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Human asexuality

Phuong N Tran, Cameron J Tate, Melanie C Ridgway, Kevin J Saliba, Kiaran Kirk, Alexander G Maier
Ketotifen has recently been reported to inhibit the growth of both asexual and sexual malaria parasites. A parasite transporter, PfgABCG2, has been implicated in its mechanism of action. Human dihydrofolate reductase (hDHFR) is the most commonly used selectable marker to create transgenic Plasmodium falciparum cell lines. Growth assays using transgenic P. falciparum parasites with different selectable markers revealed that the presence of hDHFR rather than the absence of PfgABCG2 is responsible for a shift in the parasite's sensitivity to ketotifen...
September 22, 2016: International Journal for Parasitology, Drugs and Drug Resistance
Amélie Le Bihan, Ruben de Kanter, Iñigo Angulo-Barturen, Christoph Binkert, Christoph Boss, Reto Brun, Ralf Brunner, Stephan Buchmann, Jeremy Burrows, Koen J Dechering, Michael Delves, Sonja Ewerling, Santiago Ferrer, Christoph Fischli, Francisco Javier Gamo-Benito, Nina F Gnädig, Bibia Heidmann, María Belén Jiménez-Díaz, Didier Leroy, Maria Santos Martínez, Solange Meyer, Joerg J Moehrle, Caroline L Ng, Rintis Noviyanti, Andrea Ruecker, Laura María Sanz, Robert W Sauerwein, Christian Scheurer, Sarah Schleiferboeck, Robert Sinden, Christopher Snyder, Judith Straimer, Grennady Wirjanata, Jutta Marfurt, Ric N Price, Thomas Weller, Walter Fischli, David A Fidock, Martine Clozel, Sergio Wittlin
BACKGROUND: Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. Herein, the preclinical characterization of one of these compounds, ACT-451840, conducted in partnership with academic and industrial groups is presented...
October 2016: PLoS Medicine
Robert J Hart, Emmanuel Cornillot, Amanah Abraham, Emily Molina, Catherine S Nation, Choukri Ben Mamoun, Ahmed S I Aly
The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown...
2016: Scientific Reports
N Estiarte, C B Lawrence, V Sanchis, A J Ramos, A Crespo-Sempere
Alternaria alternata is a common filamentous fungus that contaminates various fruits, grains and vegetables causing important economic losses to farmers and the food industry. A. alternata is a mycotoxigenic mould, which may jeopardize human and animal health. Two of the most common A. alternata mycotoxins found in food and feed are alternariol and alternariol monomethyl ether. In this study we examined the role of LaeA and VeA, two regulatory proteins belonging to the velvet family, which have been described to be involved in several functions in many fungi including secondary metabolism...
September 8, 2016: International Journal of Food Microbiology
Paul E Verweij, Jianhua Zhang, Alfons J M Debets, Jacques F Meis, Frank L van de Veerdonk, Sijmen E Schoustra, Bas J Zwaan, Willem J G Melchers
Aspergillus fumigatus causes a range of diseases in human beings, some of which are characterised by fungal persistence. A fumigatus can persist by adapting to the human lung environment through physiological and genomic changes. The physiological changes are based on the large biochemical versatility of the fungus, and the genomic changes are based on the capacity of the fungus to generate genetic diversity by spontaneous mutations or recombination and subsequent selection of the genotypes that are most adapted to the new environment...
September 13, 2016: Lancet Infectious Diseases
Kristina Gupta
This article explores the relationship between contemporary asexual lives and compulsory sexuality, or the privileging of sexuality and the marginalizing of nonsexuality. Drawing on 30 in-depth interviews, I identify four ways the asexually identified individuals in this study saw themselves as affected by compulsory sexuality: pathologization, isolation, unwanted sex and relationship conflict, and the denial of epistemic authority. I also identify five ways these asexually identified individuals disrupted compulsory sexuality: adopting a language of difference and a capacity to describe asexuality; deemphasizing the importance of sexuality in human life; developing new types of nonsexual relationships; constituting asexuality as a sexual orientation or identity; and engaging in community building and outreach...
September 15, 2016: Journal of Homosexuality
Veer Bahadur Singh, Harish Kumar, Babu Lal Meena, Subhash Chandra, Jatin Agrawal, Naresh Kanogiya
INTRODUCTION: Malaria is the most important parasitic disease of humans causes clinical illness over 300-500 million people globally and over one million death every year globally. The involvement of the nervous system in malaria is studied in this paper, to help formulate a strategy for better malaria management. AIM: To study the Neuropsychiatric manifestation in malaria. MATERIALS AND METHODS: This was a prospective observational study in 170 patients with a clinical diagnosis of malaria admitted in various medical wards of medicine department of PBM Hospital, Bikaner during epidemic of malaria...
July 2016: Journal of Clinical and Diagnostic Research: JCDR
Z W de Beer, T A Duong, M J Wingfield
One of the causal agents of human sporotrichosis, Sporothrix schenckii, is the type species of the genus Sporothrix. During the course of the last century the asexual morphs of many Ophiostoma spp. have also been treated in Sporothrix. More recently several DNA-based studies have suggested that species of Sporothrix and Ophiostoma converge in what has become known as Ophiostoma s. lat. Were the one fungus one name principles adopted in the Melbourne Code to be applied to Ophiostoma s. lat., Sporothrix would have priority over Ophiostoma, resulting in more than 100 new combinations...
2016: Studies in Mycology
Suraya A Diaz, Stephen R Martin, Steven A Howell, Munira Grainger, Robert W Moon, Judith L Green, Anthony A Holder
Aldolase has been implicated as a protein coupling the actomyosin motor and cell surface adhesins involved in motility and host cell invasion in the human malaria parasite Plasmodium falciparum. It binds to the cytoplasmic domain (CTD) of type 1 membrane proteins of the thrombospondin-related anonymous protein (TRAP) family. Other type 1 membrane proteins located in the apical organelles of merozoites, the form of the parasite that invades red blood cells, including apical membrane antigen 1 (AMA1) and members of the erythrocyte binding ligand (EBL) and reticulocyte binding homologue (RH) protein families have been implicated in host cell binding and invasion...
2016: PloS One
Kyousuke Kobayashi, Kentaro Kato
The malaria parasite Plasmodium falciparum infects human erythrocytes and reproduces asexually through an intraerythrocytic developmental cycle. In vitro culture of P. falciparum allows investigation of the parasite's blood-stage development, which spans approximately 48h from the time of invasion to the lysis of mature schizonts to release merozoites. To focus on a specific step in the developmental cycle, synchronization techniques are utilized. D-sorbitol treatment and the Percoll-sorbitol method have been used; however, these techniques have limitations in terms of the degree of synchronization achieved, the amount of synchronized parasite acquired, convenience, reproducibility, and cost...
September 3, 2016: Parasitology International
Saima M Sidik, Diego Huet, Suresh M Ganesan, My-Hang Huynh, Tim Wang, Armiyaw S Nasamu, Prathapan Thiru, Jeroen P J Saeij, Vern B Carruthers, Jacquin C Niles, Sebastian Lourido
Apicomplexan parasites are leading causes of human and livestock diseases such as malaria and toxoplasmosis, yet most of their genes remain uncharacterized. Here, we present the first genome-wide genetic screen of an apicomplexan. We adapted CRISPR/Cas9 to assess the contribution of each gene from the parasite Toxoplasma gondii during infection of human fibroblasts. Our analysis defines ∼200 previously uncharacterized, fitness-conferring genes unique to the phylum, from which 16 were investigated, revealing essential functions during infection of human cells...
September 8, 2016: Cell
Mun-Gu Jung, Sung Su Kim, Jae-Hyuk Yu, Kwang-Soo Shin
The G-protein-coupled receptor (GPCR) family represents the largest and most varied collection of membrane embedded proteins that are sensitized by ligand binding and interact with heterotrimeric G proteins. Despite their presumed critical roles in fungal biology, the functions of the GPCR family members in the opportunistic human pathogen Aspergillus fumigatus are largely unknown, as only two (GprC and GprD) of the 15 predicted GPCRs have been studied. Here, we characterize the gprK gene, which is predicted to encode a hybrid GPCR with both 7-transmembrane and regulator of G-protein signaling (RGS) domains...
2016: PloS One
Jan D Warncke, Ioannis Vakonakis, Hans-Peter Beck
During the asexual cycle, Plasmodium falciparum extensively remodels the human erythrocyte to make it a suitable host cell. A large number of exported proteins facilitate this remodeling process, which causes erythrocytes to become more rigid, cytoadherent, and permeable for nutrients and metabolic products. Among the exported proteins, a family of 89 proteins, called the Plasmodium helical interspersed subtelomeric (PHIST) protein family, has been identified. While also found in other Plasmodium species, the PHIST family is greatly expanded in P...
December 2016: Microbiology and Molecular Biology Reviews: MMBR
Elisa Ventura-Aquino, Raúl G Paredes
INTRODUCTION: Many different animal models of sexual medicine have been developed, demonstrating the complexity of studying the many interactions that influence sexual responses. A great deal of effort has been invested in measuring sexual motivation using different behavioral models mainly because human behavior is more complex than any model can reproduce. AIM: To compare different animal models of male and female behaviors that measure sexual motivation as a key element in sexual medicine and focus on models that use a combination of molecular techniques and behavioral measurements...
August 23, 2016: Sexual Medicine Reviews
Anders Wallqvist, Xin Fang, Shivendra G Tewari, Ping Ye, Jaques Reifman
BACKGROUND: The malarial parasite Plasmodium falciparum undergoes a complex life cycle, including an intraerythrocytic developmental cycle, during which it is metabolically dependent on the infected human red blood cell (RBC). To describe whole cell metabolic activity within both P. falciparum and RBCs during the asexual reproduction phase of the intraerythrocytic developmental cycle, we developed an integrated host-parasite metabolic modeling framework driven by time-dependent gene expression data...
2016: BMC Systems Biology
Wesley C Van Voorhis, John H Adams, Roberto Adelfio, Vida Ahyong, Myles H Akabas, Pietro Alano, Aintzane Alday, Yesmalie Alemán Resto, Aishah Alsibaee, Ainhoa Alzualde, Katherine T Andrews, Simon V Avery, Vicky M Avery, Lawrence Ayong, Mark Baker, Stephen Baker, Choukri Ben Mamoun, Sangeeta Bhatia, Quentin Bickle, Lotfi Bounaadja, Tana Bowling, Jürgen Bosch, Lauren E Boucher, Fabrice F Boyom, Jose Brea, Marian Brennan, Audrey Burton, Conor R Caffrey, Grazia Camarda, Manuela Carrasquilla, Dee Carter, Maria Belen Cassera, Ken Chih-Chien Cheng, Worathad Chindaudomsate, Anthony Chubb, Beatrice L Colon, Daisy D Colón-López, Yolanda Corbett, Gregory J Crowther, Noemi Cowan, Sarah D'Alessandro, Na Le Dang, Michael Delves, Joseph L DeRisi, Alan Y Du, Sandra Duffy, Shimaa Abd El-Salam El-Sayed, Michael T Ferdig, José A Fernández Robledo, David A Fidock, Isabelle Florent, Patrick V T Fokou, Ani Galstian, Francisco Javier Gamo, Suzanne Gokool, Ben Gold, Todd Golub, Gregory M Goldgof, Rajarshi Guha, W Armand Guiguemde, Nil Gural, R Kiplin Guy, Michael A E Hansen, Kirsten K Hanson, Andrew Hemphill, Rob Hooft van Huijsduijnen, Takaaki Horii, Paul Horrocks, Tyler B Hughes, Christopher Huston, Ikuo Igarashi, Katrin Ingram-Sieber, Maurice A Itoe, Ajit Jadhav, Amornrat Naranuntarat Jensen, Laran T Jensen, Rays H Y Jiang, Annette Kaiser, Jennifer Keiser, Thomas Ketas, Sebastien Kicka, Sunyoung Kim, Kiaran Kirk, Vidya P Kumar, Dennis E Kyle, Maria Jose Lafuente, Scott Landfear, Nathan Lee, Sukjun Lee, Adele M Lehane, Fengwu Li, David Little, Liqiong Liu, Manuel Llinás, Maria I Loza, Aristea Lubar, Leonardo Lucantoni, Isabelle Lucet, Louis Maes, Dalu Mancama, Nuha R Mansour, Sandra March, Sheena McGowan, Iset Medina Vera, Stephan Meister, Luke Mercer, Jordi Mestres, Alvine N Mfopa, Raj N Misra, Seunghyun Moon, John P Moore, Francielly Morais Rodrigues da Costa, Joachim Müller, Arantza Muriana, Stephen Nakazawa Hewitt, Bakela Nare, Carl Nathan, Nathalie Narraidoo, Sujeevi Nawaratna, Kayode K Ojo, Diana Ortiz, Gordana Panic, George Papadatos, Silvia Parapini, Kailash Patra, Ngoc Pham, Sarah Prats, David M Plouffe, Sally-Ann Poulsen, Anupam Pradhan, Celia Quevedo, Ronald J Quinn, Christopher A Rice, Mohamed Abdo Rizk, Andrea Ruecker, Robert St Onge, Rafaela Salgado Ferreira, Jasmeet Samra, Natalie G Robinett, Ulrich Schlecht, Marjorie Schmitt, Filipe Silva Villela, Francesco Silvestrini, Robert Sinden, Dennis A Smith, Thierry Soldati, Andreas Spitzmüller, Serge Maximilian Stamm, David J Sullivan, William Sullivan, Sundari Suresh, Brian M Suzuki, Yo Suzuki, S Joshua Swamidass, Donatella Taramelli, Lauve R Y Tchokouaha, Anjo Theron, David Thomas, Kathryn F Tonissen, Simon Townson, Abhai K Tripathi, Valentin Trofimov, Kenneth O Udenze, Imran Ullah, Cindy Vallieres, Edgar Vigil, Joseph M Vinetz, Phat Voong Vinh, Hoan Vu, Nao-Aki Watanabe, Kate Weatherby, Pamela M White, Andrew F Wilks, Elizabeth A Winzeler, Edward Wojcik, Melanie Wree, Wesley Wu, Naoaki Yokoyama, Paul H A Zollo, Nada Abla, Benjamin Blasco, Jeremy Burrows, Benoît Laleu, Didier Leroy, Thomas Spangenberg, Timothy Wells, Paul A Willis
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery...
July 2016: PLoS Pathogens
Sensen Lin, Xiaodan Lyu, Jun Yu, Li Sun, Danyu Du, Yanqi Lai, Hongyang Li, Ying Wang, Luyong Zhang, Hongping Yin, Shengtao Yuan
BACKGROUND: Cordyceps has long been used to treat cancer. However, its pharmacologically active components as well as the molecular mechanisms underlying its effects are still unclear. PURPOSE: To investigate the effect of MHP-1, a newly isolated polysaccharide from Mortierella hepialid (the asexual structure of C. sinensis), on breast cancer metastasis. STUDY DESIGN: The effect of MHP-1 on breast cancer cell migration, epithelial-mesenchymal transition (EMT) and TGF-β signaling were investigated in vitro and in vivo...
September 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Caeul Lim, Ligia Pereira, Kathryn Shaw Saliba, Anjali Mascarenhas, Jennifer N Maki, Laura Chery, Edwin Gomes, Pradipsinh K Rathod, Manoj T Duraisingh
Plasmodium vivax, the most widely distributed human malaria parasite, is restricted to reticulocytes, limiting its asexual proliferation. In recent years, cases of severe and high-level P. vivax parasitemia have been reported, challenging the assumption that all isolates are equally restricted. In this article, we analyze the reticulocyte preference of a large number of Indian P. vivax isolates. Our results show that P. vivax isolates significantly vary in their level of reticulocyte preference. In addition, by carefully staging the parasites, we find that P...
October 1, 2016: Journal of Infectious Diseases
Dewaldt Engelbrecht, Thérèsa Louise Coetzer
The asexual erythrocytic cycle of the protozoan parasite Plasmodium falciparum is responsible for the pathogenesis of malaria and causes the overwhelming majority of malaria deaths. Rapidly increasing parasitaemia during this 48 hcycle threatens the survival of the human host and the parasite prior to transmission of the slow-maturing sexual stages to the mosquito host. The parasite may utilize regulated cell death (RCD) to control the burden of infection on the host and thus aid its own survival and transmission...
July 14, 2016: Parasitology International
Sarah Guégan, Dea Garcia-Hermoso, Karine Sitbon, Sarah Ahmed, Philippe Moguelet, Françoise Dromer, Olivier Lortholary
Background.  Coelomycetes are rarely but increasingly reported in association with human infections involving mostly skin and subcutaneous tissues, both in immunocompetent and immunocompromised patients. Coelomycetes constitute a heterogeneous group of filamentous fungi with distinct morphological characteristics in culture, namely an ability to produce asexual spores within fruit bodies. Methods.  We included all cases of proven primary cutaneous and/or subcutaneous infections due to coelomycetes received for identification at the French National Reference Center for Invasive Mycoses and Antifungals between 2005 and 2014...
April 2016: Open Forum Infectious Diseases
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