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https://www.readbyqxmd.com/read/28317157/design-and-synthesis-of-novel-anti-plasmodial-histone-deacetylase-inhibitors-containing-an-alkoxyamide-connecting-unit
#1
Leandro A Alves Avelar, Jana Held, Jessica A Engel, Parichat Sureechatchaiyan, Finn K Hansen, Alexandra Hamacher, Matthias U Kassack, Benjamin Mordmüller, Katherine T Andrews, Thomas Kurz
Despite recent declines in mortality, malaria remains an important global health problem. New therapies are needed, including new drugs with novel modes of action compared to existing agents. Among new potential therapeutic targets for malaria, inhibition of parasitic histone deacetylases (HDACs) is a promising approach. Homology modeling of PfHDAC1, a known target of some anti-plasmodial HDAC inhibitors, revealed a unique threonine residue at the rim of the active site in close proximity to the location of the cap group of vorinostat-type HDAC inhibitors...
March 20, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28314772/two-phylogenetically-and-compartmentally-distinct-cdp-diacylglycerol-synthases-cooperate-for-lipid-biogenesis-in-toxoplasma-gondii
#2
Pengfei Kong, Christoph-Martin Ufermann, Diana Lm Zimmermann, Qing Yin, Xun Suo, J Bernd Helms, Jos F Brouwers, Nishith Gupta
Toxoplasma gondii is among the most prevalent protozoan parasites, which infects a wide range of organisms including one-third of the human population. Its rapid intracellular replication within a vacuole requires efficient synthesis of glycerophospholipids. Cytidine diphosphate-diacylglycerol (CDP-DAG) serves as a major precursor for phospholipid synthesis. Given the peculiarities of lipid biogenesis, understanding the mechanism and physiological importance of CDP-DAG synthesis is particularly relevant in T...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28259146/conservation-of-estrogen-receptor-function-in-invertebrate-reproduction
#3
Brande L Jones, Chris Walker, Bahareh Azizi, Laren Tolbert, Loren Dean Williams, Terry W Snell
BACKGROUND: Rotifers are microscopic aquatic invertebrates that reproduce both sexually and asexually. Though rotifers are phylogenetically distant from humans, and have specialized reproductive physiology, this work identifies a surprising conservation in the control of reproduction between humans and rotifers through the estrogen receptor. Until recently, steroid signaling has been observed in only a few invertebrate taxa and its role in regulating invertebrate reproduction has not been clearly demonstrated...
March 4, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28249563/genome-wide-transcriptomics-of-aging-in-the-rotifer-brachionus-manjavacas-an-emerging-model-system
#4
Kristin E Gribble, David B Mark Welch
BACKGROUND: Understanding gene expression changes over lifespan in diverse animal species will lead to insights to conserved processes in the biology of aging and allow development of interventions to improve health. Rotifers are small aquatic invertebrates that have been used in aging studies for nearly 100 years and are now re-emerging as a modern model system. To provide a baseline to evaluate genetic responses to interventions that change health throughout lifespan and a framework for new hypotheses about the molecular genetic mechanisms of aging, we examined the transcriptome of an asexual female lineage of the rotifer Brachionus manjavacas at five life stages: eggs, neonates, and early-, late-, and post-reproductive adults...
March 1, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28196534/comparative-genomics-reveals-high-biological-diversity-and-specific-adaptations-in-the-industrially-and-medically-important-fungal-genus-aspergillus
#5
Ronald P de Vries, Robert Riley, Ad Wiebenga, Guillermo Aguilar-Osorio, Sotiris Amillis, Cristiane Akemi Uchima, Gregor Anderluh, Mojtaba Asadollahi, Marion Askin, Kerrie Barry, Evy Battaglia, Özgür Bayram, Tiziano Benocci, Susanna A Braus-Stromeyer, Camila Caldana, David Cánovas, Gustavo C Cerqueira, Fusheng Chen, Wanping Chen, Cindy Choi, Alicia Clum, Renato Augusto Corrêa Dos Santos, André Ricardo de Lima Damásio, George Diallinas, Tamás Emri, Erzsébet Fekete, Michel Flipphi, Susanne Freyberg, Antonia Gallo, Christos Gournas, Rob Habgood, Matthieu Hainaut, María Laura Harispe, Bernard Henrissat, Kristiina S Hildén, Ryan Hope, Abeer Hossain, Eugenia Karabika, Levente Karaffa, Zsolt Karányi, Nada Kraševec, Alan Kuo, Harald Kusch, Kurt LaButti, Ellen L Lagendijk, Alla Lapidus, Anthony Levasseur, Erika Lindquist, Anna Lipzen, Antonio F Logrieco, Andrew MacCabe, Miia R Mäkelä, Iran Malavazi, Petter Melin, Vera Meyer, Natalia Mielnichuk, Márton Miskei, Ákos P Molnár, Giuseppina Mulé, Chew Yee Ngan, Margarita Orejas, Erzsébet Orosz, Jean Paul Ouedraogo, Karin M Overkamp, Hee-Soo Park, Giancarlo Perrone, Francois Piumi, Peter J Punt, Arthur F J Ram, Ana Ramón, Stefan Rauscher, Eric Record, Diego Mauricio Riaño-Pachón, Vincent Robert, Julian Röhrig, Roberto Ruller, Asaf Salamov, Nadhira S Salih, Rob A Samson, Erzsébet Sándor, Manuel Sanguinetti, Tabea Schütze, Kristina Sepčić, Ekaterina Shelest, Gavin Sherlock, Vicky Sophianopoulou, Fabio M Squina, Hui Sun, Antonia Susca, Richard B Todd, Adrian Tsang, Shiela E Unkles, Nathalie van de Wiele, Diana van Rossen-Uffink, Juliana Velasco de Castro Oliveira, Tammi C Vesth, Jaap Visser, Jae-Hyuk Yu, Miaomiao Zhou, Mikael R Andersen, David B Archer, Scott E Baker, Isabelle Benoit, Axel A Brakhage, Gerhard H Braus, Reinhard Fischer, Jens C Frisvad, Gustavo H Goldman, Jos Houbraken, Berl Oakley, István Pócsi, Claudio Scazzocchio, Bernhard Seiboth, Patricia A vanKuyk, Jennifer Wortman, Paul S Dyer, Igor V Grigoriev
BACKGROUND: The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus. RESULTS: We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera...
February 14, 2017: Genome Biology
https://www.readbyqxmd.com/read/28195530/structural-basis-for-inhibition-of-erythrocyte-invasion-by-antibodies-to-plasmodium-falciparum-protein-cyrpa
#6
Lin Chen, Yibin Xu, Wilson Wong, Jennifer K Thompson, Julie Healer, Ethan D Goddard-Borger, Michael C Lawrence, Alan F Cowman
Plasmodium falciparum causes malaria in humans with over 450,000 deaths annually. The asexual blood stage involves invasion of erythrocytes by merozoites, in which they grow and divide to release daughter merozoites, which in turn invade new erythrocytes perpetuating the cycle responsible for malaria. A key step in merozoite invasion is the essential binding of PfRh5/CyRPA/PfRipr complex to basigin, a step linked to the formation of a pore between merozoites and erythrocytes. We show CyRPA interacts directly with PfRh5...
February 14, 2017: ELife
https://www.readbyqxmd.com/read/28195309/ploidy-tug-of-war-evolutionary-and-genetic-environments-influence-the-rate-of-ploidy-drive-in-a-human-fungal-pathogen
#7
Aleeza C Gerstein, Heekyung Lim, Judith Berman, Meleah A Hickman
Variation in baseline ploidy is seen throughout the tree of life, yet the factors that determine why one ploidy level is maintained over another remain poorly understood. Experimental evolution studies using asexual fungal microbes with manipulated ploidy levels intriguingly reveals a propensity to return to the historical baseline ploidy, a phenomenon that we term 'ploidy drive'. We evolved haploid, diploid, and polyploid strains of the human fungal pathogen Candida albicans under three different nutrient limitation environments to test whether these conditions, hypothesized to select for low ploidy levels, could counteract ploidy drive...
February 14, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28192727/ecotoxicological-assessments-show-sucralose-and-fluoxetine-affect-the-aquatic-plant-lemna-minor
#8
Cherisse Amy-Sagers, Keith Reinhardt, Danelle M Larson
Pharmaceuticals and personal care products (PPCP) are prevalent in aquatic systems, yet the fate and impacts on aquatic plants needs quantification for many compounds. We measured and detected sucralose (an artificial sweetener), fluoxetine (an antidepressant), and other PPCP in the Portneuf River in Idaho, USA, where Lemna minor (an aquatic plant in the environment and used in ecotoxicology studies) naturally occurs. Sucralose was hypothesized to negatively affect photosynthesis and growth of L. minor because sucralose is a chlorinated molecule that may be toxic or unusable for plant metabolism...
April 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28154481/diversity-of-marine-derived-aspergillus-from-tidal-mudflats-and-sea-sand-in-korea
#9
Seobihn Lee, Myung Soo Park, Young Woon Lim
Aspergillus (Trichocomaceae, Eurotiales, and Ascomycota) is a genus of well-defined asexual spore-forming fungi that produce valuable compounds such as secondary metabolites and enzymes; however, some species are also responsible for diseases in plants and animals, including humans. To date, 26 Aspergillus species have been reported in Korea, with most species located in terrestrial environments. In our study, Aspergillus species were isolated from mudflats and sea sand along the western and southern coasts of Korea...
December 2016: Mycobiology
https://www.readbyqxmd.com/read/28138844/haplotyping-a-non-meiotic-diploid-fungal-pathogen-using-induced-aneuploidies-and-snp-cgh-microarray-analysis
#10
Judith Berman, Anja Forche
The generation of haplotype information has recently become very attractive due to its utility for identifying mutations associated with human disease and for the development of personalized medicine. Haplotype information also is crucial for studying recombination mechanisms and genetic diversity, and for analyzing allele-specific gene expression. Classic haplotyping methods require the analysis of hundreds of meiotic progeny. To facilitate haplotyping in the non-meiotic human fungal pathogen Candida albicans, we exploited trisomic heterozygous chromosomes generated via the UAU1 selection strategy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28129569/investigating-the-antiplasmodial-activity-of-primary-sulfonamide-compounds-identified-in-open-source-malaria-data
#11
Gillian M Fisher, Silvia Bua, Sonia Del Prete, Megan S J Arnold, Clemente Capasso, Claudiu T Supuran, Katherine T Andrews, Sally-Ann Poulsen
In the past decade there has been a significant reduction in deaths due to malaria, in part due to the success of the gold standard antimalarial treatment - artemisinin combination therapies (ACTs). However the potential threat of ACT failure and the lack of a broadly effective malaria vaccine are driving efforts to discover new chemical entities (NCEs) to target this disease. The primary sulfonamide (PS) moiety is a component of several clinical drugs, including those for treatment of kidney disease, glaucoma and epilepsy, however this chemotype has not yet been exploited for malaria...
January 13, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28107502/rnai-based-functional-genomics-identifies-new-virulence-determinants-in-mucormycosis
#12
Trung Anh Trieu, María Isabel Navarro-Mendoza, Carlos Pérez-Arques, Marta Sanchis, Javier Capilla, Patricia Navarro-Rodriguez, Loida Lopez-Fernandez, Santiago Torres-Martínez, Victoriano Garre, Rosa María Ruiz-Vázquez, Francisco E Nicolás
Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28096162/impact-of-extended-artesunate-duration-on-parasitological-outcome-in-a-cytocidal-murine-malaria-model
#13
Leah A Walker, David J Sullivan
Artemisinin-based combination therapies are a key pillar in global malaria control and are recommended as a first-line Plasmodium falciparum treatment. They rely upon a rapid, 4-log reduction in parasitemia by artemisinin compounds with a short half-life and the killing of remaining parasites by a partner compound with a longer half-life. Current treatment guidelines stipulate giving three 24 hour interval doses or six 12 hour interval doses over a 3-day period. Due to the short half-life of artesunate and artemether, almost all of the resulting cytocidal activity is confined within a single 48 hour asexual P...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28062360/determination-of-glutathione-redox-potential-and-ph-value-in-subcellular-compartments-of-malaria-parasites
#14
Franziska Mohring, Mahsa Rahbari, Bernd Zechmann, Stefan Rahlfs, Jude M Przyborski, Andreas J Meyer, Katja Becker
The malaria parasite Plasmodium falciparum is exposed to multiple sources of oxidative challenge during its complex life cycle in the Anopheles vector and its human host. In order to further elucidate redox-based parasite host cell interactions and mechanisms of drug action, we targeted the genetically encoded glutathione redox sensor roGFP2 coupled to human glutaredoxin 1 (roGFP2-hGrx1) as well as the ratiometric pH sensor pHluorin to the apicoplast and the mitochondrion of P. falciparum. Using live cell imaging, this allowed for the first time the determination of the pH values of the apicoplast (7...
March 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28057055/functional-characterization-of-plasmodium-berghei-psop25-during-ookinete-development-and-as-a-malaria-transmission-blocking-vaccine-candidate
#15
Wenqi Zheng, Fei Liu, Yiwen He, Qingyang Liu, Gregory B Humphreys, Takafumi Tsuboi, Qi Fan, Enjie Luo, Yaming Cao, Liwang Cui
BACKGROUND: Plasmodium ookinete surface proteins as post-fertilization target antigens are potential malaria transmission-blocking vaccine (TBV) candidates. Putative secreted ookinete protein 25 (PSOP25) is a highly conserved ookinete surface protein, and has been shown to be a promising novel TBV target. Here, we further investigated the TBV activities of the full-length recombinant PSOP25 (rPSOP25) protein in Plasmodium berghei, and characterized the potential functions of PSOP25 during the P...
January 5, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28055573/guidelines-for-the-detection-of-babesia-and-theileria-parasites
#16
Laetitia Lempereur, Relja Beck, Isabel Fonseca, Cátia Marques, Ana Duarte, Marcos Santos, Sara Zúquete, Jacinto Gomes, Gernot Walder, Ana Domingos, Sandra Antunes, Gad Baneth, Cornelia Silaghi, Patricia Holman, Annetta Zintl
The genera Babesia and Theileria (phylum Apicomplexa, order Piroplasmida) are mainly transmitted by Ixodid ticks in which the sexual part of their life cycle followed by sporogony takes place. They include protozoan parasites that infect erythrocytes of a variety of vertebrate hosts, including domestic and wild animals, with some Babesia spp. also infecting humans. Babesia sporozoites transmitted in the tick's saliva during the bloodmeal directly infect erythrocytes, where they asexually multiply to produce pear-shaped merozoites in the process of merogony; whereas a pre-erythrocytic schizogonic life stage in leukocytes is found in Theileria and precedes merogony in the erythrocytes...
January 2017: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/28052996/novel-bioengineered-three-dimensional-human-intestinal-model-for-long-term-infection-of-cryptosporidium-parvum
#17
Maria A DeCicco RePass, Ying Chen, Yinan Lin, Wenda Zhou, David L Kaplan, Honorine D Ward
Cryptosporidium spp. are apicomplexan parasites of global importance that cause human diarrheal disease. In vitro culture models that may be used to study this parasite and that have physiological relevance to in vivo infection remain suboptimal. Thus, the pathogenesis of cryptosporidiosis remains poorly characterized, and interventions for the disease are limited. In this study, we evaluated the potential of a novel bioengineered three-dimensional (3D) human intestinal tissue model (which we developed previously) to support long-term infection by Cryptosporidium parvum Infection was assessed by immunofluorescence assays and confocal and scanning electron microscopy and quantified by quantitative reverse transcription-PCR...
March 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28043178/towards-clinical-development-of-a-pfs48-45-based-transmission-blocking-malaria-vaccine
#18
Michael Theisen, Matthijs M Jore, Robert Sauerwein
Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45...
January 9, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28027318/stage-specific-changes-in-plasmodium-metabolism-required-for-differentiation-and-adaptation-to-different-host-and-vector-environments
#19
Anubhav Srivastava, Nisha Philip, Katie R Hughes, Konstantina Georgiou, James I MacRae, Michael P Barrett, Darren J Creek, Malcolm J McConville, Andrew P Waters
Malaria parasites (Plasmodium spp.) encounter markedly different (nutritional) environments during their complex life cycles in the mosquito and human hosts. Adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (TCA) metabolism in mosquito stages. Here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage-specific changes in Plasmodium berghei carbon metabolism and determine the functional significance of these changes on parasite survival in the blood and mosquito stages...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27997583/rapid-generation-of-marker-free-p-falciparum-fluorescent-reporter-lines-using-modified-crispr-cas9-constructs-and-selection-protocol
#20
Catherin Marin Mogollon, Fiona J A van Pul, Takashi Imai, Jai Ramesar, Séverine Chevalley-Maurel, Guido M de Roo, Sabrina A J Veld, Hans Kroeze, Blandine M D Franke-Fayard, Chris J Janse, Shahid M Khan
The CRISPR/Cas9 system is a powerful genome editing technique employed in a wide variety of organisms including recently the human malaria parasite, P. falciparum. Here we report on further improvements to the CRISPR/Cas9 transfection constructs and selection protocol to more rapidly modify the P. falciparum genome and to introduce transgenes into the parasite genome without the inclusion of drug-selectable marker genes. This method was used to stably integrate the gene encoding GFP into the P. falciparum genome under the control of promoters of three different Plasmodium genes (calmodulin, gapdh and hsp70)...
2016: PloS One
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