Review
Cell Biology
M. Edward Quach
Summary: Platelet adhesion to vascular damage sites is a critical early step in hemostasis, with the GPIb-IX-V glycoprotein playing a key role in this process. In addition to aiding adhesion, GPIb-IX-V is crucial for platelet survival and regulation of clearance, working alongside multiple mechanisms to maintain a normal platelet count and ensure functional viability in circulation by removing aged or activated platelets. Dysregulation of platelet clearance, particularly through GPIb-IX-V, contributes to various bleeding disorders, including thrombocytopenia in conditions like VWD and immune thrombocytopenia.
Article
Multidisciplinary Sciences
Anna Kobsar, Karina Koehnlechner, Philipp Klingler, Marius Niklaus, Julia Zeller-Hahn, Angela Koessler, Katja Weber, Markus Boeck, Juergen Koessler
Summary: This study discussed the storage of platelet concentrates at cold temperature as an alternative to the current standard of storage at room temperature. It was found that cold-induced attenuation of inhibitory signaling can promote platelet reactivity, making short-term refrigeration a rational approach to obtain platelet concentrates with higher functional reactivity for the treatment of hemorrhage.
SCIENTIFIC REPORTS
(2022)
Review
Cell Biology
Eva Kummer, Nenad Ban
Summary: Mitochondria are cellular organelles that generate chemical energy through oxidative phosphorylation. They have their own genetic information and unique translation machinery, but also heavily rely on nuclear-encoded proteins and engage in inter-compartmental crosstalk with the cell to regulate their proteome and respond to stress. Understanding the mechanisms and regulation of mitochondrial protein synthesis has increased our knowledge of mitochondrial function and its integration with overall cell physiology.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Hanqi Zhao, Dana V. Devine
Summary: Cold-stored platelets are gaining attention due to their superior hemostatic effectiveness, reduced bacterial growth, and longer shelf lives. However, further experimental studies are needed before reintroducing them in clinical settings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Computer Science, Information Systems
Gyeongyong Lee, Jaewook Kwak, Joonyong Jeong, Daeyong Lee, Moonseok Jang, Jungwook Choi, Yong Ho Song
Summary: This study proposes a command scheduling scheme to prioritize flash read commands for improving the read performance and reducing read latency. Experiments show that the proposed scheme reduces average read latency by up to 51% compared to existing schemes, demonstrating effective performance improvement in small map caches.
Article
Public, Environmental & Occupational Health
Kimiyo Kikuchi, Margaret Gyapong, Akira Shibanuma, Evelyn Ansah, Sumiyo Okawa, Sheila Addei, Keiko Nanishi, Charlotte Tawiah, Junko Yasuoka, Francis Yeji, Abraham Oduro, Seth Owusu-Agyei, Gloria Quansah-Asare, Abraham Hodgson, Masamine Jimba
Summary: The EMBRACE intervention program in Ghana effectively improved the continuum of care for pregnant women and newborns, as shown by the increase in completion rate and decrease in newborns with danger signs. The program was evaluated using the RE-AIM framework and demonstrated great potential for scaling across real-world settings.
JOURNAL OF GLOBAL HEALTH
(2021)
Article
Microbiology
James A. Watson, Stephen M. Kissler, Nicholas P. J. Day, Yonatan H. Grad, Nicholas J. White
Summary: The study proposes a consensus methodology for evaluating candidate SARS-CoV-2 antiviral drugs, using viral clearance as a pharmacodynamic measure. The authors suggest that the rate of viral clearance, estimated from viral densities following peak viral load, is a robust summary of viral clearance. They also recommend conducting pharmacometric antiviral assessments in the early stages of COVID-19 illness with serial qPCR samples taken over one week.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Fiorella A. Solari, Daniel Krahn, Frauke Swieringa, Steven Verhelst, Tienush Rassaf, Alpaslan Tasdogan, Rene P. Zahedi, Kristina Lorenz, Thomas Renne, Johan W. M. Heemskerk, Albert Sickmann
Summary: Platelets are small anucleate cell fragments in the blood, playing a vital role in thrombosis and hemostasis. Dysfunctions in platelets are associated with bleeding, increased risk of thromboembolic events, and cardiovascular diseases. Advanced proteomic methods can help understand the roles of platelets in various physiological processes and aid in drug development and diagnostic marker identification.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Microbiology
Daniel Goncalves-Carneiro, Paul D. Bieniasz
Summary: The development of safe and effective vaccines against viruses is crucial for disease control. Recent advancements in DNA synthesis technology have fueled research efforts in generating attenuated viruses through synonymous mutations. Understanding the molecular mechanisms of attenuation by genetic recoding of viruses could provide insights for vaccine development.
Article
Multidisciplinary Sciences
Clemens Hinterleitner, Jasmin Straehle, Elke Malenke, Martina Hinterleitner, Melanie Henning, Marco Seehawer, Tatjana Bilich, Jonas Heitmann, Martina Lutz, Sven Mattern, Sophia Scheuermann, Marius Horger, Stefanie Maurer, Juliane Walz, Falko Fend, Rupert Handgretinger, Christian Seitz, Bettina Weigelin, Stephan Singer, Helmut Salih, Oliver Borst, Hans-Georg Kopp, Lars Zender
Summary: This study demonstrates that platelet-derived PD-L1 can serve as a prognostic and predictive biomarker in non-small cell lung cancer patients, playing a role in tumor immune evasion and affecting T cell function. An algorithm was developed to calculate the adjusted PD-L1 payload of platelets (pPD-L1(Adj.)), which showed superior predictive ability for therapy response compared to standard histological PD-L1 quantification.
NATURE COMMUNICATIONS
(2021)
Article
Health Care Sciences & Services
Annarita Fiorillo, Veronica Morea, Gianni Colotti, Andrea Ilari
Summary: Huntington Disease is a lethal neurodegenerative disorder caused by the abnormal expansion of the HTT gene, and current research suggests that degrading mHtt through the ubiquitin-proteasome system plays a more crucial role in delaying disease progression. PROTACs, which can target specific E3 ubiquitin ligases, may be a promising strategy for Huntington Disease therapy.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Medicine, Research & Experimental
Andrea Andrews-Morger, Michael Reutlinger, Neil Parrott, Andres Olivares-Morales
Summary: Achieving appropriate pharmacokinetics is crucial in drug discovery and development. Recent studies have shown that machine learning-based strategies can accurately predict clearance and improve the prediction of other PK parameters. However, in vitro measurement of CLint,u is still necessary.
MOLECULAR PHARMACEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Sean X. Gu, Sanjana Dayal
Summary: Aging is a major risk factor for various diseases, including cardiovascular disease. Reactive oxygen species and oxidative stress have been shown to play a role in age-related vascular diseases. Platelets, as key contributors in vascular disease progression, undergo oxidative changes that are associated with comorbid conditions such as diabetes, atherosclerosis, obesity, and cancer. Understanding the mechanistic links between oxidative stress and vascular diseases is crucial for developing targeted therapeutic strategies for age-associated vascular diseases.
Article
Nanoscience & Nanotechnology
Jiazhen Hou, Wei Xiong, Xinyue Shao, Li Lang, Ya Chang, Guihua Chen, Li Wang, Zhicheng Wang, Yongzhuo Huang
Summary: By utilizing a resveratrol-loaded liposomal system, platelet oxidative stress and platelet storage lesion (PSL) can be alleviated, improving the quality and functions of platelets in storage and prolonging their shelf life, thereby reducing platelet wastage.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Nanoscience & Nanotechnology
Jiazhen Hou, Wei Xiong, Xinyue Shao, Li Lang, Ya Chang, Guihua Chen, Li Wang, Zhicheng Wang, Yongzhuo Huang
Summary: This study explored the use of a resveratrol-loaded liposomal system (Res-Lipo) to improve the quality and functions of platelets in storage and mitigate platelet storage lesion (PSL). Res-Lipo effectively scavenged intracellular reactive oxygen species (ROS), inhibited platelet apoptosis and activation during storage, and extended the platelet survival time in vivo.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Hematology
Yingchun Wang, Wenchun Chen, Wei Zhang, Melissa M. Lee-Sundlov, Caterina Casari, Michael C. Berndt, Francois Lanza, Wolfgang Bergmeier, Karin M. Hottmeister, X. Frank Zhang, Renhao Li
Summary: During infection, neuraminidase removes sialic acid from platelet GPIb alpha, leading to their rapid clearance. This mechanism may explain many puzzling and seemingly contradictory observations associated with clearance of desialylated or hyposialylated platelets.
Article
Chemistry, Multidisciplinary
Yuesong Hu, Victor Pui-Yan Ma, Rong Ma, Wenchun Chen, Yuxin Duan, Roxanne Glazier, Brian G. Petrich, Renhao Li, Khalid Salaita
Summary: This study developed a DNA-based microparticle tension sensor for investigating mechanotransduction at curved interfaces with high throughput. The method successfully mapped and measured T-cell receptor forces and platelet integrin forces, demonstrating its potential in screening drugs that modulate cellular mechanics.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Hematology
M. Edward Quach, Wenchun Chen, Yingchun Wang, Hans Deckmyn, Francois Lanza, Bernhard Nieswandt, Renhao Li
Summary: The study identified a novel rat monoclonal antibody 3G6 that acts as a positive modulator of GPIb beta, enhancing GPIb-IX binding and activation. In contrast, another antibody RAM.1 inhibits GPIb-IX signaling, suggesting that changes in GPIb beta conformation may be crucial for outside-in activation via GPIb-IX.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Kayleigh M. Voos, Wenpeng Cao, Nicholas A. Arce, Emily R. Legan, Yingchun Wang, Asif Shajahan, Parastoo Azadi, Pete Lollar, Xiaohui Frank Zhang, Renhao Li
Summary: Desialylation of O-glycans around A1 increases its activity by destabilizing the AIM, leading to enhanced binding activity and platelet aggregation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Jasmine Ito, Wallace Hunter Baldwin, Courtney Cox, John F. Healey, Ernest T. Parker, Emily R. Legan, Renhao Li, Surinder Gill, Glaivy Batsuli
Summary: This study evaluated the impact of site-specific N-linked glycan removal on FVIII properties, cell internalization, and antibody responses. The results showed that modifying FVIII N-linked glycans reduced endocytosis by dendritic cells and binding of specific antibodies, but did not significantly affect inhibitor formation in hemophilia A mice.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Wenchun Chen, Moriah S. Wilson, Yingchun Wang, Wolfgang Bergmeier, Francois Lanza, Renhao Li
Summary: This study investigated the role of RAM.1 antibody in platelet clearance mediated by trigger sequence exposure. The results showed that RAM.1 can attenuate platelet clearance and prolong platelet lifespan, providing key evidence for the causative link between trigger sequence exposure and accelerated platelet clearance. This suggests the potential therapeutic development of a RAM.1 derivative for treating GPIb-IX-mediated thrombocytopenia.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Editorial Material
Cell Biology
Renhao Li
Article
Hematology
Nicholas A. Arce, Yi Liu, Wenchun Chen, X. Frank Zhang, Renhao Li
Summary: This study aimed to determine and characterize the autoinhibitory properties of mouse VWF. The results showed that recombinant mouse AIM-A1 binds with higher affinity to GPIb alpha than its human counterpart. Activated A1 fragments lacking the AIM can effectively agglutinate platelets across the species barrier. The unfolding force of mouse AIM was found to be similar to the human AIM. These findings suggest that the regulation of VWF-GPIb alpha binding has been specifically tuned to work optimally in different rheological architectures, potentially due to differences in the AIM sequence.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Emily R. Legan, Yi Liu, Nicholas A. Arce, Ernest T. Parker, Pete Lollar, X. Frank Zhang, Renhao Li
Summary: Type 2B von Willebrand disease is an inherited bleeding disorder caused by point mutations in the von Willebrand factor A1 domain and autoinhibitory module, leading to enhanced binding to GPIb alpha. The severity of bleeding complications and platelet levels in patients varies depending on the underlying mutation. This study examines the thermodynamic stability, conformational dynamics, and biomechanical regulation of these mutations to understand the heterogeneity among them.
Article
Medical Laboratory Technology
Wenxin Huang, Renhao Li, Jue Zhang, Yiliang Cheng, Devi P. Ramakrishnan, Roy L. Silverstein
Summary: CD36 is a receptor for oxidized LDL and other endogenous danger signals that promotes athero-thrombotic processes. It physically associates with other transmembrane proteins and the N-terminal transmembrane domain is hypothesized to be involved in these interactions. By using peptide treatments and functional experiments, it was found that CD36 nTMD peptide decreased CD36 surface associations with tetraspanin CD9 and ameliorated pathologically important CD36 mediated responses to oxLDL.
TRANSLATIONAL RESEARCH
(2023)
Letter
Hematology
Yingchun Wang, Renhao Li
Article
Biochemical Research Methods
Rong Ma, Sk Aysha Rashid, Arventh Velusamy, Brendan R. Deal, Wenchun Chen, Brian Petrich, Renhao Li, Khalid Salaita
Summary: Tension-activated cell tagging (TaCT) is a novel method that utilizes flow cytometry to sort mechanically active cells.
Article
Engineering, Biomedical
Yuxin Duan, Fania Szlam, Yuesong Hu, Wenchun Chen, Renhao Li, Yonggang Ke, Roman Sniecinski, Khalid Salaita
Summary: A detection method utilizing Cas12a has been reported to amplify cellular traction forces and evaluate platelet dysfunction. This method enables the extraction of individualized dose-response curves for antiplatelet drugs and the screening of genes, cell-adhesion ligands, drugs, or metabolites that modulate cell mechanics.
NATURE BIOMEDICAL ENGINEERING
(2023)