Large-scale dynamics of the mesosphere and lower thermosphere: an analysis using the extended Canadian Middle Atmosphere Model

The extended Canadian Middle Atmosphere Model is used to investigate the large-scale dynamics of the mesosphere and lower thermosphere (MLT). It is shown that the 4-day wave is substantially amplified in southern polar winter in the presence of instabilities arising from strong vertical shears in the MLT zonal mean zonal winds brought about by parameterized nonorographic gravity wave drag. A weaker 4-day wave in northern polar winter is attributed to the weaker wind shears that result from weaker parameterized wave drag. The 2-day wave also exhibits a strong dependence on zonal wind shears, in agreement with previous modeling studies. In the equatorial upper mesosphere, the migrating diurnal tide provides most of the resolved westward wave forcing, which varies semiannually in conjunction with the tide itself; resolved forcing by eastward traveling disturbances is dominated by smaller scales. Nonmigrating tides and other planetary-scale waves play only a minor role in the zonal mean zonal momentum budget in the tropics at these heights. Resolved waves are shown to play a significant role in the zonal mean meridional momentum budget in the MLT, impacting significantly on gradient wind balance. Balance fails at low latitudes as a result of a strong Reynolds stress associated with the migrating diurnal tide, an effect which is most pronounced at equinox when the tide is strongest. Resolved and parameterized waves account for most of the imbalance at higher latitudes in summer. This results in the gradient wind underestimating the actual eastward wind reversal by up to 40%

Chronic testicular Chlamydia muridarum infection impairs mouse fertility and offspring development

With approximately 131 million new genital tract infections occurring each year, Chlamydia is the most common sexually transmitted bacterial pathogen worldwide. Male and female infections occur at similar rates and both cause serious pathological sequelae. Despite this, the impact of chlamydial infection on male fertility has long been debated, and the effects of paternal chlamydial infection on offspring development are unknown. Using a male mouse chronic infection model, we show that chlamydial infection persists in the testes, adversely affecting the testicular environment. Infection increased leukocyte infiltration, disrupted the blood:testis barrier and reduced spermiogenic cell numbers and seminiferous tubule volume. Sperm from infected mice had decreased motility, increased abnormal morphology, decreased zona-binding capacity, and increased DNA damage. Serum anti-sperm antibodies were also increased. When both acutely and chronically infected male mice were bred with healthy female mice, 16.7% of pups displayed developmental abnormalities. Female offspring of chronically infected sires had smaller reproductive tracts than offspring of noninfected sires. The male pups of infected sires displayed delayed testicular development, with abnormalities in sperm vitality, motility, and sperm-oocyte binding evident at sexual maturity. These data suggest that chronic testicular Chlamydia infection can contribute to male infertility, which may have an intergenerational impact on sperm quality

TLR2, but Not TLR4, Is Required for Effective Host Defence against Chlamydia Respiratory Tract Infection in Early Life

Chlamydia pneumoniae commonly causes respiratory tract infections in children, and epidemiological investigations strongly link infection to the pathogenesis of asthma. The immune system in early life is immature and may not respond appropriately to pathogens. Toll-like receptor (TLR)2 and 4 are regarded as the primary pattern recognition receptors that sense bacteria, however their contribution to innate and adaptive immunity in early life remains poorly defined. We investigated the role of TLR2 and 4 in the induction of immune responses to Chlamydia muridarum respiratory infection, in neonatal wild-type (Wt) or TLR2-deficient (−/−), 4−/− or 2/4−/− BALB/c mice. Wt mice had moderate disease and infection. TLR2−/− mice had more severe disease and more intense and prolonged infection compared to other groups. TLR4−/− mice were asymptomatic. TLR2/4−/− mice had severe early disease and persistent infection, which resolved thereafter consistent with the absence of symptoms in TLR4−/− mice. Wt mice mounted robust innate and adaptive responses with an influx of natural killer (NK) cells, neutrophils, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, and activated CD4+ and CD8+ T-cells into the lungs. Wt mice also had effective production of interferon (IFN)γ in the lymph nodes and lung, and proliferation of lymph node T-cells. TLR2−/− mice had more intense and persistent innate (particularly neutrophil) and adaptive cell responses and IL-17 expression in the lung, however IFNγ responses and T-cell proliferation were reduced. TLR2/4−/− mice had reduced innate and adaptive responses. Most importantly, neutrophil phagocytosis was impaired in the absence of TLR2. Thus, TLR2 expression, particularly on neutrophils, is required for effective control of Chlamydia respiratory infection in early life. Loss of control of infection leads to enhanced but ineffective TLR4-mediated inflammatory responses that prolong disease symptoms. This indicates that TLR2 agonists may be beneficial in the treatment of early life Chlamydia infections and associated diseases

The Coupled Model Intercomparison Project (CMIP)

The Coupled Model Intercomparison Project (CMIP) was established to study and intercompare climate simulations made with coupled ocean-atmosphere-cryosphere-land GCMs. There are two main phases (CMIP1 and CMIP2), which study, respectively, 1) the ability of models to simulate current climate, and 2) model simulations of climate change due to an idealized change in forcing (a 1% per year CO2 increase). Results from a number of CMIP projects were reported at the first CMIP Workshop held in Melbourne, Australia, in October 1998. Some recent advances in global coupled modeling related to CMIP were also reported. Presentations were based on preliminary unpublished results. Key outcomes from the workshop were that 1) many observed aspects of climate variability are simulated in global coupled models including the North Atlantic oscillation and its linkages to North Atlantic SSTs, El Niño-like events, and monsoon interannual variability; 2) the amplitude of both high- and low-frequency global mean surface temperature variability in many global coupled models is less than that observed, with the former due in part to simulated ENSO in the models being generally weaker than observed, and the latter likely to be at least partially due to the uncertainty in the estimates of past radiative forcing; 3) an El Niño-like pattern in the mean SST response with greater surface warming in the eastern equatorial Pacific than the western equatorial Pacific is found by a number of models in global warming climate change experiments, but other models have a more spatially uniform or even a La Niña-like, response; 4) flux adjustment, by definition, improves the simulation of mean present-day climate over oceans, does not guarantee a drift-free climate, but can produce a stable base state in some models to enable very long term (1000 yr and longer) integrations-in these models it does not appear to have a major effect on model processes or model responses to increasing CO2; and 5) recent multicentury integrations show that a stable surface climate can be attained without flux adjustment (though still with some systematic simulation errors)

CCL5 regulation of mucosal chlamydial immunity and infection

<p>Abstract</p> <p>Background</p> <p>Following genital chlamydial infection, an early T helper type 1 (Th1)-associated immune response precedes the activation and recruitment of specific Th1 cells bearing distinct chemokine receptors, subsequently leading to the clearance of <it>Chlamydia</it>. We have shown that CCR5, a receptor for CCL5, is crucial for protective chlamydial immunity. Our laboratory and others have also demonstrated that CCL5 deficiencies found in man and animals can increase the susceptibility and progression of infectious diseases by modulating mucosal immunity. These findings suggest the CCR5-CCL5 axis is necessary for optimal chlamydial immunity. We hypothesized CCL5 is required for protective humoral and cellular immunity against <it>Chlamydia</it>.</p> <p>Results</p> <p>The present study revealed that CCR5 and CCL5 mRNAs are elevated in the spleen, iliac lymph nodes (ILNs), and genital mucosa following <it>Chlamydia muriduram </it>challenge. Antibody (Ab)-mediated inhibition of CCL5 during genital chlamydial infection suppressed humoral and Th1 > Th2 cellular responses by splenic-, ILN-, and genital mucosa-derived lymphocytes. Antigen (Ag)-specific proliferative responses of CD4⁺T cells from spleen, ILNs, and genital organs also declined after CCL5 inhibition.</p> <p>Conclusion</p> <p>The suppression of these responses correlated with delayed clearance of <it>C. muriduram</it>, which indicate chlamydial immunity is mediated by Th1 immune responses driven in part by CCL5. Taken together with other studies, the data show that CCL5 mediates the temporal recruitment and activation of leukocytes to mitigate chlamydial infection through enhancing adaptive mucosal humoral and cellular immunity.</p

Structures of tetrasilylmethane derivatives (XMe2Si)2C(SiMe3)2 (X = H, Cl, Br) in the gas phase, and their dynamic structures in solution

The structures of the molecules (XMe2Si)2C(SiMe3)2, where X = H, Cl, Br, have been determined by gas electron diffraction (GED) using the SARACEN method of restraints, with all analogues existing in the gas phase as mixtures of C1- and C2-symmetric conformers. Variable temperature 1H and 29Si solution-phase NMR studies, as well as 13C NMR and 1H/29Si NMR shift correlation and 1H NMR saturation transfer experiments for the chlorine and bromine analogues, are reported. At low temperatures in solution there appear to be two C1 conformers and two C2 conformers, agreeing with the isolated-molecule calculations used to guide the electron diffraction refinements. For (HMe2Si)2C(SiMe3)2 the calculations indicated six conformers close in energy, and these were modeled in the GED refinement

Genome-wide regulation of innate immunity by juvenile hormone and 20-hydroxyecdysone in the Bombyx fat body

<p>Abstract</p> <p>Background</p> <p>Insect innate immunity can be affected by juvenile hormone (JH) and 20-hydroxyecdysone (20E), but how innate immunity is developmentally regulated by these two hormones in insects has not yet been elucidated. In the silkworm, <it>Bombyx mori</it>, JH and 20E levels are high during the final larval molt (4 M) but absent during the feeding stage of 5^thinstar (5 F), while JH level is low and 20E level is high during the prepupal stage (PP). Fat body produces humoral response molecules and hence is considered as the major organ involved in innate immunity.</p> <p>Results</p> <p>A genome-wide microarray analysis of <it>Bombyx </it>fat body isolated from 4 M, 5 F and PP uncovered a large number of differentially-expressed genes. Most notably, 6 antimicrobial peptide (AMP) genes were up-regulated at 4 M versus PP suggesting that <it>Bombyx </it>innate immunity is developmentally regulated by the two hormones. First, JH treatment dramatically increased AMP mRNA levels and activities. Furthermore, 20E treatment exhibited inhibitory effects on AMP mRNA levels and activities, and RNA interference of the 20E receptor <it>EcR</it>-<it>USP </it>had the opposite effects to 20E treatment.</p> <p>Conclusion</p> <p>Taken together, we demonstrate that JH acts as an immune-activator while 20E inhibits innate immunity in the fat body during <it>Bombyx </it>postembryonic development.</p

Differentiation of Gram-Negative Bacterial Aerosol Exposure Using Detected Markers in Bronchial-Alveolar Lavage Fluid

The identification of biosignatures of aerosol exposure to pathogens has the potential to provide useful diagnostic information. In particular, markers of exposure to different types of respiratory pathogens may yield diverse sets of markers that can be used to differentiate exposure. We examine a mouse model of aerosol exposure to known Gram negative bacterial pathogens, Francisella tularensis novicida and Pseudomonas aeruginosa. Mice were subjected to either a pathogen or control exposure and bronchial alveolar lavage fluid (BALF) was collected at four and twenty four hours post exposure. Small protein and peptide markers within the BALF were detected by matrix assisted laser desorption/ionization (MALDI) mass spectrometry (MS) and analyzed using both exploratory and predictive data analysis methods; principle component analysis and degree of association. The markers detected were successfully used to accurately identify the four hour exposed samples from the control samples. This report demonstrates the potential for small protein and peptide marker profiles to identify aerosol exposure in a short post-exposure time frame

Interleukin-13 Promotes Susceptibility to Chlamydial Infection of the Respiratory and Genital Tracts

Chlamydiae are intracellular bacteria that commonly cause infections of the respiratory and genital tracts, which are major clinical problems. Infections are also linked to the aetiology of diseases such as asthma, emphysema and heart disease. The clinical management of infection is problematic and antibiotic resistance is emerging. Increased understanding of immune processes that are involved in both clearance and immunopathology of chlamydial infection is critical for the development of improved treatment strategies. Here, we show that IL-13 was produced in the lungs of mice rapidly after Chlamydia muridarum (Cmu) infection and promoted susceptibility to infection. Wild-type (WT) mice had increased disease severity, bacterial load and associated inflammation compared to IL-13 deficient (−/−) mice as early as 3 days post infection (p.i.). Intratracheal instillation of IL-13 enhanced bacterial load in IL-13−/− mice. There were no differences in early IFN-g and IL-10 expression between WT and IL-13−/− mice and depletion of CD4+ T cells did not affect infection in IL-13−/− mice. Collectively, these data demonstrate a lack of CD4+ T cell involvement and a novel role for IL-13 in innate responses to infection. We also showed that IL-13 deficiency increased macrophage uptake of Cmu in vitro and in vivo. Moreover, the depletion of IL-13 during infection of lung epithelial cells in vitro decreased the percentage of infected cells and reduced bacterial growth. Our results suggest that enhanced IL-13 responses in the airways, such as that found in asthmatics, may promote susceptibility to chlamydial lung infection. Importantly the role of IL-13 in regulating infection was not limited to the lung as we showed that IL-13 also promoted susceptibility to Cmu genital tract infection. Collectively our findings demonstrate that innate IL-13 release promotes infection that results in enhanced inflammation and have broad implications for the treatment of chlamydial infections and IL-13-associated diseases

Insights on the Neuromagnetic Representation of Temporal Asymmetry in Human Auditory Cortex.

Communication sounds are typically asymmetric in time and human listeners are highly sensitive to this short-term temporal asymmetry. Nevertheless, causal neurophysiological correlates of auditory perceptual asymmetry remain largely elusive to our current analyses and models. Auditory modelling and animal electrophysiological recordings suggest that perceptual asymmetry results from the presence of multiple time scales of temporal integration, central to the auditory periphery. To test this hypothesis we recorded auditory evoked fields (AEF) elicited by asymmetric sounds in humans. We found a strong correlation between perceived tonal salience of ramped and damped sinusoids and the AEFs, as quantified by the amplitude of the N100m dynamics. The N100m amplitude increased with stimulus half-life time, showing a maximum difference between the ramped and damped stimulus for a modulation half-life time of 4 ms which is greatly reduced at 0.5 ms and 32 ms. This behaviour of the N100m closely parallels psychophysical data in a manner that: i) longer half-life times are associated with a stronger tonal percept, and ii) perceptual differences between damped and ramped are maximal at 4 ms half-life time. Interestingly, differences in evoked fields were significantly stronger in the right hemisphere, indicating some degree of hemispheric specialisation. Furthermore, the N100m magnitude was successfully explained by a pitch perception model using multiple scales of temporal integration of auditory nerve activity patterns. This striking correlation between AEFs, perception, and model predictions suggests that the physiological mechanisms involved in the processing of pitch evoked by temporal asymmetric sounds are reflected in the N100m