Measuring intense rotation and dissipation in turbulent flows

Turbulent flows are highly intermittent--for example, they exhibit intense bursts of vorticity and strain. Kolmogorov theory describes such behaviour in the form of energy cascades from large to small spatial and temporal scales, where energy is dissipated as heat. But the causes of high intermittency in turbulence, which show non-gaussian statistics, are not well understood. Such intermittency can be important, for example, for enhancing the mixing of chemicals, by producing sharp drops in local pressure that can induce cavitation (damaging mechanical components and biological organisms), and by causing intense vortices in atmospheric flows. Here we present observations of the three components of velocity and all nine velocity gradients within a small volume, which allow us to determine simultaneously the dissipation (a measure of strain) and enstrophy (a measure of rotational energy) of a turbulent flow. Combining the statistics of all measurements and the evolution of individual bursts, we find that a typical sequence for intense events begins with rapid strain growth, followed by rising vorticity and a final sudden decline in stretching. We suggest two mechanisms which can produce these characteristics, depending whether they are due to the advection of coherent structures through our observed volume or caused locally.     

The effect of chronic heat stress on cortisol levels in the antarctic fishPagothenia borchgrevinki

Radioimmunoassay was used to determine levels of the stress-inducible glucocorticoid, cortisol, circulating in the plasma of the extremely stenothermal Antarctic fishPagothenia borchgrevinki at rest and after heat stress. Fish sampled immediately after capture (–1.9°C) had low cortisol levels (10.4±1.4 ng ml^–1, mean±SEM) as did fish which were laboratory rested for 3 days. Sudden exposure to 5°C (48h) resulted in a peak cortisol value after 3 h (69.9±6.8 ng ml^–1) whereas exposure to 8°C (6h) resulted in a peak value after 1 h (73.5±8.0 ng ml^–1). At both temperatures levels remained significantly elevated (p<0.05) for the entire period of exposure. Increased temperature also resulted in a significant change in haemoglobin, haematocrit and mean cell haemoglobin concentration (MCHC) (p<0.05). Plasma lactate was significantly elevated only after exposure to 8°C (p<0.05). Plasma cortisol levels fromP. borchgrevinki are reported here for the first time and show this cryopelagic Antarctic species to have an unusual hormonal stress profile.     

Impaired PtdIns(4,5)P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking

Phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) has an important function in cell regulation both as a precursor of second messenger molecules and by means of its direct interactions with cytosolic and membrane proteins. Biochemical studies have suggested a role for PtdIns(4,5)P2 in clathrin coat dynamics, and defects in its dephosphorylation at the synapse produce an accumulation of coated endocytic intermediates. However, the involvement of PtdIns(4,5)P2 in synaptic vesicle exocytosis remains unclear. Here, we show that decreased levels of PtdIns(4,5)P2 in the brain and an impairment of its depolarization-dependent synthesis in nerve terminals lead to early postnatal lethality and synaptic defects in mice. These include decreased frequency of miniature currents, enhanced synaptic depression, a smaller readily releasable pool of vesicles, delayed endocytosis and slower recycling kinetics. Our results demonstrate a critical role for PtdIns(4,5)P2 synthesis in the regulation of multiple steps of the synaptic vesicle cycle.     

Observational evidence for an ocean heat pump induced by tropical cyclones

Ocean mixing affects global climate and the marine biosphere because it is linked to the ocean's ability to store and transport heat and nutrients. Observations have constrained the magnitude of upper ocean mixing associated with certain processes, but mixing rates measured directly are significantly lower than those inferred from budget analyses, suggesting that other processes may play an important role. The winds associated with tropical cyclones are known to lead to localized mixing of the upper ocean, but the hypothesis that tropical cyclones are important mixing agents at the global scale has not been tested. Here we calculate the effect of tropical cyclones on surface ocean temperatures by comparing surface temperatures before and after storm passage, and use these results to calculate the vertical mixing induced by tropical cyclone activity. Our results indicate that tropical cyclones are responsible for significant cooling and vertical mixing of the surface ocean in tropical regions. Assuming that all the heat that is mixed downwards is balanced by heat transport towards the poles, we calculate that approximately 15 per cent of peak ocean heat transport may be associated with the vertical mixing induced by tropical cyclones. Furthermore, our analyses show that the magnitude of this mixing is strongly related to sea surface temperature, indicating that future changes in tropical sea surface temperatures may have significant effects on ocean circulation and ocean heat transport that are not currently accounted for in climate models.     

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.     

Structural features underlying the selectivity of the kinase inhibitors NBC and dNBC: role of a nitro group that discriminates between CK2 and DYRK1A

8-hydroxy-4-methyl-9-nitrobenzo(g)chromen-2-one (NBC) has been found to be a fairly potent ATP site-directed inhibitor of protein kinase CK2 (Ki = 0.22 μM). Here, we show that NBC also inhibits PIM kinases, especially PIM1 and PIM3, the latter as potently as CK2. Upon removal of the nitro group, to give 8-hydroxy-4-methyl-benzo(g)chromen-2-one (here referred to as “denitro NBC”, dNBC), the inhibitory power toward CK2 is almost entirely lost (IC₅₀ > 30 μM) whereas that toward PIM1 and PIM3 is maintained; in addition, dNBC is a potent inhibitor of a number of other kinases that are weakly inhibited or unaffected by NBC, with special reference to DYRK1A whose IC₅₀ values with NBC and dNBC are 15 and 0.60 μM, respectively. Therefore, the observation that NBC, unlike dNBC, is a potent inducer of apoptosis is consistent with the notion that this effect is mediated by inhibition of endogenous CK2. The structural features underlying NBC selectivity have been revealed by inspecting its 3D structure in complex with the catalytic subunit of Z. mays CK2. The crucial role of the nitro group is exerted both through a direct electrostatic interaction with the side chain of Lys68 and, indirectly, by enhancing the acidic dissociation constant of the adjacent hydroxyl group which interacts with a conserved water molecule in the deepest part of the cavity. By contrast, the very same nitro group is deleterious for the binding to the active site of DYRK1A, as disclosed by molecular docking. This provides the rationale for preferential inhibition of DYRK1A by dNBC.     

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.