Assessment of algorithms for computing moist available potential energy

Atmospheric moist available potential energy (MAPE) has been traditionally defined as the potential energy of a moist atmosphere relative to that of the adiabatically sorted reference state defining a global potential energy minimum. Although the Munkres algorithm can in principle find such a reference state exactly, its computational cost has prompted much interest in developing heuristic methods for computing MAPE in practice. Comparisons of the accuracy of such approximate algorithms have so far been limited to a small number of test cases; this work provides an assessment of the algorithms’ performance across a wide range of atmospheric soundings, in two different locations. We determine that the divide-and-conquer algorithm is the best suited to practical application, but suffers from the previously unexplored shortcoming that it can produce a reference state with higher potential energy than the actual state, resulting in a negative value of MAPE. Additionally, we show that it is possible to construct an algorithm exploiting a previously derived theoretical expression linking MAPE to Convective Available Potential Energy (CAPE). This approach has a similar accuracy to existing approximate sorting algorithms, whilst providing greater insight into the physical source of MAPE. In light of these results, we discuss possible ways to improve on the construction of APE theory for a moist atmosphere

Marginal stability and predator-prey behaviour within storm tracks

A predator-prey relationship between storm track intensity and growth rate is revealed in reanalysis data for the North Atlantic and North Pacific, as well as in an idealised global circulation model with a zonally asymmetric heating dipole. Averaging in the phase space of these two quantities reveals that both quantities oscillate on approximately monthly timescales. These oscillations occur due to quasi-periodic bursts in storm track activity that reduce excess baroclinicity and bring the flow back towards a state that is marginally stable to those bursts. Many detailed properties of these oscillations are reproduced well by a two-dimensional dynamical system, especially in respect of the North Atlantic storm track which is more zonally constrained compared to the North Pacific. It is predicted and observed that on average stronger storm events occur less frequently but grow on a shorter timescale. The results suggest that nonlinearly oscillating behaviour around a state of baroclinic neutrality is a general feature of localised storm tracks, and they offer a new perspective on the study of baroclinic instability

Purinergic signaling: a common path in the macrophage response against Mycobacterium tuberculosis and Toxoplasma gondii.

Immune responses are essential for the protection of the host against external dangers or infections and are normally efficient in the clearance of invading microbes. However, some intracellular pathogens have developed strategies to replicate and survive within host cells resulting in latent infection associated with strong inflammation. This excessive response can cause cell and tissue damage and lead to the release of the intracellular content, in particular the nucleotide pool, into the extracellular space. Over the last decade, new studies have implicated metabolites from the purinergic pathway in shaping the host immune response against intracellular pathogens and proved their importance in the outcome of the infection. This review aims to summarize how the immune system employs the purinergic system either to fight the pathogen, or to control collateral tissue damage. This will be achieved by focusing on the macrophage response against two intracellular pathogens, the human etiologic agent of tuberculosis, Mycobacterium tuberculosis and the protozoan parasite, Toxoplasma gondii

Promoter variation in the DC-SIGN-encoding gene CD209 is associated with tuberculosis.

BACKGROUND: Tuberculosis, which is caused by Mycobacterium tuberculosis, remains one of the leading causes of mortality worldwide. The C-type lectin DC-SIGN is known to be the major M. tuberculosis receptor on human dendritic cells. We reasoned that if DC-SIGN interacts with M. tuberculosis, as well as with other pathogens, variation in this gene might have a broad range of influence in the pathogenesis of a number of infectious diseases, including tuberculosis. METHODS AND FINDINGS: We tested whether polymorphisms in CD209, the gene encoding DC-SIGN, are associated with susceptibility to tuberculosis through sequencing and genotyping analyses in a South African cohort. After exclusion of significant population stratification in our cohort, we observed an association between two CD209 promoter variants (-871G and -336A) and decreased risk of developing tuberculosis. By looking at the geographical distribution of these variants, we observed that their allelic combination is mainly confined to Eurasian populations. CONCLUSIONS: Our observations suggest that the two -871G and -336A variants confer protection against tuberculosis. In addition, the geographic distribution of these two alleles, together with their phylogenetic status, suggest that they may have increased in frequency in non-African populations as a result of host genetic adaptation to a longer history of exposure to tuberculosis. Further characterization of the biological consequences of DC-SIGN variation in tuberculosis will be crucial to better appreciate the role of this lectin in interactions between the host immune system and the tubercle bacillus as well as other pathogens

Evolution of forced shear flows in polytropic atmospheres: A comparison of forcing methods and energetics

Shear flows are ubiquitous in astrophysical objects including planetary and stellar interiors, where their dynamics can have significant impact on thermo-chemical processes. Investigating the complex dynamics of shear flows requires numerical calculations that provide a long time evolution of the system. To achieve a sufficiently long lifetime in a local numerical model the system has to be forced externally. However, at present, there exist several different forcing methods to sustain large-scale shear flows in local models. In this paper we examine and compare various methods used in the literature in order to resolve their respective applicability and limitations. These techniques are compared during the exponential growth phase of a shear flow instability, such as the Kelvin-Helmholtz (KH) instability, and some are examined during the subsequent non-linear evolution. A linear stability analysis provides reference for the growth rate of the most unstable modes in the system and a detailed analysis of the energetics provides a comprehensive understanding of the energy exchange during the system's evolution. Finally, we discuss the pros and cons of each forcing method and their relation with natural mechanisms generating shear flows

Spatial and Temporal Scales of Sverdrup Balance

Sverdrup balance underlies much of the theory of ocean circulation and provides a potential tool for describing the interior ocean transport from only the wind stress. Using both a model state estimate and an eddy-permitting coupled climate model, this study assesses to what extent and over what spatial and temporal scales Sverdrup balance describes the meridional transport. The authors find that Sverdrup balance holds to first order in the interior subtropical ocean when considered at spatial scales greater than approximately 5°. Outside the subtropics, in western boundary currents and at short spatial scales, significant departures occur due to failures in both the assumptions that there is a level of no motion at some depth and that the vorticity equation is linear. Despite the ocean transport adjustment occurring on time scales consistent with the basin-crossing times for Rossby waves, as predicted by theory, Sverdrup balance gives a useful measure of the subtropical circulation after only a few years. This is because the interannual transport variability is small compared to the mean transports. The vorticity input to the deep ocean by the interaction between deep currents and topography is found to be very large in both models. These deep transports, however, are separated from upper-layer transports that are in Sverdrup balance when considered over large scales

The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection

Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host's immune system. Here, we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed cells into potent bactericidal phagocytes. We found that 579 and 1,495 genes were respectively differentially expressed in naive- and M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of lysosome-associated genes. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB, involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections

Early growth response gene-2 (Egr-2) regulates the development of B and T cells

The study was supported by Arthritis Research UK. Copyright @ 2011 Li et al.BACKGROUND: Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development. METHODS AND FINDINGS: The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2+ lymphocytes resulted in a severe reduction of CD4+CD8+ (DP) cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP) T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow. CONCLUSIONS: Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.This article is provided by the Brunel Open Access publishing fund

Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages

This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments