Non-invasive in vivo imaging in small animal research

Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Positron Emission Tomography (PET), bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.

Modern humans in Sarawak, Malaysian Borneo, during Oxygen Isotope Stage 3: palaeoenvironmental evidence from the Great Cave of Niah

During recent reinvestigations in the Great Cave of Niah in Borneo, the ‘Hell Trench’ sedimentary sequence seen by earlier excavators was re-exposed. Early excavations here yielded the earliest anatomically-modern human remains in island Southeast Asia. Calibrated radiocarbon dates, pollen, algal microfossils, palynofacies, granulometry and geochemistry of the ‘Hell Trench’ sequence provide information about environmental and vegetational changes, elements of geomorphic history and information about human activity. The ‘Hell’ sediments were laid down episodically in an ephemeral stream or pool. The pollen suggests cyclically changing vegetation with forest habitats alternating with more open environments; indicating that phases with both temperatures and precipitation reduced compared with the present. These events can be correlated with global climate change sequences to produce a provisional dating framework. During some forest phases, high counts of Justicia, a plant which today colonises recently burnt forest areas, point to fire in the landscape. This may be evidence for biomass burning by humans, presumably to maintain forest-edge habitats. There is evidence from palynofacies for fire on the cave floor in the ‘Hell’ area. Since the area sampled is beyond the limit of plant growth, this is evidence for human activity. The first such evidence is during an episode with significant grassland indicators, suggesting that people may have reached the site during a climatic phase characterised by relatively open habitats ~50 ka. Thereafter, people were able to maintain a relatively consistent presence at Niah. The human use of the ‘Hell’ area seems to have intensified through time, probably because changes in the local hydrological regime made the area dryer and more suitable for human use.

Tracking biological invasions in space and time: elucidating the invasive history of the green alga Codium fragile using old DNA

With the advent of 'ancient DNA' studies on preserved material of extant and extinct species, museums and herbaria now represent an important although still underutilized resource in molecular ecology. The ability to obtain sequence data from archived specimens can reveal the recent history of cryptic species and introductions. We have analysed extant and herbarium samples of the highly invasive green alga Codium fragile, many over 100 years old, to identify cryptic accessions of the invasive strain known as C. fragile ssp. tomentosoides, which can be identified by a unique haplotype. Molecular characterization of specimens previously identified as native in various regions shows that the invasive tomentosoides strain has been colonizing new habitats across the world for longer than records indicate, in some cases nearly 100 years before it was noticed. It can now be found in the ranges of all the other native haplotypes detected, several of which correspond to recognized subspecies. Within regions in the southern hemisphere there was a greater diversity of haplotypes than in the northern hemisphere, probably as a result of dispersal by the Antarctic Circumpolar Current. The findings of this study highlight the importance of herbaria in preserving contemporaneous records of invasions as they occur, especially when invasive taxa are cryptic.

Cutting edge: Langerin+ dendritic cells in the mesenteric lymph node set the stage for skin and gut immune system cross-talk.

Topical transcutaneous immunization (TCI) presents many clinical advantages, but its underlying mechanism remains unknown. TCI induced Ag-specific IgA Ab-secreting cells expressing CCR9 and CCR10 in the small intestine in a retinoic acid-dependent manner. These intestinal IgA Abs were maintained in Peyer\'s patch-null mice but abolished in the Peyer\'s patch- and lymph node-null mice. The mesenteric lymph node (MLN) was shown to be the site of IgA isotype class switching after TCI. Unexpectedly, langerin(+)CD8alpha(-) dendritic cells emerged in the MLN after TCI; they did not migrate from the skin but rather differentiated rapidly from bone marrow precursors. Depletion of langerin(+) cells impaired intestinal IgA Ab responses after TCI. Taken together, these findings suggest that MLN is indispensable for the induction of intestinal IgA Abs following skin immunization and that cross-talk between the skin and gut immune systems might be mediated by langerin(+) dendritic cells in the MLN.

Modelling the MAPK signalling pathway using a two-stage identification algorithm

Signal transduction pathways describe the dynamics of cellular response to input signalling molecules at receptors on the cell membrane. The Mitogen-Activated Protein Kinase (MAPK) cascade is one of such pathways that are involved in many important cellular processes including cell growth and proliferation. This paper describes a black-box model of this pathway created using an advanced two-stage identification algorithm. Identification allows us to capture the unique features and dynamics of the pathway and also opens up the possibility of regulatory control design. In the approach described, an optimal model is obtained by performing model subset selection in two stages, where the terms are first determined by a forward selection method and then modified using a backward selection model refinement. The simulation results demonstrate that the model selected using the two-stage algorithm performs better than with the forward selection method alone.