Heparan sulphate bound growth factors: a mechanism for stromal cell mediated haemopoiesis

The proliferation and development of haemopoietic stem cells takes place in close association with marrow stromal cells. This intimate cell contact presumably enables the stem cells and their progeny to respond to stimuli present on the stromal cell surface. While the nature of these stimuli has not been determined, it is likely that growth factors play some role. Recently, it was demonstrated that the natural and the recombinant haemopoietic growth factor, granulocyte/macrophage colony stimulating factor (GM-CSF), could be adsorbed out of solution by an extract of human marrow stromal extracellular matrix (ECM) with retention of biological activity. However, the precise ECM molecules involved were not identified. Here, we clearly demonstrate that the major sulphated glycosaminoglycan of mouse marrow stroma, heparan sulphate, possesses the ability to adsorb both GM-CSF and the multilineage haemopoietic growth factor, Interleukin 3 (IL-3). Furthermore, these growth factors, once bound, can be presented in the biologically active form to haemopoietic cells.     

Neuropeptide Y in the guinea-pig biliary tract

Summary High concentrations of neuropeptide Y (NPY) have been demonstrated in the gall bladder (16.7±5.4 pmol/g), cystic duct (25.4±9.2 pmol/g) and common bile duct (54.7±11.5 pmol/g) of the guinea-pig using a recently developed radio-immunoassay. Immunoreactive NPY containing nerves were demonstrated in all layers of the biliary tree using immunocytochemistry, being particularly dense in the myenteric and mucosal plexuses.Acknowledgments. JMA is a recipient of a Wellcome Trust Training Fellowship. JG is a visiting scholar from the Department of Pathology, Peking Medical College, Peking, China.     

Domain interactions of H-2 class I antigens alter cytotoxic T-cell recognition sites

H-2 class I antigens appear to direct the recognition of virus-infected and neoplastic transformed cells by cytotoxic T lymphocytes (CTLs). Here, to identify the regions of class I antigens involved in CTL recognition, four hybrid class I genes were constructed in which exons were exchanged between the H-2Kb and H-2Db genes. These class I genes were expressed in mouse L cells and recognition of the hybrid Kb/Db antigens by CTLs and monoclonal antibodies specific for either Kb or Db was investigated. The pattern of CTL and monoclonal antibody recognition obtained indicates three correlations between structure and function of class I antigens. First, most CTL recognition sites and alloantigenic determinants are located on domains 1 and 2 of the antigen molecule. Second, these CTL recognition sites and alloantigenic determinants are not influenced by interaction of domains 1 and 2 with polymorphic regions of domain 3. Third, in contrast, interaction between domains 1 and 2 alters these CTL recognition sites and alloantigenic determinants. The alteration of CTL recognition sites by interaction between domains 1 and 2 suggests that a CTL site may be formed by amino acids from both domains 1 and 2, or that the conformation of amino acids at a CTL site may be altered by interactions between domains 1 and 2. Through these two features, the conformation of CTL recognition sites on H-2 class I antigens may be sensitive to alteration by interaction of either domain 1 or 2 with viral antigens.     

Calcium channels activated by hydrogen peroxide mediate abscisic acid signalling in guard cells

Drought is a major threat to agricultural production. Plants synthesize the hormone abscisic acid (ABA) in response to drought, triggering a signalling cascade in guard cells that results in stomatal closure, thus reducing water loss. ABA triggers an increase in cytosolic calcium in guard cells ([Ca2+]cyt) that has been proposed to include Ca2+ influx across the plasma membrane. However, direct recordings of Ca2+ currents have been limited and the upstream activation mechanisms of plasma membrane Ca2+ channels remain unknown. Here we report activation of Ca2+-permeable channels in the plasma membrane of Arabidopsis guard cells by hydrogen peroxide. The H2O2-activated Ca2+ channels mediate both influx of Ca2+ in protoplasts and increases in [Ca2+]cyt in intact guard cells. ABA induces the production of H2O2 in guard cells. If H2O2 production is blocked, ABA-induced closure of stomata is inhibited. Moreover, activation of Ca2+ channels by H2O2 and ABA- and H2O2-induced stomatal closing are disrupted in the recessive ABA-insensitive mutant gca2. These data indicate that ABA-induced H2O2 production and the H2O2-activated Ca2+ channels are important mechanisms for ABA-induced stomatal closing.     

Network anatomy and in vivo physiology of visual cortical neurons

In the cerebral cortex, local circuits consist of tens of thousands of neurons, each of which makes thousands of synaptic connections. Perhaps the biggest impediment to understanding these networks is that we have no wiring diagrams of their interconnections. Even if we had a partial or complete wiring diagram, however, understanding the network would also require information about each neuron's function. Here we show that the relationship between structure and function can be studied in the cortex with a combination of in vivo physiology and network anatomy. We used two-photon calcium imaging to characterize a functional property--the preferred stimulus orientation--of a group of neurons in the mouse primary visual cortex. Large-scale electron microscopy of serial thin sections was then used to trace a portion of these neurons' local network. Consistent with a prediction from recent physiological experiments, inhibitory interneurons received convergent anatomical input from nearby excitatory neurons with a broad range of preferred orientations, although weak biases could not be rejected.     

The excitation of solar-like oscillations in a δSct star by efficient envelope convection

Delta Scuti (δSct) stars are opacity-driven pulsators with masses of 1.5-2.5 M⊙, their pulsations resulting from the varying ionization of helium. In less massive stars such as the Sun, convection transports mass and energy through the outer 30 per cent of the star and excites a rich spectrum of resonant acoustic modes. Based on the solar example, with no firm theoretical basis, models predict that the convective envelope in δSct stars extends only about 1 per cent of the radius, but with sufficient energy to excite solar-like oscillations. This was not observed before the Kepler mission, so the presence of a convective envelope in the models has been questioned. Here we report the detection of solar-like oscillations in the δSct star HD187547, implying that surface convection operates efficiently in stars about twice as massive as the Sun, as the ad hoc models predicted.     

In defence of inclusive fitness theory

Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Arguably the defining characteristic of the scientific process is its capacity for self-criticism and correction. Nowak et al. challenge proposed connections between relatedness and the evolution of eusociality, suggest instead that defensible nests and "spring-loaded" traits are key, and present alternative modelling approaches. They then dismiss the utility of Hamilton's insight that relatedness has a profound evolutionary effect, formalized in his widely accepted inclusive fitness theory as Hamilton's rule ("Rise and fall of inclusive fitness theory"). However, we believe that Nowak et al. fail to make their case for logical, theoretical and empirical reasons.     

Anthropogenic greenhouse gas contribution to flood risk in England and Wales in autumn 2000

Interest in attributing the risk of damaging weather-related events to anthropogenic climate change is increasing. Yet climate models used to study the attribution problem typically do not resolve the weather systems associated with damaging events such as the UK floods of October and November 2000. Occurring during the wettest autumn in England and Wales since records began in 1766, these floods damaged nearly 10,000 properties across that region, disrupted services severely, and caused insured losses estimated at ￡1.3 billion (refs 5, 6). Although the flooding was deemed a 'wake-up call' to the impacts of climate change at the time, such claims are typically supported only by general thermodynamic arguments that suggest increased extreme precipitation under global warming, but fail to account fully for the complex hydrometeorology associated with flooding. Here we present a multi-step, physically based 'probabilistic event attribution' framework showing that it is very likely that global anthropogenic greenhouse gas emissions substantially increased the risk of flood occurrence in England and Wales in autumn 2000. Using publicly volunteered distributed computing, we generate several thousand seasonal-forecast-resolution climate model simulations of autumn 2000 weather, both under realistic conditions, and under conditions as they might have been had these greenhouse gas emissions and the resulting large-scale warming never occurred. Results are fed into a precipitation-runoff model that is used to simulate severe daily river runoff events in England and Wales (proxy indicators of flood events). The precise magnitude of the anthropogenic contribution remains uncertain, but in nine out of ten cases our model results indicate that twentieth-century anthropogenic greenhouse gas emissions increased the risk of floods occurring in England and Wales in autumn 2000 by more than 20%, and in two out of three cases by more than 90%.