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https://www.readbyqxmd.com/read/28637278/functional-and-structural-analysis-of-at-specific-minor-groove-binders-that-disrupt-dna-protein-interactions-and-cause-disintegration-of-the-trypanosoma-brucei-kinetoplast
#1
Cinthia R Millan, Francisco J Acosta-Reyes, Laura Lagartera, Godwin U Ebiloma, Leandro Lemgruber, J Jonathan Nué Martínez, Núria Saperas, Christophe Dardonville, Harry P de Koning, J Lourdes Campos
Trypanosoma brucei, the causative agent of sleeping sickness (Human African Trypanosomiasis, HAT), contains a kinetoplast with the mitochondrial DNA (kDNA), comprising of >70% AT base pairs. This has prompted studies of drugs interacting with AT-rich DNA, such as the N-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide dihydrochloride] and 2 [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2-yl)amino)benzamide] as potential drugs for HAT...
June 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28636879/delineating-neuroinflammation-parasite-cns-invasion-and-blood-brain-barrier-dysfunction-in-an-experimental-murine-model-of-human-african-trypanosomiasis
#2
Jean Rodgers, Barbara Bradley, Peter G E Kennedy
Although Trypanosoma brucei spp. was first detected by Aldo Castellani in CSF samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the CNS. In this investigation, we have applied contrast-enhance magnetic resonance imaging (MRI) to study the effects of trypanosome infection on the blood-brain barrier (BBB) in the well-established GVR35 mouse model of sleeping sickness...
June 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28636751/using-experimentation-to-understand-the-10-year-snowshoe-hare-cycle-in-the-boreal-forest-of-north-america
#3
C J Krebs, R Boonstra, S Boutin
Population cycles have long fascinated ecologists from the time of Charles Elton in the 1920s. The discovery of large population fluctuations in undisturbed ecosystems challenged the idea that pristine nature was in a state of balance. The 10-year cycle of snowshoe hares (Lepus americanus Erxleben) across the boreal forests of Canada and Alaska is a classic cycle, recognized by fur traders for more than 300 years. Since the 1930s ecologists have investigated the mechanisms that might cause these cycles. Proposed causal mechanisms have varied from sunspots to food supplies, parasites, diseases, predation, and social behaviour...
June 21, 2017: Journal of Animal Ecology
https://www.readbyqxmd.com/read/28636672/metabolomic-profile-and-nucleoside-composition-of-cordyceps-nidus-sp-nov-cordycipitaceae-a-new-source-of-active-compounds
#4
Juan Chiriví, Giovanna Danies, Rocio Sierra, Nicolas Schauer, Sandra Trenkamp, Silvia Restrepo, Tatiana Sanjuan
Cordyceps sensu lato is a genus of arthropod-pathogenic fungi, which have been used traditionally as medicinal in Asia. Within the genus, Ophiocordyceps sinensis is the most coveted and expensive species in China. Nevertheless, harvesting wild specimens has become a challenge given that natural populations of the fungus are decreasing and because large-scale culture of it has not yet been achieved. The worldwide demand for products derived from cultivable fungal species with medicinal properties has increased recently...
2017: PloS One
https://www.readbyqxmd.com/read/28636632/parasitoid-wasp-usurps-its-host-to-guard-its-pupa-against-hyperparasitoids-and-induces-rapid-behavioral-changes-in-the-parasitized-host
#5
Prabitha Mohan, Palatty Allesh Sinu
Some parasites have an ability to fabricate the behavior of their host and impel the host to guard parasites' offspring, which is popularly called as bodyguard manipulation. Psalis pennatula larva parasitized by a braconid parasitoid wasp Microplitis pennatula exhibits some behavioral changes including the guarding of the parasitoid pupa from its natural enemies. We hypothesized that these behavioral change exhibited by the parasitized host larva are induced by the parasitoid and can be considered as an example of bodyguard manipulation...
2017: PloS One
https://www.readbyqxmd.com/read/28635957/itk-signalling-via-the-ras-irf4-pathway-regulates-the-development-and-function-of-tr1-cells
#6
Weishan Huang, Sabrina Solouki, Nicholas Koylass, Song-Guo Zheng, Avery August
Type 1 regulatory T (Tr1) cells differentiate in response to signals engaging the T cell receptor (TCR), express high levels of the immunosuppressive cytokine IL-10, but not Foxp3, and can suppress inflammation and promote immune tolerance. Here we show that ITK, an important modulator of TCR signalling, is required for the TCR-induced development of Tr1 cells in various organs, and in the mucosal system during parasitic and viral infections. ITK kinase activity is required for mouse and human Tr1 cell differentiation...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635544/heparin-new-life-for-an-old-drug
#7
Carlos Raúl Aláez-Versón, Elena Lantero, Xavier Fernàndez-Busquets
Heparin is one of the oldest drugs, which nevertheless remains in widespread clinical use as an inhibitor of blood coagulation. The history of its identification a century ago unfolded amid one of the most fascinating scientific controversies turning around the distribution of credit for its discovery. The composition, purification and structure-function relationship of this naturally occurring glycosaminoglycan regarding its classical role as anticoagulant will be dealt with before proceeding to discuss its therapeutic potential in, among other, inflammatory and infectious disease, cancer treatment, cystic fibrosis and Alzheimer's disease...
June 21, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28635366/redox-biology-of-leishmania-and-macrophage-targeted-nanoparticles-for-therapy
#8
Hafiz Shoaib Sarwar, Sohail Akhtar, Muhammad Farhan Sohail, Zaeema Naveed, Muhammad Rafay, Akhtar Nadhman, Masoom Yasinzai, Gul Shahnaz
Intramacrophage parasite 'Leishmania' has developed various mechanisms for proficient uptake into macrophages and phagosome regulation to avoid macrophage's oxidative burst induced by peroxide, hydroxyl radical, hypochlorous acid and peroxynitrite production. One major barrier for impairing the accession of old fashioned anti-Leishmanial drugs is intrinsic incapability to pass through cell membranes and limiting their abilities to ultimately destroy intracellular pathogens. Receptor-mediated targeted drug delivery to the macrophages by using nanoparticles emerges as promising strategy to improve therapeutic efficacy of old-fashioned drug...
June 21, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28635296/benzoxaborole-antimalarial-agents-part-5-lead-optimization-of-novel-amide-pyrazinyloxy-benzoxaboroles-and-identification-of-a-preclinical-candidate
#9
Yong-Kang Zhang, Jacob J Plattner, Eric E Easom, Robert Toms Jacobs, Denghui Guo, Yvonne R Freund, Pamela Berry, Vic Ciaravino, John C L Erve, Philip J Rosenthal, Brice Campo, Francisco-Javier Gamo, Laura M Sanz, Jianxin Cao
Carboxamide pyrazinyloxy benzoxaboroles were investigated with the goal to identify a molecule with satisfactory antimalarial activity, physicochemical properties, pharmacokinetic profile, in vivo efficacy, and safety profile. This optimization effort discovered 46, which met our target candidate profile. Compound 46 had excellent activity against cultured Plasmodium falciparum, and in vivo against P. falciparum and P. berghei in infected mice. It exhibited good PK properties in mouse, rat and dog. It was highly active against other eleven P...
June 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28634775/hydrophilic-acylated-surface-protein-a-haspa-of-leishmania-donovani-expression-purification-and-biophysico-chemical-characterization
#10
Manoj Kumar, Kishu Ranjan, Vijay Singh, Chandramani Pathak, Anju Pappachan, Desh Deepak Singh
Hydrophilic acylated surface proteins (HASPs) are acidic surface proteins which get localized on the surface of Leishmania parasite during infective stages through a "non-classical" pathway. In this study, we report the heterologous expression and purification of Leishmania donovani HASPA (r-LdHASPA) in E. coli system and its partial characterization. The structural aspects of the purified protein were analyzed using CD spectroscopy and modeling studies which indicate that r-LdHASPA consists of random coils...
June 21, 2017: Protein Journal
https://www.readbyqxmd.com/read/28634639/the-curious-case-of-achromobacter-eurydice-a-gram-variable-pleomorphic-bacterium-associated-with-european-foulbrood-disease-in-honeybees
#11
REVIEW
Silvio Erler, Oleg Lewkowski, Anja Poehlein, Eva Forsgren
Honeybees are prone to parasite and pathogen infestations/infections due to their social colony life. Bacterial pathogens in particular lead to destructive infections of the brood. European foulbrood is caused by the bacterium Melissococcus plutonius in combination with several other Gram-positive bacteria (Achromobacter eurydice, Bacillus pumilus, Brevibacillus laterosporus, Enterococcus faecalis, Paenibacillus alvei, Paenibacillus dendritiformis) involved as secondary invaders following the initial infection...
June 21, 2017: Microbial Ecology
https://www.readbyqxmd.com/read/28634476/changes-in-n-p-supply-ratios-affect-the-ecological-stoichiometry-of-a-toxic-cyanobacterium-and-its-fungal-parasite
#12
Thijs Frenken, Joren Wierenga, Alena S Gsell, Ellen van Donk, Thomas Rohrlack, Dedmer B Van de Waal
Human activities have dramatically altered nutrient fluxes from the landscape into receiving waters. As a result, not only the concentration of nutrients in surface waters has increased, but also their elemental ratios have changed. Such shifts in resource supply ratios will alter autotroph stoichiometry, which may in turn have consequences for higher trophic levels, including parasites. Here, we hypothesize that parasite elemental composition will follow changes in the stoichiometry of its host, and that its reproductive success will decrease with host nutrient limitation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28634407/analysis-of-survival-and-hatching-transcriptomes-from-potato-cyst-nematodes-globodera-rostochiensis-and-g-pallida
#13
Marc-Olivier Duceppe, Joël Lafond-Lapalme, Juan Emilio Palomares-Rius, Michaël Sabeh, Vivian Blok, Peter Moffett, Benjamin Mimee
Potato cyst nematodes (PCNs), Globodera rostochiensis and G. pallida, cause important economic losses. They are hard to manage because of their ability to remain dormant in soil for many years. Although general knowledge about these plant parasitic nematodes has considerably increased over the past decades, very little is known about molecular events involved in cyst dormancy and hatching, two key steps of their development. Here, we have studied the progression of PCN transcriptomes from dry cysts to hatched juveniles using RNA-Seq...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634394/the-roles-of-toll-like-receptor-4-in-the-pathogenesis-of-pathogen-associated-biliary-fibrosis-caused-by-clonorchis-sinensis
#14
Chao Yan, Bo Li, Fang Fan, Ying Du, Rui Ma, Xiao-Dan Cheng, Xiang-Yang Li, Bo Zhang, Qian Yu, Yu-Gang Wang, Ren-Xian Tang, Kui-Yang Zheng
Pathogen-associated biliary fibrosis (PABF) is a type of liver fibrosis characterized by injuries of cholangiocytes and extra cellular matrix (ECM) deposition around bile ducts caused by various bacteria, fungi, virus and parasites. Recent studies show that TLR4 plays an important role in several other types of liver fibrosis, but the mechanism of TLR4 in PABF is yet really unclear. In the present study, a PABF mouse model was established by a trematode infection-Clonorchis sinensis which dwells in the bile ducts and causes severe biliary fibrosis of mice...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634388/mito-xenophagic-killing-of-bacteria-is-coordinated-by-a-metabolic-switch-in-dendritic-cells
#15
Nadine Radomski, Danny Kägebein, Elisabeth Liebler-Tenorio, Axel Karger, Elke Rufer, Birke Andrea Tews, Stefanie Nagel, Rebekka Einenkel, Anne Müller, Annica Rebbig, Michael R Knittler
Chlamydiae are bacterial pathogens that grow in vacuolar inclusions. Dendritic cells (DCs) disintegrate these compartments, thereby eliminating the microbes, through auto/xenophagy, which also promotes chlamydial antigen presentation via MHC I. Here, we show that TNF-α controls this pathway by driving cytosolic phospholipase (cPLA)2-mediated arachidonic acid (AA) production. AA then impairs mitochondrial function, which disturbs the development and integrity of these energy-dependent parasitic inclusions, while a simultaneous metabolic switch towards aerobic glycolysis promotes DC survival...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634346/generating-conditional-gene-knockouts-in-plasmodium-a-toolkit-to-produce-stable-dicre-recombinase-expressing-parasite-lines-using-crispr-cas9
#16
Ellen Knuepfer, Marta Napiorkowska, Christiaan van Ooij, Anthony A Holder
Successful establishment of CRISPR/Cas9 genome editing technology in Plasmodium spp. has provided a powerful tool to transform Plasmodium falciparum into a genetically more tractable organism. Conditional gene regulation approaches are required to study the function of gene products critical for growth and erythrocyte invasion of blood stage parasites. Here we employ CRISPR/Cas9 to facilitate use of the dimerisable Cre-recombinase (DiCre) that is frequently used to mediate the excision and loss of loxP-flanked DNA sequences in a rapamycin controlled manner...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634183/syk-inhibitors-interfere-with-erythrocyte-membrane-modification-during-p-falciparum-growth-and-suppress-parasite-egress
#17
Antonella Pantaleo, Kristina R Kesely, Maria Carmina Pau, Ioannis Tsamesidis, Evelin Schwarzer, Oleksii A Skorokhod, Huynh D Chien, Marta Ponzi, Lucia Bertuccini, Philip S Low, Francesco M Turrini
Band 3 (a.k.a. the anion exchanger, SLCA1, AE1) constitutes the major attachment site of the spectrin-based cytoskeleton to the erythrocyte's lipid bilayer and thereby contributes critically to the stability of the red cell membrane. During the intra-erythrocytic stage of Plasmodium falciparum's life cycle, band 3 becomes tyrosine phosphorylated in response to oxidative stress, leading to a decrease in its affinity for the spectrin/actin cytoskeleton and causing global membrane destabilization. Because this membrane weakening is hypothesized to facilitate parasite egress and the consequent dissemination of released merozoites throughout the bloodstream, we decided to explore which tyrosine kinase inhibitors might block the kinase-induced membrane destabilization...
June 20, 2017: Blood
https://www.readbyqxmd.com/read/28634143/pcr-based-verification-of-positive-rapid-diagnostic-tests-for-intestinal-protozoa-infections-with-variable-test-band-intensity
#18
Sören L Becker, Ivan Müller, Pascal Mertens, Mathias Herrmann, Leyli Zondie, Lindsey Beyleveld, Markus Gerber, Rosa du Randt, Uwe Pühse, Cheryl Walter, Jürg Utzinger
Stool-based rapid diagnostic tests (RDTs) for pathogenic intestinal protozoa (e.g. Cryptosporidium spp. and Giardia intestinalis) allow for prompt diagnosis and treatment in resource-constrained settings. Such RDTs can improve individual patient management and facilitate population-based screening programmes in areas without microbiological laboratories for confirmatory testing. However, RDTs are difficult to interpret in case of 'trace' results with faint test band intensities and little is known about whether such ambiguous results might indicate 'true' infections...
June 17, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28634105/genetic-diversity-in-the-c-terminus-of-merozoite-surface-protein-1-among-plasmodium-knowlesi-isolates-from-selangor-and-sabah-borneo-malaysia
#19
Nan Jiun Yap, Xiang Ting Goh, Anson V Koehler, Timothy William, Tsin Wen Yeo, Indra Vythilingam, Robin B Gasser, Yvonne A L Lim
Plasmodium knowlesi, a malaria parasite of macaques, has emerged as an important parasite of humans. Despite the significance of P. knowlesi malaria in parts of Southeast Asia, very little is known about the genetic variation in this parasite. Our aim here was to explore sequence variation in a molecule called the 42kDa merozoite surface protein-1 (MSP-1), which is found on the surface of blood stages of Plasmodium spp. and plays a key role in erythrocyte invasion. Several studies of P. falciparum have reported that the C-terminus (a 42kDa fragment) of merozoite surface protein-1 (MSP-142; consisting of MSP-119 and MSP-133) is a potential candidate for a malaria vaccine...
June 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28634009/the-fish-parasite-ichthyophthirius-multifiliis-host-immunology-vaccines-and-novel-treatments
#20
REVIEW
Louise von Gersdorff Jørgensen
Ichthyophthirius multifiliis, the causative agent of white spot disease (Ichthyophthiriasis) is a major burden for fish farmers and aquarists globally. The parasite infects the skin and the gills of freshwater fish, which may acquire a protective adaptive immune response against this disease, making vaccine strategies feasible. However, there is no prophylactic treatment available and repetitive treatments with auxiliary substances are needed to control the infection. Historically, a variety of drugs and chemicals have been used to combat the disease but due to changing regulations and recognition of carcinogenic and environmentally damaging effects the most efficient compounds are prohibited...
June 17, 2017: Fish & Shellfish Immunology
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