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https://www.readbyqxmd.com/read/28769924/thymic-stromal-lymphopoietin-is-critical-for-regulation-of-proinflammatory-cytokine-response-and-resistance-to-experimental-trypanosoma-congolense-infection
#1
Chukwunonso Onyilagha, Rani Singh, Abdelilah Soussi Gounni, Jude Ezeh Uzonna
African trypanosomiasis (sleeping sickness) poses serious threat to human and animal health in sub-Saharan Africa. Because there is currently no vaccine for preventing this disease and available drugs are not safe, understanding the mechanisms that regulate resistance and/or susceptibility to the disease could reveal novel targets for effective disease therapy and prevention. Thymic stromal lymphopoietin (TSLP) plays a critical role in driving Th2 immune response. Although susceptibility to experimental Trypanosoma congolense infection in mice is associated with excessive proinflammatory responses due in part to impaired Th2 response, the role of TSLP in resistance to African trypanosomiasis has not been well studied...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28766862/inhibition-of-protein-protein-interactions-new-options-for-developing-drugs-against-neglected-tropical-diseases
#2
Thorsten Berg
Wake up! Sleeping sickness and Chagas disease are neglected tropical diseases caused by trypanosome infections. Small molecules that disrupt a crucial protein-protein interaction in the parasites offer a new approach to drug development for these diseases.
August 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28760415/surface-glycans-a-therapeutic-opportunity-for-kinetoplastid-diseases
#3
REVIEW
Víctor M Castillo-Acosta, Jan Balzarini, Dolores González-Pacanowska
Trypanosomal diseases are in need of innovative therapies that exploit novel mechanisms of action. The cell surface of trypanosomatid parasites is characterized by a dense coat of glycoconjugates with important functions in host cell recognition, immune evasion, infectivity, and cell function. The nature of parasite surface glycans is highly dynamic and changes during differentiation and in response to different stimuli through the action of glycosyltransferases and glycosidases. Here we propose a new approach to antiparasitic drug discovery that involves the use of carbohydrate-binding agents that bind specifically to cell-surface glycans, giving rise to cytotoxic events and parasite death...
July 28, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28750007/adding-tsetse-control-to-medical-activities-contributes-to-decreasing-transmission-of-sleeping-sickness-in-the-mandoul-focus-chad
#4
Mahamat Hissene Mahamat, Mallaye Peka, Jean-Baptiste Rayaisse, Kat S Rock, Mahamat Abdelrahim Toko, Justin Darnas, Guihini Mollo Brahim, Ali Bachar Alkatib, Wilfrid Yoni, Inaki Tirados, Fabrice Courtin, Samuel P C Brand, Cyrus Nersy, Idriss Oumar Alfaroukh, Steve J Torr, Mike J Lehane, Philippe Solano
BACKGROUND: Gambian sleeping sickness or HAT (human African trypanosomiasis) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by riverine species of tsetse. A global programme aims to eliminate the disease as a public health problem by 2020 and stop transmission by 2030. In the South of Chad, the Mandoul area is a persistent focus of Gambian sleeping sickness where around 100 HAT cases were still diagnosed and treated annually until 2013. Pre-2014, control of HAT relied solely on case detection and treatment, which lead to a gradual decrease in the number of cases of HAT due to annual screening of the population...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28749453/mindfulness-based-stress-reduction-therapy-improves-patient-and-caregiver-reported-outcomes-in-cirrhosis
#5
Jasmohan S Bajaj, Michael Ellwood, Timothy Ainger, Thomas Burroughs, Andrew Fagan, Edith A Gavis, Douglas M Heuman, Michael Fuchs, Binu John, James B Wade
OBJECTIVES: Patient-reported outcomes such as health-related quality of life (HRQOL) are impaired in cirrhosis due to under-treated mood and sleep disorders, which can adversely impact their caregivers. Mindfulness-based stress reduction (MBSR) can improve patient-reported outcomes (PRO) in non-cirrhotic patients but their impact in cirrhosis is unclear. To evaluate the effect of MBSR and supportive group therapy on mood, sleep and HRQOL in cirrhotic patients and their caregivers. METHODS: Cirrhotic outpatients with mild depression (Beck Depression Inventory (BDI)>14) on screening with an adult caregiver were enrolled...
July 27, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28742275/the-proteome-and-transcriptome-of-the-infectious-metacyclic-form-of-trypanosoma-brucei-define-quiescent-cells-primed-for-mammalian-invasion
#6
Romain Christiano, Nikolay G Kolev, Huafang Shi, Elisabetta Ullu, Tobias C Walther, Christian Tschudi
The infectious metacyclic forms of Trypanosoma brucei result from a complex development in the tsetse fly vector. When they infect mammals, they cause African sleeping sickness in humans. Due to scarcity of biological material and difficulties of the tsetse fly as an experimental system, very limited information is available concerning the gene expression profile of metacyclic forms. We used an in vitro system based on expressing the RNA binding protein 6 to obtain infectious metacyclics and determined their protein and mRNA repertoires by mass-spectrometry (MS) based proteomics and mRNA sequencing (RNA-Seq) in comparison to non-infectious procyclic trypanosomes...
July 25, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28739368/andrographolide-induces-oxidative-stress-dependent-cell-death-in-unicellular-protozoan-parasite-trypanosoma-brucei
#7
Malabika Banerjee, Debaprasad Parai, Pranab Dhar, Manab Roy, Rajib Barik, Subrata Chattopadhyay, Samir Kumar Mukherjee
African sleeping sickness is a parasitic disease in humans and livestock caused by Trypanosoma brucei throughout sub-Saharan Africa. Absence of appropriate vaccines and prevalence of drug resistance proclaim that a new way of therapeutic interventions is essential against African trypanosomiasis. In the present study, we have looked into the effect of andrographolide (andro), a diterpenoid lactone from Andrographis paiculata on Trypanosoma brucei PRA 380. Although andro has been recognized as a promosing anti-cancer drug, its usefulness against Trypanosoma spp remained unexplored...
July 21, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28733613/rnai-screening-identifies-trypanosoma-brucei-stress-response-protein-kinases-required-for-survival-in-the-mouse
#8
Fernando Fernandez-Cortes, Tiago D Serafim, Jonathan M Wilkes, Nathaniel G Jones, Ryan Ritchie, Richard McCulloch, Jeremy C Mottram
Protein kinases (PKs) are a class of druggable targets in Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (sleeping sickness), yet little is known about which PKs are essential for survival in mammals. A recent kinome-wide RNAi screen with 176 individual bloodstream form Trypanosoma brucei lines identified PKs required for proliferation in culture. In order to assess which PKs are also potential virulence factors essential in vivo, lines were pooled, inoculated into mice, and screened for loss of fitness after 48 h RNAi...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28727848/the-nuclear-proteome-of-trypanosoma-brucei
#9
Carina Goos, Mario Dejung, Christian J Janzen, Falk Butter, Susanne Kramer
Trypanosoma brucei is a protozoan flagellate that is transmitted by tsetse flies into the mammalian bloodstream. The parasite has a huge impact on human health both directly by causing African sleeping sickness and indirectly, by infecting domestic cattle. The biology of trypanosomes involves some highly unusual, nuclear-localised processes. These include polycistronic transcription without classical promoters initiated from regions defined by histone variants, trans-splicing of all transcripts to the exon of a spliced leader RNA, transcription of some very abundant proteins by RNA polymerase I and antigenic variation, a switch in expression of the cell surface protein variants that allows the parasite to resist the immune system of its mammalian host...
2017: PloS One
https://www.readbyqxmd.com/read/28726862/a-targeted-delivery-strategy-for-the-development-of-potent-trypanocides
#10
Heeren M Gordhan, Jillian E Milanes, Yijian Qiu, Jennifer E Golden, Kenneth A Christensen, James C Morris, Daniel C Whitehead
A new drug delivery strategy was investigated for the development of potent anti-parasitic compounds against Trypanosoma brucei, the causative agent of African sleeping sickness. Thus, potent in vitro hexokinase inhibitors were rendered cytotoxic by appending a tripeptide peroxosomal targeting sequence that facilitated delivery of the molecular cargo to the appropriate organelle in the parasite.
July 20, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28715456/the-trypanosoma-brucei-dihydroxyacetonephosphate-acyltransferase-tbdat-is-dispensable-for-normal-growth-but-important-for-synthesis-of-ether-glycerophospholipids
#11
Rachel Zufferey, Karim Pirani, Melanie Cheung-See-Kit, Sungsu Lee, Tyler A Williams, Daniel G Chen, Md Faruk Hossain
Glycerophospholipids are the most abundant constituents of biological membranes in Trypanosoma brucei, which causes sleeping sickness in humans and nagana in cattle. They are essential cellular components that fulfill various important functions beyond their structural role in biological membranes such as in signal transduction, regulation of membrane trafficking or control of cell cycle progression. Our previous studies have established that the glycerol-3-phosphate acyltransferase TbGAT is dispensable for growth, viability, and ester lipid biosynthesis suggesting the existence of another initial acyltransferase(s)...
2017: PloS One
https://www.readbyqxmd.com/read/28713858/life-stage-specific-cargo-receptors-facilitate-glycosylphosphatidylinositol-anchored-surface-coat-protein-transport-in-trypanosoma-brucei
#12
Emilia K Kruzel, George P Zimmett, James D Bangs
The critical virulence factor of bloodstream-form Trypanosoma brucei is the glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG). Endoplasmic reticulum (ER) exit of VSG is GPI dependent and relies on a discrete subset of COPII machinery (TbSec23.2/TbSec24.1). In other systems, p24 transmembrane adaptor proteins selectively recruit GPI-anchored cargo into nascent COPII vesicles. Trypanosomes have eight putative p24s (TbERP1 to TbERP8) that are constitutively expressed at the mRNA level...
July 2017: MSphere
https://www.readbyqxmd.com/read/28713431/an-unexpected-cause-of-bradycardia-in-a-patient-with-bacterial-meningitis
#13
Petros Ioannou, Magdalini Velegraki, Stella Soundoulounaki, Achilleas Gikas, Diamantis P Kofteridis
Sinus bradycardia which is a sinus rhythm with a resting heart rate of less than 60 bpm is caused by intrinsic cardiac disorders like sick sinus syndrome or inferior myocardial infarction, metabolic and environmental causes (such as hypothyroidism and electrolyte disorders), medications (such as beta-blockers and amiodarone), infection (such as myocarditis), increased intracranial pressure, and toxic exposure, while it can sometimes be a normal phenomenon, especially during sleep, in athletes, and during pregnancy...
2017: Case Reports in Medicine
https://www.readbyqxmd.com/read/28706938/inhibitors-of-glycosomal-protein-import-provide-new-leads-against-trypanosomiasis
#14
COMMENT
Vishal C Kalel, Leonidas Emmanouilidis, Maciej Dawidowski, Wolfgang Schliebs, Michael Sattler, Grzegorz M Popowicz, Ralf Erdmann
Vector-borne trypanosomatid parasite infections in tropical and sub-tropical countries constitute a major threat to humans and livestock. Trypanosoma brucei parasites are transmitted by tsetse fly and lead to African sleeping sickness in humans and Nagana in cattle. In Latin American countries, Trypanosoma cruzi infections spread by triatomine kissing bugs lead to Chagas disease. Various species of Leishmania transmitted to humans by phlebotomine sandflies manifest in a spectrum of diseases termed Leishmaniasis...
July 3, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28684718/steroid-alkaloids-from-holarrhena-africana-with-strong-activity-against-trypanosoma-brucei-rhodesiense
#15
Charles Okeke Nnadi, Ngozi Justina Nwodo, Marcel Kaiser, Reto Brun, Thomas J Schmidt
In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, "sleeping sickness"), we have investigated extracts from the leaves and bark of the West African Holarrhenaafricana (syn. Holarrhena floribunda; Apocynaceae). The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT). Bioactivity-guided chromatographic fractionation of the alkaloid-rich fractions resulted in the isolation of 17 steroid alkaloids, one nitrogen-free steroid and one alkaloid-like non-steroid...
July 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28673422/human-african-trypanosomiasis
#16
REVIEW
Philippe Büscher, Giuliano Cecchi, Vincent Jamonneau, Gerardo Priotto
Human African trypanosomiasis (sleeping sickness) is a parasitic infection that almost invariably progresses to death unless treated. Human African trypanosomiasis caused devastating epidemics during the 20th century. Thanks to sustained and coordinated efforts over the past 15 years, the number of reported cases has fallen to an historically low level. Fewer than 3000 cases were reported in 2015, and the disease is targeted for elimination by WHO. Despite these recent successes, the disease is still endemic in parts of sub-Saharan Africa, where it is a considerable burden on rural communities, most notably in central Africa...
June 30, 2017: Lancet
https://www.readbyqxmd.com/read/28673370/preface-glasgow-encounters-with-tropical-diseases
#17
Francis E G Cox
The period 1875-1925 was remarkable in the history of parasitology mainly for the elucidation of the life cycles of parasites causing important parasitic diseases and the incrimination of vectors in their transmission. These discoveries were made by a small number of scientists working in the tropics a number of whom were Scots. Sir Patrick Manson, the discoverer of the mosquito transmission of filarial worms, was instrumental in directly or indirectly encouraging other Scots including Douglas Argyll-Robertson, David Blacklock, David Bruce, David Cunningham, Robert Leiper, William Leishman, George Low, Muriel Robertson and Ronald Ross, who all made significant discoveries across a wide spectrum of tropical diseases...
July 4, 2017: Parasitology
https://www.readbyqxmd.com/read/28671870/the-double-edged-sword-of-evolution
#18
Etty Kruzel-Davila, Karl Skorecki
Two gene variants provide different levels of protection against sleeping sickness, but this comes with an increased risk of developing chronic kidney disease.
July 3, 2017: ELife
https://www.readbyqxmd.com/read/28668681/targeting-the-active-sites-of-malarial-proteases-for-antimalarial-drug-discovery-approaches-progress-and-challenges
#19
REVIEW
Kuldeep K Roy
Malaria is an infectious disease causing huge mortality and morbidity worldwide. Although antimalarial drugs are effective in several parts of the world, there is a serious threat to malaria control that malaria parasites are continuously developing widespread resistance against currently available antimalarial drugs, including artemisinin. Such widespread antimalarial drug resistance certifies the need of improving the efficacy of existing or new drugs, and developing alternative treatments through the identification of novel drug targets and development of candidate drugs...
June 28, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28642005/expression-purification-and-crystallization-of-type-1-isocitrate-dehydrogenase-from-trypanosoma-brucei-brucei
#20
Xinying Wang, Daniel Ken Inaoka, Tomoo Shiba, Emmanuel Oluwadare Balogun, Stefan Allmann, Yoh-Ichi Watanabe, Michael Boshart, Kiyoshi Kita, Shigeharu Harada
Isocitrate dehydrogenases (IDHs) are metabolic enzymes that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate. Depending on the electron acceptor and subcellular localization, these enzymes are classified as NADP(+)-dependent IDH1 in the cytosol or peroxisomes, NADP(+)-dependent IDH2 and NAD(+)-dependent IDH3 in mitochondria. Trypanosoma brucei is a protozoan parasite that causes African sleeping sickness in humans and Nagana disease in animals. Here, for the first time, a putative glycosomal T...
October 2017: Protein Expression and Purification
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