488 research outputs found

    Computational Fitness Landscape for All Gene-Order Permutations of an RNA Virus

    Get PDF
    How does the growth of a virus depend on the linear arrangement of genes in its genome? Answering this question may enhance our basic understanding of virus evolution and advance applications of viruses as live attenuated vaccines, gene-therapy vectors, or anti-tumor therapeutics. We used a mathematical model for vesicular stomatitis virus (VSV), a prototype RNA virus that encodes five genes (N-P-M-G-L), to simulate the intracellular growth of all 120 possible gene-order variants. Simulated yields of virus infection varied by 6,000-fold and were found to be most sensitive to gene-order permutations that increased levels of the L gene transcript or reduced levels of the N gene transcript, the lowest and highest expressed genes of the wild-type virus, respectively. Effects of gene order on virus growth also depended upon the host-cell environment, reflecting different resources for protein synthesis and different cell susceptibilities to infection. Moreover, by computationally deleting intergenic attenuations, which define a key mechanism of transcriptional regulation in VSV, the variation in growth associated with the 120 gene-order variants was drastically narrowed from 6,000- to 20-fold, and many variants produced higher progeny yields than wild-type. These results suggest that regulation by intergenic attenuation preceded or co-evolved with the fixation of the wild type gene order in the evolution of VSV. In summary, our models have begun to reveal how gene functions, gene regulation, and genomic organization of viruses interact with their host environments to define processes of viral growth and evolution

    Beyond Remittance: Evading Uselessness and Seeking Personhood in Fouta Djallon, Guinea

    Get PDF
    Remittance networks built through transnational migration have transformed local economies as well as social lives in many parts of the world. In this article, I examine the relationship between transnational migration and local business practices for ethnic Fulɓe people from the Fouta Djallon highlands of Guinea. Although some Fouta Djallon residents have withstood poverty with the help of remittances from migrant relatives, many migrants fail to earn money abroad. But despite slim chances of success, migration remains a popular undertaking, especially for young men. Meanwhile, non-migrants engage in small business projects that yield little or no income. Analyzing informants’ critiques of “uselessness,” I argue that both near- impossible migration quests and seemingly irrational business practices are linked by a common desire to achieve social personhood under adverse structural conditions. Apparent striving for success mitigates failure to send or earn money, even while reproducing ideals of mobility and entrepreneurship in responsible personhood

    Transcriptomic Analysis of Host Immune and Cell Death Responses Associated with the Influenza A Virus PB1-F2 Protein

    Get PDF
    Airway inflammation plays a major role in the pathogenesis of influenza viruses and can lead to a fatal outcome. One of the challenging objectives in the field of influenza research is the identification of the molecular bases associated to the immunopathological disorders developed during infection. While its precise function in the virus cycle is still unclear, the viral protein PB1-F2 is proposed to exert a deleterious activity within the infected host. Using an engineered recombinant virus unable to express PB1-F2 and its wild-type homolog, we analyzed and compared the pathogenicity and host response developed by the two viruses in a mouse model. We confirmed that the deletion of PB1-F2 renders the virus less virulent. The global transcriptomic analyses of the infected lungs revealed a potent impact of PB1-F2 on the response developed by the host. Thus, after two days post-infection, PB1-F2 invalidation severely decreased the number of genes activated by the host. PB1-F2 expression induced an increase in the number and level of expression of activated genes linked to cell death, inflammatory response and neutrophil chemotaxis. When generating interactive gene networks specific to PB1-F2, we identified IFN-γ as a central regulator of PB1-F2-regulated genes. The enhanced cell death of airway-recruited leukocytes was evidenced using an apoptosis assay, confirming the pro-apoptotic properties of PB1-F2. Using a NF-kB luciferase adenoviral vector, we were able to quantify in vivo the implication of NF-kB in the inflammation mediated by the influenza virus infection; we found that PB1-F2 expression intensifies the NF-kB activity. Finally, we quantified the neutrophil recruitment within the airways, and showed that this type of leukocyte is more abundant during the infection of the wild-type virus. Collectively, these data demonstrate that PB1-F2 strongly influences the early host response during IAV infection and provides new insights into the mechanisms by which PB1-F2 mediates virulence

    Comparative analysis of the impact of geological activity on astronomical sites of the Canary Islands, Hawaii and Chile

    Full text link
    An analysis of the impact of seismic and volcanic activity was carried out at selected astronomical sites, namely the observatories of El Teide (Tenerife, Canary Islands), Roque de los Muchachos (La Palma, Canary Islands), Mauna Kea (Hawaii) and Paranal (Chile) and the candidate site of Cerro Ventarrones (Chile). Hazard associated to volcanic activity is low or negligible at all sites, whereas seismic hazard is very high in Chile and Hawaii. The lowest geological hazard in both seismic and volcanic activity was found at Roque de los Muchachos observatory, in the island of La Palma.Comment: 12 pages and 11 figure

    On the interpretation of removable interactions: A survey of the field 33 years after Loftus

    Get PDF
    In a classic 1978 Memory &Cognition article, Geoff Loftus explained why noncrossover interactions are removable. These removable interactions are tied to the scale of measurement for the dependent variable and therefore do not allow unambiguous conclusions about latent psychological processes. In the present article, we present concrete examples of how this insight helps prevent experimental psychologists from drawing incorrect conclusions about the effects of forgetting and aging. In addition, we extend the Loftus classification scheme for interactions to include those on the cusp between removable and nonremovable. Finally, we use various methods (i.e., a study of citation histories, a questionnaire for psychology students and faculty members, an analysis of statistical textbooks, and a review of articles published in the 2008 issue of Psychology andAging) to show that experimental psychologists have remained generally unaware of the concept of removable interactions. We conclude that there is more to interactions in a 2 × 2 design than meets the eye

    Understanding cyclic seismicity and ground deformation patterns at volcanoes: intriguing lessons from Tungurahua volcano, Ecuador

    Get PDF
    Cyclic seismicity and ground deformation patterns are observed on many volcanoes worldwide where seismic swarms and the tilt of the volcanic flanks provide sensitive tools to assess the state of volcanic activity. Ground deformation at active volcanoes is often interpreted as pressure changes in a magmatic reservoir, and tilt is simply translated accordingly into inflation and deflation of such a reservoir. Tilt data recorded by an instrument in the summit area of Tungurahua volcano in Ecuador, however, show an intriguing and unexpected behaviour on several occasions: prior to a Vulcanian explosion when a pressurisation of the system would be expected, the tilt signal declines significantly, hence indicating depressurisation. At the same time, seismicity increases drastically. Envisaging that such a pattern could carry the potential to forecast Vulcanian explosions on Tungurahua, we use numerical modelling and reproduce the observed tilt patterns in both space and time. We demonstrate that the tilt signal can be more easily explained as caused by shear stress due to viscous flow resistance, rather than by pressurization of the magmatic plumbing system. In general, our numerical models prove that if magma shear viscosity and ascent rate are high enough, the resulting shear stress is sufficient to generate a tilt signal as observed on Tungurahua. Furthermore, we address the interdependence of tilt and seismicity through shear stress partitioning and suggest that a joint interpretation of tilt and seismicity can shed new light on the eruption potential of silicic volcanoes

    Whole Genomes of Chandipura Virus Isolates and Comparative Analysis with Other Rhabdoviruses

    Get PDF
    The Chandipura virus (CHPV) belonging to the Vesiculovirus genus and Rhabdoviridae family, has recently been associated with a number of encephalitis epidemics, with high mortality in children, in different parts of India. No full length genome sequences of CHPV isolates were available in GenBank and little is known about the molecular markers for pathogenesis. In the present study, we provide the complete genomic sequences of four isolates from epidemics during 2003–2007. These sequences along with the deduced sequence of the prototype isolate of 1965 were analysed using phylogeny, motif search, homology modeling and epitope prediction methods. Comparison with other rhaboviruses was also done for functional extrapolations. All CHPV isolates clustered with the Isfahan virus and maintained several functional motifs of other rhabdoviruses. A notable difference with the prototype vesiculovirus, Vesicular Stomatitis Virus was in the L-domain flanking sequences of the M protein that are known to be crucial for interaction with host proteins. With respect to the prototype isolate, significant additional mutations were acquired in the 2003–2007 isolates. Several mutations in G mapped onto probable antigenic sites. A mutation in N mapped onto regions crucial for N-N interaction and a putative T-cell epitope. A mutation in the Casein kinase II phosphorylation site in P may attribute to increased rates of phosphorylation. Gene junction comparison revealed changes in the M-G junction of all the epidemic isolates that may have implications on read-through and gene transcription levels. The study can form the basis for further experimental verification and provide additional insights into the virulence determinants of the CHPV
    corecore