Pedochemical evolution and trace elements availability to plants in ophiolitic soils

SCI. TOT. ENVIR

Pedochemical evolution and trace elements availability to plants in ophiolitic soils

SCI. TOT. ENVIR

Pedochemical evolution and trace elements availability to plants in ophiolitic soils

SCI. TOT. ENVIR

Design, synthesis and biological evaluation of new bacterial RNAP inhibitors

Bacterial resistance to antibiotics has been well documented since the emergence of resistance to the beta-lactams during the 1930s. The World Health Organisation considers it to be one of the three greatest threats to human health. Since the late 1980s, the pharmaceutical industry has relied upon the synthesis of analogues based on established classes to combat resistance. However, resistance mechanisms for these classes quickly evolve to render these derivatives ineffective, offering only short-term solutions. There is, therefore, an urgent need for the identification of new antibacterial scaffolds, as well as novel bacterial targets, which do not share this cross-resistance. Structure-based drug design is a rational approach to drug discovery which uses protein structures and computational simulations to guide the design process and deliver lead molecules with greater efficiency. SPROUT is a de novo molecular design program for the generation of small molecule inhibitors, developed within our research group at the University of Leeds. Recent in silica efforts to design novel inhibitors of RNA polymerase (RNAP), an established antibacterial drug target, have focussed on the newly identified myxopyronin B (MyxB) binding region. In conjunction with the X-ray co-crystal structure of Thermus thermophilus RNAP-MyxB, SPROUT has been used to deSign putative ligands, and analogues of MyxB, for the MyxB region. Several series of molecules have been prepared and a number of these compounds displayed IC50 values between 5 and 10 uM against Escherichia coli RNAP. In parallel, a drug delivery approach has been explored to circumvent the problem of enzyme inhibitors that lack cell membrane penetration. Expanding our focus to include scaffolds that inhibit other antibacterial targets, we have conjugated 'warheads' to bacterial iron-transporters called siderophores to enhance their antibacterial activity against Staphylococcus aureus (64 ug/ml), compared to that displayed by the parent scaffold (256 ug/ml). Combining this delivery approach with structure based molecular design represents a new strategy for the generation of novel antibacterial scaffolds, tackling the fundamental problem of poor success in discovering new antibacterial agents over the last 30 years.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Early Miocene pyroclastic rocks of the Bükkalja lgnimbrite Field (North Hungary) - A preliminary stratigraphic report

This preliminary report provides a detailed description of several stratigraphie sequenees of the Early Miocene Bükkalja Ignimbrite Field, summarizing the main volcanosedimentological eharacters. Many volcanological features suggest that most of the deposits can be classified as high volume pyroclastie flows (ignimbrite). Two major ignimbritie units have been distinguished, which may belong to two different stages of the vo1canism and form a SW-NE orientated belt. The first (lower) unit is eharaeterized predominantly by non-welded ignimbrites, whereas the second (upper) unit, usually found south of the first unit, shows variable degrees of welding. Hydrovolcanic deposits also occur in different stratigraphie horizons. The final phases of volcanism could have been contemporancous with lacustrine sedimentation