Article
Immunology
Daniela Barbieri, Lina Gomez, Ludivine Royer, Florian Dupuy, Jean-Francois Franetich, Maurel Tefit, Marie-Esther N'Dri, Dominique Mazier, Olivier Silvie, Alicia Moreno-Sabater, Catherine Lavazec
Summary: In this study, it was found that the drug tadalafil can block malaria parasite transmission by altering the mechanical properties of infected erythrocytes. Results from in vivo experiments using a humanized mouse model showed that tadalafil treatment increased the stiffness of gametocyte-infected erythrocytes, leading to their retention by the spleen.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Sven Kratochvil, Chen-Hsiang Shen, Ying-Cing Lin, Kai Xu, Usha Nair, Lais Da Silva Pereira, Prabhanshu Tripathi, Johan Arnold, Gwo-Yu Chuang, Eleonora Melzi, Arne Schon, Baoshan Zhang, Marlon Dillon, Brian Bonilla, Barbara J. Flynn, Kathrin H. Kirsch, Neville K. Kisalu, Patience K. Kiyuka, Tracy Liu, Li Ou, Marie Pancera, Reda Rawi, Mateo Reveiz, Kareen Seignon, Lawrence T. Wang, Michael T. Waring, John Warner, Yongping Yang, Joseph R. Francica, Azza H. Idris, Robert A. Seder, Peter D. Kwong, Facundo D. Batista
Summary: This study demonstrates the use of repeat antigens to evade immune responses and the successful improvement of a highly effective anti-malarial antibody in a mouse model, showcasing the potential of using vaccination and bioinformatic analysis to enhance protective capacity.
Article
Biology
Marie Miglianico, Judith M. Bolscher, Martijn W. Vos, Karin J. M. Koolen, Marloes de Bruijni, Deeya S. Rajagopal, Emily Chen, Michael Kiczun, David Gray, Brice Campo, Robert W. Sauerwein, Koen J. Dechering
Summary: This study reveals that chemical intervention against malaria parasites mostly occurs during the liver schizogony stage, with limited effects on sporozoite viability and motility. However, ten compounds showed significant impact on liver schizont development.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Maureen Ty, Shenghuan Sun, Perri C. Callaway, John Rek, Kathleen D. Press, Kattria van der Ploeg, Jason Nideffer, Zicheng Hu, Sandy Klemm, William Greenleaf, Michele Donato, Stephen Tukwasibwe, Emmanuel Arinaitwe, Felistas Nankya, Kenneth Musinguzi, Dean Andrew, Lauren de la Parte, Diego Martinez Mori, Savannah N. Lewis, Saki Takahashi, Isabel Rodriguez-Barraquer, Bryan Greenhouse, Catherine Blish, P. J. Utz, Purvesh Khatri, Grant Dorsey, Moses Kamya, Michelle Boyle, Margaret Feeney, Isaac Ssewanyana, Prasanna Jagannathan
Summary: Repeated malaria exposure leads to expansion of atypical CD56neg NK cells in Ugandan children, characterized by transcriptional, epigenetic, and phenotypic differences from CD56dim NK cells. CD56neg NK cells display enhanced functionality and greater antibody-dependent cellular cytotoxicity. Higher frequencies of CD56neg NK cells are associated with protection against symptomatic malaria. Continuous exposure to Plasmodium falciparum is necessary to maintain this modified, adaptive-like NK cell subset, as frequencies rapidly decline after reductions in malaria transmission.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Rebecca Webster, Hayley Mitchell, Jenny M. Peters, Juanita Heunis, Brighid O'Neill, Jeremy Gower, Sean Lynch, Helen Jennings, Fiona H. Amante, Stacey Llewellyn, Louise Marquart, Adam J. Potter, Geoffrey W. Birrell, Michael D. Edstein, G. Dennis Shanks, James S. McCarthy, Bridget E. Barber
Summary: A single low dose of tafenoquine can effectively reduce the transmission of Plasmodium falciparum parasites to mosquitoes, although there is a delay in its effect.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Anna M. Rodriguez, Malayna G. Hambly, Sandeep Jandu, Raquel Simao-Gurge, Casey Lowder, Edwin E. Lewis, Jeffrey A. Riffell, Shirley Luckhart
Summary: The study found that provisioning An. stephensi with histamine at levels consistent with severe malaria can enhance mosquito behaviors and parasite infection success, thus promoting malaria transmission.
Article
Pharmacology & Pharmacy
Nanang Rudianto Ariefta, Baldorj Pagmadulam, Coh-ichi Nihei, Yoshifumi Nishikawa
Summary: This study evaluated the growth-inhibitory effects of the antimalarial agent sparsomycin against drug-resistant malaria parasites. The results showed that sparsomycin had inhibitory effects on both sensitive and resistant strains of the parasites. This study suggests that sparsomycin has potential as an alternative treatment for malaria.
Article
Medicine, General & Internal
Kassoum Kayentao, Aissata Ongoiba, Anne C. Preston, Sara A. Healy, Safiatou Doumbo, Didier Doumtabe, Abdrahamane Traore, Hamadi Traore, Adama Djiguiba, Shanping Li, Mary E. Peterson, Shinyi Telscher, Azza H. Idris, Neville K. Kisalu, Kevin Carlton, Leonid Serebryannyy, Sandeep Narpala, Adrian B. McDermott, Martin Gaudinski, Siriman Traore, Hamidou Cisse, Mamadou Keita, Jeff Skinner, Zonghui Hu, Amatigue Zeguime, Adama Ouattara, M'Bouye Doucoure, Amagana Dolo, Abdoulaye Djimde, Boubacar Traore, Robert A. Seder, Peter D. Crompton
Summary: A phase 2 trial in Mali showed that CIS43LS was protective against P. falciparum infection over a 6-month malaria season, with 40 mg dosage showing 88.2% efficacy and 10 mg dosage showing 75.0% efficacy compared to placebo.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Medicine, General & Internal
Kassoum Kayentao, Aissata Ongoiba, Anne C. Preston, Sara A. Healy, Safiatou Doumbo, Didier Doumtabe, Abdrahamane Traore, Hamadi Traore, Adama Ouattara, Shanping Li, Mary E. Peterson, Shinyi Telscher, Azza H. Idris, Neville K. Kisalu, Kevin Carlton, Leonid Serebryannyy, Sandeep Narpala, Adrian B. McDermott, Martin Gaudinski, Siriman Traore, Hamidou Cisse, Mamadou Keita, Jeff Skinner, Zonghui Hu, Amatigue Zeguime, Adama Ouattara, M'Bouye Doucoure, Amagana Dolo, Abdoulaye Djimde, Boubacar Traore, Robert A. Seder, Peter D. Crompton
Summary: A phase 2 trial conducted in Mali showed that a single intravenous infusion of CIS43LS was safe and effective in preventing Plasmodium falciparum infection over a 6-month malaria season.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Andreas Giannisis, Kalicharan Patra, Anna K. Edlund, Lur Agirrezabala Nieto, Joan Benedicto-Gras, Simon Moussaud, Andres de la Rosa, Daniel Twohig, Tore Bengtsson, Yuan Fu, Guojun Bu, Greg Bial, Lander Foquet, Christina Hammarstedt, Stephen Strom, Kristina Kannisto, Jacob Raber, Ewa Ellis, Henrietta M. Nielsen
Summary: Liver-generated plasma apoE, although it does not enter the brain, is correlated with the risk and biomarker levels of Alzheimer's disease (AD). Carriers of APOE ε4, the strongest genetic risk factor for AD, show lower plasma apoE and altered brain integrity even in mid-life. This study investigates the role of liver-derived apoE in promoting neurodegeneration and emphasizes the potential importance of the liver in the APOE ε4-associated risk of neurodegenerative disease.
MOLECULAR PSYCHIATRY
(2022)
Article
Nanoscience & Nanotechnology
Kassoum Kayentao, Aissata Ongoiba, Anne C. Preston, Sara A. Healy, Safiatou Doumbo, Didier Doumtabe, Abdrahamane Traore, Hamadi Traore, Adama Djiguiba, Shanping Li, Mary E. Peterson, Shinyi Telscher, Azza H. Idris, Neville K. Kisalu, Kevin Carlton, Leonid Serebryannyy, Sandeep Narpala, Adrian B. McDermott, Martin Gaudinski, Siriman Traore, Hamidou Cisse, Mamadou Keita, Jeff Skinner, Zonghui Hu, Amatigue Zeguime, Adama Ouattara, M'Bouye Doucoure, Amagana Dolo, Abdoulaye Djimde, Boubacar Traore, Robert A. Seder, Peter D. Crompton, Mali Malaria mAb Trial Team
Summary: CIS43LS, a monoclonal antibody, showed protective effects against Plasmodium falciparum infection during the malaria season in Mali without significant safety concerns.
Article
Microbiology
Nanang R. Ariefta, Baldorj Pagmadulam, Masaki Hatano, Noriko Ikeda, Kunio Isshiki, Kazuaki Matoba, Masayuki Igarashi, Coh-ichi Nihei, Yoshifumi Nishikawa
Summary: The increasing burden and spread of resistant malaria parasites have driven the demand for a new therapeutic agent. Phebestin showed nanomolar efficacy against Plasmodium falciparum 3D7 and inhibited parasite multiplication in vitro. It exhibited no cytotoxicity against human cells and inhibited parasite stages at high concentrations. In vivo evaluation in mice infected with different malaria strains also showed promising results.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Jan Stephan Wichers-Misterek, Annika M. Binder, Paolo Mesen-Ramirez, Lilian Patrick Dorner, Soraya Safavi, Gwendolin Fuchs, Tobias L. Lenz, Anna Bachmann, Danny Wilson, Friedrich Frischknecht, Tim-Wolf Gilberger
Summary: The unique three-membrane pellicle is a key feature driving the transition between different life cycle stages of the malaria parasite. A novel subpellicular microtubule-associated protein, SPM3, was identified in the genus Plasmodium. Knockout of this protein resulted in malformed gametocytes and aberrant microtubules in Plasmodium falciparum, while in Plasmodium berghei, it caused perturbed microtubule architecture, aberrant sporozoite motility, and decreased transmission efficiency.
Article
Immunology
Manon Alkema, Isaie J. Reuling, Gerdie M. de Jong, Kjerstin Lanke, Luc E. Coffeng, Geert-Jan van Gemert, Marga van de Vegte-Bolmer, Quirijn de Mast, Reinout van Crevel, Karen Ivinson, Christian F. Ockenhouse, James S. McCarthy, Robert Sauerwein, Katharine A. Collins, Teun Bousema
Summary: The study found that the method of infection through mosquito bites or induced blood-stage malaria has a significant impact on gametocyte production, despite similar asexual parasite densities. The findings suggest that induced blood-stage malaria may be more conducive to gametocyte production compared to mosquito bites.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Chemistry, Multidisciplinary
Vinay Shankar Tiwari, Prince Joshi, Kanchan Yadav, Anamika Sharma, Sushobhan Chowdhury, Ashan Manhas, Niti Kumar, Renu Tripathi, Wahajul Haq
Summary: A series of novel 4-aminoquinoline analogues with a methyl group were synthesized and evaluated for their antimalarial activity, showing good potential in inhibiting Plasmodium falciparum with low toxicity levels. The introduction of a 4-methylamino substitution is well tolerated and holds promise for the discovery of new antimalarial agents against drug-resistant malaria.
Article
Biochemistry & Molecular Biology
Andre L. Samson, Cheree Fitzgibbon, Komal M. Patel, Joanne M. Hildebrand, Lachlan W. Whitehead, Joel S. Rimes, Annette V. Jacobsen, Christopher R. Horne, Xavier J. Gavin, Samuel N. Young, Kelly L. Rogers, Edwin D. Hawkins, James M. Murphy
Summary: This study presents a toolbox of antibodies for immunofluorescent detection of core necroptosis effectors RIPK1, RIPK3, and MLKL in human and mouse cells. The researchers found that not all commonly used antibodies are suitable for monitoring necroptosis through immunofluorescence microscopy, and methanol fixation is preferred for robust detection of specific RIPK1, RIPK3, and MLKL signals.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Multidisciplinary Sciences
Dhanushika Ratnayake, Phong D. Nguyen, Fernando J. Rossello, Verena C. Wimmer, Jean L. Tan, Laura A. Galvis, Ziad Julier, Alasdair J. Wood, Thomas Boudier, Abdulsalam I. Isiaku, Silke Berger, Viola Oorschot, Carmen Sonntag, Kelly L. Rogers, Christophe Marcelle, Graham J. Lieschke, Mikael M. Martino, Jeroen Bakkers, Peter D. Currie
Summary: Through muscle injury models in zebrafish, it has been found that specific macrophage populations 'dwell' within the injury site, providing a transient niche for stem cell proliferation. The signals released by these macrophages directly stimulate stem cell proliferation, governing the repair process.
Article
Microbiology
Simona Seizova, Ushma Ruparel, Alexandra L. Garnham, Stefanie M. Bader, Alessandro D. Uboldi, Michael J. Coffey, Lachlan W. Whitehead, Kelly L. Rogers, Christopher J. Tonkin
Summary: This study reveals that bradyzoites of Toxoplasma gondii alter the gene expression of infected host cells by exporting specific proteins, leading to suppression of interferon signaling. The exported protein IST plays a critical role in limiting interferon signaling. Furthermore, bradyzoite protein export protects host cells from interferon-induced cell death.
CELL HOST & MICROBE
(2022)
Article
Multidisciplinary Sciences
Zhong Yan Gan, Sylvie Callegari, Simon A. Cobbold, Thomas R. Cotton, Michael J. Mlodzianoski, Alexander F. Schubert, Niall D. Geoghegan, Kelly L. Rogers, Andrew Leis, Grant Dewson, Alisa Glukhova, David Komander
Summary: The research on the activation mechanism of PINK1 using crystallography and cryo-electron microscopy revealed the orientation of unphosphorylated yet active PINK1 on mitochondria, conformational changes to an active ubiquitin kinase state, and the role of regulatory PINK1 oxidation. The study also elucidates how PINK1 interacts with the mitochondrial outer membrane and suggests that PINK1 activity may be modulated by mitochondrial reactive oxygen species.
Article
Immunology
Saskia C. van der Boor, Geert-Jan van Gemert, Alex E. J. Hanssen, Youri M. van Waardenburg, Matthew B. B. McCall, Teun Bousema, Johannes H. W. de Wilt, Robert W. Sauerwein, Annie S. P. Yang
Summary: The study discovered that while Plasmodium falciparum sporozoites can invade porcine hepatocytes, their development arrests at the mid-stage possibly due to the inability to mobilize critical nutrients across the parasitophorous vacuolar membrane.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Entomology
Natalie Lissenden, Jennifer S. Armistead, Katherine Gleave, Seth R. Irish, Jackline L. Martin, Louisa A. Messenger, Sarah J. Moore, Corine Ngufor, Natacha Protopopoff, Richard Oxborough, Angus Spiers, Rosemary S. Lees
Summary: Mosquitoes are becoming increasingly resistant to pyrethroid insecticides, leading to the development of new insecticide-treated nets. However, there is a lack of standardized methods to measure the efficacy of these nets against mosquitoes in the long term.
Article
Medicine, Research & Experimental
Amanda Fabra-Garcia, Annie S. P. Yang, Marije C. Behet, Zen Yap, Youri van Waardenburg, Swarnendu Kaviraj, Kjerstin Lanke, Geert-Jan Van Gemert, Matthijs M. Jore, Teun Bousema, Robert W. Sauerwein
Summary: Sporozoite-based vaccine strategies are effective in preventing Plasmodium falciparum malaria. The circum-sporozoite protein (CSP) is currently the main target for vaccine development, but this study found that antibodies targeting non-CSP proteins can also inhibit parasite invasion and development.
Correction
Multidisciplinary Sciences
Zhong Yan Gan, Sylvie Callegari, Simon A. Cobbold, Thomas R. Cotton, Michael J. Mlodzianoski, Alexander F. Schubert, Niall D. Geoghegan, Kelly L. Rogers, Andrew Leis, Grant Dewson, Alisa Glukhova, David Komander
Article
Entomology
Rosemary S. Lees, Jennifer S. Armistead, Salum Azizi, Edi Constant, Christen Fornadel, John E. Gimnig, Janet Hemingway, Daniel Impoinvil, Seth R. Irish, William Kisinza, Natalie Lissenden, Henry D. Mawejje, Louisa A. Messenger, Sarah Moore, Corine Ngufor, Richard Oxborough, Natacha Protopopoff, Hilary Ranson, Graham Small, Joseph Wagman, David Weetman, Sarah Zohdy, Angus Spiers
Summary: To test the effectiveness and durability of new bed nets, it is necessary to study and test insecticide-resistant mosquitoes. A group of experts collaborated to develop a protocol for standardized monitoring and accurate characterization of resistant mosquitoes, providing valuable guidance for malaria control programs and stakeholders.
Article
Biology
Michal Pasternak, Julie M. J. Verhoef, Wilson Wong, Tony Triglia, Michael J. Mlodzianoski, Niall Geoghegan, Cindy Evelyn, Ahmad Z. Wardak, Kelly Rogers, Alan F. Cowmarc
Summary: The RhopH complex is not formed during merozoite invasion. Clag3 is released directly into the host cell cytoplasm, while RhopH2 and RhopH3 are released into the nascent parasitophorous vacuole. Export of RhopH2 and RhopH3 from the parasitophorous vacuole into the infected erythrocyte cytoplasm enables assembly of the Clag3/RhopH2/RhopH3 complex and its incorporation into the host cell membrane concomitant with activation of nutrient uptake.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Charles Bayly-Jones, Christopher J. Lupton, Claudia Fritz, Hariprasad Venugopal, Daniel Ramsbeck, Michael Wermann, Christian Jaeger, Alex de Marco, Stephan Schilling, Dagmar Schlenzig, James C. Whisstock
Summary: Meprin alpha, a zinc-dependent metalloprotease, is mainly expressed in the brush border membrane of proximal tubules in the kidney and enterocytes in the small intestine and colon. It plays important roles in inflammation, immunity, and extracellular matrix remodelling. Dysregulated meprin alpha is associated with various diseases. Cryo-electron microscopy reveals the unique structure of meprin alpha, including its giant helical assembly and the distinctive active site.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Zilu Wang, Huimin Hu, Luuk Heitink, Kelly Rogers, Yue You, Tao Tan, Connie Li Wai Suen, Alex Garnham, Hao Chen, Elizabeth Lieschke, Sarah T. T. Diepstraten, Catherine Chang, Diane Moujalled, Kate Sutherland, Guillaume Lessene, Oliver M. M. Sieber, Jane Visvader, Gemma L. L. Kelly, Andreas Strasser
Summary: APR-246 can kill malignant cells irrespective of their TP53/TRP53 status. It induces various programmed cell death pathways, such as apoptosis, necroptosis, and ferroptosis. Therefore, the clinical testing of APR-246 should be expanded to cancers expressing wild-type TP53 or TP53-deficient.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Chemistry, Medicinal
Simon J. A. Wiedemeyer, Guojie Wu, T. L. Phuong Pham, Heike Lang-Henkel, Benjamin Perez Urzua, James C. Whisstock, Ruby H. P. Law, Torsten Steinmetzer
Summary: Two series of macrocyclic plasmin inhibitors with high selectivity were synthesized, and crystal structures of these inhibitors in complex with a Ser195Ala microplasmin mutant were determined. The inhibitors bind to the open active site of plasmin without steric hindrance, explaining their excellent selectivity against other trypsin-like serine proteases. The substitution of the N-terminal phenylsulfonyl group of a previously described inhibitor led to two analogues with sub-nanomolar inhibition constants.
Article
Biology
Charles Bayly-Jones, Bill H. T. Ho, Corinna Lau, Eleanor W. W. Leung, Laura D'Andrea, Christopher J. J. Lupton, Susan M. M. Ekkel, Hariprasad Venugopal, James C. C. Whisstock, Tom E. E. Mollnes, Bradley A. A. Spicer, Michelle A. A. Dunstone
Summary: The cryo-EM structure of monoclonal antibody aE11 bound to polyC9 reveals that the binding site within the Membrane Attack Complex is a quaternary discontinuous epitope formed by two separate surfaces of the oligomeric C9 periphery.
COMMUNICATIONS BIOLOGY
(2023)
Correction
Biochemistry & Molecular Biology
Zilu Wang, Huimin Hu, Luuk Heitink, Kelly Rogers, Yue You, Tao Tan, Connie Li Wai Suen, Alex Garnham, Hao Chen, Elizabeth Lieschke, Sarah T. Diepstraten, Catherine Chang, Tianwei Chen, Diane Moujalled, Kate Sutherland, Guillaume Lessene, Oliver M. Sieber, Jane Visvader, Gemma L. Kelly, Andreas Strasser
CELL DEATH AND DIFFERENTIATION
(2023)