RelB nuclear translocation mediated by C-terminal activator regions of Epstein-Barr virus-encoded latent membrane protein 1 and its effect on antigen-presenting function in B cells.

Previous studies have shown that Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) is uniquely able to up-regulate the expression of the peptide transporters (referred to as TAP-1 and TAP-2) and major histocompatibility complex (MHC) class I in Burkitt's lymphoma (BL) cell lines. This up-regulation is often accompanied by a restoration of antigen-presenting function as measured by the ability of these cells to present endogenously expressed viral antigen to cytotoxic T lymphocytes. Here we show that the expression of LMP1 resulted in up-regulation and nuclear translocation of RelB that were coincident with increased expression of MHC class I in BL cells. Deletion of the C-terminal activator regions (CTARs) of LMP1 significantly impaired the abilities of LMP1 to translocate RelB into the nucleus and to up-regulate the expression of antigen-processing genes. Further analysis with single-point mutations within the CTARs confirmed that the residues critical for NF-kappa B activation directly contribute to antigen-processing function regulation in BL cells. This LMP1-mediated effect was blocked following expression of either dominant negative I kappa B alpha S32/36A, an NF-kappa B inhibitor, or antisense RelB. These observations indicate that upregulation of antigen-presenting function in B cells mediated by LMP1 is signaled through the NF-kappa B subunit RelB. The data provide a mechanism by which LMP1 modulates immunogenicity of Epstein-Barr virus-infected normal and malignant cells.     

Pseudo-halide derivatives of titanocene: synthesis and cytotoxicity studies

The well-known anticancer drug candidate bis-[(p-methoxybenzyl)cyclopentadienyl] titanium(IV) dichloride (Titanocene ) was reacted with sodium azide or potassium cyanate, thiocyanate or selenocyanate in order to give pseudo-halide analogues of Titanocene . and were characterised by single crystal X-ray diffraction, which confirmed the expected nitrogen binding of the cyanate and thiocyanate to the titanium centre. All four titanocenes had their cytotoxicity investigated through preliminary in vitro testing on the LLC-PK (pig kidney epithelial) cell line in an MTT based assay in order to determine their IC50 values. Titanocenes were found to have IC50 values of 24 (± 8) μM, 101 (± 14) μM, 54 (± 21) μM and 27 (± 4) μM respectively. All four titanocene derivatives show significant cytotoxicity improvement when compared to unsubstituted titanocene dichloride and and showed similiar cytotoxic behaviour to Titanocene in vitro.     

Does biogeographical history matter? Diversity and distribution of lotic midges (Diptera: Chironomidae) in the Australian Wet Tropics

Abstract We examined broad scale patterns of diversity and distribution of lotic Chironomidae (Diptera) within the Wet Tropics bioregion of northern Queensland, Australia. Field surveys across broad latitudinal and altitudinal gradients within the Wet Tropics revealed a fauna of 87 species‐level taxa in 49 genera comprising three main elements: a small genuinely tropical fraction, and larger cosmopolitan and Gondwanan components. The latter group originated when Australia, as part of the ancient Gondwana supercontinent, was situated over Antarctic latitudes with a cooler, wetter climate than today. In the Wet Tropics, cool Gondwanan taxa occurred predominantly in upland and shaded lowland sites, but no species appeared narrowly temperature restricted, and there was no faunal zonation with altitude. Most chironomid species occurred at all latitudes within the Wet Tropics, with no evidence for an enduring effect of the historical rainforest contractions on current‐day distribution patterns. These findings contrast with those for aquatic faunas elsewhere in the world and for the terrestrial Wet Tropics fauna. We relate this to the generally broad environmental tolerances of Australian chironomids, and comment on why the latitudinal diversity gradient does not apply to the Australian chironomid fauna.     

Species partitioning in a temperate mountain chain: Segregation by habitat vs. interspecific competition

Disentangling the relative influence of the environment and biotic interactions in determining species coexistence patterns is a major challenge in ecology. The zonation occurring along elevation gradients, or at bioclimatic contact zones, offers a good opportunity to improve such understanding because the small scale at which the partitioning occurs facilitates inference based on experiments and ecological modelling. We studied the influence of abiotic gradients, habitat types, and interspecific competition in determining the spatial turnover between two pipit and two bunting species in NW Spain. We explored two independent lines of evidence to draw inference about the relative importance of environment and biotic interactions in driving range partitioning along elevation, latitude, and longitude. We combined occurrence data with environmental data to develop joint species distribution models (JSDM), in order to attribute co‐occurrence (or exclusion) to shared (or divergent) environmental responses and to interactions (attraction or exclusion). In the same region, we tested for interference competition by means of playback experiments in the contact zone. The JSDMs highlighted different responses for the two species pairs, although we did not find direct evidence of interspecific aggressiveness in our playback experiments. In pipits, partitioning was explained by divergent climate and habitat requirements and also by the negative correlations between species not explained by the environment. This significant residual correlation may reflect forms of competition others than direct interference, although we could not completely exclude the influence of unmeasured environmental predictors. When bunting species co‐occurred, it was because of shared habitat preferences, and a possible limitation to dispersal might cause their partitioning. Our results indicate that no single mechanism dominates in driving the distribution of our study species, but rather distributions are determined by the combination of many small forces including biotic and abiotic determinants of niche, whose relative strengths varied among species.     

Conservation implications of limited genetic diversity and population structure in Tasmanian devils (<Emphasis Type="Italic">Sarcophilus harrisii</Emphasis>)

Tasmanian devils face a combination of threats to persistence, including devil facial tumor disease (DFTD), an epidemic transmissible cancer. We used RAD sequencing to investigate genome-wide patterns of genetic diversity and geographic population structure. Consistent with previous results, we found very low genetic diversity in the species as a whole, and we detected two broad genetic clusters occupying the northwestern portion of the range, and the central and eastern portions. However, these two groups overlap across a broad geographic area, and differentiation between them is modest (\({{F}_{\text{ST}}}\)?=?0.1081). Our results refine the geographic extent of the zone of mixed ancestry and substructure within it, potentially informing management of genetic variation that existed in pre-diseased populations of the species. DFTD has spread across both genetic clusters, but recent evidence points to a genomic response to selection imposed by DFTD. Any allelic variation for resistance to DFTD may be able to spread across the devil population under selection by DFTD, and/or be present as standing variation in both genetic regions.     

Anticipating changes to future connectivity within a network of marine protected areas

Continental boundary currents are projected to be altered under future scenarios of climate change. As these currents often influence dispersal and connectivity among populations of many marine organisms, changes to boundary currents may have dramatic implications for population persistence. Networks of marine protected areas (MPAs) often aim to maintain connectivity, but anticipation of the scale and extent of climatic impacts on connectivity are required to achieve this critical conservation goal in a future of climate change. For two key marine species (kelp and sea urchins), we use oceanographic modelling to predict how continental boundary currents are likely to change connectivity among a network of MPAs spanning over 1000 km of coastline off the coast of eastern Australia. Overall change in predicted connectivity among pairs of MPAs within the network did not change significantly over and above temporal variation within climatic scenarios, highlighting the need for future studies to incorporate temporal variation in dispersal to robustly anticipate likely change. However, the intricacies of connectivity between different pairs of MPAs were noteworthy. For kelp, poleward connectivity among pairs of MPAs tended to increase in the future, whereas equatorward connectivity tended to decrease. In contrast, for sea urchins, connectivity among pairs of MPAs generally decreased in both directions. Self‐seeding within higher‐latitude MPAs tended to increase, and the role of low‐latitude MPAs as a sink for urchins changed significantly in contrasting ways. These projected changes have the potential to alter important genetic parameters with implications for adaptation and ecosystem vulnerability to climate change. Considering such changes, in the context of managing and designing MPA networks, may ensure that conservation goals are achieved into the future.     

Vascular oxygen sensing: detection of novel candidates by proteomics and organ culture.

We have shown that the specific inhibition of hypoxia-induced relaxation by organ culture in porcine coronary arteries can be mimicked by treatment of control vessels with the protein synthesis inhibitor, cycloheximide. We hypothesize that organ culture of vascular smooth muscle results in the decreased expression of proteins that are critical for vascular oxygen sensing. Using two-dimensional gel electrophoresis and mass spectroscopy, we identified such candidate proteins. The expressions of the smooth muscle-specific protein, SM22, and tropomyosin are decreased after 24 h in organ culture. These results were confirmed by Western blot analysis. Other smooth muscle proteins (actin and calponin) exhibited little change. We also demonstrate a 50% downregulation in the small G protein, Rho, a potent modulator of Ca(2+)-independent force. These results indicate that organ culture preferentially inhibits the expression of certain smooth muscle proteins. This change in protein expression after organ culture correlates with the specific inhibition of hypoxic vasorelaxation. These results provide novel target pathways for investigation that are potentially important for vascular oxygen sensing.