Structural differences in lipomannans from pathogenic and nonpathogenic mycobacteria that impact CD1b-restricted T cell responses

Mannosylated molecules on the Mycobacterium tuberculosis surface are important determinants in the immunopathogenesis of tuberculosis. To date, much attention has been paid to mannose-capped lipoarabinomannan, which mediates phagocytosis and intracellular trafficking of M. tuberculosis by engaging the macrophage mannose receptor and subsequently binds to intracellular CD1b molecules for presentation to T cells. Another important mannosylated lipoglycan on the M. tuberculosis surface is lipomannan (LM). Comparative structural detail of the LMs from virulent and avirulent strains is limited as is knowledge regarding their differential capacity to be recognized by the adaptive immune response. Here, we purified LM from the avirulent M. smegmatis and the virulent M. tuberculosis H(37)R(v), performed a comparative structural biochemical analysis, and addressed their ability to stimulate CD1b-restricted T cell clones. We found that M. tuberculosis H(37)R(v) produces a large neutral LM (TB-LM); in contrast, M. smegmatis produces a smaller linear acidic LM (SmegLM) with a high succinate content. Correspondingly, TB-LM was not as efficiently presented to CD1b-restricted T cells as SmegLM. Thus, here we correlate the structure-function relationships for LMs with CD1b-restricted T cell responses and provide evidence that the structural features of TB-LM contribute to its diminished T cell responsiveness.     

Phylogeny of replication initiator protein TrfA reveals a highly divergent clade of incompatibility group P1 plasmids

Incompatibility group P1 (IncP-1) plasmid diversity was evaluated based on replication initiator protein (TrfA) phylogeny. A new and highly divergent clade was identified. Replication assays indicated that TrfA of recently discovered IncP-1 plasmids from Xylella fastidiosa and Verminephrobacter eiseniae initiated plasmid replication using cognate or heterologous origins of replication.     

Utilization of Inhaled Corticosteroids for Infants with Bronchopulmonary Dysplasia

Objective

To determine demographic and clinical variables associated with inhaled corticosteroid administration and to evaluate between-hospital variation in inhaled steroid use for infants with bronchopulmonary dysplasia (BPD).

Design

Retrospective Cohort Study.

Setting

Neonatal units of 35 US children''s hospitals; as recorded in the Pediatric Health Information System (PHIS) database.

Patients

1429 infants with evolving BPD at 28 days who were born at <29 weeks gestation with birth weight <1500 grams, admitted within the first 7 postnatal days, and discharged between January 2007–June 2011.

Results

Inhaled steroids were prescribed to 25% (n = 352) of the cohort with use steadily increasing during the first two months of hospitalization. The most frequently prescribed steroid was beclomethasone (n = 194, 14%), followed by budesonide (n = 125, 9%), and then fluticasone (n = 90, 6%). Birth gestation <24 weeks, birth weight 500–999 grams, and prolonged ventilation all increased the adjusted odds of ever receiving inhaled corticosteroids (p<0.05). Wide variations between hospitals in the frequency of infants ever receiving inhaled steroids (range: 0–60%) and the specific drug prescribed were noted. This variation persisted, even after controlling for observed confounders.

Conclusions

Inhaled corticosteroid administration to infants with BPD is common in neonatal units within U.S. Children''s hospitals. However, its utilization varies markedly between centers from no treatment at some institutions to the majority of infants with BPD being treated at others. This supports the need for further research to identify the benefits and potential risks of inhaled steroid usage in infants with BPD.     

Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy?

Introduction

Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti-tumor necrosis factor (TNF) therapy. The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy.

Methods

Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNF therapy regarding clinical parameters, inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients'' sclerostin levels, sclerostin binding low-density lipoprotein receptor-related protein 6 (LRP6) and BMD were evaluated at the same time points and compared to controls.

Results

At baseline, AS patients had lower sclerostin levels (60.5 ± 32.7 vs. 96.7 ± 52.9 pmol/L, P = 0.002) and comparable sclerostin binding to LRP6 (P = 0.387) than controls. Improvement of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis quality of life (ASQoL) was observed at baseline vs. 6 vs. 12 months (P < 0.01). Concomitantly, a gradual increase in spine BMD (P < 0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r = 0.468, P < 0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (P <0.01). Sclerostin levels progressively increased [baseline (60.5 ± 32.7) vs. 6 months (67.1 ± 31.9) vs. 12 months (72.7 ± 32.3) pmol/L, P <0.001]. At 12 months, the sclerostin levels remained significantly lower in patients compared to controls (72.7 ± 32.3 vs. 96.70 ± 52.85 pmol/L, P = 0.038). Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high C reactive protein (CRP) (≥ 5 mg/l) compared to the other 20 patients with normal CRP (P = 0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (P = 0.023). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio = 7.43, 95% CI 1.23 to 45.01, P = 0.020) than those with higher sclerostin values.

Conclusions

Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy.     

Analysis of non-TIR NBS-LRR resistance gene analogs in <Emphasis Type="Italic">Musa acuminata</Emphasis> Colla: Isolation,RFLP marker development,and physical mapping

Background  

Many commercial banana varieties lack sources of resistance to pests and diseases, as a consequence of sterility and narrow genetic background. Fertile wild relatives, by contrast, possess greater variability and represent potential sources of disease resistance genes (R-genes). The largest known family of plant R-genes encode proteins with nucleotide-binding site (NBS) and C-terminal leucine-rich repeat (LRR) domains. Conserved motifs in such genes in diverse plant species offer a means for isolation of candidate genes in banana which may be involved in plant defence.     

Effects of citrus and avocado irrigation and nitrogen-form soil amendment on host selection by adult Homalodisca vitripennis (Hemiptera: Cicadellidae)

Host plant water status is thought to influence dispersal of the xylophagous leafhopper Homalodisca vitripennis Germar, especially where plants are grown under high evaporative demand. Preference by adult H. vitripennis for plants grown under different water deficit and nitrogen form fertilization regimens was studied under laboratory conditions. Leafhopper abundance and ovipositional preference were studied on potted 'Washington navel' orange and 'Haas' avocado in cage choice tests, and feeding rate was estimated using excreta produced by insects confined on plants. A similar study compared responses to citrus treated with 1:1 and 26:1 ratios of fertigated nitrate-N to ammonium-N. The insects were more abundant, oviposited, and fed significantly more on surplus-irrigated plants than on plants under moderate continuous deficit irrigation except avocado feeding, which was nearly significant. Plants exposed to drought became less preferred after 3 and 7 d in avocado and citrus, respectively. Citrus xylem fluid tension at this point was estimated at 0.93 MPa. A corresponding pattern of decline in feeding rate was observed on citrus, but on avocado, feeding rate was low overall and not statistically different between treatments. No statistical differences in abundance, oviposition, or feeding were detected on citrus fertigated with 26:1 or 1:1 ratios of nitrate-N to ammonium-N. Feeding occurred diurnally on both plant species. Discussion is provided on the potential deployment of regulated deficit irrigation to manage H. vitripennis movement as part of a multitactic effort to minimize the risk of disease outbreaks from Xylella fastidiosa Wells et al. in southern California agriculture.