Renaissance Techniques of Italy and Northern Europe: Comparison and Contrast of Regional Techniques

Beginning in the late 15th century, the Renaissance was a time of rebirth which led to the creation of new artwork. During this time there were economic conditions that allowed patrons to fund the creation of masterpieces. Religion was a prevalent subject in Italian Renaissance art. New ideas would influence the creation of painting, sculpture, and architecture. Through the influence of Italian art, the countries of Northern Europe had a cultural rebirth, which would heavily influence Christian humanism. This period would lead to the creation of new art created in the Low Countries beginning in the late 15th century. Artists produced genre painting and developed different painting techniques

Japanese Influence on Western Impressionists: The Reciprocal Exchange of Artiistic Techniques

In 1853, Commodore Perry reopened Japanese ports to the rest of the world. Japanese products made their way into Western markets (Ives). Products like fans, kimonos, lacquers, and other products became popular. This created the movement of Japanism, which is characterized by the influence of Japanese culture. For artists, there was a focus on Japanese art. Western artists looked at the techniques, compositional methods, and subject matter common in woodblock prints. Woodblock prints, from the Edo period, became an influence for the Impressionist movement in Paris during the nineteenth century. Similarly, the Western influence on Japan affected art during the Edo period

Cancer stem cells in malignant peripheral nerve sheath tumor: Biology and therapeutic ramifications [abstract]

Neuroscience - Vision and Functional Brain Imaging Poster SessionAlthough monoclonal in origin, most tumors appear to contain heterogeneous populations of cancer cells. One possible explanation of this tumor heterogeneity is that human tumors are not merely monoclonal expansions of a single transformed cell, but rather caricatures of normal tissues, and their growth is sustained by cancer stem cells (CSCs). This conceptual shift has important implications, not only for understanding tumor biology but also for developing and evaluating effective anticancer therapies. These CSCs are thought to be more resistant to apoptosis, to survive therapy and to eventually give rise to second-line tumors, which are harder to eliminate by the first-line therapy. In this proposal, we are introducing our data in detection of CSCs in malignant peripheral nerve sheath tumors (MPNSTs) for the first time, and explain our plans for studying the biology of these cells in order to develop a therapeutic strategy for targeting them. We have identified a sub-population of cells in primary human MPNST cells which are positive for CD133 (a well-known marker for CSCs) and other stem cell markers. We have also studied the characteristics of Ras signaling pathway in these cells showing enhanced activation of Ras, Ral, PI3K and ERK. Now, we plan to not only study the biological characteristics of these cells further but also intend to “custom design” a new protocol for targeting them on the basis of specific characteristics of Ras pathway in these cells. If MPNST CSCs could be targeted, it can result in an efficient regression of tumors and enhancement of therapeutic success in MPNST patients

Metagenomic identification and characterisation of emerging and re-emerging viruses causing disease in febrile patients.

Publications resulting from the thesis: 1. Wise EL, Pullan ST, Márquez S, Paz V, Mosquera JD, Zapata S, et al. Isolation of Oropouche Virus from Febrile Patient, Ecuador. Emerg Infect Dis. 2018 May;24(5):935–7. doi:10.3201/eid2405.171569. 2. Gutierrez B, Wise EL, Pullan ST, Logue CH, Bowden TA, Escalera-Zamudio M, et al. The evolutionary dynamics of Oropouche Virus in South America. J Virol. Dec 2019, JVI.01127-19; doi: 10.1128/JVI.01127-19. 3. Wise EL, Márquez S, Mellors J, Paz V, Atkinson B, Gutierrez B, et al. Oropouche virus cases identified in Ecuador using an optimised qRT-PCR informed by metagenomic sequencing. PLOS Neglected Tropical Diseases 14(1): e0007897. doi: 10.1371/journal.pntd.0007897.Emerging infectious diseases (EID) significantly impact public health and have the potential to cause pandemics. Outbreaks of EID have increased in recent decades, with RNA viruses responsible for a substantial proportion of them. Outbreaks are more likely to occur in areas with high biodiversity, poor sanitation and public health infrastructure, and limited resources for EID control. Furthermore, clinical symptoms of many viral infections overlap, making them challenging to diagnose correctly. Metagenomic sequencing (metagenomics) negates the need for targeted detection assays, generates virus genome information and can detect novel or genetically divergent viruses. Through combining targeted PCR-based assays with untargeted metagenomics, this project aimed to detect infections in two cohorts of patients with fever from low-and-middle income countries (Sierra Leone and Ecuador), characterise any viruses identified and pursue further knowledge relevant to EID. Plasmodium, Leptospira and Ebola virus (EBOV) infections were detected in Sierra Leonean patient samples using PCR-based assays. Human immunodeficiency virus, GB virus C (human pegivirus) and hepatitis B virus were identified in 36 PCR-negative Sierra Leonean patient samples using metagenomics. The detection of EBOV was surprising because the patients tested negative for EBOV RNA using a qRT-PCR assay at the time of sampling; further investigation suggested the discrepancies were related to assay sensitivity. This project detected and isolated Oropouche virus (OROV), an emerging arbovirus, from a patient from Ecuador for the first time. Metagenomics revealed that the Ecuadorian strain was divergent from other strains at an established diagnostic qRT-PCR binding site. This information allowed the optimisation of a qRT-PCR assay, which subsequently identified further OROV infections within the patient cohort. Adoption of this assay in relevant countries could enhance OROV surveillance and diagnosis. This demonstrates the value of using metagenomics alongside PCR-based assays in screening studies to ensure diagnostic assays can detect current strains. In addition to OROV, Dengue virus, Hepatitis A virus, Zika virus, and Leptospira were identified in Ecuadorian patient samples. Phylogenetic analyses of OROV sequences suggested that an OROV outbreak occurred in Esmeraldas, Ecuador in 2016. OROV vector Culicoides paraensis is not present in this area, raising the question of alternative insect vectors. Experiments demonstrated that OROV replicates in Aedes spp. cell lines. These species are important mosquito vectors of other arboviral diseases and this finding warrants further investigation. Further experimental work identified human fibroblasts and hepatocytes as potentially relevant to OROV pathogenesis in humans.Public Health Englan

Towards high-resolution quantitative assessment of vascular dysfunction

Neurovascular alterations are increasingly recognized as a key feature of many brain diseases. They can manifest as a reduction in resting cerebral blood flow or cerebrovascular reactivity (CVR) in the whole brain or in specific regions, depending on the underlying condition. Neurovascular impairment is observed in hypertension, Alzheimer’s disease, stroke, multiple sclerosis and cerebral small vessel disease. Magnetic resonance imaging (MRI)-derived CVR mapping is a reliable marker of vascular dysfunction and has been performed mainly at standard functional MRI (fMRI) resolutions of 2–3 mm using the blood oxygen level dependent (BOLD) contrast. However, vascular alterations may occur at a finer scale (i.e., in the capillary bed) which would be better characterized with smaller voxel sizes. Capillaries in gray matter deliver oxygen and glucose to neural tissue and are arranged in a mesh structure, with variable density across the cortical depth. Given that the human cortex is, on average, 2.5 mm thick, submillimetric voxel sizes are effective in increasing the spatial specificity of measurements of hemodynamic and metabolic changes. Novel MRI sequences offer the possibility to map physiological parameters at high resolution with relatively simple experimental setups. In particular, pairing the BOLD acquisition with a contrast sensitive to blood volume changes, while administering a mild hypercapnic challenge, allows for simultaneous mapping of CVR, cerebral metabolic rate of oxygen consumption and other relevant parameters at a high resolution and can be performed at the clinical field strength of 3 T. We propose that this approach will help provide crucial insights into vascular impairment

In search of a marker of altered cerebrovascular function in hypertension: Analysis of the fractional amplitude of low-frequency fluctuations in UK Biobank resting state fMRI data

The selfish brain mechanism proposes that in some patients with impaired cerebral blood flow (CBF) or cerebrovascular function, hypertension may develop as a compensatory mechanism that aims to maintain CBF by increasing systemic blood pressure through an increase in cardiovascular sympathetic tone. The amplitude of low frequency fluctuations (ALFF) in the resting state blood oxygenation level dependent (BOLD) functional MRI signal has been previously posited as an index of cerebrovascular reactivity. We investigated whether regional fractional ALFF (fALFF) differs between 2054 hypertensives and 1724 normotensives using data from the UK Biobank dataset. Our primary hypothesis was that cerebrovascular function in the medulla and other regions involved in sympathetic regulation differs between hypertensives and normotensives, and that this is reflected by regional variations in fALFF. There is a significant regional variation in fALFF (F(14) =1126.17, p < 2 × 10−16, partial η2 = 0.22), but this regional variation does not differ between hypertensives and normotensives (F(14) = 0.23, p = 0.99, partial η2 = 8 × 10−5). Prospective longitudinal studies of cerebral haemodynamics in hypertensives and normotensives are required to further investigate the selfish brain mechanism

Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus

In 2009, a novel lyssavirus (subsequently named Ikoma lyssavirus, IKOV) was detected in the brain of an African civet (Civettictis civetta) with clinical rabies in the Serengeti National Park of Tanzania. The degree of nucleotide divergence between the genome of IKOV and those of other lyssaviruses predicted antigenic distinction from, and lack of protection provided by, available rabies vaccines. In addition, the index case was considered likely to be an incidental spillover event, and therefore the true reservoir of IKOV remained to be identified. The advent of sensitive molecular techniques has led to a rapid increase in the discovery of novel viruses. Detecting viral sequence alone, however, only allows for prediction of phenotypic characteristics and not their measurement. In the present study we describe the in vitro and in vivo characterization of IKOV, demonstrating that it is (1) pathogenic by peripheral inoculation in an animal model, (2) antigenically distinct from current rabies vaccine strains and (3) poorly neutralized by sera from humans and animals immunized against rabies. In a laboratory mouse model, no protection was elicited by a licensed rabies vaccine. We also investigated the role of bats as reservoirs of IKOV. We found no evidence for infection among 483 individuals of at least 13 bat species sampled across sites in the Serengeti and Southern Kenya