48 research outputs found
Accuracy in mineral identification: image spectral and spatial resolutions and mineral spectral properties
Problems related to airborne hyperspectral image data are reviewed and the requirements for data analysis applied
to mineralogical (rocks and soils) interpretation are discussed. The variability of mineral spectral features, including
absorption position, shape and depth is considered and interpreted as due to chemical composition, grain size
effects and mineral association. It is also shown how this variability can be related to well defined geologic processes.
The influence of sensor noise and diffuse atmospheric radiance in classification accuracy is also analyzed
Rewriting DNA Methylation Signatures at Will:The Curable Genome Within Reach?
DNA methyltransferases are important enzymes in a broad range of organisms. Dysfunction of DNA methyltransferases in humans leads to many severe diseases, including cancer. This book focuses on the biochemical properties of these enzymes, describing their structures and mechanisms in bacteria, humans and other species, including plants, and also explains the biological processes of reading of DNA methylation and DNA demethylation. It covers many emerging aspects of the biological roles of DNA methylation functioning as an essential epigenetic mark and describes the role of DNA methylation in diseases. Moreover, the book explains modern technologies, like targeted rewriting of DNA methylation by designed DNA methyltransferases, as well as technological applications of DNA methyltransferases in DNA labelling. Finally, the book summarizes recent methods for the analysis of DNA methylation in human DNA. Overall, this book represents a comprehensive state-of-the-art- work and is a must-have for advanced researchers in the field of DNA methylation and epigenetics
The Varicella-Zoster Virus ORF47 Kinase Interferes with Host Innate Immune Response by Inhibiting the Activation of IRF3
The innate immune response constitutes the first line of host defence that limits viral spread and plays an important role in the activation of adaptive immune response. Viral components are recognized by specific host pathogen recognition receptors triggering the activation of IRF3. IRF3, along with NF-κB, is a key regulator of IFN-β expression. Until now, the role of IRF3 in the activation of the innate immune response during Varicella-Zoster Virus (VZV) infection has been poorly studied. In this work, we demonstrated for the first time that VZV rapidly induces an atypical phosphorylation of IRF3 that is inhibitory since it prevents subsequent IRF3 homodimerization and induction of target genes. Using a mutant virus unable to express the viral kinase ORF47p, we demonstrated that (i) IRF3 slower-migrating form disappears; (ii) IRF3 is phosphorylated on serine 396 again and recovers the ability to form homodimers; (iii) amounts of IRF3 target genes such as IFN-β and ISG15 mRNA are greater than in cells infected with the wild-type virus; and (iv) IRF3 physically interacts with ORF47p. These data led us to hypothesize that the viral kinase ORF47p is involved in the atypical phosphorylation of IRF3 during VZV infection, which prevents its homodimerization and subsequent induction of target genes such as IFN-β and ISG15
A Gammaherpesvirus Cooperates with Interferon-alpha/beta-Induced IRF2 to Halt Viral Replication, Control Reactivation, and Minimize Host Lethality
The gammaherpesviruses, including Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), establish latency in memory B lymphocytes and promote lymphoproliferative disease in immunocompromised individuals. The precise immune mechanisms that prevent gammaherpesvirus reactivation and tumorigenesis are poorly defined. Murine gammaherpesvirus 68 (MHV68) is closely related to EBV and KSHV, and type I (alpha/beta) interferons (IFNαβ) regulate MHV68 reactivation from both B cells and macrophages by unknown mechanisms. Here we demonstrate that IFNβ is highly upregulated during latent infection, in the absence of detectable MHV68 replication. We identify an interferon-stimulated response element (ISRE) in the MHV68 M2 gene promoter that is bound by the IFNαβ-induced transcriptional repressor IRF2 during latency in vivo. The M2 protein regulates B cell signaling to promote establishment of latency and reactivation. Virus lacking the M2 ISRE (ISREΔ) overexpresses M2 mRNA and displays uncontrolled acute replication in vivo, higher latent viral load, and aberrantly high reactivation from latency. These phenotypes of the ISREΔ mutant are B-cell-specific, require IRF2, and correlate with a significant increase in virulence in a model of acute viral pneumonia. We therefore identify a mechanism by which a gammaherpesvirus subverts host IFNαβ signaling in a surprisingly cooperative manner, to directly repress viral replication and reactivation and enforce latency, thereby minimizing acute host disease. Since we find ISREs 5′ to the major lymphocyte latency genes of multiple rodent, primate, and human gammaherpesviruses, we propose that cooperative subversion of IFNαβ-induced IRFs to promote latent infection is an ancient strategy that ensures a stable, minimally-pathogenic virus-host relationship
Visualising rave music in Virtual Reality: symbolic and interactive approaches
In 2019 the virtual reality experience Cyberdream VR was presented at various events including the Event Two exhibition of computer art held at the Royal College of Art. This short demo for Oculus Gear VR provided a c.5 minute sonic journey, in which the user moves through a series of symbolic environments based on the futuristic techno-utopian or dystopian imagery of 90s rave fliers. These environments accompanied an original soundtrack of rave music and vaporwave, allowing users to enjoy the music whilst feeling as though they are inside synaesthetic virtual spaces related to the symbolic imagery of rave culture. This paper will discuss the subsequent development of this project, which is now being adapted for the Oculus Quest VR headset. Rajmil Fischman’s concept of ‘Music in the Holodeck’; the fictional ’holophonor’ instrument from the TV series Futurama; or the video game Rez Infinite, are among those that suggest paradigms for performing sound and visuals in VR. Drawing upon these ideas, the current iteration of Cyberdream allows the user to trigger ‘sound instruments’ with the Oculus Quest Touch controllers. This is conceived as a means through which the user can ‘paint with sound’ in 3D space, improvising with the music, whilst also generating synaesthetic imagery. The design of these sound instruments presents interesting challenges, in order for sound to be generated in correspondence with visual imagery, where these materials may complement both the music and spatial environments. Drawing on the author’s VJ work, at the macro level of compositional structure, the latest version of the project also seeks ways to provide a more continuous experience analogous to a DJ or VJ set, through blending of music tracks between scenes. This paper will discuss on-going work on this project, advancing the discourse regarding the visualisation of hardcore rave music in virtual reality
Pseudotumoural soft tissue lesions of the hand and wrist: a pictorial review
Mimickers of soft tissue tumours in the hand and wrist are more frequent than true neoplastic lesions. Pseudotumours belong to a large and heterogeneous group of disorders, varying from normal anatomical variants, cystic lesions, post-traumatic lesions, skin lesions, inflammatory and infectious lesions, non-neoplastic vascular lesions, metabolic disorders (crystal deposition disease and amyloidosis) and miscellaneous disorders. Although the imaging approach to pseudotumoural lesions is often very similar to the approach to “true” soft tissue tumoral counterparts, further management of these lesions is different. Biopsy should be performed only in doubtful cases, when the diagnosis is unclear. Therefore, the radiologist plays a pivotal role in the diagnosis of these lesions. Awareness of the normal anatomy and existence and common imaging presentation of these diseases, in combination with relevant clinical findings (clinical history, age, location and skin changes), enables the radiologist to make the correct diagnosis in most cases, thereby limiting the need for invasive procedures
Virtual hallucinations: projects in VJing, virtual reality and cyberculture
This paper discusses a variety of the author’s artistic projects exploring altered states of consciousness and computer art. First, the paper will provide a brief overview of previous creative works, which include compositions of electroacoustic music, interactive visualisations, and visual music films. These previous works use the concept of altered states of consciousness as a compositional principle, as explored in the author’s book Inner Sound: Altered States of Consciousness in Electronic Music and Audio-Visual Media (OUP 2018). Following this, a variety of the author’s recent creative work produced from 2016–2019 will be discussed. These works include: a series of paintings that incorporate computer graphics animations when viewed in augmented reality; VJ performances constructed using direct animation on 8mm film, computer graphics animations generated from code and audio-reactive effects; and Cyberdream VR, a virtual reality experience. These interrelated projects continue to develop the author’s artistic investigations into altered states, while also referencing work such as demo scene videos; cyberdelic imagery of the type seen on fliers from the 1990s rave-era; and the recent Internet-borne subculture vaporwave, which recontextualises the aesthetics of 1980s and 1990s ambient corporate music and utopian computer graphics to construct surrealistic dystopias
Biological cycle of silicon in moso bamboo (Phyllostachys pubescens) forests in central Japan
Varicella Viruses Inhibit Interferon-Stimulated JAK-STAT Signaling through Multiple Mechanisms
Varicella zoster virus (VZV) causes chickenpox in humans and, subsequently, establishes latency in the sensory ganglia from where it reactivates to cause herpes zoster. Infection of rhesus macaques with simian varicella virus (SVV) recapitulates VZV pathogenesis in humans thus representing a suitable animal model for VZV infection. While the type I interferon (IFN) response has been shown to affect VZV replication, the virus employs counter mechanisms to prevent the induction of anti-viral IFN stimulated genes (ISG). Here, we demonstrate that SVV inhibits type I IFN-activated signal transduction via the JAK-STAT pathway. SVV-infected rhesus fibroblasts were refractory to IFN stimulation displaying reduced protein levels of IRF9 and lacking STAT2 phosphorylation. Since previous work implicated involvement of the VZV immediate early gene product ORF63 in preventing ISG-induction we studied the role of SVV ORF63 in generating resistance to IFN treatment. Interestingly, SVV ORF63 did not affect STAT2 phosphorylation but caused IRF9 degradation in a proteasome-dependent manner, suggesting that SVV employs multiple mechanisms to counteract the effect of IFN. Control of SVV ORF63 protein levels via fusion to a dihydrofolate reductase (DHFR)-degradation domain additionally confirmed its requirement for viral replication. Our results also show a prominent reduction of IRF9 and inhibition of STAT2 phosphorylation in VZV-infected cells. In addition, cells expressing VZV ORF63 blocked IFN-stimulation and displayed reduced levels of the IRF9 protein. Taken together, our data suggest that varicella ORF63 prevents ISG-induction both directly via IRF9 degradation and indirectly via transcriptional control of viral proteins that interfere with STAT2 phosphorylation. SVV and VZV thus encode multiple viral gene products that tightly control IFN-induced anti-viral responses
A Temporal Gate for Viral Enhancers to Co-opt Toll-Like-Receptor Transcriptional Activation Pathways upon Acute Infection
Viral engagement with macrophages activates Toll-Like-Receptors (TLRs) and viruses must contend with the ensuing inflammatory responses to successfully complete their replication cycle. To date, known counter-strategies involve the use of viral-encoded proteins that often employ mimicry mechanisms to block or redirect the host response to benefit the virus. Whether viral regulatory DNA sequences provide an opportunistic strategy by which viral enhancer elements functionally mimic innate immune enhancers is unknown. Here we find that host innate immune genes and the prototypical viral enhancer of cytomegalovirus (CMV) have comparable expression kinetics, and positively respond to common TLR agonists. In macrophages but not fibroblasts we show that activation of NFκB at immediate-early times of infection is independent of virion-associated protein, M45. We find upon virus infection or transfection of viral genomic DNA the TLR-agonist treatment results in significant enhancement of the virus transcription-replication cycle. In macrophage time-course infection experiments we demonstrate that TLR-agonist stimulation of the viral enhancer and replication cycle is strictly delimited by a temporal gate with a determined half-maximal time for enhancer-activation of 6 h; after which TLR-activation blocks the viral transcription-replication cycle. By performing a systematic siRNA screen of 149 innate immune regulatory factors we identify not only anticipated anti-viral and pro-viral contributions but also new factors involved in the CMV transcription-replication cycle. We identify a central convergent NFκB-SP1-RXR-IRF axis downstream of TLR-signalling. Activation of the RXR component potentiated direct and indirect TLR-induced activation of CMV transcription-replication cycle; whereas chromatin binding experiments using wild-type and enhancer-deletion virus revealed IRF3 and 5 as new pro-viral host transcription factor interactions with the CMV enhancer in macrophages. In a series of pharmacologic, siRNA and genetic loss-of-function experiments we determined that signalling mediated by the TLR-adaptor protein MyD88 plays a vital role for governing the inflammatory activation of the CMV enhancer in macrophages. Downstream TLR-regulated transcription factor binding motif disruption for NFκB, AP1 and CREB/ATF in the CMV enhancer demonstrated the requirement of these inflammatory signal-regulated elements in driving viral gene expression and growth in cells as well as in primary infection of neonatal mice. Thus, this study shows that the prototypical CMV enhancer, in a restricted time-gated manner, co-opts through DNA regulatory mimicry elements, innate-immune transcription factors to drive viral expression and replication in the face of on-going pro-inflammatory antiviral responses in vitro and in vivo and; suggests an unexpected role for inflammation in promoting acute infection and has important future implications for regulating latency