THE HCMV INTERACTOME: A QUANTITATIVE ANALYSIS OF HUMAN CYTOMEGALOVIRUS-HOST PROTEIN INTERACTIONS

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects the majority of the adult population. Similarly to other herpesvirus, it is able to enter a state of latency, persisting within the host for life. Infection of healthy individuals is normally asymptomatic, however it is among the most common causes of allograft rejection, and can lead to several life-threatening diseases in the immunocompromised. Moreover, it is the leading viral infectious cause for congenital disease. HCMV encodes 171 canonical genes, and a substantial number of non-canonical ORFs have been identified by ribosome profiling and proteomics. The functions of many canonical HCMV proteins remain poorly understood, and it is not yet clear how many non-canonical ORFs encode functional polypeptides. Recent studies have provided an extensive overview on the modulation of gene expression as well as the spatio-temporal dynamics of viral and host proteins during HCMV infection. However, characterisation of specific protein-protein interactions and the exact molecular mechanisms underpinning the biological changes observed during viral infection are beyond the scope of these approaches. Affinity-purification mass spectrometry was performed to identify binding partners for 169 canonical, and 2 non-canonical HCMV proteins in infected cells. CompPass filtering determined an extensive network of high-confidence interacting proteins, with >3,400 virus-host and >150 virus-virus protein interactions. Domain association analysis identified protein domains co-occurring with unusual frequency, while functional enrichment analysis provided an insight into novel functions of multiple viral genes as well as how HCMV systematically modulates host environment, for example interacting with transcriptional repressive complexes or families of ubiquitin E3 ligases. Furthermore, combining interaction data with a recently published systematic analysis of HCMV-induced protein degradation identified viral interactors for 31/133 degraded host targets. Finally, the uncharacterised, non-canonical ORFL147C protein was found to interact with elements of the mRNA splicing machinery, and a mutational study suggested its importance in viral replication. The interactome data will be important for future studies of herpesvirus infection

Anatomy and Sequence Architecture of the early Post-Rift in the Neuquén Basin (Argentina): A Response to Physiography and Relative Sea-level Changes

A detailed architectural and sequence stratigraphic analysis was carried out in the early-post-rift succession of central Neuque´n Basin (Middle Jurassic Cuyo Group), integrating outcrop and subsurface information from a 3,000 km2 area. Sedimentary facies analysis allowed the definition of six marine facies associations, which are grouped in two main depositional systems. During the late Toarcian to early Bathonian a storm- and wave-dominated shoreface to offshore system was developed. This is overlain by a late Bathonian–early Callovian fluvio-deltaic depositional system. The sequence stratigraphic analysis of this succession identified parasequences limited by marine flooding surfaces with little evidence of erosion. Parasequences could be grouped into four parasequence sets that show the evolution of the depositional systems and can be interpreted in terms of shoreline trajectories. In this sense, a log-term transgressive event defined by a complicated retrogradational stacking pattern and spanning for almost 10 My is identified for the older deposits. This succession is eventually replaced by a progradational unit that represents highstand conditions. The Cuyo succession identified in this part of the basin is completed by the development of a regressive surface and the onset of a deltaic depositional system with no parasequence development but indicating an abrupt basinward facies shift. The long-term transgression that dominates the early post-rift succession in this part of the basin is interpreted to represent a period of sustained accommodation creation produced by the combination of thermal subsidence, differential compaction of syn-rift deposits, and eustatic rise under a relatively low sediment supply. Changes in the stacking pattern of retrogradational parasequence sets are thought to be produced by changes in the bathymetry of the topography being flooded, which is a relic of a complex array of footwalls and shoulders generated during the syn-rift stage. Regional changes in thickness and timing for the early post-rift succession could be therefore the result of the relatively passive infill of an inherited topography of the syn-rift, suggesting that most of the accommodation was already created before the onset of the long-term transgressive trend that characterizes the post-rift succession in this part of the basin. The Cuyo Group succession reported here reflects the complexity in terms of depositional styles, sequence stratigraphic patterns, and controls that can be expected during the early-post rift infill of syn-rift structural depressions. Therefore, the results of this study can provide useful lessons for post-rift systems having prolific hydrocarbon production worldwide (e.g., in the Northern North Sea, Norwegian Sea, Thailand, and Argentina and Chile).Fil: Veiga, Gonzalo Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Schwarz, Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Spalletti, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Massaferro, Jose L. YPF S.A; Argentin

Internationalisation plan for bifanas de Vendas Novas- as tradicionais

The following project aims to prepare an internationalisation plan for bifanas de Vendas Novas- As tradicionais, a Portuguese company that sells a traditional and regional recipe at low prices. After analysing the internal and external environment of the company, followed by a quantitative and qualitative analysis with country clustering and country ranking techniques, France was selected as the most promising market. Subsequently, the franchise agreement was proposed as the best entry mode and a marketing plan, the organisational structure and some financial projections were designed, which are intended to help leading the road to a successful first international expansion

Practical service placement approach for microservices architecture

Community networks (CNs) have gained momentum in the last few years with the increasing number of spontaneously deployed WiFi hotspots and home networks. These networks, owned and managed by volunteers, offer various services to their members and to the public. To reduce the complexity of service deployment, community micro-clouds have recently emerged as a promising enabler for the delivery of cloud services to community users. By putting services closer to consumers, micro-clouds pursue not only a better service performance, but also a low entry barrier for the deployment of mainstream Internet services within the CN. Unfortunately, the provisioning of the services is not so simple. Due to the large and irregular topology, high software and hardware diversity of CNs, it requires of aPeer ReviewedPostprint (author's final draft

ARTA: An economic middleware to exchange pervasive energy and computing resources

Studies reveal that an integrated system of smart grid and cloud computing ecosystems can better attain the energy efficiency objectives, considering all the aspects. To facilitate the integration, in this paper, we introduce an agent-oriented economic middleware architecture (ARTA) to exchange pervasive energy and computing resources in different layers of the service provisioning platform, from the edge layer of micro-grid and P2P-cloud to the mass production layer of the giant power plants and data centers. ARTA follows a semi-decentralized economic model by operating through partial system view in the edge-layer negotiations and considers system dynamics and uncertainties in the agents decisions.Peer ReviewedPostprint (author's final draft

Variability of continental depositional systems during lowstand sedimentation: an example from the Kimmeridgian of the Neuquén Basin, Argentina

En la sucesión jurásico-cretácica de la Cuenca Neuquina se reconocen varias cuñas de mar bajo que se distinguen por el desarrollo de depósitos continentales y marinos someros en los sectores más distales de la cuenca, dispuestos mediante una discontinuidad basal por encima de depósitos marinos relativamente profundos. La cuña de mar bajo kimmeridgiana se acumuló inmediatamente después del ascenso del arco magmático andino y la inversión tectónica de estructuras extensionales intracuencales. Como resultado, la Cuenca Neuquina quedó compartimentalizada en tres depocentros principales, caracterizados por el dominio de sedimentos continentales acumulados bajo condiciones climáticas áridas hasta semiáridas. En el Depocentro Noroeste prevalecieron los depósitos fluviales, caracterizados por un cambio sistemático de la arquitectura fluvial desde las zonas proximales a las distales del sistema. El diseño de superposición granodecreciente en este depocentro, junto con el frecuente desarrollo de suelos hacia la parte superior del registro, sugiere el incremento progresivo de la acomodación y el emplazamiento mucho más superficial del nivel freático. Las sucesiones sedimentarias en los depocentros Sudoeste y Este están caracterizadas por la transición desde sistemas fluviales efímeros a eólicos. Sin embargo, los depósitos de la cuña de mar bajo en el depocentro oriental poseen una más amplia distribución areal y mayores espesores de los depósitos fluviales y eólicos. Importantes variaciones en el espesor y en la arquitectura de los depósitos fluviales y eólicos en los depocentros sudoriental y oriental indican que la sedimentación estuvo controlada por cambios importantes en la acomodación. Situaciones de baja acomodación favorecieron la migración lateral de los canales fluviales desarrollados en condiciones algo más húmedas, junto con el desarrollo de campos de dunas de crestas sinuosas asociados con áreas de interduna húmeda. Bajo condiciones de alta acomodación los depósitos fluviales tendieron a sistemas retrogradacionales con preservación de importantes sucesiones de sedimentos finos, junto con la formación, en especial hacia la parte superior del registro, de un importante mar de arena caracterizado por la amalgamación de dunas complejas. En contraste con la uniformidad que muestran los depósitos transgresivos y de mar alto en la Cuenca Neuquina, la cuña de mar bajo kimmeridgiana constituye un excelente ejemplo para comprender la respuesta estratigráfica a las variaciones regionales y temporales en acomodación, aportes detríticos y fisiografía como una respuesta a la interacción de los controles tectónicos y climáticos.Several second order lowstand wedges are recognized in the Jurassic-Early Cretaceous sedimentary record of the backarc Neuquén Basin (central-west Argentina). They are distinguished by sharp based continental and marginal marine siliciclastic deposits encased in offshore shales. The Kimmeridgian lowstand wedge was developed slightly after the emergence of the Andean magmatic arc and the tectonic inversion of previous intrabasinal extensional structures. As a result, the Neuquén Basin was compartmentalized into three main depocentres characterised by widespread continental sedimentation under arid to semiarid climatic conditions. A fluvial-dominated system characterised by systematic downstream changes in architectural style is recognized in the Northwestern Depocentre. A gravely and sandy bedload fluvial system was developed in the southern upstream sector, while ticker beds of finer-grained sediments formed in a distal ephemeral fluvial system prevail in the downstream part of the system. The overall fining upward stacking pattern of the sedimentary record in the Northwestern Depocentre accompanied by frequent development of soil horizons and darker deposits suggests a change towards higher accommodation and high water table emplacement. In the Southwestern and Eastern Depocentres, the sedimentary successions show a conspicuous internal transition from fluvial ephemeral fluvial systems to aeolian systems. However, the lowstand deposits of the Eastern Depocentre are characterised by a larger areal distribution and a thicker record of both the fluvial and the aeolian deposits. Marked changes in thickness and in the depositional style of the fluvial and aeolian facies associations within the Southwestern and Eastern depocentres indicate that the sedimentary infill was controlled by systematic variations in accommodation. Low accommodation conditions favoured a high degree of lateral migration of fluvial channels with substantial erosion of fine-grained deposits and the development of sinuous-crested aeolian dunes typically associated with wet interdune deposits. Under higher accommodation conditions the fluvial deposits show a retrogradational stacking with preservation of thick packages of fine-grained sediments, while a large sand sea characterised by amalgamation of dune deposits was developed in the aeolian-dominated uppermost successions. The detailed analysis of the Kimmeridgian lowstand wedge of the Neuquén Basin illustrates how facies and stratigraphic organisation responded to regional and temporal changes in basin configuration, accommodation, sediment supply and water table position. The Kimmeridgian lowstand deposits are geographically distributed as the subsequent transgressive deposits and reveal no major basinward shift during the early stages of sequence stacking. However, they show a much more complicated facies distribution. Consequently, the lowstand wedge deposits better reflect the complex interplay of episodic local tectonism, siliciclastic source area variation and climatic change.Centro de Investigaciones Geológica

Variability of continental depositional systems during lowstand sedimentation: an example from the Kimmeridgian of the Neuquén Basin, Argentina

En la sucesión jurásico-cretácica de la Cuenca Neuquina se reconocen varias cuñas de mar bajo que se distinguen por el desarrollo de depósitos continentales y marinos someros en los sectores más distales de la cuenca, dispuestos mediante una discontinuidad basal por encima de depósitos marinos relativamente profundos. La cuña de mar bajo kimmeridgiana se acumuló inmediatamente después del ascenso del arco magmático andino y la inversión tectónica de estructuras extensionales intracuencales. Como resultado, la Cuenca Neuquina quedó compartimentalizada en tres depocentros principales, caracterizados por el dominio de sedimentos continentales acumulados bajo condiciones climáticas áridas hasta semiáridas. En el Depocentro Noroeste prevalecieron los depósitos fluviales, caracterizados por un cambio sistemático de la arquitectura fluvial desde las zonas proximales a las distales del sistema. El diseño de superposición granodecreciente en este depocentro, junto con el frecuente desarrollo de suelos hacia la parte superior del registro, sugiere el incremento progresivo de la acomodación y el emplazamiento mucho más superficial del nivel freático. Las sucesiones sedimentarias en los depocentros Sudoeste y Este están caracterizadas por la transición desde sistemas fluviales efímeros a eólicos. Sin embargo, los depósitos de la cuña de mar bajo en el depocentro oriental poseen una más amplia distribución areal y mayores espesores de los depósitos fluviales y eólicos. Importantes variaciones en el espesor y en la arquitectura de los depósitos fluviales y eólicos en los depocentros sudoriental y oriental indican que la sedimentación estuvo controlada por cambios importantes en la acomodación. Situaciones de baja acomodación favorecieron la migración lateral de los canales fluviales desarrollados en condiciones algo más húmedas, junto con el desarrollo de campos de dunas de crestas sinuosas asociados con áreas de interduna húmeda. Bajo condiciones de alta acomodación los depósitos fluviales tendieron a sistemas retrogradacionales con preservación de importantes sucesiones de sedimentos finos, junto con la formación, en especial hacia la parte superior del registro, de un importante mar de arena caracterizado por la amalgamación de dunas complejas. En contraste con la uniformidad que muestran los depósitos transgresivos y de mar alto en la Cuenca Neuquina, la cuña de mar bajo kimmeridgiana constituye un excelente ejemplo para comprender la respuesta estratigráfica a las variaciones regionales y temporales en acomodación, aportes detríticos y fisiografía como una respuesta a la interacción de los controles tectónicos y climáticos.Several second order lowstand wedges are recognized in the Jurassic-Early Cretaceous sedimentary record of the backarc Neuquén Basin (central-west Argentina). They are distinguished by sharp based continental and marginal marine siliciclastic deposits encased in offshore shales. The Kimmeridgian lowstand wedge was developed slightly after the emergence of the Andean magmatic arc and the tectonic inversion of previous intrabasinal extensional structures. As a result, the Neuquén Basin was compartmentalized into three main depocentres characterised by widespread continental sedimentation under arid to semiarid climatic conditions. A fluvial-dominated system characterised by systematic downstream changes in architectural style is recognized in the Northwestern Depocentre. A gravely and sandy bedload fluvial system was developed in the southern upstream sector, while ticker beds of finer-grained sediments formed in a distal ephemeral fluvial system prevail in the downstream part of the system. The overall fining upward stacking pattern of the sedimentary record in the Northwestern Depocentre accompanied by frequent development of soil horizons and darker deposits suggests a change towards higher accommodation and high water table emplacement. In the Southwestern and Eastern Depocentres, the sedimentary successions show a conspicuous internal transition from fluvial ephemeral fluvial systems to aeolian systems. However, the lowstand deposits of the Eastern Depocentre are characterised by a larger areal distribution and a thicker record of both the fluvial and the aeolian deposits. Marked changes in thickness and in the depositional style of the fluvial and aeolian facies associations within the Southwestern and Eastern depocentres indicate that the sedimentary infill was controlled by systematic variations in accommodation. Low accommodation conditions favoured a high degree of lateral migration of fluvial channels with substantial erosion of fine-grained deposits and the development of sinuous-crested aeolian dunes typically associated with wet interdune deposits. Under higher accommodation conditions the fluvial deposits show a retrogradational stacking with preservation of thick packages of fine-grained sediments, while a large sand sea characterised by amalgamation of dune deposits was developed in the aeolian-dominated uppermost successions. The detailed analysis of the Kimmeridgian lowstand wedge of the Neuquén Basin illustrates how facies and stratigraphic organisation responded to regional and temporal changes in basin configuration, accommodation, sediment supply and water table position. The Kimmeridgian lowstand deposits are geographically distributed as the subsequent transgressive deposits and reveal no major basinward shift during the early stages of sequence stacking. However, they show a much more complicated facies distribution. Consequently, the lowstand wedge deposits better reflect the complex interplay of episodic local tectonism, siliciclastic source area variation and climatic change.Centro de Investigaciones Geológica