Generation of a poor prognostic chronic lymphocytic leukemia-like disease model: PKC subversion induces up-regulation of PKC II expression in B lymphocytes

Overwhelming evidence identifies the microenvironment as a critical factor in the development and progression of chronic lymphocytic leukemia, underlining the importance of developing suitable translational models to study the pathogenesis of the disease. We previously established that stable expression of kinase dead protein kinase C alpha in hematopoietic progenitor cells resulted in the development of a chronic lymphocytic leukemia-like disease in mice. Here we demonstrate that this chronic lymphocytic leukemia model resembles the more aggressive subset of chronic lymphocytic leukemia, expressing predominantly unmutated immunoglobulin heavy chain genes, with upregulated tyrosine kinase ZAP-70 expression and elevated ERK-MAPK-mTor signaling, resulting in enhanced proliferation and increased tumor load in lymphoid organs. Reduced function of PKCα leads to an up-regulation of PKCβII expression, which is also associated with a poor prognostic subset of human chronic lymphocytic leukemia samples. Treatment of chronic lymphocytic leukemia-like cells with the selective PKCβ inhibitor enzastaurin caused cell cycle arrest and apoptosis both in vitro and in vivo, and a reduction in the leukemic burden in vivo. These results demonstrate the importance of PKCβII in chronic lymphocytic leukemia-like disease progression and suggest a role for PKCα subversion in creating permissive conditions for leukemogenesis

Ectopic gynaecomastia on the inner aspect of the thigh in an otherwise healthy man

Peer reviewedPublisher PD

Using ecosystem engineers as tools in habitat restoration and rewilding: beaver and wetlands

Potential for habitat restoration is increasingly used as an argument for reintroducing ecosystem engineers. Beaver have well known effects on hydromorphology through dam construction, but their scope to restore wetland biodiversity in areas degraded by agriculture is largely inferred. Our study presents the first formal monitoring of a planned beaver-assisted restoration, focussing on changes in vegetation over 12 years within an agriculturally-degraded fen following beaver release, based on repeated sampling of fixed plots. Effects are compared to ungrazed exclosures which allowed the wider influence of waterlogging to be separated from disturbance through tree felling and herbivory. After 12 years of beaver presence mean plant species richness had increased on average by 46% per plot, while the cumulative number of species recorded increased on average by 148%. Heterogeneity, measured by dissimilarity of plot composition, increased on average by 71%. Plants associated with high moisture and light conditions increased significantly in coverage, whereas species indicative of high nitrogen decreased. Areas exposed to both grazing and waterlogging generally showed the most pronounced change in composition, with effects of grazing seemingly additive, but secondary, to those of waterlogging.  Our study illustrates that a well-known ecosystem engineer, the beaver, can with time transform agricultural land into a comparatively species-rich and heterogeneous wetland environment, thus meeting common restoration objectives. This offers a passive but innovative solution to the problems of wetland habitat loss that complements the role of beavers in water or sediment storage and flow attenuation. The role of larger herbivores has been significantly overlooked in our understanding of freshwater ecosystem function; the use of such species may yet emerge as the missing ingredient in successful restoration

A declining CD4 count and diagnosis of HIV-associated Hodgkin lymphoma: do prior clinical symptoms and laboratory abnormalities aid diagnosis?

BACKGROUND: The incidence of Hodgkin lymphoma (HL) among HIV-infected individuals remains unchanged since the introduction of combination antiretroviral therapy (cART). Recent epidemiological data suggest that CD4 count decline over a year is associated with subsequent diagnosis of HL. In an era of economic austerity monitoring the efficacy of cART by CD4 counts may no longer be required where CD4 count>350 cells/µl and viral load is suppressed (350 may not have delayed diagnosis

Kepler Observations of V447 Lyr: An Eclipsing U Gem Cataclysmic Variable

We present the results of an analysis of data covering 1.5 years of the dwarf nova V447 Lyr. We detect eclipses of the accretion disk by the mass donating secondary star every 3.74 hrs which is the binary orbital period. V447 Lyr is therefore the first dwarf nova in the Kepler field to show eclipses. We also detect five long outbursts and six short outbursts showing V447 Lyr is a U Gem type dwarf nova. We show that the orbital phase of the mid-eclipse occurs earlier during outbursts compared to quiescence and that the width of the eclipse is greater during outburst. This suggests that the bright spot is more prominent during quiescence and that the disk is larger during outburst than quiescence. This is consistent with an expansion of the outer disk radius due to the presence of high viscosity material associated with the outburst, followed by a contraction in quiescence due to the accretion of low angular momentum material. We note that the long outbursts appear to be triggered by a short outburst, which is also observed in the super-outbursts of SU UMa dwarf novae as observed using Kepler.Comment: Accepted by MNRA

What do you mean, I have a right to health? Participatory action research on health and human rights

What does the right to health mean to people who face inequalities and may struggle to access support? This is a pressing issue in Scotland where there is a national commitment to human rights, but where deep seated health inequalities are a major public health concern. The right to the highest attainable standard of health is recognised within the European Convention on Economic, Social and Cultural Rights and should be equally available, accessible, acceptable and of good quality to everyone