Bone formation rather than inflammation reflects Ankylosing Spondylitis activity on PET-CT: a pilot study

Introduction

Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [¹⁸F]FDG and [¹¹C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [¹⁸F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in imaging AS activity was tested using different tracers, with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference.

Methods

In a stepwise approach different PET tracers were investigated. First, whole body [¹⁸F]FDG and [¹¹C](R)PK11195 PET-CT scans were obtained of ten AS patients fulfilling the modified New York criteria. According to the BASDAI five of these patients had low and five had high disease activity. Secondly, an extra PET-CT scan using [¹⁸F]Fluoride was made of two additional AS patients with high disease activity. MRI scans of the total spine and sacroiliac joints were performed, and conventional radiographs of the total spine and sacroiliac joints were available for all patients. Scans and radiographs were visually scored by two observers blinded for clinical data.

Results

No increased [¹⁸F]FDG and [¹¹C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In contrast, MRI demonstrated a total of five bone edema lesions in three out of 10 patients. In the two additional AS patients scanned with [¹⁸F]Fluoride PET-CT, [¹⁸F]Fluoride depicted 17 regions with increased uptake in both vertebral column and sacroiliac joints. In contrast, [¹⁸F]FDG depicted only three lesions, with an uptake of five times lower compared to [¹⁸F]Fluoride, and again no [¹¹C](R)PK11195 positive lesions were found. In these two patients, MRI detected nine lesions and six out of nine matched with the anatomical position of [¹⁸F]Fluoride uptake. Conventional radiographs showed structural bony changes in 11 out of 17 [¹⁸F]Fluoride PET positive lesions.

Conclusions

Our PET-CT data suggest that AS activity is reflected by bone activity (formation) rather than inflammation. The results also show the potential value of PET-CT for imaging AS activity using the bone tracer [¹⁸F]Fluoride. In contrast to active RA, inflammation tracers [¹⁸F]FDG and [¹¹C](R)PK11195 appeared to be less useful for AS imaging.     

Arthropod Natural Enemies of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) in India

Helicoverpa armigera Hubner Lepidoptera: Noctuidae is one of the most serious insect pests in the Old World. In India, it causes substantial losses to legume, fibre, cereal oilseed and vegetable crops. This paper reviews the literature on the biology, ecology, efficacy, rearing and augmentation of endemic parasitoids and predators, as well as exotic parasitoids introduced and released in India. It also provides updated lists of H. armigera natural enemies native to India. In addition, reports of augmentative releases of Trichogramma spp., the most extensively studied natural enemy of H. armigera are summarized.     

<Emphasis Type="Italic">Burkholderia</Emphasis> Hep_Hag autotransporter (BuHA) proteins elicit a strong antibody response during experimental glanders but not human melioidosis

Background  

The bacterial biothreat agents Burkholderia mallei and Burkholderia pseudomallei are the cause of glanders and melioidosis, respectively. Genomic and epidemiological studies have shown that B. mallei is a recently emerged, host restricted clone of B. pseudomallei.     

Evolutionary dynamics of methicillin-resistant Staphylococcus aureus within a healthcare system

BackgroundIn the past decade, several countries have seen gradual replacement of endemic multi-resistant healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) with clones that are more susceptible to antibiotic treatment. One example is Singapore, where MRSA ST239, the dominant clone since molecular profiling of MRSA began in the mid-1980s, has been replaced by ST22 isolates belonging to EMRSA-15, a recently emerged pandemic lineage originating from Europe.ResultsWe investigated the population structure of MRSA in Singaporean hospitals spanning three decades, using whole genome sequencing. Applying Bayesian phylogenetic methods we report that prior to the introduction of ST22, the ST239 MRSA population in Singapore originated from multiple introductions from the surrounding region; it was frequently transferred within the healthcare system resulting in a heterogeneous hospital population. Following the introduction of ST22 around the beginning of the millennium, this clone spread rapidly through Singaporean hospitals, supplanting the endemic ST239 population. Coalescent analysis revealed that although the genetic diversity of ST239 initially decreased as ST22 became more dominant, from 2007 onwards the genetic diversity of ST239 began to increase once more, which was not associated with the emergence of a sub-clone of ST239. Comparative genomic analysis of the accessory genome of the extant ST239 population identified that the Arginine Catabolic Mobile Element arose multiple times, thereby introducing genes associated with enhanced skin colonization into this population.ConclusionsOur results clearly demonstrate that, alongside clinical practice and antibiotic usage, competition between clones also has an important role in driving the evolution of nosocomial pathogen populations.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0643-z) contains supplementary material, which is available to authorized users.     

Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-associated infection, but there is growing awareness of the emergence of multidrug-resistant lineages in community settings around the world. One such lineage is ST772-MRSA-V, which has disseminated globally and is increasingly prevalent in India. Here, we present the complete genome sequence of DAR4145, a strain of the ST772-MRSA-V lineage from India, and investigate its genomic characteristics in regards to antibiotic resistance and virulence factors.

Results

Sequencing using single-molecule real-time technology resulted in the assembly of a single continuous chromosomal sequence, which was error-corrected, annotated and compared to nine draft genome assemblies of ST772-MRSA-V from Australia, Malaysia and India. We discovered numerous and redundant resistance genes associated with mobile genetic elements (MGEs) and known core genome mutations that explain the highly antibiotic resistant phenotype of DAR4145. Staphylococcal toxins and superantigens, including the leukotoxin Panton-Valentinin Leukocidin, were predominantly associated with genomic islands and the phage φ-IND772PVL. Some of these mobile resistance and virulence factors were variably present in other strains of the ST772-MRSA-V lineage.

Conclusions

The genomic characteristics presented here emphasize the contribution of MGEs to the emergence of multidrug-resistant and highly virulent strains of community-associated MRSA. Antibiotic resistance was further augmented by chromosomal mutations and redundancy of resistance genes. The complete genome of DAR4145 provides a valuable resource for future investigations into the global dissemination and phylogeography of ST772-MRSA-V.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1599-9) contains supplementary material, which is available to authorized users.     

Isolation and characterization of microsatellite loci in wheat stem sawfly Cephus cinctus and cross‐species amplification in related species

The wheat stem sawfly is an important insect pest of wheat that can cause significant damage to yield and grain quality. Five microsatellite loci were isolated and characterized in wheat stem sawfly, Cephus cinctus, to facilitate future population genetic studies and help delineate their geographical origin. These loci were found to be polymorphic with an expected heterozygosity ranging from 0.304 to 0.937 and an observed heterozygosity ranging from 0.05 to 0.65. Successful cross‐species amplification demonstrates the potential for these markers to provide a valuable tool for future population studies among related Cephus species.     

Global remodelling of cellular microenvironment due to loss of collagen VII

The mammalian cellular microenvironment is shaped by soluble factors and structural components, the extracellular matrix, providing physical support, regulating adhesion and signalling. A global, quantitative mass spectrometry strategy, combined with bioinformatics data processing, was developed to assess proteome differences in the microenvironment of primary human fibroblasts. We studied secreted proteins of fibroblasts from normal and pathologically altered skin and their post‐translational modifications. The influence of collagen VII, an important structural component, which is lost in genetic skin fragility, was used as model. Loss of collagen VII had a global impact on the cellular microenvironment and was associated with proteome alterations highly relevant for disease pathogenesis including decrease in basement membrane components, increase in dermal matrix proteins, TGF‐β and metalloproteases, but not higher protease activity. The definition of the proteome of fibroblast microenvironment and its plasticity in health and disease identified novel disease mechanisms and potential targets of intervention.     

Biology and field performance of gryon clavigrallae (Hymenoptera: Scelionidae), an egg parasitoid of Clavigralla spp. (Hemiptera: Coreidae) in India

The biology and impact of Gryon clavigrallae Mineo, an egg parasitoid of Clavigralla scutellaris Spinola and C. gibbosa (Westwood), was investigated. The calculated developmental threshold temperatures for females and males were 15.6 degrees C and 15.8 degrees C, respectively. Emergence exceeded 94% at temperatures between 22 and 30 degrees C. Adult females lived on average 28-96 days when fed with honey. Without food, adults lived < 6 days. Mean fecundity was 56.4 eggs per female. A significant trend of lower fecundity after longer periods of host deprivation was observed. Gryon clavigrallae females successfully oviposited in host eggs of all ages though eggs < 4 days old were preferred. Total host handling times were significantly longer on C. gibbosa eggs (23.5 min) than on C. scutellaris eggs (12.0 min). Females readily distinguished parasitized from non-parasitized host eggs. Superparasitism was observed when few or no unparasitized eggs were available. Eggs of the two Clavigralla species can be separated by surface structure and condition after eclosion. Clavigralla scutellaris laid significantly larger egg clusters than C. gibbosa (19.9 versus 10.5 eggs per cluster). Gryon clavigrallae was present as soon as the first Clavigralla spp. egg clusters were found on pigeonpea. The percentage of egg clusters parasitized increased early in the season with egg cluster density and remained high (up to 83%) despite fluctuations in host density. Overall, G. clavigrallae parasitized 40 and 58% of C. gibbosa and C. scutellaris eggs. The percentage of egg clusters parasitized and the number of eggs parasitized per cluster increased significantly with egg cluster size. The overall parasitoid sex ratio was highly female biased but varied with the number of eggs parasitized per cluster.     

Trichogramma egg parasitism of Helicoverpa armigera on pigeonpea and sorghum in southern India

Trichogramma spp. (Hymenoptera: Trichogrammatidae) only rarely parasitize eggs of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) on pigeonpea (Cajanus cajan (L.) Millspaugh), while on other plants including sorghum (Sorghum bicolor (L.)) high parasitism levels of this host are found. In this study two strategies designed to increase the parasitoid activity on pigeonpea were tested in the field: intercropping pigeonpea with sorghum and mass-releasing T. chilonis Ishii. Neither strategy led to an increase in parasitism. On pigeonpea, H. armigera oviposited >74.8% of its eggs on calyxes and pods. Parasitism levels in host eggs collected from different plant structures varied significantly with 3.6, 0.3, and 40.7% of eggs on calyxes, pods, and leaves parasitized. Earlier studies have shown that calyxes and pods possess long glandular and non-glandular trichomes, and are covered by sticky trichome exudates which inhibit parasitoid searching behaviour. Parasitism levels between 27.9 and 100% were recorded from host eggs on the intercropped sorghum. Trichogramma chilonis was the dominant parasitoid species. The mean clutch size was 2.03, but up to six parasitoids emerged per egg. Progeny sex ratio (% females) decreased with clutch size, from 63.1% at a clutch size of one to 46.0% at a clutch size of five. Sticky trap catches showed that while the parasitoid population in sorghum increased when H. armigera started ovipositing, the population within pigeonpea did not benefit from either a high parasitoid population in sorghum or a high host egg density on pigeonpea. During one of five seasons studied, however, high parasitism levels (up to 73%) were recorded on pigeonpea. During this season, H. armigera oviposited on pigeonpea plants in the vegetative growth stage and a high proportion of eggs were collected from leaves. Parasitism levels were positively correlated with the percentage of eggs collected from leaves. This study shows that the parasitization efficiency of Trichogramma spp. on pigeonpea depends mainly on the location of the host eggs. This explains why parasitism levels of H. armigera eggs on pigeonpea did not increase when intercropped with sorghum or after mass-releasing T. chilonis.