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Nidhi Singh, Priyanka Shah, Hemlata Dwivedi, Shikha Mishra, Renu Tripathi, Amogh A Sahasrabuddhe, Mohammad Imran Siddiqi
N-Myristoyltransferase (NMT) catalyzes the transfer of myristate to the amino-terminal glycine of a subset of proteins, a co-translational modification involved in trafficking substrate proteins to membrane locations, stabilization and protein-protein interactions. It is a studied and validated pre-clinical drug target for fungal and parasitic infections. In the present study, a machine learning approach, docking studies and CoMFA analysis have been integrated with the objective of translation of knowledge into a pipelined workflow towards the identification of putative hits through the screening of large compound libraries...
October 21, 2016: Molecular BioSystems
Nurkhalida Kamal, Christina V Viegelmann, Carol J Clements, RuAngelie Edrada-Ebel
Fungal endophytes offer diverse and unique secondary metabolites, making these organisms potential sources of promising drug leads. The application of high-resolution-liquid chromatography mass spectrometry and nuclear magnetic resonance-based metabolomics to fungal endophytes is practical in terms of dereplication studies and the mining of bioactive compounds. In this paper, we report the application of metabolomics in parallel with anti-trypanosomal assays to determine the ideal conditions for the medium-scale fermentation of the endophyte Lasiodiplodia theobromae...
October 19, 2016: Planta Medica
Sebastian Hutchinson, Lucy Glover, David Horn
BACKGROUND: African trypanosomes cause lethal diseases in humans and animals and escape host immune attack by switching the expression of Variant Surface Glycoprotein (VSG) genes. The expressed VSGs are located at the ends of telomeric, polycistronic transcription units known as VSG expression sites (VSG-ESs). Each cell has many VSG-ESs but only one is transcribed in bloodstream-form parasites and all of them are inactive upon transmission to the insect vector mid-gut; a subset of monocistronic metacyclic VSG-ESs are then activated in the insect salivary gland...
October 18, 2016: BMC Genomics
Atchara Phumee, Apiwat Tawatsin, Usavadee Thavara, Theerakamol Pengsakul, Suwich Thammapalo, Jérôme Depaquit, Frédérick Gay, Padet Siriyasatien
Although female sand flies are best known as the vectors of Leishmania parasites and viruses, several previous reports have demonstrated that these insects can also act as vectors for the trypanosomes of bats, lizards, and snakes. In this report, we created an inventory of Phlebotomine sand flies from southern Thailand. A novel trypanosome was found in a specimen of Phlebotomus stantoni, and two sand fly species newly recorded in the country, Sergentomyia khawi and Sergentomyia hivernus, were described. PCR primer pairs specific for the internal transcribed spacer 1 (ITS1) and the small subunit ribosomal DNA (SSU rDNA) gene of trypanosomatids were used to demonstrate the presence of the parasite in the sand fly...
October 15, 2016: Journal of Medical Entomology
Aitor Casas-Sánchez, Álvaro Acosta-Serrano
Trypanosome parasites are hiding in human skin, a discovery that may undermine efforts to eliminate sleeping sickness by 2020.
October 14, 2016: ELife
Stefan Mogk, Christian M Boßelmann, Celestin N Mudogo, Jasmin Stein, Hartwig Wolburg, Michael Duszenko
African trypanosomes induce sleeping sickness. The parasites are transmitted during the blood meal of a tsetse fly and appear primarily in blood and lymph vessels, before they enter the central nervous system. During the latter stage, trypanosomes induce a deregulation of sleep-wake cycles and some additional neurological disorders. Historically, it was assumed that trypanosomes cross the blood-brain barrier and settle somewhere between the brain cells. The brain, however, is a strictly controlled and immune-privileged area that is completely surrounded by a dense barrier that covers the blood vessels: this is the blood-brain barrier...
October 14, 2016: Biological Reviews of the Cambridge Philosophical Society
Cher-Pheng Ooi, Sarah Schuster, Christelle Cren-Travaillé, Eloise Bertiaux, Alain Cosson, Sophie Goyard, Sylvie Perrot, Brice Rotureau
Trypanosoma vivax is the most prevalent trypanosome species in African cattle. It is thought to be transmitted by tsetse flies after cyclical development restricted to the vector mouthparts. Here, we investigated the kinetics of T. vivax development in Glossina morsitans morsitans by serial dissections over 1 week to reveal differentiation and proliferation stages. After 3 days, stable numbers of attached epimastigotes were seen proliferating by symmetric division in the cibarium and proboscis, consistent with colonization and maintenance of a parasite population for the remaining lifespan of the tsetse fly...
2016: Frontiers in Cellular and Infection Microbiology
Monica Rodríguez-Bolaños, Nallely Cabrera, Ruy Perez-Montfort
The reactivation of triosephosphate isomerase (TIM) from unfolded monomers induced by guanidine hydrochloride involves different amino acids of its sequence in different stages of protein refolding. We describe a systematic mutagenesis method to find critical residues for certain physico-chemical properties of a protein. The two similar TIMs of Trypanosoma brucei and Trypanosoma cruzi have different reactivation velocities and efficiencies. We used a small number of chimeric enzymes, additive mutants and planned site-directed mutants to produce an enzyme from T...
October 2016: Open Biology
Manuel Saldivia, Gloria Ceballos-Pérez, Jean-Mathieu Bart, Miguel Navarro
During infection in mammals, the protozoan parasite Trypanosoma brucei transforms from a proliferative bloodstream form to a quiescent form that is pre-adapted to host transition. AMP analogs are known to induce quiescence and also inhibit TbTOR4. To examine the role of AMP-activated kinase (AMPK) in the regulation of this developmental transition, we characterized trypanosome TbAMPK complexes. Expression of a constitutively active AMPKα1 induces quiescence of the infective form, and TbAMPKα1 phosphorylation occurs during differentiation of wild-type pleomorphic trypanosomes to the quiescent stumpy form in vivo...
October 11, 2016: Cell Reports
Jan Hubert, Martina Bicianova, Ondrej Ledvinka, Martin Kamler, Philip J Lester, Marta Nesvorna, Jan Kopecky, Tomas Erban
The honey bee, Apis mellifera, is a globally important species that suffers from a variety of pathogens and parasites. These parasites and pathogens may have sublethal effects on their bee hosts via an array of mechanisms, including through a change in symbiotic bacterial taxa. Our aim was to assess the influence of four globally widespread parasites and pathogens on the honey bee bacteriome. We examined the effects of the ectoparasitic mite Varroa destructor, the fungal pathogens Nosema apis and Nosema ceranae, and the trypanosome Lotmaria passim...
October 11, 2016: Microbial Ecology
Tom G Schwan, Job E Lopez, David Safronetz, Jennifer M Anderson, Robert J Fischer, Ousmane Maïga, Nafomon Sogoba
BACKGROUND: Fleas are obligate blood-feeding ectoparasites and vectors of several bacterial zoonotic pathogens as well as trypanosomes that parasitize rodents and other small mammals. During investigations of tick- and rodent-borne diseases in Mali, West Africa, we included fleas and rodent-borne trypanosomes, both of which are poorly known in this country, but are attracting greater public health interest. METHODS: Small mammals were captured in 20 Malian villages from December 2007 to October 2011...
October 11, 2016: Parasites & Vectors
Sanofar Abdeen, Nilshad Salim, Najiba Mammadova, Corey M Summers, Karen Goldsmith-Pestana, Diane McMahon-Pratt, Peter G Schultz, Arthur L Horwich, Eli Chapman, Steven M Johnson
Trypanosoma brucei are protozoan parasites that cause African sleeping sickness in humans (also known as Human African Trypanosomiasis-HAT). Without treatment, T. brucei infections are fatal. There is an urgent need for new therapeutic strategies as current drugs are toxic, have complex treatment regimens, and are becoming less effective owing to rising antibiotic resistance in parasites. We hypothesize that targeting the HSP60/10 chaperonin systems in T. brucei is a viable anti-trypanosomal strategy as parasites rely on these stress response elements for their development and survival...
September 22, 2016: Bioorganic & Medicinal Chemistry Letters
Federica Giordani, Liam J Morrison, Tim G Rowan, Harry P DE Koning, Michael P Barrett
Pathogenic animal trypanosomes affecting livestock have represented a major constraint to agricultural development in Africa for centuries, and their negative economic impact is increasing in South America and Asia. Chemotherapy and chemoprophylaxis represent the main means of control. However, research into new trypanocides has remained inadequate for decades, leading to a situation where the few compounds available are losing efficacy due to the emergence of drug-resistant parasites. In this review, we provide a comprehensive overview of the current options available for the treatment and prophylaxis of the animal trypanosomiases, with a special focus on the problem of resistance...
October 10, 2016: Parasitology
Ruslan Aphasizhev, Takuma Suematsu, Liye Zhang, Inna Aphasizheva
RNA uridylation is a significant transcriptome-shaping factor in protists, fungi, metazoans, and plants. The 3' U-additions are catalyzed by terminal uridyltransferases (TUTases), a diverse group of enzymes that along with non-canonical poly(A) polymerases form a distinct group in the superfamily of DNA polymerase β-like nucleotidyl transferases. Within and across studied organisms and subcellular compartments, TUTases differ in nucleotide triphosphate selectivity, interacting partners, and RNA targets. A general premise linking RNA uridylation to 3'-5' degradation received support from several studies of small RNAs and mRNA turnover...
October 7, 2016: RNA Biology
Simon Dewar, Natasha Sienkiewicz, Han B Ong, Richard J Wall, David Horn, Alan H Fairlamb
The aim of this study was to identify and characterise mechanisms of resistance to antifolate drugs in African trypanosomes. Genome-wide RNAi library screens were undertaken in bloodstream form Trypanosoma brucei exposed to the antifolates methotrexate and raltitrexed. RNAi knockdown, in conjunction with drug susceptibly and folate transport studies, were used to validate the functions of the putative folate transporters. The transport kinetics of folate and methotrexate were further characterised in whole cells...
October 4, 2016: Journal of Biological Chemistry
P Krishnamoorthy, P P Sengupta, Sangita Das, M Ligi, B R Shome, H Rahman
Aim of the present study was to assess the cytokine gene expression in liver, kidney and spleen and histopathological changes in mice infected with buffalo and dog isolates of Trypanosoma evansi. Forty-four Swiss albino mice was divided into eleven groups of four mice each and injected subcutaneously with 1 × 10(5) trypanosomes of buffalo and dog isolate to twenty mice each, four mice served as control. Mice were examined for clinical signs, blood smear for trypanosome counts. Blood for PCR, liver, kidney, spleen, heart, lung, testis and abdominal muscle for histopathology and liver, kidney, spleen for cytokine gene expression studies, were collected...
October 1, 2016: Experimental Parasitology
Geraldine Bossard, Pascal Grébaut, Sophie Thévenon, Martial Séveno, David Berthier, Philippe Holzmuller
Trypanosomes are bloodstream protozoan parasites, which are pathogens of veterinary and medical importance. Several mammalian species, including humans, can be infected by different species of the genus Trypanosoma (T. congolense, T. evansi, T. brucei, T. vivax) exhibiting more or less virulent and pathogenic phenotypes. A previous screening of the excreted-secreted proteins of T. congolense demonstrated an overexpression of several proteins correlated with the virulence and pathogenicity of the strain. Of these proteins, calreticulin (CRT) has shown differential expression between two T...
September 26, 2016: Infection, Genetics and Evolution
Yan-Zi Wen, Bi-Xiu Su, Shu-Shen Lyu, Geoff Hide, Zhao-Rong Lun, De-Hua Lai
Trehalose, a non-permeating cryoprotective agent (CPA), has been documented as less toxic and highly efficient at cryopreserving different kinds of cells or organisms. In the present study, trehalose was evaluated for its application in cryopreservation of both Trypanosoma brucei procyclic and bloodstream form cells. The cryopreservation efficiency was determined by the motility of trypanosomes after thawing, as well as a subsequent recovery and infectivity assessment. The viability of trypanosomes from cultivation that were frozen in a serial concentrations of trehalose showed similar results to classical CPAs of glycerol and DMSO...
September 27, 2016: Acta Tropica
Sébastien Brosson, Frédéric Fontaine, Marjorie Vermeersch, David Perez-Morga, Etienne Pays, Sabrina Bousbata, Didier Salmon
Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. This parasite undergoes a complex life cycle alternating between non-proliferative and dividing forms. Owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity. This activity is mainly restricted to the cytostome, by which the cargo is taken up and sorted through the endosomal vesicular network to be delivered to reservosomes, the final lysosomal-like compartments...
2016: PloS One
Soumaïla Pagabeleguem, Sophie Ravel, Ahmadou H Dicko, Marc J B Vreysen, Andrew Parker, Peter Takac, Karine Huber, Issa Sidibé, Geoffrey Gimonneau, Jérémy Bouyer
BACKGROUND: Tsetse flies occur in much of sub-Saharan Africa where they are vectors of trypanosomes that cause human and animal African trypanosomosis. The sterile insect technique (SIT) is currently used to eliminate tsetse fly populations in an area-wide integrated pest management (AW-IPM) context in Senegal and Ethiopia. Three Glossina palpalis gambiensis strains [originating from Burkina Faso (BKF), Senegal (SEN) and an introgressed strain (SENbkf)] were established and are now available for use in future AW-IPM programmes against trypanosomes in West Africa...
September 29, 2016: Parasites & Vectors
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