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https://www.readbyqxmd.com/read/29739900/bone-marrow-is-a-major-parasite-reservoir-in-plasmodium-vivax-infection
#1
Nicanor Obaldia, Elamaran Meibalan, Juliana M Sa, Siyuan Ma, Martha A Clark, Pedro Mejia, Roberto R Moraes Barros, William Otero, Marcelo U Ferreira, James R Mitchell, Danny A Milner, Curtis Huttenhower, Dyann F Wirth, Manoj T Duraisingh, Thomas E Wellems, Matthias Marti
Plasmodium vivax causes heavy burdens of disease across malarious regions worldwide. Mature P. vivax asexual and transmissive gametocyte stages occur in the blood circulation, and it is often assumed that accumulation/sequestration in tissues is not an important phase in their development. Here, we present a systematic study of P. vivax stage distributions in infected tissues of nonhuman primate (NHP) malaria models as well as in blood from human infections. In a comparative analysis of the transcriptomes of P...
May 8, 2018: MBio
https://www.readbyqxmd.com/read/29724925/uncovering-the-essential-genes-of-the-human-malaria-parasite-plasmodium-falciparum-by-saturation-mutagenesis
#2
Min Zhang, Chengqi Wang, Thomas D Otto, Jenna Oberstaller, Xiangyun Liao, Swamy R Adapa, Kenneth Udenze, Iraad F Bronner, Deborah Casandra, Matthew Mayho, Jacqueline Brown, Suzanne Li, Justin Swanson, Julian C Rayner, Rays H Y Jiang, John H Adams
Severe malaria is caused by the apicomplexan parasite Plasmodium falciparum. Despite decades of research, the distinct biology of these parasites has made it challenging to establish high-throughput genetic approaches to identify and prioritize therapeutic targets. Using transposon mutagenesis of P. falciparum in an approach that exploited its AT-rich genome, we generated more than 38,000 mutants, saturating the genome and defining mutability and fitness costs for over 87% of genes. Of 5399 genes, our study defined 2680 genes as essential for optimal growth of asexual blood stages in vitro...
May 4, 2018: Science
https://www.readbyqxmd.com/read/29723510/infection-of-mosquitoes-from-in-vitro-cultivated-plasmodium-knowlesi-h-strain
#3
Jennifer S Armistead, Roberto R Moraes Barros, Tyler J Gibson, Whitney A Kite, J Patrick Mershon, Lynn E Lambert, Sachy E Orr-Gonzalez, Juliana M Sá, John H Adams, Thomas E Wellems
In vitro studies of sexual blood stages of the most fatal malaria species, Plasmodium falciparum, have revealed key processes by which gametocytes develop and transmit infection from humans to anopheline mosquitoes. However, most malaria cases outside sub-Saharan Africa are caused by other Plasmodium spp., frequently Plasmodium vivax and Plasmodium knowlesi, a zoonotic parasite of macaque monkeys. Gametocytes of P. vivax and P. knowlesi exhibit distinct morphology, faster development, and a shorter life span compared with gametocytes of P...
April 30, 2018: International Journal for Parasitology
https://www.readbyqxmd.com/read/29705402/gene-co-expression-analysis-identifies-gene-clusters-associated-with-isotropic-and-polarized-growth-in-aspergillus-fumigatus-conidia
#4
Tim J H Baltussen, Jordy P M Coolen, Jan Zoll, Paul E Verweij, Willem J G Melchers
Aspergillus fumigatus is a saprophytic fungus that extensively produces conidia. These microscopic asexually reproductive structures are small enough to reach the lungs. Germination of conidia followed by hyphal growth inside human lungs is a key step in the establishment of infection in immunocompromised patients. RNA-Seq was used to analyze the transcriptome of dormant and germinating A. fumigatus conidia. Construction of a gene co-expression network revealed four gene clusters (modules) correlated with a growth phase (dormant, isotropic growth, polarized growth)...
April 26, 2018: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/29703959/a-cryptic-cycle-in-haematopoietic-niches-promotes-initiation-of-malaria-transmission-and-evasion-of-chemotherapy
#5
Rebecca S Lee, Andrew P Waters, James M Brewer
Blood stage human malaria parasites may exploit erythropoietic tissue niches and colonise erythroid progenitors; however, the precise influence of the erythropoietic environment on fundamental parasite biology remains unknown. Here we use quantitative approaches to enumerate Plasmodium infected erythropoietic precursor cells using an in vivo rodent model of Plasmodium berghei. We show that parasitised early reticulocytes (ER) in the major sites of haematopoiesis establish a cryptic asexual cycle. Moreover, this cycle is characterised by early preferential commitment to gametocytogenesis, which occurs in sufficient numbers to generate almost all of the initial population of circulating, mature gametocytes...
April 27, 2018: Nature Communications
https://www.readbyqxmd.com/read/29702649/high-mutation-rates-limit-evolutionary-adaptation-in-escherichia-coli
#6
Kathleen Sprouffske, José Aguílar-Rodríguez, Paul Sniegowski, Andreas Wagner
Mutation is fundamental to evolution, because it generates the genetic variation on which selection can act. In nature, genetic changes often increase the mutation rate in systems that range from viruses and bacteria to human tumors. Such an increase promotes the accumulation of frequent deleterious or neutral alleles, but it can also increase the chances that a population acquires rare beneficial alleles. Here, we study how up to 100-fold increases in Escherichia coli's genomic mutation rate affect adaptive evolution...
April 27, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29693732/dna-sequencing-to-clarify-the-taxonomical-conundrum-of-the-clinical-coelomycetes
#7
REVIEW
Nicomedes Valenzuela-Lopez, José F Cano-Lira, Alberto M Stchigel, Josep Guarro
The taxonomy of the fungi that produce human infections and that develop asexual fruiting bodies in culture has become very complex. Recent molecular studies have produced dramatic changes in their classification. Currently, the coelomycetes traditionally included in Sphaeropsidales and Melanconiales are in fact distributed across at least three different classes of the Phylum Ascomycota. Approximately 1,000 genera and 7,000 species have been grouped in the classes Dothideomycetes, Leotiomycetes and Sordariomycetes and their proper identification can only be made by analysing their DNA sequences and comparing them with those corresponding to type strains available in the adequate databases...
April 25, 2018: Mycoses
https://www.readbyqxmd.com/read/29665687/identification-of-fast-acting-2-6-disubstituted-imidazopyridines-that-are-efficacious-in-the-in-vivo-humanized-plasmodium-falciparum-nodscidil2r%C3%AE-null-mouse-model-of-malaria
#8
Aloysius T Nchinda, Claire Le Manach, Tanya Paquet, Diego Gonzalez Cabrera, Kathryn J Wicht, Christel Brunschwig, Mathew Njoroge, Efrem Abay, Dale Taylor, Nina Lawrence, Sergio Wittlin, Maria-Belen Jimenez-Diaz, Maria Santos Martínez-Martínez, Santiago Ferrer, Iñigo Angulo-Barturen, Maria Jose Lafuente-Monasterio, James Duffy, Jeremy N Burrows, Leslie J Street, Kelly Chibale
Optimization of a chemical series originating from whole-cell phenotypic screening against the human malaria parasite, Plasmodium falciparum, led to the identification of two promising 2,6-disubstituted imidazopyridine compounds, 43 and 74. These compounds exhibited potent activity against asexual blood stage parasites that, together with their in vitro Absorption, Distribution, Metabolism, and Excretion (ADME) properties, translated to in vivo efficacy with clearance of parasites in the PfSCID mouse model for malaria within 48 h of treatment...
April 17, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29664138/characterization-of-the-catalytic-subunits-of-the-rna-exosome-like-complex-in-plasmodium-falciparum
#9
Ning Jiang, Shengchao Yu, Na Yang, Ying Feng, Xiaoyu Sang, Yao Wang, Mats Wahlgren, Qijun Chen
The eukaryotic ribonucleic acid (RNA) exosome is a versatile multi-ribonuclease complex that mediates the processing, surveillance and degradation of virtually all classes of RNA in both the nucleus and cytoplasm. The complex, composed of ten to eleven subunits, has been widely described in many organisms. Bioinformatic analyses revealed that there may be also an exosome-like complex in Plasmodium falciparum, a parasite of great importance in public health, with eight predicted subunits having high sequence similarity to their counterparts in yeast and human...
April 17, 2018: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/29615054/anti-plasmodial-effect-of-plant-extracts-from-picrolemma-huberi-and-picramnia-latifolia
#10
Wendy Berthi, Alexa González, Alexandra Rios, Silvia Blair, Álvaro Cogollo, Adriana Pabón
BACKGROUND: Malaria is an infectious disease caused by parasites of the genus Plasmodium, of which Plasmodium vivax and Plasmodium falciparum are the major species that cause the disease in humans. As there are relatively few alternatives for malaria treatment, it is necessary to search for new chemotherapeutic options. Colombia possesses a great diversity of plants, which are potential sources of new compounds of medical interest. Thus, in this study the antiplasmodial effect of extracts from two species of plants from the families Simaroubaceae and Picramniaceae (Picramnia latifolia and Picrolemma huberi) was evaluated in vitro and in vivo...
April 4, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29615050/differential-activity-of-methylene-blue-against-erythrocytic-and-hepatic-stages-of-plasmodium
#11
Henriette Bosson-Vanga, Jean-François Franetich, Valérie Soulard, Daniel Sossau, Maurel Tefit, Bocar Kane, Jean-Christophe Vaillant, Steffen Borrmann, Olaf Müller, Nathalie Dereuddre-Bosquet, Roger Le Grand, Olivier Silvie, Dominique Mazier
BACKGROUND: In the context of malaria elimination/eradication, drugs that are effective against the different developmental stages of the parasite are highly desirable. The oldest synthetic anti-malarial drug, the thiazine dye methylene blue (MB), is known for its activity against Plasmodium blood stages, including gametocytes. The aim of the present study was to investigate a possible effect of MB against malaria parasite liver stages. METHODS: MB activity was investigated using both in vitro and in vivo models...
April 3, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29580379/single-cell-rna-seq-reveals-hidden-transcriptional-variation-in-malaria-parasites
#12
Adam J Reid, Arthur M Talman, Hayley M Bennett, Ana R Gomes, Mandy J Sanders, Christopher J R Illingworth, Oliver Billker, Matthew Berriman, Mara Kn Lawniczak
Single-cell RNA-sequencing is revolutionising our understanding of seemingly homogeneous cell populations but has not yet been widely applied to single-celled organisms. Transcriptional variation in unicellular malaria parasites from the Plasmodium genus is associated with critical phenotypes including red blood cell invasion and immune evasion, yet transcriptional variation at an individual parasite level has not been examined in depth. Here, we describe the adaptation of a single-cell RNA-sequencing (scRNA-seq) protocol to deconvolute transcriptional variation for more than 500 individual parasites of both rodent and human malaria comprising asexual and sexual life-cycle stages...
March 27, 2018: ELife
https://www.readbyqxmd.com/read/29564395/an-laea-and-brla-dependent-cellular-network-governs-tissue-specific-secondary-metabolism-in-the-human-pathogen-aspergillus-fumigatus
#13
Abigail L Lind, Fang Yun Lim, Alexandra A Soukup, Nancy P Keller, Antonis Rokas
Biosynthesis of many ecologically important secondary metabolites (SMs) in filamentous fungi is controlled by several global transcriptional regulators, like the chromatin modifier LaeA, and tied to both development and vegetative growth. In Aspergillus molds, asexual development is regulated by the BrlA > AbaA > WetA transcriptional cascade. To elucidate BrlA pathway involvement in SM regulation, we examined the transcriptional and metabolic profiles of Δ brlA , Δ abaA , and Δ wetA mutant and wild-type strains of the human pathogen Aspergillus fumigatus ...
March 2018: MSphere
https://www.readbyqxmd.com/read/29559909/qsar-driven-design-and-discovery-of-novel-compounds-with-antiplasmodial-and-transmission-blocking-activities
#14
Marilia N N Lima, Cleber C Melo-Filho, Gustavo C Cassiano, Bruno J Neves, Vinicius M Alves, Rodolpho C Braga, Pedro V L Cravo, Eugene N Muratov, Juliana Calit, Daniel Y Bargieri, Fabio T M Costa, Carolina H Andrade
Malaria is a life-threatening infectious disease caused by parasites of the genus Plasmodium , affecting more than 200 million people worldwide every year and leading to about a half million deaths. Malaria parasites of humans have evolved resistance to all current antimalarial drugs, urging for the discovery of new effective compounds. Given that the inhibition of deoxyuridine triphosphatase of Plasmodium falciparum ( Pf dUTPase) induces wrong insertions in plasmodial DNA and consequently leading the parasite to death, this enzyme is considered an attractive antimalarial drug target...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29530089/transcriptome-analysis-of-pig-intestinal-cell-monolayers-infected-with-cryptosporidium-parvum-asexual-stages
#15
Marzieh Ezzaty Mirhashemi, Farzad Noubary, Susan Chapman-Bonofiglio, Saul Tzipori, Gordon S Huggins, Giovanni Widmer
BACKGROUND: Human cryptosporidiosis is caused primarily by two species of apicomplexan protozoa, Cryptosporidium parvum and C. hominis. In cultured cell monolayers, the parasite undergoes two generations of asexual multiplication (merogony). However, the proportion of parasites completing the life-cycle is low and insufficient to sustain continuous propagation. Due to the intracellular location of meronts and later life-cycle stages, oocyst and sporozoites are the only forms of the parasite that can readily be isolated...
March 12, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29518888/fungal-cytochrome-p450s-and-the-p450-complement-cypome-of-fusarium-graminearum
#16
REVIEW
Jiyoung Shin, Jung-Eun Kim, Yin-Won Lee, Hokyoung Son
Cytochrome P450s (CYPs), heme-containing monooxygenases, play important roles in a wide variety of metabolic processes important for development as well as biotic/trophic interactions in most living organisms. Functions of some CYP enzymes are similar across organisms, but some are organism-specific; they are involved in the biosynthesis of structural components, signaling networks, secondary metabolisms, and xenobiotic/drug detoxification. Fungi possess more diverse CYP families than plants, animals, or bacteria...
March 7, 2018: Toxins
https://www.readbyqxmd.com/read/29507050/proteomics-of-aspergillus-fumigatus-conidia-containing-phagolysosomes-identifies-processes-governing-immune-evasion
#17
Hella Schmidt, Sebastian Vlaic, Thomas Krüger, Franziska Schmidt, Johannes Balkenhohl, Thomas Dandekar, Reinhard Guthke, Olaf Kniemeyer, Thorsten Heinekamp, Axel A Brakhage
Invasive infections by the human pathogenic fungus Aspergillus fumigatus start with the outgrowth of asexual, airborne spores (conidia) into the lung tissue of immunocompromised patients. The resident alveolar macrophages phagocytose conidia, which end up in phagolysosomes. However, A. fumigatus conidia resist phagocytic degradation to a certain degree. This is mainly attributable to the pigment 1,8-dihydroxynaphthalene (DHN) melanin located in the cell wall of conidia, which manipulates the phagolysosomal maturation and prevents their intracellular killing...
March 5, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29503181/comparative-heterochromatin-profiling-reveals-conserved-and-unique-epigenome-signatures-linked-to-adaptation-and-development-of-malaria-parasites
#18
Sabine A Fraschka, Michael Filarsky, Regina Hoo, Igor Niederwieser, Xue Yan Yam, Nicolas M B Brancucci, Franziska Mohring, Annals T Mushunje, Ximei Huang, Peter R Christensen, Francois Nosten, Zbynek Bozdech, Bruce Russell, Robert W Moon, Matthias Marti, Peter R Preiser, Richárd Bártfai, Till S Voss
Heterochromatin-dependent gene silencing is central to the adaptation and survival of Plasmodium falciparum malaria parasites, allowing clonally variant gene expression during blood infection in humans. By assessing genome-wide heterochromatin protein 1 (HP1) occupancy, we present a comprehensive analysis of heterochromatin landscapes across different Plasmodium species, strains, and life cycle stages. Common targets of epigenetic silencing include fast-evolving multi-gene families encoding surface antigens and a small set of conserved HP1-associated genes with regulatory potential...
March 14, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29482720/a-randomized-feasibility-trial-comparing-four-antimalarial-drug-regimens-to-induce-plasmodium-falciparum-gametocytemia-in-the-controlled-human-malaria-infection-model
#19
Isaie J Reuling, Lisanne A van de Schans, Luc E Coffeng, Kjerstin Lanke, Lisette Meerstein-Kessel, Wouter Graumans, Geert-Jan van Gemert, Karina Teelen, Rianne Siebelink-Stoter, Marga van de Vegte-Bolmer, Quirijn de Mast, André J van der Ven, Karen Ivinson, Cornelus C Hermsen, Sake de Vlas, John Bradley, Katharine A Collins, Christian F Ockenhouse, James McCarthy, Robert W Sauerwein, Teun Bousema
Background Malaria elimination strategies require a thorough understanding of parasite transmission from human to mosquito. A clinical model to induce gametocytes to understand their dynamics and evaluate transmission-blocking interventions (TBI) is currently unavailable. Here, we explore the use of the well-established Controlled Human Malaria Infection model (CHMI) to induce gametocyte carriage with different antimalarial drug regimens. Methods In a single centre, open-label randomised trial, healthy malaria-naive participants (aged 18-35 years) were infected with Plasmodium falciparum by bites of infected Anopheles mosquitoes (ClinicalTrials...
February 27, 2018: ELife
https://www.readbyqxmd.com/read/29477861/schistosoma-mansoni-venom-allergen-like-protein-18-smval18-is-a-plasminogen-binding-protein-secreted-during-the-early-stages-of-mammalian-host-infection
#20
Rafaela S Fernandes, Luis G V Fernandes, Andre S de Godoy, Patrícia A Miyasato, Eliana Nakano, Leonardo P Farias, Ana L T O Nascimento, Luciana C C Leite
Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma which have a complex life cycle characterized by an asexual multiplication phase in the snail intermediate host and a sexual reproduction phase in the mammalian definitive host. The initial steps of the human host infection involve the secretion of proteins contained in the acetabular glands of cercariae that promote parasite adhesion and proteolysis of the skin layers. Herein, we performed a functional analysis of SmVAL18, identified as one of the three SCP/TAPS proteins constituent of cercarial secretions...
April 2018: Molecular and Biochemical Parasitology
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