Lipid profiling of the filarial nematodes Onchocerca volvulus, Onchocerca ochengi and Litomosoides sigmodontis reveals the accumulation of nematode-specific ether phospholipids in the host

Onchocerciasis, a neglected tropical disease prevalent in western and central Africa, is a major health problem and has been targeted for elimination. The causative agent for this disease is the human parasite Onchocerca volvulus. Onchocerca ochengi and Litomosoides sigmodontis, infectious agents of cattle and rodents, respectively, serve as model organisms to study filarial nematode infections. Biomarkers to determine infection without the use of painful skin biopsies and microscopic identification of larval worms are needed and their discovery is facilitated by an improved knowledge of parasite-specific metabolites. In addition to proteins and nucleic acids, lipids may be suitable candidates for filarial biomarkers that are currently underexplored. To fill this gap, we present the phospholipid profile of the filarial nematodes O. ochengi, O. volvulus and L. sigmodontis. Direct infusion quadrupole time-of flight (Q-TOF) mass spectrometry was employed to analyze the composition of phospholipids and their molecular species in the three nematode species. Analysis of the phospholipid profiles of plasma or serum of uninfected and infected hosts showed that nematode-specific phospholipids were below detection limits. However, several phospholipids, in particular ether lipids of phosphatidylethanolamine (PE), were abundant in O. ochengi worms and in bovine nodule fluid, suggesting that these phospholipids might be released from O. ochengi into the host, and could serve as potential biomarkers. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of Australian Society for Parasitology

Recruiting and Preparing skilled personnel for leadership roles in welding and brazing

A shortage of welders and welding professionals is felt globally, and it will worsen as the current skilled and educated leave the workforce. Thus, many countries are actively designing programs to improve the image of welding and to train and educate persons to meet those needs. Virtual welding, by means of computer simulation, is one method of introducing and exciting the young about welding. Some companies are even using the virtual welder as to test or even give basic training to new employees. Females are 50% of the population, yet too few choose welding. We have good role models in the many different areas of welding and they are highlighted here. Once persons are interested in welding, they need to be properly trained and educated. Weld-Ed is a program in the USA that has 1) a model curriculum for 2-year colleges; 2) a program to update and upgrade instructors; 3) a method of pairing industry with schools and colleges to offer necessary skills and knowledge for available jobs. New technology is being used by several countries in a variety of ways to enhance training and education. Several types, including online learning and electronic devices, will be described. As persons become skilled and educated, they need a way to prove their competence. A cost-effective means of demonstrating their competence is a Certification Program. Bright young persons are needed in welding science and technology to meet national and global challenges. Our future, structures, and infrastructure depend on them

Stability of Closed Timelike Curves in Goedel Universe

We study, in some detail, the linear stability of closed timelike curves in the Goedel metric. We show that these curves are stable. We present a simple extension (deformation) of the Goedel metric that contains a class of closed timelike curves similar to the ones associated to the original Goedel metric. This extension correspond to the addition of matter whose energy-momentum tensor is analyzed. We find the conditions to have matter that satisfies the usual energy conditions. We study the stability of closed timelike curves in the presence of usual matter as well as in the presence of exotic matter (matter that does satisfy the above mentioned conditions). We find that the closed timelike curves in Goedel universe with or whithout the inclusion of regular or exotic matter are also stable under linear perturbations. We also find a sort of structural stability.Comment: 12 pages, 11 figures, RevTex, several typos corrected. GRG, in pres

Parasite-derived microRNAs in host serum as novel biomarkers of helminth infection.

BACKGROUND: MicroRNAs (miRNAs) are a class of short non-coding RNA that play important roles in disease processes in animals and are present in a highly stable cell-free form in body fluids. Here, we examine the capacity of host and parasite miRNAs to serve as tissue or serum biomarkers of Schistosoma mansoni infection. METHODS/PRINCIPAL FINDINGS: We used Exiqon miRNA microarrays to profile miRNA expression in the livers of mice infected with S. mansoni at 7 weeks post-infection. Thirty-three mouse miRNAs were differentially expressed in infected compared to naïve mice (>2 fold change, p<0.05) including miR-199a-3p, miR-199a-5p, miR-214 and miR-21, which have previously been associated with liver fibrosis in other settings. Five of the mouse miRNAs were also significantly elevated in serum by twelve weeks post-infection. Sequencing of small RNAs from serum confirmed the presence of these miRNAs and further revealed eleven parasite-derived miRNAs that were detectable by eight weeks post infection. Analysis of host and parasite miRNA abundance by qRT-PCR was extended to serum of patients from low and high infection sites in Zimbabwe and Uganda. The host-derived miRNAs failed to distinguish uninfected from infected individuals. However, analysis of three of the parasite-derived miRNAs (miR-277, miR-3479-3p and bantam) could detect infected individuals from low and high infection intensity sites with specificity/sensitivity values of 89%/80% and 80%/90%, respectively. CONCLUSIONS: This work identifies parasite-derived miRNAs as novel markers of S. mansoni infection in both mice and humans, with the potential to be used with existing techniques to improve S. mansoni diagnosis. In contrast, although host miRNAs are differentially expressed in the liver during infection their abundance levels in serum are variable in human patients and may be useful in cases of extreme pathology but likely hold limited value for detecting prevalence of infection

Goedel-type Universes and the Landau Problem

We point out a close relation between a family of Goedel-type solutions of 3+1 General Relativity and the Landau problem in S^2, R^2 and H_2; in particular, the classical geodesics correspond to Larmor orbits in the Landau problem. We discuss the extent of this relation, by analyzing the solutions of the Klein-Gordon equation in these backgrounds. For the R^2 case, this relation was independently noticed in hep-th/0306148. Guided by the analogy with the Landau problem, we speculate on the possible holographic description of a single chronologically safe region.Comment: Latex, 21 pages, 1 figure. v2 missing references to previous work on the subject adde

Differential susceptibility of Onchocerca volvulus microfilaria to ivermectin in two areas of contrasting history of mass drug administration in Cameroon: relevance of microscopy and molecular techniques for the monitoring of skin microfilarial repopulation within six months of direct observed treatment

Background Ivermectin is an excellent microfilaricide against Onchocerca volvulus. However, in some regions, long term use of ivermectin has resulted in sub-optimal responses to the treatment. More data to properly document the phenomenon in various contexts of ivermectin mass drug administration (IVM-MDA) is needed. Also, there is a need to accurately monitor a possible repopulation of skin by microfilariae following treatment. Skin snip microscopy is known to have a low sensitivity in individuals with light infections, which can be the case following treatment. This study was designed with two complementary objectives: (i) to assess the susceptibility of O. volvulus microfilariae to ivermectin in two areas undergoing IVM-MDA for different lengths of time, and (ii) to document the repopulation of skin by the O. volvulus microfilariae following treatment, using 3 independent diagnostic techniques. Method Identified microfilaridermic individuals were treated with ivermectin and re-examined after 1, 3, and 6 months using microscopy, actin real-time PCR (actin-qPCR) and O-150 LAMP assays. Susceptibility to ivermectin and trends in detecting reappearance of skin microfilariae were determined using three techniques. Microscopy was used as an imperfect gold standard to determine the performance of actin-qPCR and LAMP. Results In Bafia with over 20 years of IVM-MDA, 11/51 (21.6%) direct observe treated microfilaridemic participants were still positive for skin microfilariae after 1 month. In Melong, with 10 years of IVM-MDA, 2/29 (6.9%) treated participants were still positive. The microfilarial density reduction per skin biopsy within one month following treatment was significantly lower in participants from Bafia. In both study sites, the molecular techniques detected higher proportions of infected individuals than microscopy at all monitoring time points. LAMP demonstrated the highest levels of sensitivity and real-time PCR was found to have the highest specificity. Conclusion Patterns in skin mirofilariae clearance and repopulation were established. O. volvulus worms from Bafia with higher number of annual MDA displayed a lower clearance and higher repopulation rate after treatment with ivermectin. Molecular assays displayed higher sensitivity in monitoring O. volvulus microfilaridemia within six months following treatment

The Wolbachia endosymbiont as an anti-filarial nematode target

Human disease caused by parasitic filarial nematodes is a major cause of global morbidity. The parasites are transmitted by arthropod intermediate hosts and are responsible for lymphatic filariasis (elephantiasis) or onchocerciasis (river blindness). Within these filarial parasites are intracellular alpha-proteobacteria, Wolbachia, that were first observed almost 30 years ago. The obligate endosymbiont has been recognized as a target for anti-filarial nematode chemotherapy as evidenced by the loss of worm fertility and viability upon antibiotic treatment in an extensive series of human trials. While current treatments with doxycycline and rifampicin are not practical for widespread use due to the length of required treatments and contraindications, anti-Wolbachia targeting nevertheless appears a promising alternative for filariasis control in situations where current programmatic strategies fail or are unable to be delivered and it provides a superior efficacy for individual therapy. The mechanisms that underlie the symbiotic relationship between Wolbachia and its nematode hosts remain elusive. Comparative genomics, bioinfomatic and experimental analyses have identified a number of potential interactions, which may be drug targets. One candidate is de novo heme biosynthesis, due to its absence in the genome sequence of the host nematode, Brugia malayi, but presence in Wolbachia and its potential roles in worm biology. We describe this and several additional candidate targets, as well as our approaches for understanding the nature of the host-symbiont relationship

Anti-relapse neurons in the infralimbic cortex of rats drive relapse-suppression by drug omission cues

Drug addiction is a chronic relapsing disorder of compulsive drug use. Studies of the neurobehavioral factors that promote drug relapse have yet to produce an effective treatment. Here we take a different approach and examine the factors that suppress – rather than promote – relapse. Adapting Pavlovian procedures to suppress operant drug response, we determined the anti-relapse action of environmental cues that signal drug omission (unavailability) in rats. Under laboratory conditions linked to compulsive drug use and heightened relapse risk, drug omission cues suppressed three major modes of relapse-promotion (drug-predictive cues, stress, and drug exposure) for cocaine and alcohol. This relapse-suppression is partially driven by omission cue-reactive neurons, which constitute small subsets of glutamatergic and GABAergic cells, in the infralimbic cortex. Future studies of such neural activity-based cellular units (neuronal ensembles/memory engram cells) for relapse-suppression can be used to identify alternate targets for addiction medicine through functional characterization of anti-relapse mechanisms

Energy and Angular Momentum Densities in a Godel-Type Universe in the Teleparallel Geometry

The main scope of this research consists in evaluating the energy-momentum (gravitational field plus matter) and gravitational angular momentum densities in the universe with global rotation, considering the Godel-Obukhov metric. For this, we use the Hamiltonian formalism of the Teleparallel Equivalent of General Relativity (TEGR), which is justified for presenting covariant expressions for the considered quantities. We found that the total energy density calculated by the TEGR method is in agreement with the results reported by other authors in the literature using pseudotensors. The result found for the angular momentum density depends on the rotational parameter as expected. We also show explicitly the equivalence among the field equations of the TEGR and Einstein equations (RG), considering a perfect fluid and Godel-Obukhov metric.Comment: 20 pages, no figures. Revised in view of Referee's comments. Version to appear in the Gravitation and Cosmolog