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https://www.readbyqxmd.com/read/28087364/aquaglyceroporins-are-the-entry-pathway-of-boric-acid-in-trypanosoma-brucei
#1
Sabrina Marsiccobetre, Alexis Rodríguez-Acosta, Florian Lang, Katherine Figarella, Néstor L Uzcátegui
The boron element possesses a range of different effects on living beings. It is essential to beneficial at low concentrations, but toxic at excessive concentrations. Recently, some boron-based compounds have been identified as promising molecules against Trypanosoma brucei, the causative agent of sleeping sickness. However, until now, the boron metabolism and its access route into the parasite remained elusive. The present study addressed the permeability of T. brucei aquaglyceroporins (TbAQPs) for boric acid, the main natural boron species...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28072517/arthropod-innate-immune-systems-and-vector-borne-diseases
#2
Richard H G Baxter, Alicia Contet, Kathryn Krueger
Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases including malaria, sleeping sickness, Dengue and Zika. Yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins such as antimicrobial peptides, thioester-containing proteins, and transglutaminases effect responses such as lysis, phagocytosis, melanization and agglutination...
January 10, 2017: Biochemistry
https://www.readbyqxmd.com/read/28069461/is-acute-mountain-sickness-related-to-trait-anxiety-a-normobaric-chamber-study
#3
Martin Niedermeier, Robb Waanders, Verena Menz, Maria Wille, Martin Kopp, Martin Burtscher
INTRODUCTION: Some mountaineers are more prone to the occurrence of acute mountain sickness (AMS) than others. State anxiety during altitude exposure might be associated with AMS development. We hypothesized that trait anxiety might be higher in AMS cases compared to non-AMS cases. The aim of the present study was to study the relationship between AMS development and trait anxiety. METHODS: In an observational study design, AMS incidence during a 12-hour exposure to normobaric hypoxia (FiO2=12...
January 6, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28063399/sleep-quality-among-elderly-high-altitude-dwellers-in-ladakh
#4
Ryota Sakamoto, Kiyohito Okumiya, Tsering Norboo, Norboo Tsering, Takayoshi Yamaguchi, Mitsuhiro Nose, Shinya Takeda, Toshihiro Tsukihara, Motonao Ishikawa, Shun Nakajima, Taizo Wada, Michiko Fujisawa, Hissei Imai, Yasuko Ishimoto, Yumi Kimura, Eriko Fukutomi, Wenling Chen, Kuniaki Otsuka, Kozo Matsubayashi
It has been already known that people who temporarily stay at high altitude may develop insomnia as a symptom of acute mountain sickness. However, much less is known about people living at high altitude. The aim of this study was to determine the effect of high altitude environment on sleep quality for the elderly who have been living at high altitude for their whole lives. A cross-sectional study was conducted in Domkhar valley at altitudes of 2800-4200m, Ladakh. Sleep quality was assessed using Insomnia Severity Index (ISI)...
December 29, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/28056016/predicting-the-impact-of-intervention-strategies-for-sleeping-sickness-in-two-high-endemicity-health-zones-of-the-democratic-republic-of-congo
#5
Kat S Rock, Steve J Torr, Crispin Lumbala, Matt J Keeling
Two goals have been set for Gambian human African trypanosomiasis (HAT), the first is to achieve elimination as a public health problem in 90% of foci by 2020, and the second is to achieve zero transmission globally by 2030. It remains unclear if certain HAT hotspots could achieve elimination as a public health problem by 2020 and, of greater concern, it appears that current interventions to control HAT in these areas may not be sufficient to achieve zero transmission by 2030. A mathematical model of disease dynamics was used to assess the potential impact of changing the intervention strategy in two high-endemicity health zones of Kwilu province, Democratic Republic of Congo...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28054952/computer-aided-drug-design-using-sesquiterpene-lactones-as-sources-of-new-structures-with-potential-activity-against-infectious-neglected-diseases
#6
REVIEW
Chonny Herrera Acevedo, Luciana Scotti, Mateus Feitosa Alves, Margareth De Fátima Formiga Melo Diniz, Marcus Tullius Scotti
This review presents an survey to the biological importance of sesquiterpene lactones (SLs) in the fight against four infectious neglected tropical diseases (NTDs)-leishmaniasis, schistosomiasis, Chagas disease, and sleeping sickness-as alternatives to the current chemotherapies that display several problems such as low effectiveness, resistance, and high toxicity. Several studies have demonstrated the great potential of some SLs as therapeutic agents for these NTDs and the relationship between the protozoal activities with their chemical structure...
January 3, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28049718/patterns-of-organelle-ontogeny-through-a-cell-cycle-revealed-by-whole-cell-reconstructions-using-3d-electron-microscopy
#7
Louise Hughes, Samantha Borrett, Katie Towers, Tobias Starborg, Sue Vaughan
The major mammalian bloodstream form of the African sleeping sickness parasite Trypanosoma brucei multiplies rapidly and it is important to understand how these cells divide. Organelle inheritance involves complex spatiotemporal re-arrangements to ensure correct distribution to daughter cells. Serial block face scanning electron microscopy (SBF-SEM) was used to reconstruct whole individual cells at different stages of the cell cycle to give an unprecedented temporal, spatial and quantitative view of organelle division, inheritance and abscission in a eukaryotic cell...
January 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28043795/evaluation-of-substituted-ebselen-derivatives-as-potential-trypanocidal-agents
#8
Heeren M Gordhan, Stephen L Patrick, Maria I Swasy, Amber L Hackler, Mark Anayee, Jennifer E Golden, James C Morris, Daniel C Whitehead
Human African trypanosomiasis is a disease of sub-Saharan Africa, where millions are at risk for the illness. The disease, commonly referred to as African sleeping sickness, is caused by an infection by the eukaryotic pathogen, Trypanosoma brucei. Previously, a target-based high throughput screen revealed ebselen (EbSe), and its sulfur analog, EbS, to be potent in vitro inhibitors of the T. brucei hexokinase 1 (TbHK1). These molecules also exhibited potent trypanocidal activity in vivo. In this manuscript, we synthesized a series of sixteen EbSe and EbS derivatives bearing electron-withdrawing carboxylic acid and methyl ester functional groups, and evaluated the influence of these substituents on the biological efficacy of the parent scaffold...
December 10, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28042865/the-role-of-natural-products-in-drug-discovery-and-development-against-neglected-tropical-diseases
#9
REVIEW
Peter Mubanga Cheuka, Godfrey Mayoka, Peggoty Mutai, Kelly Chibale
Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs) affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures...
December 31, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28028818/a-mechanism-for-sickness-sleep-lessons-from-invertebrates
#10
Kristen C Davis, David M Raizen
During health, animal sleep is regulated by an internal clock and by the duration of prior wakefulness. During sickness, sleep is regulated by cytokines released from either peripheral cells or from cells within the nervous system. These cytokines regulate central nervous system neurons to induce sleep. Recent research in the invertebrates Caenorhabditis elegans and Drosophila melanogaster has led to new insights into the mechanism of sleep during sickness. Sickness is triggered by exposure to environments such as infection, heat, or ultraviolet light irradiation, all of which cause cellular stress...
December 28, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/28008825/simulating-the-elimination-of-sleeping-sickness-with-an-agent-based-model
#11
Pascal Grébaut, Killian Girardin, Valentine Fédérico, François Bousquet
Although Human African Trypanosomiasis is largely considered to be in the process of extinction today, the persistence of human and animal reservoirs, as well as the vector, necessitates a laborious elimination process. In this context, modeling could be an effective tool to evaluate the ability of different public health interventions to control the disease. Using the Cormas(®) system, we developed HATSim, an agent-based model capable of simulating the possible endemic evolutions of sleeping sickness and the ability of National Control Programs to eliminate the disease...
2016: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/28007406/adipose-tissue-a-safe-haven-for-parasites
#12
REVIEW
Herbert B Tanowitz, Philipp E Scherer, Maria M Mota, Luisa M Figueiredo
Adipose tissue (AT) is no longer regarded as an inert lipid storage, but as an important central regulator in energy homeostasis and immunity. Three parasite species are uniquely associated with AT during part of their life cycle: Trypanosoma cruzi, the causative agent of Chagas disease; Trypanosoma brucei, the causative agent of African sleeping sickness; and Plasmodium spp., the causative agents of malaria. In AT, T. cruzi resides inside adipocytes, T. brucei is found in the interstitial spaces between adipocytes, while Plasmodium spp...
December 19, 2016: Trends in Parasitology
https://www.readbyqxmd.com/read/28002454/trypanosoma-brucei-invasion-and-t-cell-infiltration-of-the-brain-parenchyma-in-experimental-sleeping-sickness-timing-and-correlation-with-functional-changes
#13
Claudia Laperchia, Maria Palomba, Paul F Seke Etet, Jean Rodgers, Barbara Bradley, Paul Montague, Gigliola Grassi-Zucconi, Peter G E Kennedy, Marina Bentivoglio
BACKGROUND: The timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications. METHODOLOGY: Using a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28002435/transcriptome-profiling-of-trypanosoma-brucei-development-in-the-tsetse-fly-vector-glossina-morsitans
#14
Amy F Savage, Nikolay G Kolev, Joseph B Franklin, Aurelien Vigneron, Serap Aksoy, Christian Tschudi
African trypanosomes, the causative agents of sleeping sickness in humans and nagana in animals, have a complex digenetic life cycle between a mammalian host and an insect vector, the blood-feeding tsetse fly. Although the importance of the insect vector to transmit the disease was first realized over a century ago, many aspects of trypanosome development in tsetse have not progressed beyond a morphological analysis, mainly due to considerable challenges to obtain sufficient material for molecular studies. Here, we used high-throughput RNA-Sequencing (RNA-Seq) to profile Trypanosoma brucei transcript levels in three distinct tissues of the tsetse fly, namely the midgut, proventriculus and salivary glands...
2016: PloS One
https://www.readbyqxmd.com/read/27974541/characterization-and-diagnostic-application-of-trypanosoma-cruzi-trypomastigote-excreted-secreted-antigens-shed-in-extracellular-vesicles-released-from-infected-mammalian-cells
#15
Norma L Bautista-López, Momar Ndao, Fabio Vasquez Camargo, Takeshi Nara, Takeshi Annoura, Darryl B Hardie, Christoph H Borchers, Armando Jardim
Chagas disease, caused by Trypanosoma cruzi, although endemic in many parts of Central and South America, is emerging as a global health threat through the potential contamination of blood supplies. Consequently, in the absence of a gold standard assay for the diagnosis of Chagas additional antigens or strategies are needed. A proteomic analysis of the trypomastigote excreted secreted antigens (TESA) associated with exosomal vesicles shed by T. cruzi identified ∼80 parasite proteins; with the majority being trans-sialidases...
December 14, 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/27955775/elimination-of-sleeping-sickness-in-uganda-could-be-jeopardised-by-conflict-in-south-sudan
#16
Albert Picado, Joseph Ndung'u
No abstract text is available yet for this article.
January 2017: Lancet Global Health
https://www.readbyqxmd.com/read/27951754/immunomodulatory-activity-of-buchholzia-coriacea-seed-methanol-extract-on-trypanosoma-brucei-brucei-infected-mice
#17
James I Eze, Chioma F Ekelozie, Nwakego E Nweze
CONTEXT: The seeds of Buchholzia coriacea Engler (Capparaceae) are used in Eastern Nigeria to treat feverish conditions, and to treat malaria and sleeping sickness that cause fever. OBJECTIVE: The current study assesses the immunomodulatory activity of Buchholzia coriacea seed extract on Trypanosoma brucei brucei infected mice. MATERIALS AND METHODS: Delayed hypersensitivity reaction, humoral antibody response and in-vivo leucocyte mobilization tests were assessed in three different experiments to determine the effect of the extract on immune response...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27941966/metabolomics-identifies-multiple-candidate-biomarkers-to-diagnose-and-stage-human-african-trypanosomiasis
#18
Isabel M Vincent, Rónán Daly, Bertrand Courtioux, Amy M Cattanach, Sylvain Biéler, Joseph M Ndung'u, Sylvie Bisser, Michael P Barrett
Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF)). Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27939999/24-methylenecyclopropane-steroidal-inhibitors-a-trojan-horse-in-ergosterol-biosynthesis-that-prevents-growth-of-trypanosoma-brucei
#19
Matthew B Miller, Presheet Patkar, Ujjal K Singha, Minu Chaudhuri, W David Nes
A new class of steroidal therapeutics based on phylogenetic-guided design of covalent inhibitors that target parasite-specific enzymes of ergosterol biosynthesis is shown to prevent growth of the protozoan-Trypanosoma brucei, responsible for sleeping sickness. In the presence of approximately 15±5μM 26,27-dehydrolanosterol, T. brucei procyclic or blood stream form growth is inhibited by 50%. This compound is actively converted by the parasite to an acceptable substrate of sterol C24-methyl transferase (SMT) that upon position-specific side chain methylation at C26 inactivates the enzyme...
December 6, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27912879/how-do-the-alkaloids-emetine-and-homoharringtonine-kill-trypanosomes-an-insight-into-their-molecular-modes-of-action
#20
Sonja Krstin, Tamer Mohamed, Xiaojuan Wang, Michael Wink
BACKGROUND: Although Trypanosoma brucei causes deadly sleeping sickness, the number of the registered medications is rather limited. Some plant alkaloids are potent trypanocidal agents. PURPOSE: In this study, we wanted to elucidate the molecular modes of trypanocidal activity of the alkaloids emetine and homoharringtonine against Trypanosoma brucei brucei. METHODS: We investigated the activity of both alkaloids regarding growth recovery from alkaloid-induced stress...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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