Article
Multidisciplinary Sciences
Maik Pietzner, Eleanor Wheeler, Julia Carrasco-Zanini, Nicola D. Kerrison, Erin Oerton, Mine Koprulu, Jian'an Luan, Aroon D. Hingorani, Steve A. Williams, Nicholas J. Wareham, Claudia Langenberg
Summary: This study integrates two proteomic technologies to analyze the effects of protein quantitative trait loci, showing that each technique captures different aspects of protein biology. The results provide a benchmark for future cross-platform discoveries and highlight the inconsistency in genetically predicted effect directions between different assays.
NATURE COMMUNICATIONS
(2021)
Article
Plant Sciences
Vinicius S. Londero, Thais A. Costa-Silva, Guilherme M. Antar, Joao B. Baitello, Larissa V. F. de Oliveira, Fernanda F. Camilo, Andrea N. L. Batista, Joao M. Batista, Andre G. Tempone, Joao Henrique G. Lago
Summary: In this study, compounds were extracted from Nectandra barbellata using an ionic liquid assisted by microwave. One sesquiterpene and three new lactones were isolated and tested against Trypanosoma cruzi. The bioactive compounds were found to act on the plasma membrane, mitochondria, and other cellular components, with no resemblance to interferent compounds predicted in silico.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Oncology
Wesley Ladeira Caputo, Milena Cremer de Souza, Caroline Rodrigues Basso, Valber de Albuquerque Pedrosa, Fabio Rodrigues Ferreira Seiva
Summary: This study provides a comprehensive analysis of differentially expressed genes in hepatocellular carcinoma (HCC), identifying potential therapeutic targets and opportunities for drug repurposing.
Review
Chemistry, Multidisciplinary
Ishrath Mohamed Irshadeen, Sarah L. Walden, Martin Wegener, Vinh X. Truong, Hendrik Frisch, James P. Blinco, Christopher Barner-Kowollik
Summary: This study utilized measuring action spectra to map covalent bond formation and cleavage, revealing that UV/vis spectra fail to accurately predict photochemical reactivity. The research demonstrates that tunable lasers can selectively excite molecules, allowing for in-depth exploration of the mechanisms of photoinduced reactions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemical Research Methods
Shirui Yang, Wenxiang Zhang, Zheyi Liu, Ziyang Zhai, Xudong Hou, Ping Wang, Guangbo Ge, Fangjun Wang
Summary: This paper systematically investigates the molecular interactions between HSA and various therapeutic drugs using a mass spectrometry-based strategy, revealing the major ligand binding sites of HSA and newly characterized drug-binding areas. The MS-LRP strategy may have important application prospects in pharmacodynamics, pharmacokinetics, and safety evaluation of small-molecule drugs.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2021)
Article
Mechanics
Jincheng Fan, Heping Xie, Shaofan Li, Heng Zhang, Yong Zhang
Summary: The paper provides new insights into the bond-based Peridynamics (BPD) and ordinary state-based Peridynamics (OSPD) models by studying the bond length change and micro-potential function. The nonlocal elastic strain energy density (NESED) and constitutive bond force densities are discussed using specific influence functions. The findings show that the proposed method can retrieve the results of the OSPD model for small deformations. Additionally, the Peridynamic model has descriptive and predictive capabilities.
ENGINEERING FRACTURE MECHANICS
(2023)
Review
Food Science & Technology
Sonia A. Soto-Rodriguez, Rodolfo Lozano-Olvera, Gabriela Ramos-Clamont Montfort, Edgar Zenteno, Jose Luis Sanchez-Salgado, Norberto Vibanco-Perez, Karla G. Aguilar Rendon
Summary: The PirAB toxins secreted by Vibrio parahaemolyticus (Vp) play a role in causing acute hepatopancreatic necrosis disease (AHPND) in Penaeid shrimp. These toxins damage the epithelial cells of the shrimp hepatopancreas (Hp) and the PirB(Vp) subunit has lectin-like activity. Understanding the toxin receptors can help prevent host disease by blocking toxin-receptor interactions. Additionally, Vp AHPND changes the microbiota in the surrounding water, resulting in a reduction of certain bacterial taxa.
Review
Biochemistry & Molecular Biology
Samuel T. Slocum, Jeffrey F. DiBerto, Bryan L. Roth
Summary: A confluence of factors has reignited interest in psychedelic drugs, with the FDA designating psilocybin as a Breakthrough Therapy for treatment-resistant depression. The clearer understanding of how these drugs exert their effects at the molecular level is essential for further development of applications in hallucinogenic and therapeutic mechanisms.
JOURNAL OF NEUROCHEMISTRY
(2022)
Review
Cell Biology
Carl Bowazolo, David Morse
Summary: The dinoflagellate Lingulodinium specializes its metabolism to perform different tasks better at specific times of day. These rhythms are circadian and controlled by an endogenous circadian clock. The metabolic rhythms are revealed by changes in gene expression at a translational level and are regulated by over three thousand transcripts.
Article
Biochemical Research Methods
Hua Li, Yilian Liu, Zhe Wang, Yuping Xie, Lijun Yang, Yanni Zhao, Ruijun Tian
Summary: This study developed a mass spectrometry-based method for analyzing the types and quantities of gangliosides at low concentrations. The findings showed that acetylated and N-acetylgalactosaminylated ganglioside species were up-regulated, while major gangliosides were down-regulated in the development of Alzheimer's disease. Certain ganglioside species were identified as time-coursed biomarkers, and one ganglioside could be a potential candidate for early diagnosis of AD.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Agriculture, Multidisciplinary
Xiongjie Zheng, Jianing Mi, Xiuxin Deng, Salim Al-Babili
Summary: Apocarotenoids play a crucial role in the color and aroma of citrus fruits, with red peels having higher levels of various apocarotenoids compared to yellow peels. Overexpressing the CitCCD4b gene in citrus can significantly increase the content of apocarotenoids, suggesting the potential for metabolic engineering of apocarotenoids and their derivatives.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
C. Wittenbecher, R. Cuadrat, L. Johnston, F. Eichelmann, S. Jaeger, O. Kuxhaus, M. Prada, F. M. Del Greco, A. A. Hicks, P. Hoffman, J. Krumsiek, F. B. Hu, M. B. Schulze
Summary: This study investigates the association between specific ceramides and dihydroceramides and the risk of developing type 2 diabetes and cardiovascular disease. The results indicate that certain ceramides and dihydroceramides are positively or negatively associated with disease risk. Moreover, the study suggests that the effects of high red meat consumption and coffee intake on disease risk are partly mediated by (dihydro)ceramides.
NATURE COMMUNICATIONS
(2022)
Review
Pharmacology & Pharmacy
Dang Ding, Shujing Xu, Edeildo Ferreira da Silva-Junior, Xinyong Liu, Peng Zhan
Summary: The (re)emergence of multidrug-resistant viruses and the emergence of new viruses have led to an urgent need for new antiviral agents. Peptidomimetics, as therapeutic drugs, offer advantages such as enhanced binding affinity, improved metabolic stability, and better bioavailability. Novel antivirals are being developed through strategies that involve modifying peptides into peptidomimetic derivatives. This review outlines various structural modification design strategies, including terminal structure modifications, pseudopeptides, amino acid modifications, inverse peptides, cyclization, and molecular hybridization, and presents successful examples of peptidomimetic designs.
DRUG DISCOVERY TODAY
(2023)
Review
Cell Biology
Miguel Sanchez-alvarez, Miguel angel del Pozo, Marta Bosch, Albert Pol
Summary: Lipid droplets are organelles that store neutral lipids and play active roles in cellular functions. Systematic molecular profiling approaches have enabled us to understand the functions and mechanisms of lipid droplets. These advances provide important knowledge about the relationships between lipid droplets and other biological processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Mathematical & Computational Biology
Shinsuke Ohnuki, Itsuki Ogawa, Kaori Itto-Nakama, Fachuang Lu, Ashish Ranjan, Mehdi Kabbage, Abraham Abera Gebre, Masao Yamashita, Sheena C. Li, Yoko Yashiroda, Satoshi Yoshida, Takeo Usui, Jeff S. Piotrowski, Brenda J. Andrews, Charles Boone, Grant W. Brown, John Ralph, Yoshikazu Ohya
Summary: This study developed a high-throughput platform for yeast morphological profiling, which can predict the intracellular targets of chemical compounds by comparing the dose-dependent morphological changes induced by the compound with the morphological changes in gene-deleted cells. The platform was successfully used to predict the mechanism of action of a novel compound and discover its antifungal properties.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Carys Davies, Cher-Pheng Ooi, Georgios Sioutas, Belinda S. Hall, Haneesh Sidhu, Falk Butter, Sam Alsford, Bill Wickstead, Gloria Rudenko
Summary: The African trypanosome Trypanosoma brucei relies on a protective VSG coat for survival in mammalian hosts. A whole genome RNAi library screen identified a novel DNA binding protein TbSAP, which plays an important role in silencing the extensive VSG repertoire in bloodstream form T. brucei.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Michele S. Y. Tan, Konstantinos Koussis, Chrislaine Withers-Martinez, Steven A. Howell, James A. Thomas, Fiona Hackett, Ellen Knuepfer, Min Shen, Matthew D. Hall, Ambrosius P. Snijders, Michael J. Blackman
Summary: The study reveals the pathway of malaria parasite egress from host erythrocytes and identifies SERA6 as a target for a new class of antimalarial drugs. Activation of SERA6 involves an autocatalytic step triggered by SUB1 cleavage, which requires interaction with the protein cofactor MSA180 for autoproteolytic maturation.
Review
Parasitology
David Horn
Summary: Genome-scale genetic screens have played a crucial role in African trypanosomes by uncovering mechanisms related to drug resistance, metabolism, and gene expression control. They have also been effective in identifying potential antitrypanosomal drug targets.
TRENDS IN PARASITOLOGY
(2022)
Article
Multidisciplinary Sciences
Yanika Borg, Sam Alsford, Vasos Pavlika, Alexei Zaikin, Darren N. Nesbeth
Summary: Kinetoplastid protozoa, with unique properties, have been shown to hold bioengineering potential. This study successfully constructed an oscillatory gene network in Trypanosoma brucei for the first time, laying the foundation for future synthetic biology research.
Article
Biochemistry & Molecular Biology
Simone Altmann, Eva Rico, Sandra Carvalho, Melanie Ridgway, Anna Trenaman, Hannah Donnelly, Michele Tinti, Susan Wyllie, David Horn
Summary: This study reports a simple method for rapid and precise editing of priority drug targets in trypanosomatids. By targeting and editing drug targets, combined with sequencing technology, potential impacts on drug efficacy can be assessed quickly.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Gustavo Bravo Ruiz, Michele Tinti, Melanie Ridgway, David Horn
Summary: VSG expression plays a crucial role in parasite virulence and is a fascinating subject in extreme biology. This study identified three candidate VSG regulators and demonstrated the role of CFB2 in controlling VSG expression through the VSG 3' UTR. Additionally, insights into the connections between VSG expression control, ribosomal protein expression, and cytokinesis were revealed.
Correction
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
NATURE REVIEWS MICROBIOLOGY
(2022)
Review
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
Summary: Leishmaniasis, Chagas disease, and human African trypanosomiasis are major causes of death and illness, particularly in low- and middle-income countries. The development of new medicines for leishmaniasis and Chagas disease is urgently needed, with limited progress in the clinical pipeline for Chagas disease. This review provides an overview of recent advances in understanding the biology of these pathogens, with a focus on drug discovery, as well as the development of new drug candidates and potential solutions to overcome challenges in clinical development.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Catarina A. Marques, Melanie Ridgway, Michele Tinti, Andrew Cassidy, David Horn
Summary: In this study, a genome-wide RNA-interference library screen was used to investigate the cell cycle defects in Trypanosoma brucei. The results provide comprehensive functional genomic evidence for the known and novel machineries, pathways, and regulators that coordinate trypanosome cell cycle progression.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Abhinay A. Ramaprasad, Paul-Christian Burda, Konstantinos Koussis, James A. Thomas, Emma I. Pietsch, Enrica P. Calvani, Steven Howell, James J. MacRae, Ambrosius Snijders, Tim-Wolf Gilberger, Michael Blackman
Summary: Malaria parasite egress from host red blood cells involves membrane poration and rupture mediated by parasite effectors. In this study, two putative pore-forming proteins were found to be non-essential for egress. Instead, a parasite enzyme called LCAT was identified as being involved in the process. Mutant parasites lacking LCAT showed abnormal egress and reduced replication rate, with drastic changes in lipid composition during the process.
Article
Chemistry, Medicinal
Livio Racane, Lucija Pticek, Sanja Kostrun, Silvana Raic-Malic, Martin Craig Taylor, Michael Delves, Sam Alsford, Francisco Olmo, Amanda Fortes Francisco, John M. Kelly
Summary: We designed and synthesized a series of symmetric benzothiazole derivatives and evaluated their efficacy against Trypanosoma brucei and Plasmodium falciparum. One compound showed high selectivity and trypanocidal activity, curing mice infected with trypanosomiasis. It also exhibited activity against the malaria parasite.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Melissa N. Hart, Franziska Mohring, Sophia M. DonVito, James A. Thomas, Nicole Mueller-Sienerth, Gavin J. Wright, Ellen Knuepfer, Helen R. Saibil, Robert W. Moon
Summary: Invasion of red blood cells by Plasmodium merozoites is crucial for their survival, and two major protein families, DBPs/EBAs and RBLs/RHs, play important roles in this process. P. knowlesi, a zoonotic malaria parasite, has larger merozoites and a smaller repertoire of DBP and RBL proteins compared to P. falciparum. By using CRISPR-Cas9 genome editing, the researchers determined the precise order of key invasion events and demonstrated distinct roles for each protein family. These findings provide insights into the phased commitment to invasion and suggest potential targets for intervention.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Douglas Escrivani, Viktor Scheidt, Michele Tinti, Joana Faria, David Horn
Summary: Some pathogens use antigenic variation to evade mammalian host adaptive immune responses. African trypanosomes employ variant surface glycoproteins (VSGs) to continually switch their active VSGs and avoid immune recognition. Switched trypanosomes compete in a predictable manner that is dependent on the activated VSG, and the population of cells that activates minichromosome derived VSGs has a competitive advantage.
Article
Microbiology
Anna Trenaman, Michele Tinti, Abdelmadjid Atrih, David Horn
Summary: Nucleoside analogs are widely used as anti-infective agents, but their potential as anti-parasitic agents has not been fully explored. This study identified two proteins, Tb927.6.2800 and HD82, associated with purine analog resistance in African trypanosomes. The findings also validated two nucleoside kinases involved in pro-drug activation. HD82, related to the mammalian nuclear viral restriction factor SAMHD1, sensitized trypanosomes to nucleoside analogs by reducing native nucleotide pools. This study provides insights into nucleoside/nucleotide metabolism and nucleoside analog resistance in trypanosomatids.
Review
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
Summary: Leishmaniasis, Chagas disease, and human African trypanosomiasis are causing significant death and morbidity, especially in low- and middle-income countries. There is a critical need for new medications for leishmaniasis and Chagas disease, while the clinical development pipeline for Chagas disease remains sparse. This review discusses recent advancements in understanding the biology of these pathogens, with a focus on drug discovery, and explores progress in developing new drug candidates and identifying potential molecular targets. The challenges in developing new clinical candidates are also discussed, along with potential solutions to overcome these hurdles.
NATURE REVIEWS MICROBIOLOGY
(2023)