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https://www.readbyqxmd.com/read/28939533/comparative-mapping-of-on-targets-and-off-targets-for-the-discovery-of-anti-trypanosomatid-folate-pathway-inhibitors
#1
Joanna Panecka-Hofman, Ina Pöhner, Francesca Spyrakis, Talia Zeppelin, Flavio Di Pisa, Lucia Dello Iacono, Alessio Bonucci, Antonio Quotadamo, Alberto Venturelli, Stefano Mangani, Maria Paola Costi, Rebecca C Wade
BACKGROUND: Multi-target approaches are necessary to properly analyze or modify the function of a biochemical pathway or a protein family. An example of such a problem is the repurposing of the known human anti-cancer drugs, antifolates, as selective anti-parasitic agents. This requires considering a set of experimentally validated protein targets in the folate pathway of major pathogenic trypanosomatid parasites and humans: (i) the primary parasite on-targets: pteridine reductase 1 (PTR1) (absent in humans) and bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), (ii) the primary off-targets: human DHFR and TS, and (iii) the secondary on-target: human folate receptor β, a folate/antifolate transporter...
September 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28938257/childhood-visceral-leishmaniasis-distinctive-features-and-diagnosis-of-a-re-emerging-disease-an-11-year-experience-from-a-tertiary-referral-center-in-athens-greece
#2
Panagiotis Krepis, Adamantia Krepi, Ioanna Argyri, Anastasios Aggelis, Alexandra Soldatou, Maria Tsolia
BACKGROUND: Visceral leishmaniasis (VL) remains a public health issue in Greece. The aim of this study was to describe the clinical and epidemiological characteristics of pediatric VL in our region as well as to evaluate the laboratory findings and the diagnostic techniques that are applied. METHODS: We retrospectively reviewed the medical records of all children diagnosed with VL in an 11-year period at a tertiary public hospital in the region of Athens. Demographic features, clinical information and laboratory findings were accessed...
September 20, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28938082/pseudacteon-phorid-flies-host-specificity-and-impacts-on-solenopsis-fire-ants
#3
Li Chen, Henry Y Fadamiro
Human commerce has resulted in the spread of the imported fire ants, Solenopsis species, worldwide. Six species of parasitic Pseudacteon phorid flies that are highly host specific to the Solenopsis saevissima complex of Solenopsis fire ants have been successfully released in the southern United States. The presence of Pseudacteon phorid flies, in addition to having direct mortality effects on their host ants, modifies foraging behavior and disrupts interspecific competition between host species and other ant species in the community...
September 22, 2017: Annual Review of Entomology
https://www.readbyqxmd.com/read/28938014/intestinal-helminth-infection-drives-carcinogenesis-in-colitis-associated-colon-cancer
#4
Eva Pastille, Annika Frede, Henry J McSorley, Jessica Gräb, Alexandra Adamczyk, Sebastian Kollenda, Wiebke Hansen, Matthias Epple, Jan Buer, Rick M Maizels, Robert Klopfleisch, Astrid M Westendorf
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host's immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs). This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation...
September 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28938001/cell-cycle-stage-specific-transcriptional-activation-of-cyclins-mediated-by-hat2-dependant-h4k10-acetylation-of-promoters-in-leishmania-donovani
#5
Udita Chandra, Aarti Yadav, Devanand Kumar, Swati Saha
Chromatin modifications affect several processes. In investigating the Leishmania donovani histone acetyltransferase HAT2, using in vitro biochemical assays and HAT2-heterozygous genomic knockout we found the constitutively nuclear HAT2 acetylated histone H4K10 in vitro and in vivo. HAT2 was essential. HAT2-depleted cells displayed growth and cell cycle defects, and poor survival in host cells. Real time PCR and DNA microarray analyses, as well as rescue experiments, revealed that downregulation of cyclins CYC4 and CYC9 were responsible for S phase and G2/M defects of HAT2-depleted cells respectively...
September 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28937821/rethinking-conventional-wisdom-are-locally-adapted-parasites-ahead-in-the-coevolutionary-race
#6
Scott L Nuismer
The metaphors of the Red Queen and the arms race have inspired a large amount of research aimed at understanding the process of antagonistic coevolution between hosts and parasites. One approach that has been heavily used is to estimate the strength of parasite local adaptation using a reciprocal cross infection or transplant study. These studies frequently conclude that the locally adapted species is ahead in the coevolutionary race. Here, I use mathematical models to decompose parasite infectivity into components attributable to local versus global adaptation and to develop a robust index of which species is ahead in the coevolutionary race, which I term coevolutionary advantage...
October 2017: American Naturalist
https://www.readbyqxmd.com/read/28937594/molecular-tools-for-the-detection-and-the-identification-of-hymenoptera-parasitoids-in-tortricid-fruit-pests
#7
Pierre Franck, Mariline Maalouly-Matar, Jérôme Olivares
Biological control requires specific tools for the accurate detection and identification of natural enemies in order to estimate variations in their abundance and their impact according to changes in environmental conditions or agricultural practices. Here, we developed two molecular methods of detection based on PCR-RFLP with universal primers and on PCR with specific primers to identify commonly occurring larval parasitoids of the tortricid fruit pests and to estimate parasitism in the codling moth. Both methods were designed based on DNA sequences of the COI mitochondrial gene for a range of parasitoids that emerged from Cydia pomonella and Grapholitamolesta caterpillars (102 parasitoids; nine species) and a range of potential tortricid hosts (40 moths; five species) damaging fruits...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28936965/-important-role-of-interleukin-35-in-infectious-diseases-and-its-significance
#8
Renqi Yao, Yao Wu, Bing Ma
Infectious diseases are resulted from the invasion of an organism's body tissues by multiple disease-causing agents. It has been demonstrated that the occurrence and development of infectious diseases are closely associated with the functional status of immune system. Cytokines play significant roles in modulating the host immune response to the clearance of pathogenic microorganisms and maintaining immune homeostasis. Interleukin-35 (IL-35), as a newly identified member of IL-12 family, exerts suppressive effect on immune response by means of a specific pattern...
September 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28936796/biosurfactants-produced-by-bacillus-subtilis-a1-and-pseudomonas-stutzeri-na3-reduce-longevity-and-fecundity-of-anopheles-stephensi-and-show-high-toxicity-against-young-instars
#9
Punniyakotti Parthipan, Raja Kumaresan Sarankumar, Anitha Jaganathan, Pandian Amuthavalli, Ranganathan Babujanarthanam, Pattanathu K S M Rahman, Kadarkarai Murugan, Akon Higuchi, Giovanni Benelli, Aruliah Rajasekar
Anopheles stephensi acts as vector of Plasmodium parasites, which are responsible for malaria in tropical and subtropical areas worldwide. Currently, malaria management is a big challenge due to the presence of insecticide-resistant strains as well as to the development of Plasmodium species highly resistant to major antimalarial drugs. Therefore, the present study focused on biosurfactant produced by two bacteria Bacillus subtilis A1 and Pseudomonas stutzeri NA3, evaluating them for insecticidal applications against malaria mosquitoes...
September 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28936360/robust-antibody-and-cd8-t-cell-responses-induced-by-p-falciparum-csp-adsorbed-to-cationic-liposomal-adjuvant-caf09-confer-sterilizing-immunity-against-experimental-rodent-malaria-infection
#10
Diego A Espinosa, Dennis Christensen, Christian Muñoz, Sanjay Singh, Emily Locke, Peter Andersen, Fidel Zavala
Despite several decades of extensive research, the development of a highly efficacious malaria vaccine has yet to be accomplished. While the RTS,S malaria vaccine candidate shows the potential to prevent a substantial number of clinical malaria cases, significant improvements in protective efficacy are still needed. Multiple studies have shown that RTS,S induces protective antibody and CD4(+) T-cell responses, but limited or negligible CD8(+) T cells. In this study, we evaluated the immunogenicity and protective capacity of full-length recombinant P...
2017: NPJ Vaccines
https://www.readbyqxmd.com/read/28936226/challenges-in-modeling-complexity-of-neglected-tropical-diseases-a-review-of-dynamics-of-visceral-leishmaniasis-in-resource-limited-settings
#11
REVIEW
Swati DebRoy, Olivia Prosper, Austin Mishoe, Anuj Mubayi
OBJECTIVES: Neglected tropical diseases (NTD), account for a large proportion of the global disease burden, and their control faces several challenges including diminishing human and financial resources for those distressed from such diseases. Visceral leishmaniasis (VL), the second-largest parasitic killer (after malaria) and an NTD affects poor populations and causes considerable cost to the affected individuals. Mathematical models can serve as a critical and cost-effective tool for understanding VL dynamics, however, complex array of socio-economic factors affecting its dynamics need to be identified and appropriately incorporated within a dynamical modeling framework...
2017: Emerging Themes in Epidemiology
https://www.readbyqxmd.com/read/28936205/homologous-recombination-in-protozoan-parasites-and-recombinase-inhibitors
#12
REVIEW
Andrew A Kelso, Sarah M Waldvogel, Adam J Luthman, Michael G Sehorn
Homologous recombination (HR) is a DNA double-strand break (DSB) repair pathway that utilizes a homologous template to fully repair the damaged DNA. HR is critical to maintain genome stability and to ensure genetic diversity during meiosis. A specialized class of enzymes known as recombinases facilitate the exchange of genetic information between sister chromatids or homologous chromosomes with the help of numerous protein accessory factors. The majority of the HR machinery is highly conserved among eukaryotes...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28935948/novel-scaffolds-for-inhibition-of-cruzipain-identified-from-high-throughput-screening-of-anti-kinetoplastid-chemical-boxes
#13
Emir Salas-Sarduy, Lionel Urán Landaburu, Joel X Karpiak, Kevin P Madauss, Juan José Cazzulo, Fernán Agüero, Vanina Eder Alvarez
American Trypanosomiasis or Chagas disease is a prevalent, neglected and serious debilitating illness caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The current chemotherapy is limited only to nifurtimox and benznidazole, two drugs that have poor efficacy in the chronic phase and are rather toxic. In this scenario, more efficacious and safer drugs, preferentially acting through a different mechanism of action and directed against novel targets, are particularly welcome. Cruzipain, the main papain-like cysteine peptidase of T...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935919/split-dosing-of-artemisinins-does-not-improve-antimalarial-therapeutic-efficacy
#14
N J White, J Watson, E A Ashley
It has been suggested recently, based on pharmacokinetic-pharmacodynamic modelling exercises, that twice daily dosing of artemisinins increases malaria parasite killing and so could "dramatically enhance and restore drug effectiveness" in artemisinin resistant P. falciparum malaria infections. It was recommended that split dosing should be incorporated into all artemisinin combination regimen designs. To explain why parasite clearance rates were not faster with split dose regimens it was concluded that splenic malaria parasite clearance capacity was readily exceeded, resulting in the accumulation of dead parasites in the circulation, that parasite clearance was therefore an unreliable measure of drug efficacy, and instead that human immunity is the primary determinant of clearance rates...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935714/profiling-mhc-ii-immunopeptidome-of-blood-stage-malaria-reveals-that-cdc1-control-the-functionality-of-parasite-specific-cd4-t-cells
#15
Marion Draheim, Myriam F Wlodarczyk, Karine Crozat, Jean-Michel Saliou, Tchilabalo Dilezitoko Alayi, Stanislas Tomavo, Ali Hassan, Anna Salvioni, Claudia Demarta-Gatsi, John Sidney, Alessandro Sette, Marc Dalod, Antoine Berry, Olivier Silvie, Nicolas Blanchard
In malaria, CD4 Th1 and T follicular helper (TFH) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins...
September 21, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28935555/vaccination-with-a-dna-vaccine-encoding-toxoplasma-gondii-rop54-induces-protective-immunity-against-toxoplasmosis-in-mice
#16
Wen-Bin Yang, Dong-Hui Zhou, Yang Zou, Kai Chen, Qing Liu, Jin-Lei Wang, Xing-Quan Zhu, Guang-Hui Zhao
Toxoplasma gondii is an obligatory intracellular protozoan, which infects most of the warm-blooded animals, causing serious public health problems and enormous economic losses worldwide. The rhoptry effector protein 54 (ROP54) has been indicated as a virulence factor that promotes Toxoplasma infection by modulating GBP2 loading onto parasite-containing vacuoles, which can modulate some aspects of the host immune response. In order to evaluate the immuno-protective value of ROP54, we constructed a eukaryotic recombinant plasmid expressing T...
September 18, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28935552/natural-products-applied-against-hydatid-cyst-protoscolices-a-review-of-past-to-present
#17
REVIEW
Mohammad Hasan Kohansal Koshki, Abbasali Nourian, Mohammad Taghi Rahimi, Ahmad Daryani, Adel Spotin, Ehsan Ahmadpour
Echinococcus granulosus is the causative agent of cystic echinococcosis (CE), which is distributed all around the world. CE is one of the most important global parasitic infectious diseases, both in humans and animals. This parasite causes hydatid cysts that can be lodge at different organs of host such as liver, lung even in heart and brain which may lead to death. Presently, numerous scolicidal chemical agents have been administrated for inactivation of the hydatid cyst contents. Because of increasing resistance and adverse effects of medications include abnormalities of liver function, abdominal pain, diarrhea, nausea, vomiting, dizziness, and headache; there is a need to find alternative therapies either with the least or without side effects...
September 18, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28935551/anti-trypanosoma-anti-leishmania-and-cytotoxic-activities-of-natural-products-from-psidium-brownianum-mart-ex-dc-and-psidium-guajava-var-pomifera-analysed-by-lc-ms
#18
Celestina Elba Sobral de Souza, Ana Raquel Pereira da Silva, Maria Celeste Vega Gomez, Míriam Rolóm, Cathia Coronel, José Galberto Martins da Costa, Amanda K Sousa, Larissa A Rolim, Francisco Hugo Sobral de Souza, Henrique Douglas Melo Coutinho
Neglected diseases are those that are prevalent in developing countries, even with a rich biodiversity. These diseases still persist because of the lack of scientific studies, government negligence or failures of the public health system. This study aims to identify the composition of extracts and fractions from Psidium brownianum and Psidium guajava through LC-MS, to evaluate its in vitro anti-parasitic and cytotoxic activity against Trypanosoma cruzi, Leishmania brasiliensis and L. infantum epismastigote and promastigote forms, as well as mammalian cells...
September 19, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28935536/the-effect-of-iron-on-metronidazole-activity-against-trichomonas-vaginalis-in-vitro
#19
Hala Salah Elwakil, Rania Ayman Tawfik, Yosra Hussein Alam-Eldin, Doaa Ashraf Nassar
Metronidazole is administered in an inactive form then activated to its cytotoxic form within the hydrogenosome of trichomonads. Two hydrogenosomal proteins, pyruvate ferredoxin oxidoreductase (PFOR) and ferredoxin, play a critical role in the reductive activation of metronidazole. The expression of these proteins and other hydrogenosomal proteins are likewise positively regulated by iron. In the present study, the effect of iron on minimal lethal concentration (MLC) of metronidazole on in vitro cultured Trichomonas vaginalis(T...
September 18, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28935212/the-value-of-anticoccidials-for-sustainable-global-poultry-production
#20
REVIEW
Stefanie Kadykalo, Tara Roberts, Michelle Thompson, Jeff Wilson, Marcelo Lang, Olivier Espeisse
Coccidiosis is a self-limiting disease that is universally present in poultry operations, causing extensive damage to the intestinal lining of the bird. Global economic losses from coccidiosis are estimated to be $3 billion per year. In-feed anticoccidial use has been the predominant form of coccidiosis control. However, due to widespread emergence of antimicrobial resistance, concerns have been raised regarding the safety of anticoccidials and potential impact on human, animal, and environmental health. To investigate the alternatives, risks, and benefits to anticoccidial use, a comprehensive review of recent literature was conducted...
September 18, 2017: International Journal of Antimicrobial Agents
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