Fungal associates of the lodgepole pine beetle, Dendroctonus murrayanae

Bark beetles are well known vectors of ophiostomatoid fungi including species of Ophiostoma, Grosmannia and Ceratocystis. In this study, the most common ophiostomatoid fungi associated with the lodgepole pine beetle, Dendroctonus murrayanae, were characterized. Pre-emergent and post-attack adult beetles were collected from lodgepole pines at four sites in British Columbia, Canada. Fungi were isolated from these beetles and identified using a combination of morphology and DNA sequence comparisons of five gene regions. In all four populations, Grosmannia aurea was the most common associate (74–100% of all beetles) followed closely by Ophiostoma abietinum (29–75%). Other fungi isolated, in order of their relative prevalence with individual beetles were an undescribed Leptographium sp. (0–13%), Ophiostoma ips (0–15%), Ophiostoma piliferum (0–11%), a Pesotum sp. (0–11%) and Ophiostoma floccosum (0–1%). Comparisons of the DNA sequences of Leptographium strains isolated in this study, with ex-type isolates of G. aurea, Grosmannia robusta, Leptographium longiclavatum, and Leptographium terebrantis, as well as with sequences from GenBank, revealed a novel lineage within the Grosmannia clavigera complex. This lineage included some of the D. murrayane isolates as well as several isolates from previous studies referred to as L. terebrantis. However, the monophyly of this lineage is not well supported and a more comprehensive study will be needed to resolve its taxonomic status as one or more novel taxa.National Science Foundation grant OISE-0434171 awarded to DLS, Natural Resources Canada, Canadian Forest Service Mountain Pine Beetle Initiative Grant to ALC, members of the Tree Co-operative Programme, the THRIP initiative of the Department of Trade and Industry, South Africa

Undetectable mannose binding lectin and corticosteroids increase serious infection risk in Rheumatoid Arthritis

Background: Infection is the leading cause of death in rheumatoid arthritis (RA). Corticosteroid (CS) use is a known and important risk factor for serious infections (SIs). Mannose binding lectin (MBL) is a genetically determined component of the innate immune system implicated in neonatal infections. Objective: Our aim was to determine whether MBL deficiency is a risk factor for SIs in RA and to compare it with CS use and also synthetic and biologic disease-modifying antirheumatic drug (DMARD) therapy. Methods: Data on 228 patients with RA were collected for up to 7 years (median = 5.9 years). Serum MBL concentrations were determined in all patients receiving synthetic (n = 96) or biologic (n = 132) DMARD therapy. Results: High rates of SIs were observed in RA irrespective of treatment (17%). Similar rates of SIs were observed in synthetic and biologic DMARD users. The rates of single and multiple Sis were similar, irrespective of the use of a biologic agent. Undetectable MBL (\u3c56 ng/mL) concentrations and maintenance prednisolone at 10 mg per day or higher were associated with an increased risk for an SI, with incident risk ratio of 4.67 (P = .001) and 4.70 (P \u3c .001), respectively. Conclusions: Undetectable MBL and prednisolone confer a high risk for an SI. The use of biologic DMARDs did not confer substantial SI risk in this observational study. MBL deficiency is hitherto an unrecognized risk factor for an SI in RA

Competition between decay and dissociation of core-excited OCS studied by X-ray scattering

We show the first evidence of dissociation during resonant inelastic soft X-ray scattering. Carbon and oxygen K-shell and sulfur L-shell resonant and non-resonant X-ray emission spectra were measured using monochromatic synchrotron radiation for excitation and ionization. After sulfur, L2,3 -> {\pi}*, {\sigma}* excitation, atomic lines are observed in the emission spectra as a consequence of competition between de-excitation and dissociation. In contrast the carbon and oxygen spectra show weaker line shape variations and no atomic lines. The spectra are compared to results from ab initio calculations and the discussion of the dissociation paths is based on calculated potential energy surfaces and atomic transition energies.Comment: 12 pages, 6 pictures, 2 tables, http://link.aps.org/doi/10.1103/PhysRevA.59.428

Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein.

Lasting protection has long been a goal for malaria vaccines. The major surface antigen on Plasmodium falciparum sporozoites, the circumsporozoite protein (PfCSP), has been an attractive target for vaccine development and most protective antibodies studied to date interact with the central NANP repeat region of PfCSP. However, it remains unclear what structural and functional characteristics correlate with better protection by one antibody over another. Binding to the junctional region between the N-terminal domain and central NANP repeats has been proposed to result in superior protection: this region initiates with the only NPDP sequence followed immediately by NANP. Here, we isolated antibodies in Kymab mice immunized with full-length recombinant PfCSP and two protective antibodies were selected for further study with reactivity against the junctional region. X-ray and EM structures of two monoclonal antibodies, mAb667 and mAb668, shed light on their differential affinity and specificity for the junctional region. Importantly, these antibodies also bind to the NANP repeat region with equal or better affinity. A comparison with an NANP-only binding antibody (mAb317) revealed roughly similar but statistically distinct levels of protection against sporozoite challenge in mouse liver burden models, suggesting that junctional antibody protection might relate to the ability to also cross-react with the NANP repeat region. Our findings indicate that additional efforts are necessary to isolate a true junctional antibody with no or much reduced affinity to the NANP region to elucidate the role of the junctional epitope in protection

Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis

© 2017 The Authors Despite aggressive antibiotic therapy, bronchopulmonary colonization by Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of-concept double-blind clinical trial. Submicromolar NO concentrations alone caused disruption of biofilms within ex vivo CF sputum and a statistically significant decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation caused significant reduction in P. aeruginosa biofilm aggregates compared with placebo across 7 days of treatment. Our results suggest a benefit of using low-dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to treat acute P. aeruginosa exacerbations in CF. Strategies to induce the disruption of biofilms have the potential to overcome biofilm-associated antibiotic tolerance in CF and other biofilm-related diseases

Natural Resources Canada

Insect outbreaks exert landscape-level influences, yet quantifying the relative contributions of various exogenous and endogenous factors that contribute to their pattern and spread remains elusive. We examine an outbreak of mountain pine beetle covering an 800 thousand ha area on the Chilcotin Plateau of British Columbia, Canada, during the 1970s and early 1980s. We present a model that incorporates the spatial and temporal arrangements of outbreaking insect populations, as well as various climatic factors that influence insect development. Onsets of eruptions of mountain pine beetle demonstrated landscape-level synchrony. On average, the presence of outbreaking populations was highly correlated with outbreaking populations within the nearest 18 km the same year and local populations within 6 km in the previous two years. After incorporating these spatial and temporal dependencies, we found that increasing temperatures contributed to explaining outbreak probabilities during this 15 yr outbreak. During collapse years, landscape-level synchrony declined while local synchrony values remained high, suggesting that in some areas host depletion was contributing to population decline. Model forecasts of outbreak propensity one year in advance at a 12 by 12 km scale provided 80% accuracy over the landscape, and never underestimated the occurrence of locally outbreaking populations. This model provides a flexible approach for linking temperature and insect population dynamics to spatial spread, and complements existing decision support tools for resource managers

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

An excess of niche differences maximizes ecosystem functioning

Ecologists have long argued that higher functioning in diverse communities arises from the niche differences stabilizing species coexistence and from the fitness differences driving competitive dominance. However, rigorous tests are lacking. We couple field-parameterized models of competition between 10 annual plant species with a biodiversity-functioning experiment under two contrasting environmental conditions, to study how coexistence determinants link to biodiversity effects (selection and complementarity). We find that complementarity effects positively correlate with niche differences and selection effects differences correlate with fitness differences. However, niche differences also contribute to selection effects and fitness differences to complementarity effects. Despite this complexity, communities with an excess of niche differences (where niche differences exceeded those needed for coexistence) produce more biomass and have faster decomposition rates under drought, but do not take up nutrients more rapidly. We provide empirical evidence that the mechanisms determining coexistence correlate with those maximizing ecosystem functioning. It is unclear how biodiversity-ecosystem functioning and species coexistence mechanisms are linked. Here, Godoy and colleagues combine field-parameterised competition models with a BEF experiment to show that mechanisms leading to more stable species coexistence lead to greater productivity, but not necessarily to enhanced functions other than primary production

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function