar access due to loss or replacement of multiple arginine residues. Rev mutations missing single arginine residues remained strictly nucleolar in pattern and participated in proviral production, however, with reduced efficiency. Viral RNA packaging also decreased in efficiency after expression of nucleolar-localizing mutations. These results were observed during propagation of variant HIV-1NL4-3 containing nucleolar-localizing mutations within the viral backbone (M4, M5, and M6). Lentiviral particles produced with Rev single-point mutations were transducible at extremely low frequency. Similarly, HIV-1NL4-3 Rev-NoLS variants lost infectivity, unlike virulent WT (wild type) HIV-1NL4-3. HIV-1NL4-3 variants were capable of CD4+ host entry and reverse transcription as WT HIV-1NL4-3, but lacked ability to complete a full infectious cycle. We currently reveal that viral integration is deregulated in the presence of Rev-NoLS mutations

The construct validity of the Dutch personality inventory for DSM-5 personality disorders (PID-5) in a clinical sample

The factor structure and the convergent validity of the Personality Inventory for DSM-5 (PID-5), a self-report questionnaire designed to measure personality pathology as advocated in the fifth edition, Section III of Diagnostic and Statistical Manual of Mental Disorders (DSM-5), are already demonstrated in general population samples, but need replication in clinical samples. In 240 Flemish inpatients, we examined the factor structure of the PID-5 by means of exploratory structural equation modeling. Additionally, we investigated differences in PID-5 higher order domain scores according to gender, age and educational level, and explored convergent and discriminant validity by relating the PID-5 with the Dimensional Assessment of Personality PathologyBasic Questionnaire and by comparing PID-5 scores of inpatients with and without a DSM-IV categorical personality disorder diagnosis. Our results confirmed the original five-factor structure of the PID-5. The reliability and the convergent and discriminant validity of the PID-5 proved to be adequate. Implications for future research are discussed

Cultivando nuevos valores en el paisaje urbano : incrementando la seguridad alimenticia y el bienestar social por medio de la ecología urbana

Landscape architecture is a design discipline and a form of art. It is an art which grows, transforms, dies and revives itself in engagement with the physical world. It needs, as a design discipline, to engage with these multiple layers of the physical world to support healthy living, beauty, renewal and even survival. The environmental and social benefits urban nature provides and relies on have in recent times been redefined as ‘ecosystem services’. As part of this discourse, landscape design is an art which is becoming all the more relevant for the physical world in the wake of escalating population growth, urbanization and climate change. There are still however left-over voids of land within our settlements that can become valuable for social, economic and environmental purposes. The paper explores the possibility of using these for allotment community gardening through a case study in Sunnyside, Pretoria. An abandoned stretch of land along the Walker Spruit served as a model for testing the hypothesis of increasing food security and social capital through a design that embraces urban ecology. The literature review provides numerous ideas and examples to substantiate the rationale of the approach. Guerrilla Gardening is investigated as a response to recent concepts of ecological justice and politics. The allotment culture is revisited as re-explored in recent times in Britain, Canada and Switzerland. Subsequently the concept of green infrastructure is used to explore the theory of a Continuous Productive Urban Landscape. The findings suggest that allotment culture and permaculture can be ways of reconnecting people with urban nature. The design concept of the ‘three natures’, builds on this underlying idea and propose how it can become a physical reality. As a result, a new identity that ties in with the original genius of place can unite two very distinct neighbourhoods in the city: Clydesdale and Sunnyside East, while providing the required social and biophysical services sustainably. The study upholds that as urban development continues to strive for greater resilience in the future, community involvement can only be central to its vision.La arquitectura de paisaje es una disciplina del diseño y también una forma de arte. Como arte crece, se transforma, muere y revive en su compromiso con el medio físico. Pero necesita, como disciplina del diseño, entramarse con las diferentes esferas del este medio físico para promover una vida saludable, la riqueza estética, la renovación y hasta la sobrevivencia. Los beneficios ambientales y sociales que la naturaleza urbana provee y en los que depende, se han definido últimamente como ‘servicios eco-sistémicos’. Como parte de esta postura, la arquitectura del paisaje cobra aún más relevancia, considerando también el rápido crecimiento demográfico a nivel mundial, la urbanización y los cambios climáticos. En nuestros centros urbanos conviven todavía espacios desarrollados con áreas vacantes, estas últimas representan un valor potencial en el aspecto social, económico y como servicios eco-sistémicos. Este artículo explora las posibilidades que estos espacios ofrecen para la agricultura urbana comunitaria desde un caso específico en Sunnyside, Pretoria. Un terreno lineal en desuso a lo largo del Walker spruit (pequeño curso de agua) sirve de modelo para analizar esta hipótesis de incrementar la seguridad alimenticia y el bienestar social a través de un diseño comprometido con la ecología urbana. El movimiento activista ‘Guerrilla Gardening’ (guerrilla jardinera), ha sido investigado como respuesta a los últimos conceptos de justicia ecológica y política. La agricultura urbana es revisada tal como ha sido reevaluada recientemente en Gran Bretaña, Canadá y Suiza. A si mismo el concepto de infraestructura verde es usado para explorar la teoría de un Paisaje Urbano Productivo y Continuo. Los resultados sugieren que la agricultura urbana y la permacultura pueden ser vehículos de reconexión entre la naturaleza y la gente. El concepto de diseño de las “tres naturalezas”, se basa en esta idea y en cómo puede convertirse en una realidad física. Como resultado, una nueva identidad en harmonía con el espíritu del lugar puede hermanar dos barrios diferentes de la ciudad, Clydesdale y Sunnyside Este, a la vez que proveyendo los requeridos servicios sociales y biofísicos sustentablemente. Este estudio defiende el hecho de que como el desarrollo urbano continúa su búsqueda de mayor autonomía, en el futuro la participación de la comunidad solo puede ser fundamental para este fin.http://www.journals.co.za/ej/ejour_sajah.htmlam201

Approaches for assessing the impacts of the Rural Development Programmes in the context of multiple intervening factors

The Common Monitoring and Evaluation Framework (CMEF) provides a single framework for monitoring and evaluation of all EU Rural Development Programmes (RDP) in the current programming period (2007-2013). It provides continuity from previous periods and constitutes a significant simplification as regards assessment of results and impacts, while at the same time offering greater flexibility to Member States. The European Evaluation Network for Rural Development has published a Working Paper on Approaches for assessing the impacts of the Rural Development Programmes in the context of multiple intervening factors. The aim of the Working Paper is to inspire and to encourage programme evaluators, not to restrict or constrain them. From a methodological perspective, the three common socio-economic impact indicators of the CMEF (economic growth, employment creation, labour productivity) are more closely related than the four common environmental impact indicators (reversing biodiversity decline, maintenance of High Nature Value faming and forestry, improvement in water quality, contribution to combating climate change).assessment of impacts, Rural Development Programmes, policy evaluation, EU policy, Agricultural and Food Policy,

Le temps partiel moins attractif ?

Dans les secteurs de l’hôtellerie-restauration et du commerce, le temps partiel a longtemps été un outil privilégié de flexibilité pour les entreprises qui cherchaient à adapter leur volume de main-d’œuvre en fonction de leurs besoins, souvent difficiles à anticiper. Cependant, à partir de la fin des années 1990, les contrats à temps partiel sont devenus de moins en moins flexibles à mesure que le législateur en encadrait et en réglementait les usages. Les pouvoirs publics ont ainsi cherché à limiter les excès des périodes antérieures et la précarité associée à ces contrats, touchant essentiellement des femmes peu diplômées. L’article s’interroge sur les effets de ces changements législatifs dans les branches et dans les entreprises : comment les acteurs nationaux les ont-ils traduits dans les conventions collectives ? Comment les entreprises ont-elles réagi et abordent-elles cette nouvelle donne législative et conventionnelle ? À partir d’une étude qualitative réalisée de 2009 à 2011, nous revenons sur les enjeux du temps partiel dans les secteurs de services et sur les conséquences de la loi et de son appropriation par les acteurs à tous les niveaux de la régulation collective (articulations entre la loi, les conventions nationales, les accords d’entreprises et les pratiques sur le terrain). Nous avançons que de nouvelles configurations organisationnelles flexibles émergent dans les entreprises, associant au temps partiel un recours accru à la polyactivité, à la polyvalence et à la polycompétence.Part time work has long been a privileged management tool for companies in the “hotel and catering” and “retail trade” service sectors seeking to adjust employment volume to companies’ needs that are not easy to anticipate. However, since the end of the nineties, these part time contracts have become less and less flexible as the legislator has increased their legal framework and regulated their use. The aim of public authorities was to minimise the lack of job security which characterised part time positions, mainly occupied by unskilled women. This article deals with the implementation of these legislative changes within the service sector: how did national industrial partners translate them into collective bargaining agreements? How did companies react to these new labour laws? Based on a qualitative study conducted from 2009 to 2011, this article analyses the issues of part time work in the service sector and the effects of new legislation at every level of collective regulation: legal structures, collective bargaining agreements, company agreements, and practical experiments in companies. The authors also give an account of new flexible organizational patterns in companies, linking part time work to more polyvalence, polyactivity and polycompetence

Isotopic and geochemical constraints on lead and fluid sources of the Pb-Zn-Ag mineralization in the polymetallic Tighza-Jbel Aouam district (central Morocco), and relationships with the geodynamic context

International audienceThe Wsingle bondAu, Pbsingle bondZnsingle bondAg, and Sbsingle bondBa mineralizations of the polymetallic Tighza-Jbel Aouam district (central Meseta, Morocco), are hosted in Paleozoic rocks surrounding late-Carboniferous granitic stocks. The Pbsingle bondZnsingle bondAg Tighza deposit formed at 254 ± 16 Ma, and is clearly disconnected from the late-Variscan Wsingle bondAu deposit (295-280 Ma). The Pbsingle bondZnsingle bondAg mineralization precipitated from a complex hydrothermal fluid. It displays air-normalized 3He/4He ratio (0.018–0.103) typical of the upper crust. This crustal component is confirmed by the oxygen and carbon isotope compositions (δ18O = +19 to +25‰; δ13C = −3.6 to −11.2‰) and the ɛNd values (−4.84 to −9.01) of gangue carbonates, which show mixing of (i) fluids that have interacted with late-Carboniferous magmatic rocks, and (ii) fluids in equilibrium with the Paleozoic metasediments. In addition, the Pbsingle bondZnsingle bondAg mineralization has 40Ar/36Ar values in the range 284–315 typical of a meteoric fluid. The radiogenic Pb isotopic compositions (207Pb/204Pb = 15.70–15.80 and 206Pb/204Pb = 18.30–18.50) suggest leaching of Pb from the surrounding Paleozoic metasediments and late-Variscan granites, whereas the low radiogenic signatures (207Pb/204Pb = 15.40 and 206Pb/204Pb = 18.05) provide evidence of a deeper source attributed to the lower crust.Crustal thinning related to extensional tectonics in late-Permian and Early-Triassic lead to high-K calc-alkaline to alkaline magmatic activity, which is evidenced by a dense SW-NE-trending dike network that pre-dated the Atlantic Ocean opening (early Liassic times). This magmatic event induced a regional heat flux increase that triggered the circulation of a complex hydrothermal fluid, which has a strong crustal component, but also a meteoric and a lower crustal components. The polymetallic district of Tighza-Jbel Aouam thus results from superposition of an intrusion related porphyry-gold mineralization (Wsingle bondAu, 286 Ma) followed by a Pbsingle bondZnsingle bondAg epithermal mineralization (254 Ma), during two distinct magmatic-hydrothermal events.The proposed metallogenic model for the Pbsingle bondZnsingle bondAg Tighza-Jbel Aouam deposit provides new constraints for the Pbsingle bondZnsingle bondAg exploration in the Moroccan Meseta. Exploration targets must take into account the following geological features: (i) Permo-triassic high-K calk-alkaline to alkaline dikes, (ii) extensional tectonics and reactivation of ancient crust-scale faults and shear zones, and (iii) Paleozoic series containing organic matter (e.g., black shales) subjected to low grade metamorphism (e.g., greenschist facies)

Regulation of host gene expression by HIV-1 TAR microRNAs

Background: The transactivating response (TAR) element of human immunodeficiency virus type 1 (HIV-1) is the source of two functional microRNAs (miRNAs), miR-TAR-5p and miR-TAR-3p. The objective of this study was to characterize the post-transcriptional regulation of host messenger RNAs (mRNAs) relevant to HIV-1 pathogenesis by HIV-1 TAR miRNAs. Results: We demonstrated that TAR miRNAs derived from HIV-1 can incorporate into host effector Argonaute protein complexes, which is required if these miRNAs are to regulate host mRNA expression. Bioinformatic predictions and reporter gene activity assays identified regulatory elements complementary and responsive to miR-TAR-5p and miR-TAR-3p in the 3’ untranslated region (UTR) of several candidate genes involved in apoptosis and cell survival. These include Caspase 8, Aiolos, Ikaros and Nucleophosmin (NPM)/B23. Analyses of Jurkat cells that stably expressed HIV-1 TAR or contained a full-length latent HIV provirus suggested that HIV-1 TAR miRNAs could regulate the expression of genes in T cells that affect the balance between apoptosis and cell survival. Conclusions: HIV-1 TAR miRNAs may contribute to the replication cycle and pathogenesis of HIV-1, by regulating host genes involved in the intricate balance between apoptosis and infected cell, to induce conditions that promote HIV-1 propagation and survival

Use of the open source software Greenstone to develop a decentralized cooperative digital library

When the Latin America and the Caribbean Social Sciences Network of Virtual Libraries was created 10 years ago, it was an easy decision to work with open software because the Latin America and the Caribbean Social Science Council (Clacso), an academic network with 195 member institutes located in 21 countries, promotes the use of open software and open access to communicate and exchange research results in digital formats. The development and daily operations of this cooperative digital library are described, including Greenstone for the reading room with advanced search capacity and Plone for the graphical interface; both allow decentralized content management with 9.000 full text publications (books, journal articles, working documents, papers) and databases

Magnetic Force Sensing Using a Self-Assembled Nanowire

We present a scanning magnetic force sensor based on an individual magnet-tipped GaAs nanowire (NW) grown by molecular beam epitaxy. Its magnetic tip consists of a final segment of single-crystal MnAs formed by sequential crystallization of the liquid Ga catalyst droplet. We characterize the mechanical and magnetic properties of such NWs by measuring their flexural mechanical response in an applied magnetic field. Comparison with numerical simulations allows the identification of their equilibrium magnetization configurations, which in some cases include magnetic vortices. To determine a NW's performance as a magnetic scanning probe, we measure its response to the field profile of a lithographically patterned current-carrying wire. The NWs' tiny tips and their high force sensitivity make them promising for imaging weak magnetic field patterns on the nanometer-scale, as required for mapping mesoscopic transport and spin textures or in nanometer-scale magnetic resonance