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Thomas W M Crozier, Michele Tinti, Richard J Wheeler, Tony Ly, Michael A J Ferguson, Angus I Lamond
We describe a single-step centrifugal elutriation method to produce synchronous G1-phase procyclic trypanosomes at a scale amenable for proteomic analysis of the cell cycle. Using ten-plex tandem mass tag (TMT) labelling and mass spectrometry (MS)-based proteomics technology, the expression levels of 5,325 proteins were quantified across the cell cycle in this parasite. Of these, 384 proteins were classified as cell-cycle regulated and subdivided into nine clusters with distinct temporal regulation. These groups included many known cell cycle regulators in trypanosomes, which validates the approach...
March 19, 2018: Molecular & Cellular Proteomics: MCP
Stephane L Ngahang Kamte, Farahnaz Ranjbarian, Kevin Cianfaglione, Stefania Sut, Stefano Dall'Acqua, Maurizio Bruno, Fariba Heshmati Afshar, Romilde Iannarelli, Giovanni Benelli, Loredana Cappellacci, Anders Hofer, Filippo Maggi, Riccardo Petrelli
The Apiaceae family encompasses aromatic plants of economic importance employed in foodstuffs, beverages, perfumery, pharmaceuticals and cosmetics. Apiaceae are rich sources of essential oils because of the wealth of secretory structures (ducts and vittae) they are endowed with. The Apiaceae essential oils are available on an industrial level because of the wide cultivation and disposability of the bulky material from which they are extracted as well as their relatively cheap price. In the fight against protozoal infections, essential oils may represent new therapeutic options...
March 14, 2018: Ecotoxicology and Environmental Safety
Godwin U Ebiloma, Teresa Díaz Ayuga, Emmanuel O Balogun, Lucía Abad Gil, Anne Donachie, Marcel Kaiser, Tomás Herraiz, Daniel K Inaoka, Tomoo Shiba, Shigeharu Harada, Kiyoshi Kita, Harry P de Koning, Christophe Dardonville
African trypanosomiasis is a neglected parasitic disease that is still of great public health relevance, and a severe impediment to agriculture in endemic areas. The pathogens possess certain unique metabolic features that can be exploited for the development of new drugs. Notably, they rely on an essential, mitochondrially-localized enzyme, Trypanosome Alternative Oxidase (TAO) for their energy metabolism, which is absent in the mammalian hosts and therefore an attractive target for the design of safe drugs...
February 26, 2018: European Journal of Medicinal Chemistry
Marilda Savoia Nascimento, Anna Maria Simonsen Stolf, Heitor Franco de Andrade Junior, Ramendra Pati Pandey, Eufrosina Setsu Umezawa
BACKGROUND: Vimentin is a main structural protein of the cell, a component of intermediate cell filaments and immersed in cytoplasm. Vimentin is mimicked by some bacterial proteins and anti-vimentin antibodies occur in autoimmune cardiac disease, as rheumatic fever. In this work we studied vimentin distribution on LLC-MK2 cells infected with T. cruzi and anti-vimentin antibodies in sera from several clinical pictures of Chagas' disease or American Trypanosomiasis, in order to elucidate any vimentin involvement in the humoral response of this pathology...
March 12, 2018: Arquivos Brasileiros de Cardiologia
Claudia Laperchia, Yuan-Zhong Xu, Dieudonné Mumba Ngoyi, Tiziana Cotrufo, Marina Bentivoglio
Neuron populations of the lateral hypothalamus which synthesize the orexin (OX)/hypocretin or melanin-concentrating hormone (MCH) peptides play crucial, reciprocal roles in regulating wake stability and sleep. The disease human African trypanosomiasis (HAT), also called sleeping sickness, caused by extracellular Trypanosoma brucei ( T. b .) parasites, leads to characteristic sleep-wake cycle disruption and narcoleptic-like alterations of the sleep structure. Previous studies have revealed damage of OX and MCH neurons during systemic infection of laboratory rodents with the non-human pathogenic T...
2018: Frontiers in Neuroanatomy
Edeltraud J Lenk, William K Redekop, Marianne Luyendijk, Christopher Fitzpatrick, Louis Niessen, Wilma A Stolk, Fabrizio Tediosi, Adriana J Rijnsburger, Roel Bakker, Jan A C Hontelez, Jan H Richardus, Julie Jacobson, Epke A Le Rutte, Sake J de Vlas, Johan L Severens
BACKGROUND: The control or elimination of neglected tropical diseases (NTDs) has targets defined by the WHO for 2020, reinforced by the 2012 London Declaration. We estimated the economic impact to individuals of meeting these targets for human African trypanosomiasis, leprosy, visceral leishmaniasis and Chagas disease, NTDs controlled or eliminated by innovative and intensified disease management (IDM). METHODS: A systematic literature review identified information on productivity loss and out-of-pocket payments (OPPs) related to these NTDs, which were combined with projections of the number of people suffering from each NTD, country and year for 2011-2020 and 2021-2030...
March 2018: PLoS Neglected Tropical Diseases
Steven Ger Nyanjom, Cyrus Tare, Fred Wamunyokoli, George Fredrick Obiero
Tsetse flies (Glossina) are vectors of African trypanosomiasis. Olfaction plays a critical role in Glossina behavior, including larviposition, feeding, and reproduction. Odorant receptors (ORs) are important in insect chemoreception as they bind volatile odorants and transport them to olfactory receptor neurons to elicit behavioral response. To better understand Glossina chemoreception, we used quantitative polymerase chain reaction to examine the expression levels of ORs in female and male Glossina morsitans morsitans Wiedemann, 1850 (Diptera: Glossinidae) antennae and legs...
February 26, 2018: Journal of Medical Entomology
Jayleen K L Gunn, Kacey C Ernst, Katherine E Center, Kristi Bischoff, Annabelle V Nuñez, Megan Huynh, Amanda Okello, Mary H Hayden
Introduction: Vector-borne diseases (VBDs) cause significant mortality and morbidity in low-income and middle-income countries and present a risk to high-income countries. Vector control programmes may confront social and cultural norms that impede their execution. Anecdotal evidence suggests that incorporating women in the design, delivery and adoption of health interventions increases acceptance and compliance. A better understanding of programmes that have attempted to increase women's involvement in vector control could help shape best practices...
2018: BMJ Global Health
Anne Meyer, Hannah R Holt, Farikou Oumarou, Kalinga Chilongo, William Gilbert, Albane Fauron, Chisoni Mumba, Javier Guitian
BACKGROUND: Animal African trypanosomiasis (AAT) and its tsetse vector are responsible for annual losses estimated in billions of US dollars ($). Recent years have seen the implementation of a series of multinational interventions. However, actors of AAT control face complex resource allocation decisions due to the geographical range of AAT, diversity of ecological and livestock systems, and range of control methods available. METHODS: The study presented here integrates an existing tsetse abundance model with a bio-economic herd model that captures local production characteristics as well as heterogeneities in AAT incidence and breed...
March 7, 2018: Parasites & Vectors
Ludmila Ferreira de Almeida Fiuza, Raiza Brandão Peres, Marianne Rocha Simões-Silva, Patricia Bernardino da Silva, Denise da Gama Jaen Batista, Cristiane França da Silva, Aline Nefertiti Silva da Gama, Tummala Rama Krishna Reddy, Maria de Nazaré Correia Soeiro
American trypanosomiasis or Chagas disease (CD) is a vector borne pathology caused by the parasite Trypanosoma cruzi (T. cruzi), which remains a serious global health problem. The current available treatment for CD is limited to two nitroderivatives with limited efficacy and several side effects. The rational design of ergosterol synthetic route inhibitors (e.g. CYP51 inhibitors) represents a promising strategy for fungi and trypanosomatids, exhibiting excellent anti-T.cruzi activity in pre-clinical assays...
February 23, 2018: European Journal of Medicinal Chemistry
Noel-Marie Plonski, Bianca Bissoni, Madara Hetti Arachchilage, Karl Romstedt, Edgar E Kooijman, Helen Piontkivska
Unicellular flagellates that make up the class Kinetoplastida include multiple parasites responsible for public health concerns, including Trypanosoma brucei and T. cruzi (agents of African sleeping sickness and Chagas disease, respectively), and various Leishmania species, which cause leishmaniasis. These diseases are generally difficult to eradicate, with treatments often having lethal side effects and/or being effective only during the acute phase of the diseases, when most patients are still asymptomatic...
February 28, 2018: Gene
Benoit Stijlemans, Patrick De Baetselier, Stefan Magez, Jo A Van Ginderachter, Carl De Trez
African trypanosomosis (AT) is a chronically debilitating parasitic disease of medical and economic importance for the development of sub-Saharan Africa. The trypanosomes that cause this disease are extracellular protozoan parasites that have developed efficient immune escape mechanisms to manipulate the entire host immune response to allow parasite survival and transmission. During the early stage of infection, a profound pro-inflammatory type 1 activation of the mononuclear phagocyte system (MPS), involving classically activated macrophages (i...
2018: Frontiers in Immunology
Chiara Tesoriero, Yuan-Zhong Xu, Dieudonné Mumba Ngoyi, Marina Bentivoglio
Trypanosoma brucei ( T. b. ) gambiense is the parasite subspecies responsible for most reported cases of human African trypanosomiasis (HAT) or sleeping sickness. This severe infection leads to characteristic disruption of the sleep-wake cycle, recalling attention on the circadian timing system. Most animal models of the disease have been hitherto based on infection of laboratory rodents with the T. b. brucei subspecies, which is not infectious to humans. In these animal models, functional, rather than structural, alterations of the master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), have been reported...
2018: Frontiers in Neuroanatomy
Naveed Sabir, Zafar Iqbal Chaudhry, Asim Aslam, Khushi Muhammad, Muhammad Shahid, Abid Hussain, Shahzad Akbar Khan, Ishtiaq Ahmad
Trypanosomiasis is an important protozoal disease with a diverse range of susceptible host including human. In the current study, molecular characterization of prevalent species was done through a pan-trypanosome polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). A total of three hundred (n = 300) equines including horses, donkeys and mules (100 each) were randomly selected and the equine blood samples were subjected to screening for trypanosomes through microhaematocrit centrifuge technique (MHCT), conventional PCR, semi-nested PCR and RFLP...
March 2018: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
Cécile Minet, Sophie Thevenon, Isabelle Chantal, Philippe Solano, David Berthier
The CRISPR-Cas system, which was originally identified as a prokaryotic defense mechanism, is increasingly being used for the functional study of genes. This technology, which is simple, inexpensive and efficient, has aroused a lot of enthusiasm in the scientific community since its discovery, and every month many publications emanate from very different communities reporting on the use of CRISPR-Cas9. Currently, there are no vaccines to control neglected tropical diseases (NTDs) caused by Trypanosomatidae, particularly Human African Trypanosomiasis (HAT) and Animal African Trypanosomoses (AAT), and treatments are cumbersome and sometimes not effective enough...
February 24, 2018: Infection, Genetics and Evolution
Eva Doleželová, David Terán, Ondřej Gahura, Zuzana Kotrbová, Michaela Procházková, Dianne Keough, Petr Špaček, Dana Hocková, Luke Guddat, Alena Zíková
Due to toxicity and compliance issues and the emergence of resistance to current medications new drugs for the treatment of Human African Trypanosomiasis are needed. A potential approach to developing novel anti-trypanosomal drugs is by inhibition of the 6-oxopurine salvage pathways which synthesise the nucleoside monophosphates required for DNA/RNA production. This is in view of the fact that trypanosomes lack the machinery for de novo synthesis of the purine ring. To provide validation for this approach as a drug target, we have RNAi silenced the three 6-oxopurine phosphoribosyltransferase (PRTase) isoforms in the infectious stage of Trypanosoma brucei demonstrating that the combined activity of these enzymes is critical for the parasites' viability...
February 26, 2018: PLoS Neglected Tropical Diseases
Freddie Kansiime, Seraphine Adibaku, Charles Wamboga, Franklin Idi, Charles Drago Kato, Lawrence Yamuah, Michel Vaillant, Deborah Kioy, Piero Olliaro, Enock Matovu
BACKGROUND: While the combination of nifurtimox and eflornithine (NECT) is currently recommended for the treatment of the late stage human African trypansomiasis (HAT), single-agent eflornithine was still the treatment of choice when this trial commenced. This study intended to provide supportive evidence to complement previous trials. METHODS: A multi-centre randomised, open-label, non-inferiority trial was carried out in the Trypanosoma brucei gambiense endemic districts of North-Western Uganda to compare the efficacy and safety of NECT (200 mg/kg eflornithine infusions every 12 h for 7 days and 8 hourly oral nifurtimox at 5 mg/kg for 10 days) to the standard eflornithine regimen (6 hourly at 100 mg/kg for 14 days)...
February 22, 2018: Parasites & Vectors
Magambo Phillip Kimuda, Harry Noyes, Julius Mulindwa, John Enyaru, Vincent Pius Alibu, Issa Sidibe, Dieuodonne Mumba Ngoyi, Christiane Hertz-Fowler, Annette MacLeod, Özlem Tastan Bishop, Enock Matovu
BACKGROUND: Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT...
February 22, 2018: PLoS Neglected Tropical Diseases
Ning Zhang, Martin Zoltner, Ka-Fai Leung, Paul Scullion, Sebastian Hutchinson, Ricardo C Del Pino, Isabel M Vincent, Yong-Kang Zhang, Yvonne R Freund, Michael R K Alley, Robert T Jacobs, Kevin D Read, Michael P Barrett, David Horn, Mark C Field
Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in Trypanosoma brucei...
February 9, 2018: PLoS Pathogens
Simon Alderton, Ewan T Macleod, Neil E Anderson, Gwen Palmer, Noreen Machila, Martin Simuunza, Susan C Welburn, Peter M Atkinson
BACKGROUND: This paper presents the development of an agent-based model (ABM) to incorporate climatic drivers which affect tsetse fly (G. m. morsitans) population dynamics, and ultimately disease transmission. The model was used to gain a greater understanding of how tsetse populations fluctuate seasonally, and investigate any response observed in Trypanosoma brucei rhodesiense human African trypanosomiasis (rHAT) disease transmission, with a view to gaining a greater understanding of disease dynamics...
February 2018: PLoS Neglected Tropical Diseases
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