Article
Biochemistry & Molecular Biology
Cornelia Boehm, Nikolina Todorovic, Marco Balasso, Geoffrey Gourinchas, Andreas Winkler
Summary: Protein dynamics are crucial for the catalytic function of enzymes, the interaction of protein complexes, and signal integration in regulatory proteins. In the context of multi-domain proteins involved in light-regulation of enzymatic effectors, the central role of conformational dynamics is well established, requiring a complex interplay of functional elements to maintain functionality.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Laxmi Dhungel, Lindsey Burcham, Joo Youn Park, Harshini Devi Sampathkumar, Albert Cudjoe, Keun Seok Seo, Heather Jordan
Summary: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, with mycolactone as a major virulence factor. In rural West Africa, where the disease is endemic, infected lesions can be colonized by quorum sensing bacteria without typical pathology. The pathogenesis of M. ulcerans may involve synergistic or antagonistic mechanisms within a polymicrobial network. Mycolactone was found to impact S. aureus metabolism and virulence gene expression, providing insight into interspecific interactions that may be useful for treatment and prevention.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Multidisciplinary Sciences
Deepak Srivastava
Summary: The cytokine meteorin-like (METRNL) has been found to improve cardiac function in mice after a heart attack.
Article
Oncology
Ai Kotani, Masatoshi Ito, Kai Kudo
Summary: Research on extracellular vesicles (EVs) in cancer biology has mainly focused on the functions of microRNAs (miRNAs) and proteins, while the roles of lipids in EVs and the potential of newly discovered cargoes like long noncoding RNAs (lncRNAs) and circular RNAs have received less attention. Recent studies have revealed the importance of phospholipids in EV membrane in cell communication and lipid mediator generation, showing potential in cancer biology.
SEMINARS IN CANCER BIOLOGY
(2021)
Editorial Material
Biochemical Research Methods
Vivien Marx
Summary: Chemical modifications to DNA, histones and RNA play a crucial role in making functional changes. Scientists are actively studying methods to monitor and understand these modifications and their interactions.
Review
Medical Laboratory Technology
Priyanila Magesh, Sanu Thankachan, Thejaswini Venkatesh, Padmanaban S. Suresh
Summary: The fibroblasts in the breast tumor microenvironment are crucial for tumor progression and metastasis, as they provide energy to adjacent cancer cells through metabolic reprogramming and secrete growth factors to promote tumor growth and dissemination. Identifying effective strategies to target the reprogrammed metabolism and communication between fibroblasts and cancer cells could lead to promising anti-cancer therapeutics.
CLINICA CHIMICA ACTA
(2021)
Review
Oncology
Deborah A. Silverman, Vena K. Martinez, Patrick M. Dougherty, Jeffrey N. Myers, George A. Calin, Moran Amit
Summary: Recent research has shown that high intratumoral nerve density is associated with poor prognosis and high recurrence rates across various solid tumor types. Cancer cells express neurotrophic markers and release axon-guidance molecules to promote axonogenesis. Tumors recruit new neural progenitors and rewire established nerves to adrenergic phenotypes, which in turn, facilitate cancer progression through various mechanisms such as stimulating angiogenesis and promoting the expansion of cancer stem cells.
Review
Medicine, General & Internal
Ahmed Ahmed Touni, Rohan S. Shivde, Harika Echuri, Rasha T. A. Abdel-Aziz, Hossam Abdel-Wahab, Roopal V. Kundu, I. Caroline Le Poole
Summary: Vitiligo is a common skin disorder characterized by the progressive loss of melanocytes. Keratinocytes, which are closely associated with melanocytes, play a crucial role in maintaining melanocyte function and homeostasis. Dysfunctional keratinocytes contribute to melanocyte loss through apoptosis, impairment of adhesion, presentation of melanocyte antigens, and recruitment of inflammatory T cells. Keratinocytes also fail to produce essential factors for melanocyte survival and interfere with repigmentation. Therefore, keratinocyte dysfunction is implicated in the development of vitiligo.
FRONTIERS IN MEDICINE
(2023)
Review
Gastroenterology & Hepatology
Giada De Palma, David E. Reed, Premysl Bercik
Summary: Visceral hypersensitivity, caused by central or peripheral factors, or their combination, is a fundamental mechanism of chronic visceral pain disorders. The gut microbiota, as an important regulator of gut function, has been identified as a key peripheral factor in the pathophysiology of visceral hypersensitivity. Diet-microbiota interactions play a crucial role in the genesis of visceral sensitivity, as changes in pain signaling may occur via diet-induced changes in secretion of mediators by the microbiota and/or host cells.
Review
Cell Biology
Miguel Ramirez Moreno, Natalia A. Bulgakova
Summary: EGFR and E-cadherin are major regulators of proliferation and differentiation in epithelial cells, and defects in either can lead to malignancies. The reciprocal interactions between EGFR and E-cadherin contribute to tumorigenesis and cancer cell invasion through modulation of adhesion and activity regulation. Understanding the crosstalk between EGFR and E-cadherin is important for tissue morphogenesis, homeostasis, and cancer progression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Mary Jo Cantoria, Elaheh Alizadeh, Janani Ravi, Reeba P. Varghese, Nawat Bunnag, Kelvin W. Pond, Arminja N. Kettenbach, Yashi Ahmed, Andrew L. Paek, John J. Tyson, Konstantin Doubrovinski, Ethan Lee, Curtis A. Thorne
Summary: In this study, it was found that the cellular response to Wnt ligands is proportional to their concentration. Positive feedback between the scaffold protein Axin and the kinase GSK3 resulted in bistable behavior of the destruction complex. Experimental evidence showed that the cellular concentration of beta-catenin exhibited an all-or-none response with sustained memory.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Computer Science, Information Systems
Nicola Lusardi, Nicola Corna, Fabio Garzetti, Simone Salgaro, Angelo Geraci
Summary: The paper investigates the issue of electromagnetic interference between channels, focusing on the impact of cross-talk on the timing parameters in TDC measurements. A systematic analysis based on Code-Density Test is utilized to detect and categorize the sources of cross-talk, leading to proposed solutions to minimize the different causes.
Article
Chemistry, Multidisciplinary
Anna Grochmal, Ben Woods, Lilia Milanesi, Manuel Perez-Soto, Salvador Tomas
Summary: Research on mimicking biological systems reveals that minimal environmental changes can trigger high avidity membrane receptor assembly, which can be modulated by weakly binding divalent ligands. Mathematical models and equations can predict the modulation intensity of the ligand-messenger on the ligand-receptor ON signal, providing valuable tools for studying membrane receptors in biological and biomimetic systems.
Article
Cell Biology
Alec M. Avey, Keith Baar
Summary: In organisms, the initial formation of a functional tendon relies on chemical signals from muscles, and further study is needed on how myokines affect tendon maturation, maintenance, and regeneration with age. An experimental framework is proposed to investigate the muscle-tendon crosstalk, aiming to develop new interventions for tendon development and function improvement.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Review
Cell Biology
Vanessa M. Ruscetta, Taj J. J. Seaton, Aleen Shakeel, Stanley N. S. Vasconcelos, Russell D. D. Viirre, Marc J. J. Adler, Michael F. F. Olson
Summary: Cytoskeleton organization and dynamics are regulated by post-translational modifications of key target proteins, including the phosphorylation of myosin light chain proteins by MRCK kinases. Compared to ROCK kinases, the contributions of MRCK kinases are less characterized due to the late discovery of selective inhibitors. The recent development of selective MRCK inhibitors has expanded the tools to study MRCK function and shown therapeutic benefits in cancer studies.
Article
Medicine, Research & Experimental
Monica L. Fernandez-Quintero, Katharina B. Kroell, Lukas J. Grunewald, Anna-Lena M. Fischer, Jakob R. Riccabona, Klaus R. Liedl
Summary: Designing different antibody formats, such as bispecific antibodies, is critical for the advancement of the biotherapeutic market. This study investigates the influence of point mutations in the antigen-binding site on heavy and light chain pairing preferences using molecular dynamics simulations. The findings provide mechanistic insights into antibody interfaces and can help advance the design of bispecific antibodies.
Article
Multidisciplinary Sciences
Jenna J. Guthmiller, Julianna Han, Henry A. Utset, Lei Li, Linda Yu-Ling Lan, Carole Henry, Christopher T. Stamper, Meagan McMahon, George O'Dell, Monica L. Fernandez-Quintero, Alec W. Freyn, Fatima Amanat, Olivia Stovicek, Lauren Gentles, Sara T. Richey, Alba Torrents de la Pena, Victoria Rosado, Haley L. Dugan, Nai-Ying Zheng, Micah E. Tepora, Dalia J. Bitar, Siriruk Changrob, Shirin Strohmeier, Min Huang, Adolfo Garcia-Sastre, Klaus R. Liedl, Jesse D. Bloom, Raffael Nachbagauer, Peter Palese, Florian Krammer, Lynda Coughlan, Andrew B. Ward, Patrick C. Wilson
Summary: A new class of broadly neutralizing antibodies has been discovered that can target multiple strains of influenza viruses, including potential pandemic threats. These antibodies utilize specific epitopes for neutralization, which is crucial for the design of universal influenza virus vaccines. It is found that antibodies targeting these epitopes are widespread in the human body.
Article
Biochemistry & Molecular Biology
Monica L. Fernandez-Quintero, Anna Vangone, Johannes R. Loeffler, Clarissa A. Seidler, Guy Georges, Klaus R. Liedl
Summary: Structure-based antibody design and accurate predictions of antibody-antigen interactions are challenging tasks in computational biology. Molecular dynamics simulations reveal that a single static X-ray structure is insufficient to understand the determinants of antibody-antigen recognition. This study investigates antibodies that undergo significant conformational changes upon antigen binding and demonstrates that the paratope states can be utilized to enhance antibody-antigen docking.
Article
Biochemistry & Molecular Biology
Ferenc Torok, Kamer Tezcan, Ludovica Filippini, Monica L. Fernandez-Quintero, Lucia Zanetti, Klaus R. Liedl, Raphaela S. Drexel, Joerg Striessnig, Nadine J. Ortner
Summary: Germline gain-of-function missense variants in the CACNA1D gene can cause severe neurodevelopmental disorders with or without endocrine symptoms. We report a 4-week-old newborn with a novel de novo missense variant F747S in the Cav1.3 alpha 1-subunit, which is associated with a prominent jittering phenotype, developmental delay, elevated aldosterone level, and transient hypoglycemia. Functional experiments confirmed the pathogenicity of the variant and revealed significant changes in channel gating. The increased sensitivity to the L-type Ca2+ channel blocker isradipine suggests its potential as a treatment option for carriers of this mutation.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Rafael Eduardo Oliveira Rocha, Diego Cesar Batista Mariano, Tiago Silva Almeida, Leon Sulfierry CorreaCosta, Pedro Henrique Camargo Fischer, Lucianna Helene Santos, Ernesto Raul Caffarena, Carlos Henrique da Silveira, Leonida M. Lamp, Monica Lisa Fernandez-Quintero, Klaus Roman Liedl, Raquel Cardoso De Melo-Minardi, Leonardo Henrique Franca de Lima
Summary: In this study, the molecular basis of the thermostabilization of the Paenibacillus polymyxa GH1 beta-glucosidase by two-point mutations was investigated through molecular dynamics simulations and computational analyses. Three classic mechanisms were found to contribute to the stabilization of the thermostable mutants.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Review
Virology
Siwy Ling Yang, Riccardo Delli Ponti, Yue Wan, Roland G. Huber
Summary: This review article summarizes the importance of RNA viruses and their impact on society and the economy. It presents the significance of studying genome folding and the use of computational and high-throughput RNA structure-mapping approaches. The focus is on the genome structures of dengue, Zika, and SARS-CoV-2 viruses.
Article
Food Science & Technology
Linda Ahammer, Jana Unterhauser, Reiner Eidelpes, Christina Meisenbichler, Bettina Nothegger, Claudia E. Covaciu, Valentina Cova, Anna S. Kamenik, Klaus R. Liedl, Kathrin Breuker, Klaus Eisendle, Norbert Reider, Thomas Letschka, Martin Tollinger
Summary: The protein Mal d 1, responsible for most allergic reactions to apples in the northern hemisphere, can be chemically modified by ascorbic acid, which attenuates IgE binding in apple-allergic patients by partially masking an antibody binding site on the allergen.
Article
Clinical Neurology
Roland G. Huber, Swapnil Pandey, Deepak Chhangani, Diego E. Rincon-Limas, Nathan P. Staff, Crystal Jing Jing Yeo
Summary: This study used proteomics data from induced pluripotent stem cell-derived motor neurons of amyotrophic lateral sclerosis (ALS) patients to identify potential diagnostic and prognostic biomarkers. Through stratification and analysis, differentially expressed proteins indicative of disease severity and progression rate were identified as candidate ALS-related and prognostic biomarkers. The study also utilized RNAi screening and machine learning algorithms to validate and predict novel mechanisms and diagnostic biomarkers in ALS.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Chemistry, Physical
Emmanuella Li, Michelle Y. Yaochai, Joanna M. Ng, Roland G. Huber, Peter J. Bond, Alexander Krah
Summary: Biological macromolecules exhibit biochemical activity near their glass transition temperature, which is likely influenced by their interaction with water molecules. Experimental evidence has shown that the presence of bioprotective compounds, such as sucrose and trehalose, can raise the transition temperature of a protein. In this study, molecular dynamics simulations were used to investigate the transition temperatures of lysozyme in different chemical environments, including water, a sucrose/water mixture, and a trehalose/water mixture. Through this approach, multiple temperature-dependent transitions were identified, suggesting that water-induced transitions occur at various temperatures rather than a single temperature. These findings have implications for selecting stabilizing additives in industries like biotechnology, pharmaceuticals, and food production.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Biochemistry & Molecular Biology
Clarissa A. Seidler, Janik Kokot, Monica L. Fernandez-Quintero, Klaus R. Liedl
Summary: In this study, the conformational diversity of four VHH variants and their binding to hen egg-white lysozyme (HEL) were investigated. It was found that with an increase in affinity, the stability of the VHH structure increased and the residues contributing to antigen binding underwent significant changes. In addition, it was observed that the investigated nanobodies followed the conformational selection paradigm, with the binding competent conformation pre-existing within the structural ensembles without the presence of the antigen.
Article
Biochemistry & Molecular Biology
Nancy D. Pomarici, Roberta Cacciato, Janik Kokot, Monica L. Fernandez-Quintero, Klaus R. Liedl
Summary: This study investigates the evolution of immunoglobulin isotypes, highlighting the preserved features and the parts that have mutated over time. Coupled residues in the evolution process are crucial for maintaining the immunoglobulin fold and interactions with other domains. By comparing biophysical properties across different animal classes and isotypes, conserved residues in evolution can be identified. This study offers a general overview of the evolution of immunoglobulin isotypes and advances the understanding of their characteristic biophysical properties for guiding protein design.
Article
Biochemistry & Molecular Biology
Priscilla L. S. Boon, Ana S. Martins, Xin Ni Lim, Francisco J. Enguita, Nuno C. Santos, Peter J. Bond, Yue Wan, Ivo C. Martins, Roland G. Huber
Summary: Dengue virus is a significant health risk in tropical and subtropical regions. The structure of the packaged genome in complex with C proteins remains elusive. This study investigates the interactions of C proteins with viral RNA and shows their role in coordinating key interactions for proper packaging of viral RNA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Sunita Awate, Salma Mubarka, Roland G. Huber
Summary: Lates calcarifer, also known as Barramundi or Asian seabass, is a highly productive fish species suitable for large-scale aquaculture. However, the dense populations in aquaculture settings increase the risk of infectious diseases, which negatively impact yield. Immunization of juveniles and development of new immunization agents are crucial for improving aquaculture efficiency and food security.
Article
Food Science & Technology
Ricarda Zeindl, Annika L. Franzmann, Monica L. Fernandez-Quintero, Clarissa A. Seidler, Valentin J. Hoerschinger, Klaus R. Liedl, Martin Tollinger
Summary: Allergies related to kiwi consumption are on the rise, with cross-reactivity with birch pollen being a major factor. This study determined the three-dimensional structures of PR-10 proteins in kiwi fruits and found that they closely resemble the major allergen in birch pollen. Structural differences were observed compared to another kiwi allergen, Act d 11. Additionally, the study identified the presence of phenolic compound pyrogallol in kiwi proteins.
Article
Multidisciplinary Sciences
Jakob Fleischmann, Selina Schwaighofer, Louis De Falco, Florian Enzler, Andreas Feichtner, Valentina Kugler, Philipp Tschaikner, Roland G. Huber, Eduard Stefan
Summary: Selective targeting of mutated kinases in cancer therapies has the potential to improve therapeutic success and patient survival. Using the KinCon technology, we studied the activated kinase states in melanoma patients and developed personalized treatment strategies. The combination inhibition of BRAF and MEK displayed synergistic effects and induced more pronounced structural changes, as validated by the KinCon biosensor.