Mutant-selective AKT inhibition through lysine targeting and neo-zinc chelation.

Somatic alterations in the oncogenic kinase AKT1 have been identified in a broad spectrum of solid tumours. The most common AKT1 alteration replaces Glu17 with Lys (E17K) in the regulatory pleckstrin homology domain, resulting in constitutive membrane localization and activation of oncogenic signalling. In clinical studies, pan-AKT inhibitors have been found to cause dose-limiting hyperglycaemia, which has motivated the search for mutant-selective inhibitors.

Tropical cyclones: what are their impacts on phytoplankton ecology?

Following the passage of a tropical cyclone (TC) the changes in temperature, salinity, nutrient concentration, water clarity, pigments and phytoplankton taxa were assessed at 42 stations from eight sites ranging from the open ocean, through the coastal zone and into estuaries. The impacts of the TC were estimated relative to the long-term average (LTA) conditions as well as before and after the TC. Over all sites the most consistent environmental impacts associated with TCs were an average 41% increase in turbidity, a 13% decline in salinity and a 2% decline in temperature relative to the LTA.

Global patterns of change and variation in sea surface temperature and chlorophyll a.

Changes over the scale of decades in oceanic environments present a range of challenges for management and utilisation of ocean resources. Here we investigate sources of global temporal variation in Sea Surface Temperature (SST) and Ocean Colour (Chl-a) and their co-variation, over a 14 year period using statistical methodologies that partition sources of variation into inter-annual and annual components and explicitly account for daily auto-correlation. The variation in SST shows bands of increasing variability with increasing latitude, while the analysis of annual variability in Chl-a shows mostly mid-latitude high variability bands.

Interdisciplinary knowledge exchange across scales in a globally changing marine environment.

The effects of anthropogenic global environmental change on biotic and abiotic processes have been reported in aquatic systems across the world. Complex synergies between concurrent environmental stressors and the resilience of the system to regime shifts, which vary in space and time, determine the capacity for marine systems to maintain structure and function with global environmental change. Consequently, an interdisciplinary approach that facilitates the development of new methods for the exchange of knowledge between scientists across multiple scales is required to effectively understand, quantify and predict climate impacts on marine ecosystem services.

Nutrient uplift in a cyclonic eddy increases diversity, primary productivity and iron demand of microbial communities relative to a western boundary current.

The intensification of western boundary currents in the global ocean will potentially influence meso-scale eddy generation, and redistribute microbes and their associated ecological and biogeochemical functions. To understand eddy-induced changes in microbial community composition as well as how they control growth, we targeted the East Australian Current (EAC) region to sample microbes in a cyclonic (cold-core) eddy (CCE) and the adjacent EAC. Phototrophic and diazotrophic microbes were more diverse (2-10 times greater Shannon index) in the CCE relative to the EAC, and the cell size distribution in the CCE was dominated (67%) by larger micro-plankton [Formula: see text], as opposed to pico- and nano-sized cells in the EAC.

Reduction of the Powerful Greenhouse Gas N2O in the South-Eastern Indian Ocean.

Nitrous oxide (N2O) is a powerful greenhouse gas and a key catalyst of stratospheric ozone depletion. Yet, little data exist about the sink and source terms of the production and reduction of N2O outside the well-known oxygen minimum zones (OMZ). Here we show the presence of functional marker genes for the reduction of N2O in the last step of the denitrification process (nitrous oxide reductase genes; nosZ) in oxygenated surface waters (180-250 O2 μmol.

Species traits and climate velocity explain geographic range shifts in an ocean-warming hotspot.

Species' ranges are shifting globally in response to climate warming, with substantial variability among taxa, even within regions. Relationships between range dynamics and intrinsic species traits may be particularly apparent in the ocean, where temperature more directly shapes species' distributions. Here, we test for a role of species traits and climate velocity in driving range extensions in the ocean-warming hotspot of southeast Australia.

Determining the diet of larvae of western rock lobster (Panulirus cygnus) using high-throughput DNA sequencing techniques.

The Western Australian rock lobster fishery has been both a highly productive and sustainable fishery. However, a recent dramatic and unexplained decline in post-larval recruitment threatens this sustainability. Our lack of knowledge of key processes in lobster larval ecology, such as their position in the food web, limits our ability to determine what underpins this decline.

Fussy feeders: phyllosoma larvae of the Western Rocklobster (Panulirus cygnus) demonstrate prey preference.

The Western Rocklobster (Panulirus cygnus) is the most valuable single species fishery in Australia and the largest single country spiny lobster fishery in the world. In recent years a well-known relationship between oceanographic conditions and lobster recruitment has become uncoupled, with significantly lower recruitment than expected, generating interest in the factors influencing survival and development of the planktonic larval stages. The nutritional requirements and wild prey of the planktotrophic larval stage (phyllosoma) of P.

Review of fluorescent standards for calibration of in situ fluorometers: recommendations applied in coastal and ocean observing programs.

Fluorometers are widely used in ecosystem observing to monitor fluorescence signals from organic compounds, as well as to infer geophysical parameters such as chlorophyll or CDOM concentration, but measurements are susceptible to variation caused by biofouling, instrument design, sensor drift, operating environment, and calibration rigor. To collect high quality data, such sensors need frequent checking and regular calibration. In this study, a wide variety of both liquid and solid fluorescent materials were trialed to assess their suitability as reference standards for performance assessment of in situ fluorometers.

Effects of shelter and enrichment on the ecology and nutrient cycling of microbial communities of subtidal carbonate sediments.

The interactions between physical disturbances and biogeochemical cycling are fundamental to ecology. The benthic microbial community controls the major pathway of nutrient recycling in most shallow-water ecosystems. This community is strongly influenced by physical forcing and nutrient inputs.

CD20-directed small modular immunopharmaceutical, TRU-015, depletes normal and malignant B cells.

Purpose: CD20-directed therapy with rituximab is effective in many patients with malignant lymphoma or follicular lymphoma. However, relapse frequently occurs within 1 year, and patients become increasingly refractory to retreatment. Our purpose was to produce a compact, single-chain CD20-targeting immunotherapeutic that could offer therapeutic advantages in the treatment of B-cell lymphoma.

Malaria incidence and efficacy of intermittent preventive treatment in infants (IPTi).

Background: Intermittent preventive antimalarial treatment in infants (IPTi) is currently evaluated as a malaria control strategy. Among the factors influencing the extent of protection that is provided by IPTi are the transmission intensity, seasonality, drug resistance patterns, and the schedule of IPTi administrations. The aim of this study was to determine how far the protective efficacy of IPTi depends on spatio-temporal variations of the prevailing incidence of malaria.

A randomized controlled trial of extended intermittent preventive antimalarial treatment in infants.

Background: Intermittent preventive antimalarial treatment in infants (IPTi) with sulfadoxine-pyrimethamine reduces falciparum malaria and anemia but has not been evaluated in areas with intense perennial malaria transmission. It is unknown whether an additional treatment in the second year of life prolongs protection.

Methods: A randomized, double-blinded, placebo-controlled trial with administration of sulfadoxine-pyrimethamine therapy at 3, 9, and 15 months of age was conducted with 1070 children in an area in Ghana where malaria is holoendemic.