Article
Immunology
Kazutoyo Miura, Eizo Takashima, Thao P. Pham, Bingbing Deng, Luwen Zhou, Wei-Chiao Huang, Ababacar Diouf, Yonas T. Gebremicale, Mayumi Tachibana, Tomoko Ishino, C. Richter King, Jonathan F. Lovell, Carole A. Long, Takafumi Tsuboi
Summary: This study identifies functional epitopes within the malaria transmission-blocking vaccine Pfs230, using antibody depletion and enrichment techniques. Multiple functional epitopes were found and the feasibility of using synthetic peptide antigens for a malaria TBV was established.
Article
Immunology
Nan Hou, Shanshan Li, Ning Jiang, Xianyu Piao, Yu Ma, Shuai Liu, Qijun Chen
Summary: The study uncovered the developmental transcriptome of asexual parasites of P. falciparum and identified a group of previously unknown merozoite proteins that may play crucial roles in the invasion process of merozoites.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Brittany N. Araj, Bruce Swihart, Robert Morrison, Patricia Gonzales Hurtado, Andrew Teo, Almahamoudou Mahamar, Oumar Attaher, Bacary S. Diarra, Santara Gaoussou, Djibrilla Issiaka, Alassane Dicko, Patrick E. Duffy, Michal Fried
Summary: The study utilized proteomic analyses of PfEMP1 from clinical parasite isolates collected from Malian children to identify targets of immunity. Peptide-specific antibody responses in children were examined, and it was found that high antibody levels to specific PfEMP1 domains correlated with decreased parasite burden in future infections. These findings suggest that certain PfEMP1 domains play a role in protective immunity against malaria.
Article
Immunology
Daisuke Ito, Jun-Hu Chen, Eizo Takashima, Tomoyuki Hasegawa, Hitoshi Otsuki, Satoru Takeo, Amporn Thongkukiatkul, Eun-Taek Han, Takafumi Tsuboi
Summary: Malaria is responsible for half a million deaths annually, with the parasite's intraerythrocytic lifecycle being a major cause. By generating monoclonal antibodies against Plasmodium falciparum schizont-rich parasites, several apical organellar proteins were identified and characterized for their roles in erythrocyte invasion and parasite development.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Parasitology
Juan M. Balbin, Gary K. Heinemann, Lee M. Yeoh, Tim-Wolf Gilberger, Mark Armstrong, Michael F. Duffy, Paul R. Gilson, Danny W. Wilson
Summary: Plasmodium falciparum regulates gene expression throughout its lifecycle, with certain proteins playing a role during the invasion and establishment of infection in host red blood cells. This study focuses on two zinc finger proteins, PfCZIF1 and PfCZIF2, which are highly expressed during late schizogony. While PfCZIF1 and PfCZIF2 are not essential for blood stage growth, at least one of them is required for parasite growth in vitro. These proteins are peripherally associated with a membrane and may regulate the expression of proteins exported into the red blood cell cytosol after merozoite invasion.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2023)
Article
Immunology
Jacqueline S. Eacret, Elizabeth M. Parzych, Donna M. Gonzales, James M. Burns
Summary: The use of PfMSP8 as a carrier to optimize a PfMSP2-based subunit malaria vaccine showed promising results in terms of antibody production and T cell recognition. The choice of adjuvant impacted the specificity and functionality of induced antibodies.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Julie Healer, Jennifer K. K. Thompson, Karen L. L. Mackwell, Cecille D. D. Browne, Benjamin A. A. Seager, Anna Ngo, Kym N. N. Lowes, Sarah E. E. Silk, David Pulido, Lloyd D. W. King, Jayne M. M. Christen, Amy R. R. Noe, Vinayaka Kotraiah, Paul J. J. Masendycz, Rajkannan Rajagopalan, Leanne Lucas, Marianne M. M. Stanford, Lorraine Soisson, Carter Diggs, Robin Miller, Susan Youll, Kaye Wycherley, Simon J. J. Draper, Alan F. F. Cowman
Summary: This study assessed the potential of a protein-in-adjuvant blood stage malaria vaccine based on a combination of RH5, Ripr, and CyRPA. The results showed that this vaccine could induce highly inhibitory parasite neutralizing antibodies against Plasmodium falciparum.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Anne S. Knudsen, Kasper H. Bjornsson, Maria R. Bassi, Melanie R. Walker, Andreas Kok, Bogdan Cristinoi, Anja R. Jensen, Lea Barfod
Summary: Monoclonal antibodies specific to PfCyRPA were found to neutralize the in vitro growth of Ghanaian field isolates and laboratory-adapted parasite lines, with subsets of mAbs binding to distinct sites on PfCyRPA showing potentiated neutralizing effects when combined. Additionally, combinations of PfCyRPA- and PfRh5-specific mAbs were demonstrated to act synergistically to neutralize parasite growth, highlighting the importance of targeting defined protective epitopes on multiple parasite antigens to improve blood-stage vaccine efficacy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Parasitology
Qinwen Xu, Sihong Liu, Kokouvi Kassegne, Bo Yang, Jiachen Lu, Yifan Sun, Wenli Zhong, Miaosa Zhang, Yaobao Liu, Guoding Zhu, Jun Cao, Yang Cheng
Summary: The study revealed highly conserved gene sequences of PoMSP1(19) in Plasmodium ovale. Recombinant PoMSP1(19)-GST proteins showed high immunogenicity in mice, inducing a strong antibody response. Protein microarrays exhibited 89.96% sensitivity and 75% specificity in detecting immune responses in patients infected with P. ovale.
PARASITES & VECTORS
(2021)
Article
Biology
Abdirahman Abdi, Fiona Achcar, Lauriane Sollelis, Joao Luiz Silva-Filho, Kioko Mwikali, Michelle Muthui, Shaban Mwangi, Hannah W. Kimingi, Benedict Orindi, Cheryl Andisi Kivisi, Manon Alkema, Amrita Chandrasekar, Peter C. Bull, Philip Bejon, Katarzyna Modrzynska, Teun Bousema, Matthias Marti
Summary: The malaria parasite life cycle involves asexual replication in human blood and differentiation into gametocytes for transmission to mosquitoes. Host factors influence the commitment to differentiate into gametocytes, but the exact mechanism is still unclear. In this study, we analyzed data from 828 children in Kenya over 18 years to understand the relationship between host immunity, parasite growth, and transmission investment. We found that reduced plasma lysophosphatidylcholine levels, which are associated with inflammatory responses, are correlated with increased transmission investment and reduced asexual replication.
Article
Multidisciplinary Sciences
Georg Meisl, Catherine K. Xu, Jonathan D. Taylor, Thomas C. T. Michaels, Aviad Levin, Daniel Otzen, David Klenerman, Steve Matthews, Sara Linse, Maria Andreasen, Tuomas P. J. Knowles
Summary: The study reveals that both disease-related proteins and proteins with functional roles in biology are capable of self-replication. However, the rate of self-replication is insignificant on the biologically relevant time scale for proteins fulfilling structural roles, while disease-related proteins can self-replicate quickly within the associated disease's time scale.
Article
Immunology
Irene Molina-de la Fuente, Maria Jose Sagrado Benito, Laurence Flevaud, Janet Ousley, Harriet Akello Pasquale, Ahmed Julla, Abdirashid M. Abdi, Buai Tut Chol, Bakri Abubakr, Agustin Benito, Cristian Casademont, Carolina Nanclares, Pedro Berzosa
Summary: Deletions of pfhrp2 and pfhrp3 genes pose a threat to the global use of Plasmodium falciparum malaria rapid diagnostic tests. In South Sudan, the frequencies of pf-hrp2 deletion, pfhrp3 deletion, and double deletions were 15.6%, 20.0%, and 7.5% respectively. Deletions were approximately twice as prevalent in monoclonal infections compared to polyclonal infections.
EMERGING INFECTIOUS DISEASES
(2023)
Article
Microbiology
Huong Giang Le, Haung Naw, Jung-Mi Kang, Tuan Cuong Vo, Moe Kyaw Myint, Zaw Than Htun, Jinyoung Lee, Won Gi Yoo, Tong-Soo Kim, Ho-Joon Shin, Byoung-Kuk Na
Summary: This study analyzed the antimalarial drug resistance genes in malaria parasites in the Mandalay region of Myanmar and found substantial levels of mutations conferring antimalarial drug resistance. Continuous monitoring of these mutations is necessary to provide useful information for policymakers.
Article
Multidisciplinary Sciences
Rispah Abdallah, Jaime Louzada, Christina Carlson, Dragan Ljolje, Venkatachalam Udhayakumar, Joseli Oliveira-Ferreira, Naomi W. Lucchi
Summary: The state of Roraima in Brazil has experienced an increase in imported Plasmodium falciparum infections from neighboring countries. A study was conducted to determine the prevalence and quantify the imported malaria cases. The study found that 80% of the malaria patients likely acquired infections in Venezuela, with the rest acquiring in other neighboring countries. The findings support the hypothesis that imported malaria contributes significantly to malaria cases in Roraima.
SCIENTIFIC REPORTS
(2022)
Article
Infectious Diseases
Alistair R. D. McLean, Chanida Indrasuta, Zay Soe Khant, Aung Kyaw Phyo, Sai Maung Maung, James Heaton, Hein Aung, Ye Aung, Kyaw Soe, Myo Maung Maung Swe, Lorenz von Seidlein, Ni Ni Tun, Kyaw Myo Tun, Nicholas P. J. Day, Elizabeth A. Ashley, Thaung Hlaing, Thar Tun Kyaw, Arjen M. Dondorp, Mallika Imwong, Nicholas J. White, Frank M. Smithuis
Summary: In regions with artemisinin resistance, mass drug administration of dihydroartemisinin-piperaquine can effectively reduce Plasmodium falciparum prevalence. This study demonstrated a significant decrease in P falciparum prevalence in clusters receiving MDA intervention, highlighting the importance of community case management in accelerating malaria elimination.
LANCET INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Bankala Krishnarjuna, Punnepalli Sunanda, Jessica Villegas-Moreno, Agota Csoti, Rodrigo A. Morales, Dorothy C. C. Wai, Gyorgy Panyi, Peter Prentis, Raymond S. Norton
Summary: Acrorhagin I is a disulfide-rich peptide found in sea anemones, showing toxicity towards crabs but no activity on voltage-gated ion channels. The peptide's structure resembles a toxin from a marine worm, suggesting a recurring motif in disulfide-rich peptides in marine organisms. Metal ion interaction studies indicated potential modulation of its function by zinc and nickel.
JOURNAL OF STRUCTURAL BIOLOGY
(2021)
Editorial Material
Chemistry, Multidisciplinary
Haribabu Arthanari, Kandala V. R. Chary, Thomas Szyperski, Krishna V. Ramanathan, Ramakrishna V. Hosur, Nagarajarao Suryaprakash, Srinivasarao Raghothama, Naranamangalam R. Jagannathan, Raymond S. Norton, Erode N. Prabhakaran, Paturu Kondaish, Sulakshana P. Mukherjee, Satish Kumar Adiga, RamaKrishna Vadrevu, Anirban Bhunia, David Joseph
MAGNETIC RESONANCE IN CHEMISTRY
(2021)
Article
Immunology
Sreedam C. Das, Jason D. Price, Katharine Gosling, Nicola MacLennan, Ricardo Ataide, Jeffrey Seow, Vashti Irani, Ines I. Atmosukarto, Robin F. Anders, Jack S. Richards, Christopher A. MacRaild, Raymond S. Norton
Summary: The study showed that immunizing mice with MSP2 engrafted onto liposomes using a C-terminal tether mimicking the native GPI anchor resulted in enhanced immune responses directed towards conserved epitopes in MSP2. The induced antibodies were cross-reactive with isolated 3D7 and FC27 merozoites, indicating a strain-transcendent immune response. Liposomal formulation of MSP2 induced higher titres of complement-fixing antibodies compared to MSP2 formulated in Montanide ISA720.
Article
Immunology
Jeffrey Seow, Sreedam C. Das, Rodrigo A. V. Morales, Ricardo Ataide, Bankala Krishnarjuna, Mitchell Silk, David K. Chalmers, Jack Richards, Robin F. Anders, Christopher A. MacRaild, Raymond S. Norton
Summary: The malaria vaccine candidate MSP2 has shown promise in clinical trials, with potential for reducing parasite densities. By focusing on the conserved regions of MSP2, the immune response can be directed towards more accessible and favorable epitopes. The structure-based approach in peptide vaccine design has the potential to be applied not only to MSP2-based malaria vaccines, but also to other intrinsically disordered antigens.
Article
Chemistry, Medicinal
Joseph A. Nicolazzo, Yijun Pan, Ilenia Di Stefano, Kwok H. C. Choy, Sanjeevini Babu Reddiar, Yi Ling Low, Dorothy C. C. Wai, Raymond S. Norton, Liang Jin
Summary: This study evaluated the impact of the Kv1.3 channel blocker HsTX1[R14A] on microglial-mediated neuroinflammation. The results showed that HsTX1[R14A] attenuated the transcription and release of TNF-α and IL-6 in microglia, and reduced the levels of pro-inflammatory mediators in a mouse model of neuroinflammation.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
David A. Eagles, Natalie J. Saez, Bankala Krishnarjuna, Julia J. Bradford, Yanni K. -Y. Chin, Hana Starobova, Alexander Mueller, Melissa E. Reichelt, Eivind A. B. Undheim, Raymond S. Norton, Walter G. Thomas, Irina Vetter, Glenn F. King, Samuel D. Robinson
Summary: This study discovered a peptide toxin, MIITX2-Mg1a, in the venom of the Australian giant red bull ant that mimics vertebrate epidermal growth factor. It acts as a potent agonist of the mammalian EGF receptor ErbB1, causing long-lasting hypersensitivity in mice.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Arfatur Rahman, Macgregor A. Matthews, Cameron J. Nowell, David K. Chalmers, Philip E. Thompson, Sandra E. Nicholson, Nicholas Barlow, Raymond S. Norton
Summary: In this study, a peptide inhibitor was conjugated with a cell-penetrating peptide (CPP) to deliver into macrophages and enhance NO production, which is significant for the development of new antibiotics targeting the host innate immune response.
BIOORGANIC CHEMISTRY
(2022)
Editorial Material
Pharmacology & Pharmacy
Raymond S. Norton, Denise V. Tambourgi
Article
Chemistry, Medicinal
Billy J. Williams -Noonan, Melissa N. Speer, Tu C. Le, Maiada M. Sadek, Philip E. Thompson, Raymond S. Norton, Elizabeth Yuriev, Nicholas Barlow, David K. Chalmers, Irene Yarovsky
Summary: This study introduces a random forest machine learning model for predicting the permeation rates of cell membranes, using a dataset of over 1000 macrocyclic compounds. The model, based on easily calculable chemical features, outperforms other models in terms of performance metrics. It provides design guidelines for membrane-permeating macrocycles.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Medicine, Research & Experimental
Sanjeevini Babu Reddiar, Michael de Veer, Brett M. Paterson, Tara Sepehrizadeh, Dorothy C. C. Wai, Agota Csoti, Gyorgy Panyi, Joseph A. Nicolazzo, Raymond S. Norton
Summary: This study investigates the in vivo distribution of HsTX1[R14A] peptide in mice and finds increased uptake in a LPS-induced mouse model of neuroinflammation, as well as accumulation in inflamed joints.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Medicinal
Karoline Sanches, Viktor Prypoten, K. George Chandy, David K. Chalmers, Raymond S. Norton
Summary: Peptide toxins like ShK can inhibit the KV1.3 potassium channel and may have potential therapeutic applications for autoimmune and neuroinflammatory diseases. ShK and its homolog HmK exhibit different dynamic behaviors, with ShK showing higher affinity for the KV1.3 channel.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Food Science & Technology
Hayden L. Smith, Peter J. Prentis, Scott E. Bryan, Raymond S. Norton, Daniel A. Broszczak
Summary: The venom delivery system of Phylum Cnidaria is unique, consisting of individual organelles known as nematocysts. Acontia, found in a limited number of sea anemone species, are packed with large nematocysts used for defense. This study identified the venom profile of acontia in Calliactis polypus, revealing limited toxin diversity and a novel toxin with two ShK-like domains. This research provides a foundation for further investigating the function of acontial toxins in sea anemones.
Review
Biochemistry & Molecular Biology
K. George Chandy, Karoline Sanches, Raymond S. Norton
Summary: The voltage-gated potassium channel K(V)1.3 is an important therapeutic target for autoimmune and neuroinflammatory diseases. Recent structural studies have provided insights into the conformational changes of the channel and the mechanism of ion permeation. These findings contribute to a better understanding of the slow inactivation mechanism of K(V) channels and can guide the development of future immunotherapeutics targeting K(V)1.3.
Article
Biochemistry & Molecular Biology
Karoline Sanches, Lauren M. Ashwood, Abisola Ave-Maria Olushola-Siedoks, Dorothy C. C. Wai, Arfatur Rahman, Kashmala Shakeel, Muhammad Umair Naseem, Gyorgy Panyi, Peter J. Prentis, Raymond S. Norton
Summary: Diverse structural scaffolds have been found in peptides from sea anemones, including the common ShKT scaffold. While some ShKT peptides from sea anemones inhibit K-V 1.x channels, others do not. Using NMR and molecular dynamics simulations, a new ShKT peptide from the sea anemone Telmatactis stephensoni was studied and found to have no activity against K-V 1.x channels. The exposure of dyad residues during MD simulations is correlated with the ability of ShKT peptides to block K-V 1.x channels.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Chemistry, Inorganic & Nuclear
Yu Wang, Hongze Hu, Siming Yuan, Yunyan Li, Kaiming Cao, Hongbin Sun, Yangzhong Liu
Summary: The research finds that copper can bind to RNF11 and disrupt its structure and function. This may affect the ubiquitination process of RNF11 as well as its function as a transcriptional regulator.
INORGANIC CHEMISTRY FRONTIERS
(2022)