Integrated planning and management of freshwater habitats,including wetlands

Freshwater habitats play a very important role in sustaining human activities. Natural functions of wetlands, and other freshwater habitats, generate a wide array of resources that directly or indirectly support the economic and social welfare of diverse groups of people. This role is being seriously weakened as a result of inappropriate planning and management approaches which fail to maintain the functional integrity of the freshwater ecosystems with the result that the flow and quality of resources is degraded. This paper illustrates some of the major functions of wetlands and presents a case for developing integrated planning and management practices that protect the health and productivity of freshwater wetlands and seek to optimise the sustainable use of the flows of resources they generate.     

Selective Expansion of Chimeric Antigen Receptor-targeted T-cells with Potent Effector Function using Interleukin-4

Polyclonal T-cells can be directed against cancer using transmembrane fusion molecules known as chimeric antigen receptors (CARs). Although preclinical studies have provided encouragement, pioneering clinical trials using CAR-based immunotherapy have been disappointing. Key obstacles are the need for robust expansion ex vivo followed by sustained survival of infused T-cells in patients. To address this, we have developed a system to achieve selective proliferation of CAR⁺ T-cells using IL-4, a cytokine with several pathophysiologic and therapeutic links to cancer. A chimeric cytokine receptor (4αβ) was engineered by fusion of the IL-4 receptor α (IL-4Rα) ectodomain to the β_c subunit, used by IL-2 and IL-15. Addition of IL-4 to T-cells that express 4αβ resulted in STAT3/STAT5/ERK phosphorylation and exponential proliferation, mimicking the actions of IL-2. Using receptor-selective IL-4 muteins, partnering of 4αβ with γ_c was implicated in signal delivery. Next, human T-cells were engineered to co-express 4αβ with a CAR specific for tumor-associated MUC1. These T-cells exhibited an unprecedented capacity to elicit repeated destruction of MUC1-expressing tumor cultures and expanded through several logs in vitro. Despite prolonged culture in IL-4, T-cells retained specificity for target antigen, type 1 polarity, and cytokine dependence. Similar findings were observed using CARs directed against two additional tumor-associated targets, demonstrating generality of application. Furthermore, this system allows rapid ex vivo expansion and enrichment of engineered T-cells from small blood volumes, under GMP-compliant conditions. Together, these findings provide proof of principle for the development of IL-4-enhanced T-cell immunotherapy of cancer.     

Survey of 1977 crop year preharvest corn for vomitoxin.

Fifty-two preharvest corn samples were collected in mid-October 1977 from 26 farms in a four-county area of northwest Ohio. Vomitoxin ranging from 0.5 to 10 microgram/g was found in 24 of the samples. Analysis for vomitoxin was by gas-liquid chromatography. Preceding harvest in northwest Ohio, unusual wet conditions prevailed, making it favorable for Fusarium growth. Gibberella zeae-infected kernels ranged from 2 to 50% of the kernels analyzed for 44 corn samples, and 8 corn samples showed no infection.     

Evaluation of Sclerotinia sclerotiorum as a potential mycotoxin producer on soybeans

Solvent extracts of Sclerotinia sclerotiorum sclerotia were nontoxic to mice and chicken embryos; psoralens were not detected. Solvent extracts of soybeans inoculated with 10 strains of S. sclerotiorum were toxic on injection but nontoxic on per os administration to mice. The presence of chlorinated hydrocarbons in the soybeans may partially help explain toxicity by intraperitineal injection.     

Social and economic policy issues relevant to marine aquaculture

This paper presents a critical review of current social, economic and policy issues relevant to marine aquaculture (mariculture) in Europe. Tools for identifying the full range of social, economic and environmental issues that influence the sustainable development of mariculture are examined. Under present sectoral approaches to policy, investment, development planning and natural resources management, these issues continue to be treated in isolation. The four main challenges presented in this paper are: (i) how to create a more objective information base with which to assess the social, economic and environmental factors that condition the sustainability of mariculture; (ii) how to provide information from different disciplines in an easy to obtain and compatible format; (iii) how to better integrate knowledge and skills from different disciplines to create a holistic and robust framework for assessing options for mariculture development that integrates social, economic and environmental parameters; and (iv) the effective integration of these assessments into the formulation of policy, investment strategies, spatial plans and natural resources management for coastal areas. Specific issues that need to be addressed within the framework for the integrated evaluation of the economic, social and environmental parameters governing the sustainable development of mariculture include: ? development of more accurate information on the economic, social and environmental benefits and costs of well‐planned and managed mariculture; ? clearer definition of gaps in existing knowledge on factors critical to the sustainable and equitable development of mariculture; ? development of pro‐active consideration of the coastal land and water resource requirements of mariculture as part of strategic economic planning, spatial planning and natural resources management; ? the need for more equitable treatment of mariculture regarding rights of access to sites for development and use of resources; ? development of awareness among decision‐makers, planners, and managers from different sectoral agencies of the contribution that mariculture may make in promoting the sustainable use of coastal ecosystems; ? promotion of a shift in emphasis away from controlling the end use of resources and toward a more balanced approach to coastal development where emphasis is also given to maintaining the health and productivity of coastal ecosystems and the resources they generate that sustain different forms of activity, including mariculture.     

Targeting DYRK1A/B kinases to modulate p21-cyclin D1-p27 signalling and induce anti-tumour activity in a model of human glioblastoma

The dual-specificity tyrosine-regulated kinases DYRK1A and DYRK1B play a key role in controlling the quiescence-proliferation switch in cancer cells. Serum reduction of U87MG 2D cultures or multi-cellular tumour spheroids induced a quiescent like state characterized by increased DYRK1B and p27, and decreased pRb and cyclin D1. VER-239353 is a potent, selective inhibitor of the DYRK1A and DYRK1B kinases identified through fragment and structure-guided drug discovery. Inhibition of DYRK1A/B by VER-239353 in quiescent U87MG cells increased pRb, DYRK1B and cyclin D1 but also increased the cell cycle inhibitors p21 and p27. This resulted in exit from G0 but subsequent arrest in G1. DYRK1A/B inhibition reduced the proliferation of U87MG cells in 2D and 3D culture with greater effects observed under reduced serum conditions. Paradoxically, the induced re-expression of cell cycle proteins by DYRK1A/B inhibition further inhibited cell proliferation. Cell growth arrest induced in quiescent cells by DYRK1A/B inhibition was reversible through the addition of growth-promoting factors. DYRK inhibition-induced DNA damage and synergized with a CHK1 inhibitor in the U87MG spheroids. In vivo, DYRK1A/B inhibition-induced tumour stasis in a U87MG tumour xenograft model. These results suggest that further evaluation of VER-239353 as a treatment for glioblastoma is therefore warranted.     

Application of a Gondwanan perspective to restore ecological integrity in the south‐western Australian global biodiversity hotspot

Bounded by ocean and desert, the isolated, predominately Mediterranean‐climate region of south‐western Australia (SWA) includes nine bioregions (circa 44 million hectares). The ecological integrity of the landscapes in this global biodiversity hotspot has been compromised by deforestation, fragmentation, exploitation, and introduced biota. Nature and degree of transformation varies between four interconnected landscapes (Swan Coastal Plain; South‐west Forests; Wandoo Woodlands; and Great Western Woodlands). A Gondwanan perspective emphasizes a venerable biota and a cultural component to deep time. The particular importance of remnants and protected areas is recognized in restoring ecological integrity to Gondwanan landscapes. The nature and magnitude of the restoration task in these ancient, and neighboring, landscapes require higher levels of investment and more time than do recent landscapes. The protection, conservation, restoration, and rehabilitation of ecological integrity require multiple approaches in each landscape as well as consideration of the whole. Active conservation of biota and minimizing the impact of industrial‐ and agricultural‐use are priorities. Integrating a climate focus and rethinking fire are critical restoration considerations to future trajectories under anthropogenic climate change. A legislative mandate to coordinate industrial‐scale restoration and active conservation to build from protected areas must become a societal priority to restore ecological integrity.     

Specific oncogenic activity of the Src-family tyrosine kinase c-Yes in colon carcinoma cells

c-Yes, a member of the Src tyrosine kinase family, is found highly activated in colon carcinoma but its importance relative to c-Src has remained unclear. Here we show that, in HT29 colon carcinoma cells, silencing of c-Yes, but not of c-Src, selectively leads to an increase of cell clustering associated with a localisation of β-catenin at cell membranes and a reduction of expression of β-catenin target genes. c-Yes silencing induced an increase in apoptosis, inhibition of growth in soft-agar and in mouse xenografts, inhibition of cell migration and loss of the capacity to generate liver metastases in mice. Re-introduction of c-Yes, but not c -Src, restores transforming properties of c-Yes depleted cells. Moreover, we found that c-Yes kinase activity is required for its role in β-catenin localisation and growth in soft agar, whereas kinase activity is dispensable for its role in cell migration. We conclude that c-Yes regulates specific oncogenic signalling pathways important for colon cancer progression that is not shared with c-Src.     

Solid-phase synthesis of alpha-substituted 3-bisarylthio N-hydroxy propionamides as specific MMP inhibitors

A novel series of potent and specific MMP-2,3,9,13 inhibitors has been obtained by modulation on solid phase by alpha and aryl substitutions on 3-arylthio-N-hydroxy-propionamides starting from itaconic acid.