Article
Medicine, General & Internal
Melissa D. Conrad, Victor Asua, Shreeya Garg, David Giesbrecht, Karamoko Niare, Sawyer Smith, Jane F. Namuganga, Thomas Katairo, Jennifer Legac, Rebecca M. Crudale, Patrick K. Tumwebaze, Samuel L. Nsobya, Roland A. Cooper, Moses R. Kamya, Grant Dorsey, Jeffrey A. Bailey, Philip J. Rosenthal
Summary: This study identified multifocal emergence and spread of Plasmodium falciparum with partial resistance to artemisinins in Uganda. The emergence and spread of resistance were predominantly observed in areas where effective malaria control had been discontinued or transmission was unstable.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Hematology
Divya Beri, Manpreet Singh, Marilis Rodriguez, Mihaela Barbu-Stevanovic, Giselle Rasquinha, Avital Mendelson, Xiuli An, Deepa Manwani, Karina Yazdanbakhsh, Cheryl A. Lobo
Summary: Sickle red blood cells (RBCs) naturally resist hemoparasite infections, and this study investigates the factors involved in this resistance using Babesia divergens grown in sickle (SS) and sickle trait (AS) cells. Factors such as oxygenation, fetal hemoglobin positivity, cellular redox environment and parasite dynamics influence the proliferation of Babesia in different RBCs. By developing an image flow cytometric tool, the researchers were able to identify sickled cells and constituent Hb, and found that hypoxic conditions impaired parasite growth while oxygenation alleviated cell sickling and inhibited parasite proliferation. Host-cells of choice were identified as HbF+-SS under both hypoxic and hyperoxic conditions. These findings contribute to understanding the natural resistance to Babesia and can aid in developing novel therapies against human babesiosis.
Article
Multidisciplinary Sciences
Brendan Fries, Carlos A. Guerra, Guillermo A. Garcia, Sean L. Wu, Jordan M. Smith, Jeremias Nzamio Mba Oyono, Olivier T. Donfack, Jose Osa Osa Nfumu, Simon Hay, David L. Smith, Andrew J. Dolgert
Summary: Different population layers performed differently in matching the gold standard distribution at different population densities. Choosing the appropriate population map has a significant impact on burden estimates in a malaria model.
Article
Multidisciplinary Sciences
Huan Cao, Aristotelis Antonopoulos, Sadie Henderson, Heather Wassall, John Brewin, Alanna Masson, Jenna Shepherd, Gabriela Konieczny, Bhinal Patel, Maria-Louise Williams, Adam Davie, Megan A. Forrester, Lindsay Hall, Beverley Minter, Dimitris Tampakis, Michael Moss, Charlotte Lennon, Wendy Pickford, Lars Erwig, Beverley Robertson, Anne Dell, Gordon D. Brown, Heather M. Wilson, David C. Rees, Stuart M. Haslam, J. Alexandra Rowe, Robert N. Barker, Mark A. Vickers
Summary: The surface-exposed high mannose N-glycans on diseased or oxidized red blood cells bind to mannose receptor CD206 on phagocytes, mediating phagocytosis in sickle cell disease and malaria. This recognition of surface N-linked high mannose glycans as a response to cellular stress is a common molecular mechanism in the pathogenesis of sickle cell disease and resistance to severe malaria in individuals with sickle cell trait.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Shoaib Ashraf, Areeba Khalid, Jerrin Kuriakose, Akilan Palanisami, Yanfang Feng, Tayyaba Hasan
Summary: This study introduces a light-based photochemical approach, Photodynamic Therapy (PDT), utilizing ALA-PpIX synthesis for effective destruction of Plasmodium falciparum, paving the way for the REAP strategy. This provides a new treatment avenue for multi-drug resistant severe malaria and other intracellular blood pathogens dependent on heme-synthesis.
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
(2021)
Article
Cell Biology
Ayushi Chaurasiya, Swati Garg, Ashish Khanna, Chintam Narayana, Ved Prakash Dwivedi, Nishant Joshi, e Zill Anam, Niharika Singh, Jhalak Singhal, Shikha Kaushik, Amandeep Kaur Kahlon, Pallavi Srivastava, Manisha Marothia, Mukesh Kumar, Santosh Kumar, Geeta Kumari, Akshay Munjal, Sonal Gupta, Preeti Singh, Soumya Pati, Gobardhan Das, Ram Sagar, Anand Ranganathan, Shailja Singh
Summary: Pathogens hijack host metabolic status to facilitate their propagation, and inhibition of pathogen-mediated host NAD(+) modulation is a promising approach to interfere with infection dissemination.
CELL DEATH DISCOVERY
(2021)
Article
Multidisciplinary Sciences
Theresa Reiker, Monica Golumbeanu, Andrew Shattock, Lydia Burgert, Thomas A. Smith, Sarah Filippi, Ewan Cameron, Melissa A. Penny
Summary: Individual-based models are essential in the global fight against infectious diseases, but the complexity of the models can pose challenges for calibration. The authors propose using a Bayesian optimization framework to calibrate a complex malaria transmission simulator, resulting in improved fitting outcomes compared to previous calibrations.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Jean C. Digitale, Perri C. Callaway, Maureen Martin, George Nelson, Mathias Viard, John Rek, Emmanuel Arinaitwe, Grant Dorsey, Moses Kamya, Mary Carrington, Isabel Rodriguez-Barraquer, Margaret E. Feeney
Summary: The study identified a relationship between KIR and HLA genotypes and the risk of Plasmodium falciparum infection, where the presence of HLA-C2 and HLA-Bw4 increased the likelihood of infection, while HLA-C1 decreased it.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Elina Lidumniece, Chrislaine Withers-Martinez, Fiona Hackett, Christine R. Collins, Abigail J. Perrin, Konstantinos Koussis, Claudine Bisson, Michael J. Blackman, Aigars Jirgensons
Summary: Malaria is a devastating infectious disease causing over 400,000 deaths annually. Researchers have developed substrate-based peptidic boronic acids that inhibit a parasite protease called SUB1, preventing parasite replication through egress and potentially serving as a new class of antimalarial drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
James A. Watson, Sophie Uyoga, Perpetual Wanjiku, Johnstone Makale, Gideon M. Nyutu, Neema Mturi, Elizabeth C. George, Charles J. Woodrow, Nicholas P. J. Day, Philip Bejon, Robert O. Opoka, Arjen M. Dondorp, Chandy C. John, Kathryn Maitland, Thomas N. Williams, Nicholas J. White
Summary: Severe malaria caused by Plasmodium falciparum is difficult to accurately diagnose in children in high-transmission settings. A combination of platelet count and plasma PfHRP2 concentration can be used to identify severe falciparum malaria in severely ill patients. About one-third of children enrolled in clinical studies of severe malaria in high-transmission settings in Africa had other causes of their severe illness.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
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.
Review
Multidisciplinary Sciences
Yonas Yimam, Mehdi Mohebali, Mohammad Javad Abbaszadeh Afshar
Summary: This study compared the diagnostic performance of a new ultrasensitive rapid diagnostic test (us-RDT) and a conventional rapid diagnostic test (co-RDT) for detecting malaria. The results showed that us-RDT had higher sensitivity, especially in asymptomatic individuals and low transmission areas.
Article
Biotechnology & Applied Microbiology
Jack Adderley, Christian Doerig
Summary: This study fills gaps in the kinomes of Plasmodium falciparum and Plasmodium vivax, highlighting their similarities and differences for target selection. It also identifies kinases that are not suitable targets for drug discovery due to their high similarity with human counterparts.
Review
Immunology
Cindy S. Chu, Marie Stolbrink, Daniel Stolady, Makoto Saito, Candy Beau, Kan Choun, Tha Gay Wah, Ne Mu, Klay Htoo, Be Nu, Arunrot Keereevijit, Jacher Wiladpaingern, Verena Carrara, Aung Pyae Phyo, Khin Maung Lwin, Christine Luxemburger, Stephane Proux, Prakaykaew Charunwatthana, Rose McGready, Nicholas J. White, Francois Nosten
Summary: This study reviewed all malaria cases managed by the Shoklo Malaria Research Unit along the Thailand-Myanmar border between 2000 and 2016. The results showed that Plasmodium falciparum and Plasmodium vivax malaria had higher incidence and mortality rates in this area compared to areas of low seasonal malaria transmission.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Immunology
Manuela Hauser, Jean-Bertin B. Kabuya, Molly Mantus, Luc K. Kamavu, James L. Sichivula, Wycliffe M. Matende, Nora Fritschi, Timothy Shields, Frank Curriero, Anton Kvit, Gershom Chongwe, William J. Moss, Nicole Ritz, Matthew M. Ippolito
Summary: This study examined the clinical features of malaria in refugee children in high-transmission areas of Africa. The findings showed that refugee children had higher malaria prevalence and mortality rates, partly due to delayed presentation and malnutrition. Interventions tailored to the refugee context, including rapid diagnosis and referral, are necessary to reduce malaria mortality.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Leander B. Crocker, Ju Hyun Lee, Suraj Mital, Gabrielle C. Mills, Sina Schack, Andrea Bistrovic-Popov, Christoph O. Franck, Ioanna Mela, Clemens F. Kaminski, Graham Christie, Ljiljana Fruk
Summary: The rise in antibiotic-resistant bacteria and zoonotic viral pandemics has created a need for the development of effective pathogen reduction strategies. Photodynamic inactivation (PDI) is an efficient strategy that can bypass typical resistance mechanisms. Riboflavin, which naturally occurs in the body, has been widely used in PDI applications due to its ability to release reactive oxygen species (ROS) when exposed to light. By designing the core structure of riboflavin derivatives, researchers were able to create more effective PDI agents against E. coli and a SARS-CoV-2 surrogate. The toxicity of these derivatives towards human fibroblast cells was also studied to assess their potential therapeutic applications.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Joseph E. Chambers, Nikita Zubkov, Marketa Kubankova, Jonathon Nixon-Abell, Ioanna Mela, Susana Abreu, Max Schwiening, Giulia Lavarda, Ismael Lopez-Duarte, Jennifer A. Dickens, Tomas Torres, Clemens F. Kaminski, Liam J. Holt, Edward Avezov, James A. Huntington, Peter St George-Hyslop, Marina K. Kuimova, Stefan J. Marciniak
Summary: This study investigates the mechanism of protein misfolding in alpha(1)-antitrypsin deficiency, leading to cirrhosis. The researchers find that alpha(1)-antitrypsin polymers undergo a phase transition, forming a protein matrix that hinders the mobility of ER proteins. This phase transition is promoted by ER stress and facilitated by the ER chaperone calreticulin. The study also reveals that immobilization of ER chaperones within the polymer matrix contributes to ER dysfunction. These findings provide insights into proteinopathies and suggest ER chaperones as potential therapeutic targets.
Review
Chemistry, Multidisciplinary
Wei Li, Gabriele S. Kaminski Schierle, Bingfu Lei, Yingliang Liu, Clemens F. Kaminski
Summary: Super-resolution imaging techniques have become popular for visualizing cellular structures with nanometric resolution. This review focuses on the use of fluorescent nanoparticles (NPs) as bright and photostable probes for super-resolution imaging. The review provides an overview of different super-resolution methods, discusses their demands on the properties of fluorescent NPs, and reviews the features, strengths, and weaknesses of each NP class. The future outlook and opportunities in material science for the development of probes for multiplexed subcellular imaging with nanometric resolution are also discussed.
Article
Microscopy
Romain F. Laine, Chetan Poudel, Clemens F. Kaminski
Summary: Fluorescence lifetime imaging (FLIM) is a method for quantifying sub-cellular processes in living cells. Existing methods for extracting lifetime from FLIM data have limitations, and this paper presents an improved centroid method (CMM) for higher speed and photon efficiency. By developing and generalizing the method, the paper introduces a new approach that can rapidly and accurately extract fluorescence lifetime over a wide dynamic range.
JOURNAL OF MICROSCOPY
(2022)
Article
Chemistry, Multidisciplinary
Karan Bali, Zeinab Mohamed, Anna Scheeder, Anna-Maria Pappa, Susan Daniel, Clemens F. Kaminski, Roisin M. Owens, Ioanna Mela
Summary: The rise of antibiotic resistance is an increasingly serious global human health issue with significant socioeconomic implications. This study uses outer membrane vesicles to mimic bacterial membranes and explore the composition and properties of complex bilayer systems, providing a high-resolution platform for the development of next-generation antibiotics.
Article
Biophysics
Zeinab Sadjadi, Doriane Vesperini, Annalena M. Laurent, Lena Barnefske, Emmanuel Terriac, Franziska Lautenschlaeger, Heiko Rieger
Summary: Migrating cells encounter various topographic features and obstacles in crowded biological environments. Experimental results show that cells are temporarily trapped near pillars, regardless of the vertical and horizontal confinement. Decreasing the vertical confinement does not affect cell velocity, but reduces persistence, leading to a loss of directional control. Decreasing the pillar spacing increases the escape time of cells from local traps and reduces the diffusion constant.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Ponnuswamy Mohanasundaram, Leila S. Coelho-Rato, Mayank Kumar Modi, Marta Urbanska, Franziska Lautenschlaeger, Fang Cheng, John E. Eriksson
Summary: Vimentin regulates cell size and autophagy through the mTORC1 signaling pathway, and this effect is manifested at the organism level in mice.
Article
Biochemical Research Methods
Ahmad Ahsan Nawaz, Despina Soteriou, Catherine K. Xu, Ruchi Goswami, Maik Herbig, Jochen Guck, Salvatore Girardo
Summary: Cell sorting based on mechanical properties has the potential to revolutionize the isolation of cells from heterogeneous populations. However, current methods sacrifice sorting rate for purity. We present a label-free cell sorting method using focused travelling surface acoustic wave in combination with real-time deformability cytometry, which enables high-throughput and high purity sorting of cells with different physical parameters. Our system also allows sorting of small cell fractions from concentrated populations, demonstrating the flexibility and applicability of the method.
Article
Nanoscience & Nanotechnology
Geyunjian H. Zhu, Mohammad Azharuddin, Bapan Pramanik, Karin Roberg, Sujoy Kumar Biswas, Padraig D'arcy, Meng Lu, Apanpreet Kaur, Alexander Chen, Ashis Kumar Dhara, Alexandru Chivu, Yunhui Zhuang, Andrew Baker, Xiewen Liu, David Fairen-Jimenez, Bismoy Mazumder, Rongjun Chen, Clemens F. Kaminski, Gabriele S. Kaminski Schierle, Jorma Hinkula, Nigel K. H. Slater, Hirak K. Patra
Summary: Despite advancements in nanomedicine research, there are limited nanoformulations available on the market and few have been translated to clinics. This study introduces an instant drug formulation method using a coacervate-like nanosystem, which enhances intracellular drug delivery. The results demonstrate the feasibility of this technique and its potential application in the nanomedicine field to overcome the challenges of large-scale production and long-term storage of nanomaterials.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Nanoscience & Nanotechnology
Karan Bali, Charlotte Guffick, Reece McCoy, Zixuan Lu, Clemens F. Kaminski, Ioanna Mela, Roisin M. Owens, Hendrik W. van Veen
Summary: With the increasing threat of antibiotic resistance, there is a need to develop antimicrobials against highly resistant pathogenic bacteria. This study focuses on the ATP-binding cassette (ABC) transporter MsbA, which is crucial for the survival of Gram-negative pathogenic bacteria. Supported lipid bilayers (SLBs) integrated with various microscopy and electrochemical techniques were used to investigate the structure and function of MsbA. The results showed that electrochemical impedance spectroscopy (EIS) combined with biochemical detection could effectively monitor the activity of MsbA and potential inhibitors, providing a platform for the development of next-generation antimicrobials.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Raphael P. B. Jacquat, Georg Krainer, Quentin A. E. Peter, Ali Nawaz Babar, Oliver Vanderpoorten, Catherine K. Xu, Timothy J. Welsh, Clemens F. Kaminski, Ulrich F. Keyser, Jeremy J. Baumberg, Tuomas P. J. Knowles
Summary: This paper presents an approach called nanocavity diffusional sizing (NDS) that relies on nanocavity confinement to measure the size of nanoscale particles and single biomolecules in solution. It uses particle residence times within nanofluidic cavities to determine their hydrodynamic radii. Experimental results show that the residence times scale linearly with the sizes of nanoscale colloids, protein aggregates, and single DNA oligonucleotides. NDS offers a new optofluidic approach for rapid and quantitative sizing of nanoscale particles with potential applications in nanobiotechnology, biophysics, and clinical diagnostics.
Article
Chemistry, Physical
Lucas Daniel Wittwer, Felix Reichel, Paul Mueller, Jochen Guck, Sebastian Aland
Summary: Real-time deformability cytometry (RT-DC) is a method that quantifies cell features on a single-cell level in real-time, and here we present two new lookup tables for RT-DC based on a neo-Hookean hyperelastic material obtained through simulations. The influence of the shear-thinning behavior of the surrounding medium on cell deformation in RT-DC is also analyzed, and insights about cell strain and stresses are provided. The new lookup tables and numerical cell shapes are freely available for use.
Article
Chemistry, Physical
Beyza Bueyuekurganci, Santanu Kumar Basu, Markus Neuner, Jochen Guck, Andreas Wierschem, Felix Reichel
Summary: In this study, a full shear-rheological description of methyl cellulose (MC) solutions was provided at different shear rates. The results showed that MC solutions exhibited power-law viscosity behavior and showed first normal stress difference at high shear rates. Furthermore, the impact of MC concentration on the rheology of the solutions was investigated, and the entanglement concentration was found to be approximately 0.64%. These findings contribute to a better understanding of the viscoelastic behavior of MC solutions and can be considered when modeling stress in microfluidic channels.
Article
Cell Biology
Divyendu Goud Thalla, Franziska Lautenschlaeger
Summary: Vimentin is an intracellular cytoskeletal protein that can be secreted outside of the cell in response to various conditions. This extracellular vimentin plays a significant role in pathological conditions such as viral infection, cancer, immune response, and wound healing. The effects of extracellular vimentin can be both beneficial and detrimental, depending on its localization outside the cell.
CURRENT OPINION IN CELL BIOLOGY
(2023)
Article
Materials Science, Multidisciplinary
Nicolas Hauck, Timon Beck, Gheorghe Cojoc, Raimund Schlussler, Saeed Ahmed, Ivan Raguzin, Martin Mayer, Jonas Schubert, Paul Muller, Jochen Guck, Julian Thiele
Summary: Stretching individual living cells with light is a common method for evaluating their mechanical properties. However, the heat generated by the laser light used in optical stretchers can unintentionally alter the cells' mechanical properties. To address this issue, researchers have developed cell-sized elastic poly(N-isopropylacrylamide) (PNIPAAm) microgels that can indicate temperature changes through hydrogel swelling. By analyzing the effects of different gelation methods on the microgel network heterogeneity, micromechanics, and temperature response, the researchers have enhanced the use of standardized microgels for calibrating and validating cell mechanics analysis.
MATERIALS ADVANCES
(2022)
