Human cytomegalovirus pUL29/28 and pUL38 repression of p53-regulated p21CIP1 and caspase 1 promoters during infection

During infection by human cytomegalovirus (HCMV), the tumor suppressor protein p53, which promotes efficient viral gene expression, is stabilized. However, the expression of numerous p53-responsive cellular genes is not upregulated. The molecular mechanism used to manipulate the transcriptional activity of p53 during infection remains unclear. The HCMV proteins IE1, IE2, pUL44, and pUL84 likely contribute to the regulation of p53. In this study, we used a discovery-based approach to identify the protein targets of the HCMV protein pUL29/28 during infection. Previous studies have demonstrated that pUL29/28 regulates viral gene expression by interacting with the chromatin remodeling complex NuRD. Here, we observed that pUL29/28 also associates with p53, an additional deacetylase complex, and several HCMV proteins, including pUL38. We confirmed the interaction between p53 and pUL29/28 in both the presence and absence of infection. HCMV pUL29/28 with pUL38 altered the activity of the 53-regulatable p21CIP1 promoter. During infection, pUL29/28 and pUL38 contributed to the inhibition of p21CIP1 as well as caspase 1 expression. The expression of several other p53-regulating genes was not altered. Infection using a UL29-deficient virus resulted in increased p53 binding and histone H3 acetylation at the responsive promoters. Furthermore, expression of pUL29/28 and its interacting partner pUL38 contributed to an increase in the steady-state protein levels of p53. This study identified two additional HCMV proteins, pUL29/28 and pUL38, which participate in the complex regulation of p53 transcriptional activity during infection

Metastatic colonization potential of primary tumour cells in mice.

A model has been developed for studying the capability of cells from primary murine mammary tumours to establish colonies in distant organs. The model involves the i.v. inoculation of disaggregated tumour cells into autologous and syngeneic recipients. The results show that the metastatic colonization potential of cells from a given tumour is consistent within the animals of an inoculated batch. Also, the findings are uniform in the autologous host and the syngeneic recipients. Tumours vary in their colonization potential and can be classified in 2 main groups designated high and low. These findings indicate that: (i) cells from 37% of mammary tumours can heavily colonize the lungs when inoculated i.v., even though the incidence of metastatic spread of these tumours in the undisturbed animal is almost zero. Thus, the relative infrequency of spontaneous metastasis from murine mammary tumours is not due to inability of the tumour cells to survive and colonize once free in the blood stream; and (ii) the colonization potential of the tumours is an intrinsic property of the tumour cells rather than of the host, whose prior acquaintance with the cells does not seem to confer resistance to colonization. The model presents opportunities for identification of possible differences between tumours of high and low colonization potential, and is being used to study cellular properties which favour colonization of distant organs by comparison of observations in vitro with the behaviour of cells from the same tumour in vivo

Correlation of collagenase secretion with metastatic-colonization potential in naturally occurring murine mammary tumours.

We report evidence for the secretion of a true mammalian collagenase active against Type 1 collagen, by naturally-occurring mammary tumours of the mouse and show that tumours capable of heavily colonizing the lungs secrete significantly more of this enzyme than those with low pulmonary-colonization potential, or non-neoplastic proliferating (e.g. lactating) mammary tissue. Plasminogen activator is secreted in greater quantity by tumours than by normal tissues, but there is no significant difference in the amount produced by tumours with high or low pulmonary-colonization potential. These findings correlate well with our earlier morphological observations of marked connective tissue destruction in the vicinity of invading tumours and metastatic deposits, and indicate that protease release is implicated in the mechanism of tumour spread

Contrasting regulation of leaf gas exchange of semi-arid tree species under repeated drought.

Predicting how plants respond to drought requires an understanding of how physiological mechanisms and drought response strategies occur, as these strategies underlie rates of gas exchange and productivity. We assessed the response of 11 plant traits to repeated experimental droughts in four co-occurring species of central Australia. The main goals of this study were to: (i) compare the response to drought between species; (ii) evaluate whether plants acclimated to repeated drought; and (iii) examine the degree of recovery in leaf gas exchange after cessation of drought. Our four species of study were two tree species and two shrub species, which field studies have shown to occupy different ecohydrological niches. The two tree species (Eucalyptus camaldulensis Dehnh. and Corymbia opaca (D.J.Carr & S.G.M.Carr) K.D.Hill & L.A.S.Johnson) had large reductions in stomatal conductance (gs) values, declining by 90% in the second drought. By contrast, the shrub species (Acacia aptaneura Maslin & J.E.Reid and Hakea macrocarpa A.Cunn. ex R.Br.) had smaller reductions gs in the second drought of 52 and 65%, respectively. Only A. aptaneura showed a physiological acclimatation to drought due to small declines in gs versus ᴪpd (0.08 slope) during repeated droughts, meaning they maintained higher rates of gs compared with plants that only experienced one final drought (0.19 slope). All species in all treatments rapidly recovered leaf gas exchange and leaf mass per area following drought, displaying physiological plasticity to drought exposure. This research refines our understanding of plant physiological responses to recurrent water stress, which has implications for modelling of vegetation, carbon assimilation and water use in semi-arid environments under drought

An early developmental vertebrate model for nanomaterial safety:Bridging cell-based and mammalian toxicity assessment

Background. With the rise in production of nanoparticles for an ever-increasing number of applications, there is an urgent need to efficiently assess their potential toxicity. We propose a nanoparticle hazard assessment protocol that combines mammalian cytotoxicity data with embryonic vertebrate abnormality scoring to determine an overall toxicity index. Results. We observed that, after exposure to a range of nanoparticles, Xenopus phenotypic scoring showed a strong correlation with cell based in vitro assays. Magnetite-cored nanoparticles, negative for toxicity in vitro and Xenopus, were further confirmed as non-toxic in mice. Conclusion. The results highlight the potential of Xenopus embryo analysis as a fast screening approach for toxicity assessment of nanoparticles, which could be introduced for the routine testing of nanomaterials

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Speculations on the application of foliar 13C discrimination to reveal groundwater dependency of vegetation and provide estimates of root depth and rates of groundwater use

© Author(s) 2018. Groundwater-dependent vegetation is globally distributed, having important ecological, social, and economic value. Along with the groundwater resources upon which it depends, this vegetation is under increasing threat through excessive rates of groundwater extraction. In this study we examined one shallow-rooted and two deep-rooted tree species at multiple sites along a naturally occurring gradient in depth-to-groundwater. We measured (i) stable isotope ratios of leaves (δ 13C), xylem, and groundwater (δ 2H and δ 18O); and (ii) leaf-vein density. We established that foliar discrimination of 13C (Δ13C) is a reliable indicator of groundwater use by vegetation and can also be used to estimate rooting depth. Through comparison with a continental-scale assessment of foliar Δ13C, we also estimated the upper limits to annual rates of groundwater use. We conclude that maximum rooting depth for both deep-rooted species ranged between 9.4 and 11.2 m and that annual rates of groundwater use ranged from ca. 1400 to 1700 mm for Eucalyptus camaldulensis and from 600 to 900 mm for Corymbia opaca. Several predictions about hydraulic and leaf traits arising from the conclusion that these two species made extensive use of groundwater were supported by additional independent studies of these species in central Australia