Metabolic profiling of a transgenic Caenorhabditis elegans Alzheimer model

Despite decades of research, no early-onset biomarkers are currently available for Alzheimer’s disease, a cureless neurodegenerative disease afflicting millions worldwide. In this study, transgenic Caenorhabditis elegans were used to investigate changes in the metabolome after induced expression of amyloid-β. GC- and LC–MS-based platforms determined a total of 157 differential features. Some of these were identified using in-house (GC–MS) or public libraries (LC–MS), revealing changes in allantoin, cystathionine and tyrosine levels. Since C. elegans is far better suited to metabolomics studies than most other model systems, the accordance of these findings with vertebrate literature is promising and argues for further use of C. elegans as a model of human pathology in the study of AD

An uncommon cause of asymptomatic crazy paving pattern

A 54-year-old man presented at our department complaining of chest wall pain with clinical suspicion of rib fractures. Neither the clinical examination, the medical history of the patient nor the laboratory findings revealed any abnormalities. The patient mentioned chronic use of Trazolan® (trazodon)

Covert deformed wing virus infections have long-term deleterious effects on honeybee foraging and survival

Several studies have suggested that covert stressors can contribute to bee colony declines. Here we provide a novel case study and show using radio-frequency identification (RFID) tracking technology that covert deformed wing virus (DWV) infections in adult honeybee workers seriously impact longterm foraging and survival under natural foraging conditions. In particular, our experiments show that adult workers injected with low doses of DWV experienced increased mortality rates, that DWV caused workers to start foraging at a premature age, and that the virus reduced the workers’ total activity span as foragers. Altogether, these results demonstrate that covert deformed wing virus infections have strongly deleterious effects on honey bee foraging and survival. These results are consistent with previous studies that suggested DWV to be an important contributor to the ongoing bee declines in Europe and the US. Overall, our study underlines the strong impact that covert pathogen infections can have on individual and group-level performance in bees

Design optimization of multibody systems by sequential approximation

Abstract. Design optimization of multibody systems is usually established by a direct coupling of multibody system analysis and mathematical programming algorithms. However, a direct coupling is hindered by the transient and computationally complex behavior of many multibody systems. In structural optimization often approximation concepts are used instead to interface numerical analysis and optimization. This paper shows that such an approach is valuable for the optimization of multibody systems as well. A design optimization tool has been developed for multibody systems that generates a sequence of approximate optimization problems. The approach is illustrated by three examples: an impact absorber, a slider-crank mechanism, and a stress-constrained four-bar mechanism. Furthermore, the consequences for an accurate and efficient accompanying design sensitivity analysis are discussed

Retention of structure, antigenicity, and biological function of pneumococcal surface protein A (PspA) released from polyanhydride nanoparticles

Pneumococcal surface protein A (PspA) is a choline-binding protein which is a virulence factor found on the surface of all Streptococcus pneumoniae strains. Vaccination with PspA has been shown to be protective against a lethal challenge with S. pneumoniae, making it a promising immunogen for use in vaccines. Herein, the design of a PspA-based subunit vaccine using polyanhydride nanoparticles as a delivery platform is described. Nanoparticles based on sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy)hexane (CPH) and 1,8-bis-(p-carboxyphenoxy)-3,6- dioxaoctane (CPTEG), specifically 50:50 CPTEG:CPH and 20:80 CPH:SA, were used to encapsulate and release PspA. The protein released from the nanoparticle formulations retained its primary and secondary structure as well as its antigenicity. The released PspA was also biologically functional based on its ability to bind to apolactoferrin and prevent its bactericidal activity towards Escherichia coli. When the PspA nanoparticle formulations were administered subcutaneously to mice, the animals elicited a high titer and high avidity anti-PspA antibody response. Together, these studies provide a framework for the rational design of a vaccine against S. pneumoniae based on polyanhydride nanoparticles

A conserved neuropeptide system links head and body motor circuits to enable adaptive behavior

Neuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here, we show that the Caenorhabditis elegans NLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2. We show ckr-2 deletion reduces body bend depth during movement under basal conditions. We demonstrate CKR-1 is a functional NLP-12 receptor and define its expression in the nervous system. In contrast to basal locomotion, biased CKR-1 GPCR stimulation of head motor neurons promotes turning during local searching. Deletion of ckr-1 reduces head neuron activity and diminishes turning while specific ckr-1 overexpression or head neuron activation promote turning. Thus, our studies suggest locomotor responses to changing food availability are regulated through conditional NLP-12 stimulation of head or body wall motor circuits

A Conserved Neuropeptide System Links Head and Body Motor Circuits to Enable Adaptive Behavior

Neuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here, we show that the Caenorhabditis elegans NLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2. We show ckr-2 deletion reduces body bend depth during movement under basal conditions. We demonstrate CKR-1 is a functional NLP-12 receptor and define its expression in the nervous system. In contrast to basal locomotion, biased CKR-1 GPCR stimulation of head motor neurons promotes turning during local searching. Deletion of ckr-1 reduces head neuron activity and diminishes turning while specific ckr-1 overexpression or head neuron activation promote turning. Thus, our studies suggest locomotor responses to changing food availability are regulated through conditional NLP-12 stimulation of head or body wall motor circuits

The UA9 experimental layout

The UA9 experimental equipment was installed in the CERN-SPS in March '09 with the aim of investigating crystal assisted collimation in coasting mode. Its basic layout comprises silicon bent crystals acting as primary collimators mounted inside two vacuum vessels. A movable 60 cm long block of tungsten located downstream at about 90 degrees phase advance intercepts the deflected beam. Scintillators, Gas Electron Multiplier chambers and other beam loss monitors measure nuclear loss rates induced by the interaction of the beam halo in the crystal. Roman pots are installed in the path of the deflected particles and are equipped with a Medipix detector to reconstruct the transverse distribution of the impinging beam. Finally UA9 takes advantage of an LHC-collimator prototype installed close to the Roman pot to help in setting the beam conditions and to analyze the efficiency to deflect the beam. This paper describes in details the hardware installed to study the crystal collimation during 2010.Comment: 15pages, 11 figure, submitted to JINS