Henry James and the China Trade

Henry James is not usually read as having much to do with China or transpacific commerce. However, his writing reflects a sustained awareness of the early nineteenth-century China trade’s effect on the visual and cultural landscape of New England where the first American millionaires deposited fortunes amassed in a world system of commerce. References to the China Trade resonate in James’s intensely visual literary style through which he verbally sketches social landscapes that convey an aura of national culture. These social landscapes eventually register his deep alienation in regard to the moral implication of American fortunes.published_or_final_versio

Fire history of the northern part of the Tasmanian Wilderness World Heritage Area and its associated regions

Fire history (from the 1820s to 2000) in the northern quarter of the Tasmanian Wilderness World Heritage Area and its associated regions is discussed in this paper. This area includes Cradle Mountain-Lake St Clair National Park, Granite Tor Conservation Area, Walls of Jerusalem National Park and the Central Plateau Conservation Area west of Great Lake. In common with fire history in southwest Tasmania, there have been major changes in fire regimes during the last 180 years, with major fires in the 1890s (most probably in 1896-97 or 1897-98 or both) and the 1930s (most probably in 1933-34). However, in contrast to southwest Tasmania, there were major fires until the early 1960s: in the early 1950s in the Cradle Mountain-Lake St Clair National Park and Granite Tor Conservation Area, and in 1960-61 in the Walls of Jerusalem National Park and the Central Plateau Conservation Area. Between the 1930s and 1960s over 40% of the study area or about 129 000 ha was burnt. About half of the study area's fire-sensitive vegetation (i.e., alpine, subalpine heath, subalpine rainforest, rainforest and native conifer) was burnt in these fires. The last of these fires - the 1960-61 Central Plateau fire was the biggest and most destructive fire in the World Heritage Area since the 1930s. Less than 3% of the study area was burnt between 1970 and 2000

Ecological observations and new locations of a rare moss Ambuchanania leucobryoides (Ambuchananiaceae)

Ambuchanania leucobryoides is a moss listed as rare under the Tasmanian Threatened Species Protection Act 1995. It is endemic to Tasmania and is monotypic at the genus and family levels. It is sister group to the widespread and speciose genus Sphagnum. In 2008, a survey funded by the Tasmanian Wilderness World Heritage Area Program (Department of Primary Industries and Water) established the exact location of the A. leucobryoides type locality and extended the known range of the moss. The moss is now known from three locations in southwest Tasmania and has a range of 1272 km. It occurs in sandy washes or “daisy pans” derived from Precambrian quartzite

Learning about sex: Results from Natsal 2000.

11-13 September 2002

Yale School of Public Health Symposium on tissue imaging mass spectrometry: illuminating phenotypic heterogeneity and drug disposition at the molecular level.

‘A picture is worth a thousand words’ is an idiom from the English language (‘borrowed’ from on old Chinese proverb) that conveys the notion that a complex idea can be succinctly and fully described by a single image. Never has this expression been truer than in the clinical and pharmaceutical arenas. Enormous strides have been made by the scientific community in the evolving field of biomedical imaging with the aim of representing and/or quantifying aspects of disease and drug action by using tools such as radiography, MRI, PET, and ultrasound. Yet linking the phenotypical data generated by these systems to the genome is a challenging task. Identifying the link between the mechanism of disease or failed drug response to the genome of an individual is difficult, because central pieces of information are missing. However, imaging mass spectrometry (IMS) can overcome this issue. IMS aims to detect the molecular constituents of the tissue; these can then be correlated with genome-related characteristics, such as gene expression patterns and possible mutations, and ultimately provide a phenotypic molecular link to the complex disease biology. The big data technology of IMS can generate spatial information of thousands of metabolites and proteins from within a tissue, facilitating a deeper understanding of the connections between the genome, phenotypic characteristics and the biological response. It is a technology that has the potential to serve as a segue between gene expression and observed biological signal

Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection.

BackgroundWe reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251) mutants with a K65R mutation in reverse transcriptase (RT), and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. Because of significant sequence differences between SIV and HIV-1 RT that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with SIV can be extrapolated to HIV-1 RT. Accordingly, to model HIV-1 RT responses, 12 macaques were inoculated with RT-SHIV, a chimeric SIV containing HIV-1 RT, and started on prolonged tenofovir therapy 5 months later.ResultsThe early virologic response to tenofovir correlated with baseline viral RNA levels and expression of the MHC class I allele Mamu-A*01. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. For most animals, the occurrence of these mutations preceded a partial rebound of plasma viremia to levels that remained on average 10-fold below baseline values. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia.ConclusionThis is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be beneficial, particularly when assisted by antiviral immune responses

The identification of mitochondrial DNA variants in glioblastoma multiforme

Background: Mitochondrial DNA (mtDNA) encodes key proteins of the electron transfer chain (ETC), which produces ATP through oxidative phosphorylation (OXPHOS) and is essential for cells to perform specialised functions. Tumor-initiating cells use aerobic glycolysis, a combination of glycolysis and low levels of OXPHOS, to promote rapid cell proliferation and tumor growth. Glioblastoma multiforme (GBM) is an aggressively malignant brain tumor and mitochondria have been proposed to play a vital role in GBM tumorigenesis. Results: Using next generation sequencing and high resolution melt analysis, we identified a large number of mtDNA variants within coding and non-coding regions of GBM cell lines and predicted their disease-causing potential through in silico modeling. The frequency of variants was greatest in the D-loop and origin of light strand replication in non-coding regions. ND6 was the most susceptible coding gene to mutation whilst ND4 had the highest frequency of mutation. Both genes encode subunits of complex I of the ETC. These variants were not detected in unaffected brain samples and many have not been previously reported. Depletion of HSR-GBM1 cells to varying degrees of their mtDNA followed by transplantation into immunedeficient mice resulted in the repopulation of the same variants during tumorigenesis. Likewise, de novo variants identified in other GBM cell lines were also incorporated. Nevertheless, ND4 and ND6 were still the most affected genes. We confirmed the presence of these variants in high grade gliomas. Conclusions: These novel variants contribute to GBM by rendering the ETC. partially dysfunctional. This restricts metabolism to anaerobic glycolysis and promotes cell proliferation