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.

Neovascular age-related macular degeneration risk based on CFH, LOC387715/HTRA1, and smoking

Age-related macular degeneration (AMD) is the major cause of blindness in the elderly. Those with the neovascular end-stage of disease have irreversible loss of central vision. AMD is a complex disorder in which genetic and environmental factors play a role. Polymorphisms in the complement factor H (CFH) gene, LOC387715, and the HTRA1 promoter are strongly associated with AMD. Smoking also contributes to the etiology. We aimed to provide a model of disease risk based on these factors.

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.

Phenotypic diversity amongst strains of Pleurotus sajor-caju: implications for cultivation in and environments

In arid regions, biodiversity and biomass are limited by water availability, and this problem has been compounded by desertification associated with global climate change. The saprotrophic macrofungi that are indigenous to hot subtropical and tropical regions, such as Pleurotus spp., can play key roles in water sequestration, nutrient cycling, human nutrition, and bioremediation of waste materials. We studied 15 strains of Pleurotus sajor-caju, a widespread and phenotypically-diverse species, to establish variability in growth response and primordium development over a range of stress parameters: osmotic potential (-0.5 to -5 MPa), temperature (5-40 degrees C) and pH (2-12). The initiation of primordia precedes basidiome production and therefore represents a key stage in bioremediation strategies and fungi-driven nutrient cycles. Primordia were produced at low pH (4-6), at suboptimal growth temperatures (<or =25 degrees C), and under moderate water stress (-0.5 to -3.5 MPa). Although the growth windows for different strains were similar, their maximum growth rates and the optimum conditions for growth varied. We discuss the phenotypic diversity of Pleurotus strains and discuss their potential for cultivation, bioremediation and ecological regeneration.

Regulation and consequences of differential gene expression in diabetic kidney disease

DIN (diabetic nephropathy) is the leading cause of end-stage renal disease worldwide and develops in 25-40% of patients with Type 1 or Type 2 diabetes mellitus. Elevated blood glucose over long periods together with glomerular hypertension leads to progressive glomerulosclerosis and tubulointerstitial fibrosis in susceptible individuals. Central to the pathology of DIN are cytokines and growth factors such as TGF-beta (transforming growth factor beta) superfamily members, including BMPs (bone morphogenetic protein) and TGF-beta 1, which play key roles in fibrogenic responses of the kidney, including podocyte loss, mesangial cell hypertrophy, matrix accumulation and tubulointerstitial fibrosis. Many of these responses can be mimicked in in vitro models of cells cultured in high glucose. We have applied differential gene expression technologies to identify novel genes expressed in in vitro and in vivo models of DN and, importantly, in human renal tissue. By mining these datasets and probing the regulation of expression and actions of specific molecules, we have identified novel roles for molecules such as Gremlin, IHG-1 (induced in high glucose-1) and CTGF (connective tissue growth factor) in DIN and potential regulators of their bioactions.

Placing political economy: organising opposition to free trade before the abolition of the Corn Laws

The unfurling of global capitalism – and its attendant effects – has long been fertile intellectual terrain for geographers. But whilst studies of the processes and mechanisms of globalisation undoubtedly assume a talismanic importance in the discipline, geographers, with few exceptions, have left examinations of early economic liberalism to historians. One such critically important episode in the evolution of the liberal economic project was the repeal of the so-called 'Corn Laws' in 1846. Whilst the precise impact of the Manchester-based Anti-Corn Law League (ACLL) continues to be a matter of conjecture, Eric Sheppard has asserted that their particular take on political economy managed to assume a 'truth-like status' and worldwide universality. But the ACLL's campaign represents only one, albeit decisive, stage in the long intellectual and practical struggle between 'protectionists' and the disciples of free trade. Studies of the non-'Manchester' components have tended to focus squarely upon national politics. This paper examines a pivotal attempt in 1838 by Lord Melbourne's Government to experiment with the effective elimination of import duties on fresh fruit. Unlike most agricultural commodities, table fruit was produced in a tightly defined area, thus allowing the Government's experiment to play out, in theory, without national political fallout. Whilst the Government's clandestine actions left little time for a concerted opposition to develop, Kentish fruit growers soon organised. A formidable lobby was forged that drew wide local support yet also evolved beyond the original 'epistemic community'. Whilst the coalition failed in their efforts to reintroduce protective duties, their actions allow us to see how protectionist ideologies and policies were vivified through practices at many different spatial scales and to better understand the complex spatiality of protectionist takes on political economy. Their campaign also changed – at least in the short term – the course of British mercantile policy.