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Elliott A, Taylor M, Mwaka AD, Anguzu R, Ogwang R, Newton C, Vincent A, Idro R, Akun P, Opar B, Marsh K, Abbo C, Nakamya P
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BMC Neurol,
2019]
BACKGROUND: Nodding syndrome is a poorly understood neurological disorder of unknown aetiology, affecting several thousand children in Africa. There has been a consistent epidemiological association with infection by the filarial parasite, Onchocerca volvulus and antibodies to leiomodin and DJ-1, cross-reacting with O.volvulus proteins, have been reported. We hypothesized that nodding syndrome is a neuro-inflammatory disorder, induced by antibodies to O.volvulus or its symbiont, Wolbachia, cross-reacting with human neuron proteins and that doxycycline, which kills Onchocerca through effects on Wolbachia, may be used as treatment. METHODS: This will be a two-arm, double-blind, placebo-controlled, randomised phase II trial of doxycycline 100mg daily for six weeks in 230 participants. Participants will be patients' ages8years with nodding syndrome. They will receive standard of care supportive treatment. All will be hospitalised for 1-2weeks during which time baseline measurements including clinical assessments, EEG, cognitive and laboratory testing will be performed and antiepileptic drug doses rationalised. Participants will then be randomised to either oral doxycycline (Azudox, Kampala Pharmaceutical Industries) 100mg daily or placebo. Treatment will be initiated in hospital and continued at home. Participants will be visited at home at 2, 4 and 6weeks for adherence monitoring. Study outcomes will be assessed at 6, 12, 18 and 24-month visits. Analysis will be by intention to treat. The primary efficacy outcome measure will be the proportion of patients testing positive and the levels or titires of antibodies to host neuron proteins (HNPs) and/or leiomodin at 24months. Secondary outcome measures will include effect of the intervention on seizure control, inflammatory markers, cognitive function, disease severity and quality of life. DISCUSSION: This trial postulates that targeting O.volvulus through drugs which kill Wolbachia can modify the pathogenic processes in nodding syndrome and improve outcomes. Findings from this study are expected to substantially improve the understanding and treatment of nodding syndrome. TRIAL REGISTRATION: Registered with clinicaltrials.gov ID: NCT02850913 on 1st August, 2016.
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J Biomol Struct Dyn,
2010]
DNA sequence influences the position of nucleosomes and chromatin architecture. The extent to which underlying DNA sequence affects nucleosome positioning is currently a topic of considerable discussion and active experimentation. To contribute to the discussion, I will outline a few of the methods, data and arguments that I find compelling and believe will ultimately resolve the question of what positions nucleosomes. Basically, I will give a portrait of my current perspective on what influences the landscape of nucleosome positioning and chromatin architecture.
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ILAR J,
2016]
Nonmammalian model organisms such as the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the zebrafish Danio rerio provide numerous experimental advantages for drug discovery including genetic and molecular tractability, amenability to high-throughput screening methods and reduced experimental costs and increased experimental throughput compared to traditional mammalian models. An interdisciplinary approach that strategically combines the study of nonmammalian and mammalian animal models with diverse experimental tools has and will continue to provide deep molecular and genetic understanding of human disease and will significantly enhance the discovery and application of new therapies to treat those diseases. This review will provide an overview of C. elegans, Drosophila, and zebrafish biology and husbandry and will discuss how these models are being used for phenotype-based drug screening and for identification of drug targets and mechanisms of action. The review will also describe how these and other nonmammalian model organisms are uniquely suited for the discovery of drug-based regenerative medicine therapies.
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Annu Rev Phytopathol,
1999]
The completion of the entire genome sequence of the free-living nematode, Caenorhabditis elegans is a tremendous milestone in modern biology. Not only will scientists be poring over data mined from this resource, but techniques and methodologies developed along the way have changed the way we can approach biological questions. The completion of the C. elegans genomic sequence will be of particular importance to scientists working on parasitic nematodes. In many cases, these nematode species present intractable challenges to those interested in their biology and genetics. The data already compared from parasites to the C. elegans database reveals a wealth of opportunities for parasite biologists. It is likely that many of the same genes will be present in parasites and that these genes will have similar functions. Additional information regarding differences between free-living and parasitic species will provide insight into the evolution and nature of parasitism. Finally, genetic and genomic approaches to the study of parasitic nematodes now have a clearly marked path to follow.
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Cir Cir,
2019]
Exposure and infections by Trypanosoma cruzi are the fourth cause of loss of potential life years between parasitic and infectious diseases. We describe the case of a 11-year-old patient with intestinal occlusion, surgically treated with intestinal volvulus, the surgical specimen is sent to histopathology reporting Chagasic megacolon. The age range of presentation is a challenge in the absence of nonspecific symptoms. There is no pediatric statistical data that define trypanosomiasis in a latent or chronic state and will be diagnosed in adult stages due to the physiopathological alterations that they will present.
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Conf Proc IEEE Eng Med Biol Soc,
2016]
In this work we will work on analogue signal processing in the neural circuit of C. elegans which is able to detect the analogue signals from the environment and produce locomotive behaviours which are in accordance with experiments. The signals in C. elegans are processed in a purely analogue procedure, since no action potential has been recorded in its neural activity. We aim to show how signal processing can be executed in analogue domain in a living creature. In order to do that we will model two different behaviours of C. elegans which are generated in the same network of neurons, klinotaxis behaviour and isothermal tracking. We will implement a Genetic Algorithm to find appropriate sets of parameters of the model. Our contribution is to show how relatively straight forward differential equations can lead to relatively complex and different behaviours.
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Behav Brain Res,
2016]
Cognitive decline is a major deficit that arises with age in humans. While some research on the underlying causes of these problems can be done in humans, harnessing the strengths of small model systems, particularly those with well-studied longevity mutants, such as the nematode C. elegans, will accelerate progress. Here we review the approaches being used to study cognitive decline in model organisms and show how simple model systems allow the rapid discovery of conserved molecular mechanisms, which will eventually enable the development of therapeutics to slow cognitive aging.
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Bulletin de la Societe Zoologique de France-Evolution et Zoologie,
1995]
Introduced in 1965, the Caenorhabditis elegans model is constructed of genetic and molecular techniques, allowing several developmental investigations specific to the model as well as fundamental. The results of the genomic sequencing project of Caenorhabditis elegans will increase the potential of this model.
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Nat Chem Biol,
2017]
The existence of small-molecule signals that influence development in Caenorhabditis elegans has been known for several decades, but only in recent years have the chemical structures of several of these signals been established. The identification of these signals has enabled connections to be made between these small molecules and fundamental signaling pathways in C. elegans that influence not only development but also metabolism, fertility, and lifespan. Spurred by these important discoveries and aided by recent advances in comparative metabolomics and NMR spectroscopy, the field of nematode chemistry has the potential to expand dramatically in the coming years. This Perspective will focus on small-molecule pheromones and hormones that influence developmental events in the nematode life cycle (ascarosides, dafachronic acids, and nemamides), will cover more recent work regarding the biosynthesis of these signals, and will explore how the discovery of these signals is transforming our understanding of nematode development and physiology.
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Tangwattanasirikun T, Meemon K, Klomchitcharoen S, Chattanupakorn S, Tangkijngamwong J, Rungpongvanich V, Phatthanaanukun P, Wongtrakoonkate P, Smerwong N, Jirapanyalerd B, Arunwiriyakit P, Wongsawat Y, Tachavises P, Gallup S, Hongeng S, Nangsue N
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Heliyon,
2022]
The ideas of deep-space human exploration, interplanetary travel, and space civilizations are becoming a reality. However, numerous hindrances remain standing in the way of accomplishing these feats, one of which is space ionizing radiation. Space ionizing radiation has become the most hazardous health risk for long-term human space exploration, as it can induce chromosomal damage and epigenetic changes. The Minerva mission aims to demonstrate cutting-edge technology to inhibit DNA damage against deep-space radiation exposure by using genetic modification. The concept of the experiment is to transform a creature with radiation intolerance into a transgenic organism that is radiation-tolerant. In this mission, Caenorhabditis elegans (C. elegans) will be genetically engineered with a protein-coding gene associated with DNA damage protection called damage suppressor (Dsup). Dsup is a nucleosome-binding protein from the tardigrade Ramazzottius varieornatus that has a unique ability to prevent DNA damage. This paper describes the feasibility of Minerva CubeSat, which will venture out to cis-lunar orbit with a biosensor payload capable of sustaining and culturing C. elegans under space environment conditions for 4 months. The mission will set in motion a paradigm shift corresponding to future space medicines and how they will be developed in the future, introducing a platform suitable for future experiments in the fields of space biology. Ultimately, the paramount objective of Minerva will be to test the limits of genetic engineering and incorporate it into the arduous journey of human perseverance to overcome the boundaries of space exploration-a vital step in making Mars colonization safe.