Microarray analysis of whole genome expression of intracellular Mycobacterium tuberculosis

Analysis of the changing mRNA expression profile of Mycobacterium tuberculosis though the course of infection promises to advance our understanding of how mycobacteria are able to survive the host immune response. The difficulties of sample extraction from distinct mycobacterial populations, and of measuring mRNA expression profiles of multiple genes has limited the impact of gene expression studies on our interpretation of this dynamic infection process. The development of whole genome microarray technology together with advances in sample collection have allowed the expression pattern of the whole M. tuberculosis genome to be compared across a number of different in vitro conditions, murine and human tissue culture models and in vivo infection samples. This review attempts to produce a summative model of the M. tuberculosis response to infection derived from or reflected in these gene expression datasets. The mycobacterial response to the intracellular environment is characterised by the utilisation of lipids as a carbon source and the switch from aerobic/microaerophilic to anaerobic respiratory pathways. Other genes induced in the macrophage phagosome include those likely to be involved in the maintenance of the cell wall and genes related to DNA damage, heat shock, iron sequestration and nutrient limitation. The comparison of transcriptional data from in vitro models of infection with complex in vivo samples, together with the use of bacterial RNA amplification strategies to sample defined populations of bacilli, should allow us to make conclusions about M. tuberculosis physiology and host microenvironments during natural infection

The frequency and properties of young tidal dwarf galaxies in nearby gas-rich groups

We present high-resolution Giant Metrewave Radio Telescope (GMRT) HI observations and deep Canada-France-Hawaii Telescope (CFHT) optical imaging of two galaxy groups: NGC 4725/47 and NGC 3166/9. These data are part of a multi-wavelength unbiased survey of the gas-rich dwarf galaxy populations in three nearby interacting galaxy groups. The NGC 4725/47 group hosts two tidal knots and one dIrr. Both tidal knots are located within a prominent HI tidal tail, appear to have sufficient mass (M_gas~10^8 M_sol) to evolve into long-lived tidal dwarf galaxies (TDGs) and are fairly young in age. The NGC 3166/9 group contains a TDG candidate, AGC 208457, at least three dIrrs and four HI knots. Deep CFHT imaging confirms that the optical component of AGC 208457 is bluer -- with a 0.28 mag g-r colour -- and a few Gyr younger than its purported parent galaxies. Combining the results for these groups with those from the NGC 871/6/7 group reported earlier, we find that the HI properties, estimated stellar ages and baryonic content of the gas-rich dwarfs clearly distinguish tidal features from their classical counterparts. We optimistically identify four potentially long-lived tidal objects associated to three separate pairs of interacting galaxies, implying that TDGs are not readily produced during interaction events as suggested by some recent simulations. The tidal objects examined in this survey also appear to have a wider variety of properties than TDGs of similar mass formed in current simulations of interacting galaxies, which could be the result of pre- or post-formation environmental influences.Comment: 18 pages, 14 figures, accepted for publication in MNRA

Rescue of glucocorticoid-programmed adipocyte inflammation by omega-3 fatty acid supplementation in the rat

BACKGROUND: Adverse fetal environments predispose offspring to pathologies associated with the metabolic syndrome. Previously we demonstrated that adult offspring of dexamethasone-treated mothers had elevated plasma insulin and pro-inflammatory cytokines, effects prevented by a postnatal diet enriched with omega (n)-3 fatty acids. Here we tested whether prenatal glucocorticoid excess also programmed the adipose tissue phenotype, and whether this outcome is rescued by dietary n-3 fatty acids. METHODS: Offspring of control and dexamethasone-treated mothers (0.75 μg/ml in drinking water, day 13 to term) were cross-fostered to mothers on a standard (Std) or high n-3 (Hn3) diet at birth. Offspring remained on these diets post-weaning, and serum and retroperitoneal fat were obtained at 6 months of age (n = 5-8 per group). Serum was analysed for blood lipids and fatty acid profiles, adipocyte cross sectional area was measured by unbiased stereological analysis and adipose expression of markers of inflammation, glucocorticoid sensitivity and lipid metabolism were determined by RT-qPCR analysis. RESULTS: Serum total fatty acid levels were elevated (P < 0.01) in male offspring of dexamethasone-treated mothers, an effect prevented by Hn3 consumption. Prenatal dexamethasone also programmed increased adipose expression of Il6, Il1b (both P < 0.05) and Tnfa (P < 0.001) mRNAs regardless of fetal sex, but again this effect was prevented (for Il6 and Il1b) by Hn3 consumption. Offspring of dexamethasone-treated mothers had increased adipose expression of Gr (P = 0.008) and Ppara (P < 0.05) regardless of sex or postnatal diet, while 11bHsd1 was upregulated in males only. The Hn3 diet increased Ppard expression and reduced adipocyte size in all offspring (both P < 0.05) irrespective of prenatal treatment. CONCLUSIONS: Prenatal glucocorticoid exposure programmed increased expression of inflammatory markers and enhanced glucocorticoid sensitivity of adipose tissue. Partial prevention of this phenotype by high n-3 consumption indicates that postnatal dietary manipulations can limit adverse fetal programming effects on adipose tissue

The influence of 'significant others' on persistent back pain and work participation: a qualitative exploration of illness perceptions

Background Individual illness perceptions have been highlighted as important influences on clinical outcomes for back pain. However, the illness perceptions of 'significant others' (spouse/partner/close family member) are rarely explored, particularly in relation to persistent back pain and work participation. The aim of this study was to initiate qualitative research in this area in order to further understand these wider influences on outcome. Methods Semi-structured interviews based on the chronic pain version of the Illness Perceptions Questionnaire-Revised were conducted with a convenience sample of UK disability benefit claimants, along with their significant others (n=5 dyads). Data were analysed using template analysis. Results Significant others shared, and perhaps further reinforced, claimants' unhelpful illness beliefs including fear of pain/re-injury associated with certain types of work and activity, and pessimism about the likelihood of return to work. In some cases, significant others appeared more resigned to the permanence and negative inevitable consequences of the claimant's back pain condition on work participation, and were more sceptical about the availability of suitable work and sympathy from employers. In their pursuit of authenticity, claimants were keen to stress their desire to work whilst emphasising how the severity and physical limitations of their condition prevented them from doing so. In this vein, and seemingly based on their perceptions of what makes a 'good' significant other, significant others acted as a 'witness to pain', supporting claimants' self-limiting behaviour and statements of incapacity, often responding with empathy and assistance. The beliefs and responses of significant others may also have been influenced by their own experience of chronic illness, thus participants lives were often intertwined and defined by illness. Conclusions The findings from this exploratory study reveal how others and wider social circumstances might contribute both to the propensity of persistent back pain and to its consequences. This is an area that has received little attention to date, and wider support of these findings may usefully inform the design of future intervention programmes aimed at restoring work participation

Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum

As nonreplicating tubercle bacilli are tolerant to the cidal action of antibiotics and resistant to multiple stresses, identification of this persister-like population of tubercle bacilli in sputum presents exciting and tractable new opportunities to investigate both responses to chemotherapy and the transmission of tuberculosis

Comparison between resistive and collisionless double tearing modes for nearby resonant surfaces

The linear instability and nonlinear dynamics of collisional (resistive) and collisionless (due to electron inertia) double tearing modes (DTMs) are compared with the use of a reduced cylindrical model of a tokamak plasma. We focus on cases where two q = 2 resonant surfaces are located a small distance apart. It is found that regardless of the magnetic reconnection mechanism, resistivity or electron inertia, the fastest growing linear eigenmodes may have high poloidal mode numbers m ~ 10. The spectrum of unstable modes tends to be broader in the collisionless case. In the nonlinear regime, it is shown that in both cases fast growing high-m DTMs lead to an annular collapse involving small magnetic island structures. In addition, collisionless DTMs exhibit multiple reconnection cycles due to reversibility of collisionless reconnection and strong ExB flows. Collisionless reconnection leads to a saturated stable state, while in the collisional case resistive decay keeps the system weakly dynamic by driving it back towards the unstable equilibrium maintained by a source term.Comment: 15 pages, 9 figure

Pre-existing dwarfs, tidal knots and a tidal dwarf galaxy: an unbiased H_I study of the gas-rich interacting galaxy group NGC 3166/9

We present Arecibo Legacy Fast ALFA (ALFALFA) and follow-up Giant Metrewave Radio Telescope (GMRT) H _I observations of the gas-rich interacting group NGC 3166/9. The sensitive ALFALFA data provide a complete census of H _I-bearing systems in the group while the high-resolution GMRT data elucidate their origin, enabling one of the first unbiased physical studies of gas-rich dwarf companions and the subsequent identification of second-generation, tidal dwarf galaxies in a nearby group. The ALFALFA maps reveal an extended H _I envelope around the NGC 3166/9 group core, which we mosaic at higher resolution using six GMRT pointings spanning ∼1 deg^2. A thorough search of the GMRT data cube reveals eight low-mass objects with gas masses ranging from 4 × 10^7 to 3 × 10^8 M_⊙ and total dynamical masses up to 1.4 × 10^9 M_⊙. A comparison of the H I fluxes measured from the GMRT data to those measured in the ALFALFA data suggests that a significant fraction (∼60 per cent) of the H _I is smoothly distributed on scales greater than 1 arcmin (∼7 kpc at the NGC 3166/9 distance). We compute stellar masses and star formation rates for the eight low-mass GMRT detections, using ancillary Sloan Digital Sky Survey (SDSS) and Galaxy Evolution Explorer (GALEX) data, and use these values to constrain their origin. Most of the detections are likely to be either pre-existing dwarf irregular galaxies or short-lived, tidally formed knots; however, one candidate, AGC 208457, is clearly associated with a tidal tail extending below NGC 3166, exhibits a dynamical to gas mass ratio close to unity and has a stellar content and star formation rate that are broadly consistent with both simulated as well as candidate tidal dwarf galaxies from the literature. Our observations therefore strongly suggest that AGC 208457 is a tidal dwarf galaxy

Optical spectroscopy of young tidal objects around two interacting galaxy pairs

We present Gemini Multi-Object Spectrograph spectra of HI-rich tidal features located around the outskirts of two interacting galaxy pairs, NGC 3166/9 and NGC 4725/47. These follow-up observations are part of a multiwavelength campaign to study the properties and frequency of tidal dwarf galaxies (TDGs) in group environments. Based on the calculated gas-phase metallicity and redshift, in addition to the previously measured HI and stellar properties, we have confirmed the tidal origins of TDG candidate AGC 208457, which has emerged from the tidal debris of an interaction between the NGC 3166/9 galaxy pair. By comparing HI and optical recessional velocities, we have also confirmed a physical association of the gaseous knots and star clusters embedded in the metal-rich tidal tail of NGC 4747.Fil: Lee-Waddell, K.. CIRO Australia Telescope National Facility; AustraliaFil: Madrid, J. P.. CIRO Australia Telescope National Facility; AustraliaFil: Spekkens, K. Royal Military College of Canada; CanadáFil: Donzelli, Carlos Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Koribalski, B. S.. CIRO Australia Telescope National Facility; AustraliaFil: Serra, P.. Università Degli Studi Di Cagliari.; ItaliaFil: Cannon, J. Macalester College. Department of Physics and Astronomy; Estados Unido