Th2 Cytokine Levels Distort the Association of IL-10 and IFN-γ with Allergic Phenotypes

The expression of allergic phenotypes involves complex inter-relationships among several Th2 and Th1 cytokines as well as the regulator cytokine interleukin (IL)-10. These direct or indirect interrelationships may distort the true associations of cytokine responses with these phenotypes. In this study, we aimed to clarify the effects of the regulatory cytokine IL-10 and Th1 cytokine interferon-gamma (IFN-?) on allergic phenotypes after adjusting for the correlations with Th2 cytokines. After adjusting for Th2 cytokines, IL-10 and IFN-? were protective against atopy. Adjusted levels of IL-10 and IFN-? stimulated with house-dust mite (HDM) were significantly lower in atopics than non-atopics, for IL-10 adjusting for IL-5 (P = 0.002), IL-13 (P = 0.012), IL-9 (P = 0.016), and IL-4 (P = 0.043), and for IFN-? adjusting for IL-5 (P = 0.005), IL-13 (P = 0.005), and IL-9 (P = 0.037). IL-10 and IFN-? levels stimulated with phytohaemagglutinin (PHA) and staphylococcal enterotoxin B (SEB) exhibited a similar pattern. The adjusted levels of IL-10 and IFN-? stimulated with HDM, PHA or SEB were all significantly negatively correlated with total serum IgE, except for IFN-? stimulated with SEB. Levels of Th2 cytokines distort the associations of IL-10 and IFN-? with allergic phenotypes. Removing the covariance with Th2 cytokines, both IL-10 and IFN-? were protective against atopy

A census of young stellar populations in the warm ULIRG PKS1345+12

We present a detailed investigation of the young stellar populations(YSP) in the radio-loud ultra luminous infrared galaxy (ULIRG) PKS1345+12, based on high resolution HST imaging and long slit spectra taken with the WHT. While the images clearly show bright knots suggestive of super star clusters(SSC), the spectra reveal the presence of YSP in the diffuse light across the full extent of the halo of the merging-double nucleus system. Spectral synthesis modelling has been used to estimate the ages of the YSP for both the SSC and the diffuse light sampled by the spectra. For the SSC we find ages t{SSC} < 6 Myr with reddenings 0.2 < E(B-V) < 0.5 and masses 10e6 < M{SSC} < 10e7 M{solar}. However, in some regions of the galaxy we find that the spectra of the diffuse light component can only be modelled with a relatively old post-starburst YSP (0.04 - 1.0 Gyr) or with a disk galaxy template spectrum. The results demonstrate the importance of accounting for reddening in photometric studies of SSC, and highlight the dangers of focussing on the highest surface brightness regions when trying to obtain a general impression of the star formation activity in the host galaxies of ULIRGs. The case of PKS1345+12 provides clear evidence that the star formation histories of the YSP in ULIRGs are complex. Intriguingly, our long-slit spectra show line splitting at the locations of the SSC, indicating that they are moving at up to 450km s-1 with respect to the local ambient gas. Given their kinematics, it is plausible that the SSC have been formed either in fast moving gas streams/tidal tails that are falling back into the nuclear regions as part of the merger process, or as a consequence of jet-induced star formation linked to the extended, diffuse radio emission detected in the halo of the galaxyComment: accepted for publication in MNRA

Two alternatively-spliced human nebulin isoforms with either exon 143 or exon 144 and their developmental regulation

Nebulin is a very large protein required for assembly of the contractile machinery in muscle. Mutations in the nebulin gene NEB are a common cause of nemaline myopathy. Nebulin mRNA is alternatively-spliced so that each mRNA contains either exon 143 or exon 144. We have produced monoclonal antibodies specific for the regions of nebulin encoded by these two exons, enabling analysis of expression of isoforms at the protein level for the first time. All antibodies recognized a protein of the expected size (600-900 kD) and stained cross-striations of sarcomeres in muscle sections. Expression of exon 143 is developmentally-regulated since newly-formed myotubes in cell culture expressed nebulin with exon 144 only; this was confirmed at the mRNA level by qPCR. In fetal muscle, nebulin with exon 143 was expressed in some myotubes by 12-weeks of gestation and strongly-expressed in most myotubes by 17-weeks. In mature human muscle, the exon 144 antibody stained all fibres, but the exon 143 antibody staining varied from very strong in some fibres to almost-undetectable in other fibres. The results show that nebulin containing exon 144 is the default isoform early in myogenesis, while regulated expression of nebulin containing exon 143 occurs at later stages of muscle development.Peer reviewe

Variation in resistance to multiple pathogen species:anther-smuts of Silene uniflora

The occurrence of multiple pathogen species on a shared host species is unexpected when they exploit the same micro-niche within the host individual. One explanation for such observations is the presence of pathogen-specific resistances segregating within the host population into sites that are differentially occupied by the competing pathogens. This study used experimental inoculations to test whether specific resistances may contribute to the maintenance of two species of anther-smut fungi, Microbotryum silenes-inflatae and Microbotryum lagerheimii, in natural populations of Silene uniflora in England and Wales. Overall, resistance to the two pathogens was strongly positively correlated among host populations and to a lesser degree among host families within populations. A few instances of specific resistance were also observed and confirmed by replicated inoculations. The results suggest that selection for resistance to one pathogen may protect the host from the emergence via host shifts of related pathogen species, and conversely that co-occurrence of two species of pathogens may be dependent on the presence of host genotypes susceptible to both

Evidence of the Key Role of H<inf>3</inf>O⁺ in Phospholipid Membrane Morphology

© 2016 American Chemical Society. This study explains the importance of the phosphate moiety and H3O+ in controlling the ionic flux through phospholipid membranes. We show that despite an increase in the H3O+ concentration when the pH is decreased, the level of ionic conduction through phospholipid bilayers is reduced. By modifying the lipid structure, we show the dominant determinant of membrane conduction is the hydrogen bonding between the phosphate oxygens on adjacent phospholipids. The modulation of conduction with pH is proposed to arise from the varying H3O+ concentrations altering the molecular area per lipid and modifying the geometry of conductive defects already present in the membrane. Given the geometrical constraints that control the lipid phase structure of membranes, these area changes predict that organisms evolving in environments with different pHs will select for different phospholipid chain lengths, as is found for organisms near highly acidic volcanic vents (short chains) or in highly alkaline salt lakes (long chains). The stabilizing effect of the hydration shells around phosphate groups also accounts for the prevalence of phospholipids across biology. Measurement of ion permeation through lipid bilayers was made tractable using sparsely tethered bilayer lipid membranes with swept frequency electrical impedance spectroscopy and ramped dc amperometry. Additional evidence of the effect of a change in pH on lipid packing density is obtained from neutron reflectometry data of tethered membranes containing perdeuterated lipids

Structural Characterization of a Model Gram-Negative Bacterial Surface Using Lipopolysaccharides from Rough Strains of <i>Escherichia coli</i>

Lipopolysaccharides (LPS) make up approximately 75% of the Gram-negative bacterial outer membrane (OM) surface, but because of the complexity of the molecule, there are very few model OMs that include LPS. The LPS molecule consists of lipid A, which anchors the LPS within the OM, a core polysaccharide region, and a variable O-antigen polysaccharide chain. In this work we used RcLPS (consisting of lipid A plus the first seven sugars of the core polysaccharide) from a rough strain of Escherichia coli to form stable monolayers of LPS at the air-liquid interface. The vertical structure RcLPS monolayers were characterized using neutron and X-ray reflectometry, while the lateral structure was investigated using grazing incidence X-ray diffraction and Brewster angle microscopy. It was found that RcLPS monolayers at surface pressures of 20 mN m(-1) and above are resolved as hydrocarbon tails, an inner headgroup, and an outer headgroup of polysaccharide with increasing solvation from tails to outer headgroups. The lateral organization of the hydrocarbon lipid chains displays an oblique hexagonal unit cell at all surface pressures, with only the chain tilt angle changing with surface pressure. This is in contrast to lipid A, which displays hexagonal or, above 20 mN m(-1), distorted hexagonal packing. This work provides the first complete structural analysis of a realistic E. coli OM surface model

Occurrence of nontuberculous mycobacteria in aquatic sources of Sri Lanka

AbstractNontuberculous mycobacteria (NTM) have been reported to cause opportunistic infections with increasing frequency, especially in immunocompromised patients. Water plays a major role in the epidemiology of nontuberculous mycobacterial infection in humans, as it is one of the natural sources for transmission of this group of organisms. The current study focused on determining the occurrence of NTM in different aquatic sources of Sri Lanka by using phenotypic tests and polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis of the rpoβ gene. Of 290 water samples, 45 (15%) were positive for NTM on culture. The percentage of mycobacteria identified at species level by phenotypic tests and PCR–RFLP analysis were 44% (20/45) and 73% (33/45), respectively. The frequency of isolation of mycobacteria from aquarium water, surface water, ground water and chlorinated water were 29% (20/70), 26% (20/76), 5% (4/76) and 1% (1/68), respectively. Eleven different NTM species were identified by PCR–RFLP analysis. M. fortuitum type I was the most frequently isolated species from all the four water sources. The current study suggests that water is an environmental source harboring NTM, a potential public health hazard especially for those with immunodeficiency

Misaligned spin and orbital axes cause the anomalous precession of DI Herculis

The orbits of binary stars precess as a result of general relativistic effects, forces arising from the asphericity of the stars, and forces from additional stars or planets in the system. For most binaries, the theoretical and observed precession rates are in agreement. One system, however -- DI Herculis -- has resisted explanation for 30 years. The observed precession rate is a factor of four slower than the theoretical rate, a disagreement that once was interpreted as evidence for a failure of general relativity. Among the contemporary explanations are the existence of a circumbinary planet and a large tilt of the stellar spin axes with respect to the orbit. Here we report that both stars of DI Herculis rotate with their spin axes nearly perpendicular to the orbital axis (contrary to the usual assumption for close binary stars). The rotationally induced stellar oblateness causes precession in the direction opposite to that of relativistic precession, thereby reconciling the theoretical and observed rates.Comment: Nature, in press [11 pg