Heterogeneity in the granulomatous response to mycobacterial infection in patients with defined genetic mutations in the interleukin 12-dependent interferon-gamma production pathway

Granulomatous Diseases Review Heterogeneity in the granulomatous response to mycobacterial infection in patients with defined genetic mutations in the interleukin 12-dependent interferon-gamma production pathway

High density mangrove plantation enhances surface accretion, surface elevation change, and tree survival in coastal areas susceptible to sea-level rise

Survival, growth, above ground biomass accumulation, soil surface elevation dynamics and nitrogen accumulation in accreted sediments were studied in experimental treatments planted with four different densities (6.96, 3.26, 1.93 and 0.95 seedlings m-2) of the mangrove Rhizophora mucronata in Puttalam Lagoon, Sri Lanka. Measurements were taken over a period of 1171 days and were compared with those from unplanted controls. Trees at the lowest density showed significantly reduced survival, whilst measures of individual tree growth did not differ significantly among treatments. Rates of surface sediment accretion (means ± S.E.) were 13.0 (±1.3), 10.5 (±0.9), 8.4 (±0.3), 6.9 (±0.5) and 5.7 (±0.3) mm yr-1 at planting densities of 6.96, 3.26, 1.93, 0.95, and 0 (unplanted control) seedlings m-2, respectively, showing highly significant differences among treatments. Mean (± S.E.) rates of surface elevation change were much lower than rates of accretion at 2.8 (±0.2), 1.6 (±0.1), 1.1 (±0.2), 0.6 (±0.2) and -0.3 (±0.1) mm yr-1 for 6.96, 3.26, 1.93, 0.95, and 0 seedlings m-2, respectively. All planted treatments appeared to accumulate greater nitrogen concentrations in the sediment compared to the unplanted control, and suggests one potential causal mechanism for the facilitatory effects observed; high densities of plants potentially contribute to the accretion of greater amounts of nutrient rich sediment. While this potential process needs further study, this study demonstrated how higher densities of mangroves enhance rates of sediment accretion and surface elevation, processes that may be crucial in mangrove ecosystem adaptation to sea level rise. There was no evidence that increasing plant density evoked a trade-off with growth and survival of the planted trees. Rather facilitatory effects enhanced survival at high densities, suggesting that local land managers may be able to take advantage of plantation densities to help mitigate sea-level rise effects by encouraging positive soil surface elevation increment, and perhaps even greater nutrient retention to promote mangrove growth and ameliorate nearshore eutrophication in tropical island environments.

Who is susceptible to conjunction fallacies in category-based induction?

Recent evidence suggests that the conjunction fallacy observed in people's probabilistic reasoning is also to be found in their evaluations of inductive argument strength. We presented 130 participants with materials likely to produce a conjunction fallacy either by virtue of a shared categorical or a causal relationship between the categories in the argument. We also took a measure of participants' cognitive ability. We observed conjunction fallacies overall with both sets of materials but found an association with ability for the categorical materials only. Our results have implications for accounts of individual differences in reasoning, for the relevance theory of induction, and for the recent claim that causal knowledge is important in inductive reasoning.

Decontextualised Minds: Adolescents with Autism are Less Susceptible to the Conjunction Fallacy than Typically Developing Adolescents

The conjunction fallacy has been cited as a classic example of the automatic contextualisation of problems. In two experiments we compared the performance of autistic and typically developing adolescents on a set of conjunction fallacy tasks. Participants with autism were less susceptible to the conjunction fallacy. Experiment 2 also demonstrated that the difference between the groups did not result from increased sensitivity to the conjunction rule, or from impaired processing of social materials amongst the autistic participants. Although adolescents with autism showed less bias in their reasoning they were not more logical than the control group in a normative sense. The findings are discussed in the light of accounts which emphasise differences in contextual processing between typical and autistic populations.

The use of a GA to improve the postbuckling strength of stiffened composite panels susceptible to secondary instabilities

The use of genetic algorithms (GAs) for structural optimisation is well established but little work has been reported on the inclusion of damage variables within an optimisation framework. This approach is particularly useful in the optimisation of composite structures which are prone to delamination damage. In this paper a challenging design problem is presented where the objective was to delay the catastrophic failure of a postbuckling secondary-bonded stiffened composite panel susceptible to secondary instabilities. It has been conjectured for some time that the sudden energy release associated with secondary instabilities may initiate structural failure, but this has proved difficult to observe experimentally. The optimisation methodology confirmed this indirectly by evolving a panel displaying a delayed secondary instability whilst meeting all other design requirements. This has important implication in the design of thin-skinned lightweight aerostructures which may exhibit this phenomenon.

In vivo glycated low-density lipoprotein is not more susceptible to oxidation than nonglycated low-density lipoprotein in type 1 diabetes

It has been suggested that low-density lipoprotein (LDL) modified by glycation may be more susceptible to oxidation and thus, enhance its atherogenicity. Using affinity chromatography, LDL glycated in vivo (G-LDL) and relatively nonglycated. (N-LDL) subfractions can be isolated from the same individual. The extent of and susceptibility to oxidation of N-LDL compared with G-LDL was determined in 15 type 1 diabetic patients. Total LDL was isolated and separated by boronate affinity chromatography into relatively glycated (G-) and nonglycated (N-) subfractions. The extent of glycation, glycoxidation, and lipoxidation, lipid soluble antioxidant content, susceptibility to in vitro oxidation, and nuclear magnetic resonance (NMR)-determined particle size and subclass distribution were determined for each subfraction. Glycation, (fructose-lysine) was higher in G-LDL versus N-LDL, (0.28 +/- 0.08 v 0.13 +/- 0.04 mmol/mol lysine, P <.0001). However, levels of glycoxidation/lipoxidation products and of antioxidants were similar or lower in G-LDL compared with N-LDL and were inversely correlated with fructose-lysine (FL) concentrations in G-LDL, but positively correlated in N-LDL. In vitro LDL (CuCl2) oxidation demonstrated a longer lag time for oxidation of G-LDL than N-LDL (50 +/- 0.16 v 37 +/- 0.15 min, P <.01), but there was no difference in the rate or extent of lipid oxidation, nor in any aspect of protein oxidation. Mean LDL particle size and subclass distribution did not differ between G-LDL and N-LDL. Thus, G-LDL from well-controlled type 1 diabetic patients is not more modified by oxidation, more susceptible to oxidation, or smaller than relatively N-LDL, suggesting alternative factors may contribute to the atherogenicity of LDL from type 1 diabetic patients.

The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. a randomized trial

Rationale: Ex vivo, bronchial epithelial cells from people with asthma are more susceptible to rhinovirus infection caused by deficient induction of the antiviral protein, IFN-b. Exogenous IFN-b restores antiviral activity.

Objectives: To compare the efficacy and safety of inhaled IFN-b with placebo administered to people with asthma after onset of cold symptoms to prevent or attenuate asthma symptoms caused by respiratory viruses.

Methods: A total of 147 people with asthma on inhaled corticosteroids (British Thoracic Society Steps 2–5), with a history of virus-associated exacerbations, were randomized to 14-day treatment with inhaled IFN-b (n = 72) or placebo (n = 75) within 24 hours of developing cold symptoms and were assessed clinically, with relevant samples collected to assess virus infection and antiviral responses.

Measurements and Main Results: A total of 91% of randomized patients developed a defined cold. In this modified intention-to-treat population, asthma symptoms did not get clinically significantly worse
(mean change in six-item Asthma Control Questionnaire ,0.5) and IFN-b treatment had no significant effect on this primary endpoint, although it enhanced morning peak expiratory flow recovery (P = 0.033), reduced the need for additional treatment, and boosted innate immunity as assessed by blood and sputum biomarkers. In an exploratory analysis of the subset ofmore difficult-to-treat, Step 4-5 peoplewith asthma (n = 27 IFN-b; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-b (P = 0.004).

Conclusions: Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-b is a potential treatment for virus-induced deteriorations of asthma in difficult-to-treat people with asthma and supports the needforfurther, adequately powered, trialsin this population. Clinical trial registered with www.clinicaltrials.gov (NCT 01126177).

The Host Defence Peptide LL-37 is Susceptible to Proteolytic Degradation by Wound Fluid Isolated from Foot Ulcers of Diabetic Patients

The pleiotropic effects of host defence peptides (HDPs), including the ability to kill microorganisms, enhance re-epithelialisation and increase angiogenesis, indicates a role for these important peptides as potential therapeutic agents in the treatment of chronic, non-healing wounds. However, the maintenance of peptide integrity, through resistance to degradation by the array of proteinases present at the wound site, is a prerequisite for clinical success. In this study we explored the degradation of exogenous LL-37, one such HDP, by wound fluid from diabetic foot ulcers to determine its susceptibility to proteolytic degradation. Our results suggest that LL-37 is unstable in the diabetic foot ulcer microenvironment. Following overnight treatment with wound fluid, LL-37 was completely degraded. Analysis of cleavage sites suggested potential involvement of both host- and bacterial-derived proteinases. The degradation products were shown to retain some antibacterial activity against Pseudomonas aeruginosa but were inactive against Staphylococcus aureus. In conclusion, our data suggest that stabilising selected peptide bonds within the sequence of LL-37 would represent an avenue for future research prior to clinical studies to address its potential as an exogenously-applied therapeutic in diabetic wounds. 

In vitro and in vivo virulence evaluation of the new genotype of porcine circovirus type 2 and identification of a new cell line permissive to virus replication

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