Mapping an atlas of tissue-specific drosophila melanogaster metabolomes by high resolution mass spectrometry

Metabolomics can provide exciting insights into organismal function, but most work on simple models has focussed on the whole organism metabolome, so missing the contributions of individual tissues. Comprehensive metabolite profiles for ten tissues from adult Drosophila melanogaster were obtained here by two chromatographic methods, a hydrophilic interaction (HILIC) method for polar metabolites and a lipid profiling method also based on HILIC, in combination with an Orbitrap Exactive instrument. Two hundred and forty two polar metabolites were putatively identified in the various tissues, and 251 lipids were observed in positive ion mode and 61 in negative ion mode. Although many metabolites were detected in all tissues, every tissue showed characteristically abundant metabolites which could be rationalised against specific tissue functions. For example, the cuticle contained high levels of glutathione, reflecting a role in oxidative defence; the alimentary canal (like vertebrate gut) had high levels of acylcarnitines for fatty acid metabolism, and the head contained high levels of ether lipids. The male accessory gland uniquely contained decarboxylated S-adenosylmethionine. These data thus both provide valuable insights into tissue function, and a reference baseline, compatible with the FlyAtlas.org transcriptomic resource, for further metabolomic analysis of this important model organism, for example in the modelling of human inborn errors of metabolism, aging or metabolic imbalances such as diabetes

Patients’ preferences for osteoporosis drug treatment: a discrete choice experiment

Summary: Active case finding for osteoporosis is used to identify patients at high fracture risk who may benefit from preventive drug treatment. We investigated the relative weight that women place on various aspects of preventive drugs in a discrete choice experiment. Our patients said they were prepared to take preventive drugs even if side effects were expected. Int

IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β2 integrin and CXCR3

<p>Abstract</p> <p>Background</p> <p>Eosinophils play an important role in the pathogenesis of bronchial asthma and its exacerbation. Recent reports suggest the involvement of IFN-γ-inducible protein of 10 kDa (IP-10) in virus-induced asthma exacerbation. The objective of this study was to examine whether CXCR3 ligands including IP-10 modify the effector functions of eosinophils.</p> <p>Methods</p> <p>Eosinophils isolated from the blood of healthy donors were stimulated with CXCR3 ligands and their adhesion to rh-ICAM-1 was then measured using eosinophil peroxidase assays. The generation of eosinophil superoxide anion (O₂^-) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) release was evaluated to determine whether CXCR3 ligands induced eosinophil degranulation. Cytokine and chemokine production by eosinophils was examined using a Bio-plex assay.</p> <p>Results</p> <p>Eosinophil adhesion to ICAM-1 was significantly enhanced by IP-10, which also significantly induced eosinophil O₂^-generation in the presence of ICAM-1. Both the enhanced adhesion and O₂^-generation were inhibited by an anti-β₂integrin mAb or an anti-CXCR3 mAb. Other CXCR3 ligands, such as monokine induced by IFN-γ (Mig) and IFN-inducible T cell α chemoattractant (I-TAC), also induced eosinophil adhesion and O₂^-generation in the presence of ICAM-1. IP-10, but not Mig or I-TAC, increased the release of EDN. IP-10 increased the production of a number of cytokines and chemokines by eosinophils.</p> <p>Conclusions</p> <p>These findings suggest that CXCR3 ligands such as IP-10 can directly upregulate the effector functions of eosinophils. These effects might be involved in the activation and infiltration of eosinophils in the airway of asthma, especially in virus-induced asthma exacerbation.</p

Modeling visual-based pitch, lift and speed control strategies in hoverflies

<div><p>To avoid crashing onto the floor, a free falling fly needs to trigger its wingbeats quickly and control the orientation of its thrust accurately and swiftly to stabilize its pitch and hence its speed. Behavioural data have suggested that the vertical optic flow produced by the fall and crossing the visual field plays a key role in this anti-crash response. Free fall behavior analyses have also suggested that flying insect may not rely on graviception to stabilize their flight. Based on these two assumptions, we have developed a model which accounts for hoverflies´ position and pitch orientation recorded in 3D with a fast stereo camera during experimental free falls. Our dynamic model shows that optic flow-based control combined with closed-loop control of the pitch suffice to stabilize the flight properly. In addition, our model sheds a new light on the visual-based feedback control of fly´s pitch, lift and thrust. Since graviceptive cues are possibly not used by flying insects, the use of a vertical reference to control the pitch is discussed, based on the results obtained on a complete dynamic model of a virtual fly falling in a textured corridor. This model would provide a useful tool for understanding more clearly how insects may or not estimate their absolute attitude.</p></div

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Transcriptome Analysis of the Desert Locust Central Nervous System: Production and Annotation of a Schistocerca gregaria EST Database

) displays a fascinating type of phenotypic plasticity, designated as ‘phase polyphenism’. Depending on environmental conditions, one genome can be translated into two highly divergent phenotypes, termed the solitarious and gregarious (swarming) phase. Although many of the underlying molecular events remain elusive, the central nervous system (CNS) is expected to play a crucial role in the phase transition process. Locusts have also proven to be interesting model organisms in a physiological and neurobiological research context. However, molecular studies in locusts are hampered by the fact that genome/transcriptome sequence information available for this branch of insects is still limited. EST information is highly complementary to the existing orthopteran transcriptomic data. Since many novel transcripts encode neuronal signaling and signal transduction components, this paper includes an overview of these sequences. Furthermore, several transcripts being differentially represented in solitarious and gregarious locusts were retrieved from this EST database. The findings highlight the involvement of the CNS in the phase transition process and indicate that this novel annotated database may also add to the emerging knowledge of concomitant neuronal signaling and neuroplasticity events. EST data constitute an important new source of information that will be instrumental in further unraveling the molecular principles of phase polyphenism, in further establishing locusts as valuable research model organisms and in molecular evolutionary and comparative entomology

Metagenomic binning of a marine sponge microbiome reveals unity in defense but metabolic specialization

Marine sponges are ancient metazoans that are populated by distinct and highly diverse microbial communities. In order to obtain deeper insights into the functional gene repertoire of the Mediterranean sponge Aplysina aerophoba, we combined Illumina short-read and PacBio long-read sequencing followed by un-targeted metagenomic binning. We identified a total of 37 high-quality bins representing 11 bacterial phyla and two candidate phyla. Statistical comparison of symbiont genomes with selected reference genomes revealed a significant enrichment of genes related to bacterial defense (restriction-modification systems, toxin-antitoxin systems) as well as genes involved in host colonization and extracellular matrix utilization in sponge symbionts. A within-symbionts genome comparison revealed a nutritional specialization of at least two symbiont guilds, where one appears to metabolize carnitine and the other sulfated polysaccharides, both of which are abundant molecules in the sponge extracellular matrix. A third guild of symbionts may be viewed as nutritional generalists that perform largely the same metabolic pathways but lack such extraordinary numbers of the relevant genes. This study characterizes the genomic repertoire of sponge symbionts at an unprecedented resolution and it provides greater insights into the molecular mechanisms underlying microbial-sponge symbiosis