Article
Multidisciplinary Sciences
Elena Muino, Olga Maisterra, Joan Jimenez-Balado, Natalia Cullell, Caty Carrera, Nuria P. Torres-Aguila, Jara Carcel-Marquez, Cristina Gallego-Fabrega, Miquel Lledos, Jonathan Gonzalez-Sanchez, Ferran Olmos-Alpiste, Eva Espejo, Alvaro March, Ramon Pujol, Ana Rodriguez-Campello, Gemma Romeral, Jurek Krupinski, Joan Marti-Fabregas, Joan Montaner, Jaume Roquer, Israel Fernandez-Cadenas
Summary: CADASIL is a small vessel disease caused by mutations in NOTCH3, leading to abnormal protein folding. The overexpression of gene E2F4 is associated with worse executive function and information processing speed in CADASIL patients. Further studies are needed to investigate the potential of E2F4 as a biomarker or therapeutic target for CADASIL.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Anjali Bhat, Haritz Irizar, Johan Hilge Thygesen, Karoline Kuchenbaecker, Oliver Pain, Rick A. Adams, Eirini Zartaloudi, Jasmine Harju-Seppanen, Isabelle Austin-Zimmerman, Baihan Wang, Rebecca Muir, Ann Summerfelt, Xiaoming Michael Du, Heather Bruce, Patricio O'Donnell, Deepak P. Srivastava, Karl Friston, L. Elliot Hong, Mei-Hua Hall, Elvira Bramon
Summary: A study identified two genes associated with MMN, which are overexpressed in the frontal cortex during prenatal development but significantly downregulated in adulthood. MMN was found to be a considerably superior psychosis endophenotype compared to three other candidate endophenotypes.
Article
Multidisciplinary Sciences
Rebecca J. Carlson, Michael D. Leiken, Alina Guna, Nir Hacohen, Paul C. Blainey
Summary: This study used high-throughput imaging technology and genome-wide CRISPR knockout screening to identify regulators of IRF3 translocation, Sendai virus localization, and peroxisomal biogenesis. The study also found that the ER-localized P5A-type ATPase ATP13A1 is essential for viral sensing and is involved in promoting the localization of MAVS to mitochondrial membranes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Geremy Sannier, Mathieu Dube, Caroline Dufour, Corentin Richard, Nathalie Brassard, Gloria-Gabrielle Delgado, Amelie Pagliuzza, Amy E. Baxter, Julia Niessl, Elsa Brunet-Ratnasingham, Roxanne Charlebois, Bertrand Routy, Jean-Pierre Routy, Remi Fromentin, Nicolas Chomont, Daniel E. Kaufmann
Summary: Understanding the diversity of HIV-1 reservoirs is crucial for a cure, but studying them at the single-cell level in primary samples is challenging. Different viral gene expression and translation patterns are observed in viremic and ART-suppressed individuals, with most reactivated proviruses found to be defective. LRAs induce a wide variety of viral gene transcription and translation patterns, with different effects on various memory cell subsets.
Article
Multidisciplinary Sciences
Satria P. Sajuthi, Jamie L. Everman, Nathan D. Jackson, Benjamin Saef, Cydney L. Rios, Camille M. Moore, Angel C. Y. Mak, Celeste Eng, Ana Fairbanks-Mahnke, Sandra Salazar, Jennifer Elhawary, Scott Huntsman, Vivian Medina, Deborah A. Nickerson, Soren Germer, Michael C. Zody, Goncalo Abecasis, Hyun Min Kang, Kenneth M. Rice, Rajesh Kumar, Noah A. Zaitlen, Sam Oh, Jose Rodriguez-Santana, Esteban G. Burchard, Max A. Seibold
Summary: By performing a transcriptome-wide association study, the researchers identified genetic determinants of airway dysfunction in asthma and discovered genetic mechanisms related to mucus pathobiology.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Austin S. Draycott, Cassandra Schaening-Burgos, Maria F. Rojas-Duran, Loren Wilson, Leonard Scharfen, Karla M. Neugebauer, Sigrid Nachtergaele, Wendy Gilbert
Summary: The study introduces a new sequencing technique called D-seq to map dihydrouridine (D) with single-nucleotide resolution in the transcriptome. Novel classes of D-containing RNA, including mRNA and snoRNA, are discovered in yeast. The D sites are concentrated in conserved stem-loop regions and are involved in splicing of pre-mRNA and translation of mRNA.
Article
Immunology
Lin Lv, Tianyun Zhang, Hanying Jia, Yanyan Zhang, Asif Ahsan, Xiaoyang Zhao, Teng Chen, Zhiqiang Shen, Ning Shen
Summary: This study investigated the temporal viral and host transcriptomes in porcine alveolar macrophages infected with virulent and attenuated African swine fever virus (ASFV) strains. The findings demonstrated that the attenuated ASFV strain HuB20 can quickly activate the host's antiviral immune response, as well as activating genes associated with RNA virus response in addition to the DNA sensing mechanism.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Qiuping Zhao, Rongmei Liu, Hui Chen, Xiaomo Yang, Jiajia Dong, Minfu Bai, Yao Lu, Yiming Leng
Summary: This study used TWAS to identify potential pathogenic genes associated with coronary atherosclerosis and explore their underlying mechanisms. They identified 19 genes using multiple approaches and confirmed the causal relationship between the NBEAL1 gene and coronary atherosclerosis. Further analysis showed that these genes were involved in asthma and leukocyte mediated immunity reaction. Single cell analysis revealed differential expression of the NBEAL1 gene in macrophages, plasma cells, and endothelial cells.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Chun Zhai, Xunjia Liu, Tao Song, Fengqun Yu, Gary Peng
Summary: This study delves into the molecular mechanism of Rlm1-mediated resistance to blackleg, revealing that various biological processes were over-represented in the resistant reaction, while significant enrichment of SA and JA pathways occurred in the susceptible reaction. The biosynthesis and signaling of SA and JA were induced more significantly in the resistant reaction, suggesting a threshold level of SA and JA signaling is required for the activation of Rlm1-mediated resistance.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Chenyin Wang, Chun Vin Lau, Fuqiang Ma, Chaogu Zheng
Summary: This study reveals the critical role of gut microbiota in regulating neurodegenerative diseases, particularly through influencing the formation and aggregation of amyloid fibrils. This provides a new research direction for the treatment of neurodegenerative diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Calwing Liao, Veikko Vuokila, Helene Catoire, Fulya Akcimen, Jay P. Ross, Cynthia V. Bourassa, Patrick A. Dion, Inge A. Meijer, Guy A. Rouleau
Summary: This study explores the biology of Tourette's Syndrome (TS) through transcriptome-wide association study and splicing analysis. It reveals increased expression of FLT3 gene in TS and its association with immune-related pathways.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Ziyue Qin, Wencan Wang, Malik Ahsan Ali, Yihan Wang, Yan Zhang, Ming Zhang, Guangbin Zhou, Jian-Dong Yang, Changjun Zeng
Summary: This study revealed the dynamic m(6)A modification of mRNAs in boar sperm during cryopreservation, which may affect mRNA expression and are closely related to sperm motility, apoptosis, and metabolism.
Article
Multidisciplinary Sciences
Yicheng Wang, Anant K. Menon, Yuta Maki, Yi-Shi Liu, Yugo Iwasaki, Morihisa Fujita, Paula A. Guerrero, Daniel Varo'n Silva, Peter H. Seeberger, Yoshiko Murakami, Taroh Kinoshite
Summary: Researchers have identified a protein called CLPTM1L that plays a crucial role in the synthesis of glycosylphosphatidylinositols (GPIs), complex glycolipids involved in cell surface protein anchoring. CLPTM1L acts as a scramblase, facilitating the translocation of GlcN-PI from the endoplasmic reticulum to the cytosol for efficient GPI biosynthesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Uwe Schulte, Fabian den Brave, Alexander Haupt, Arushi Gupta, Jiyao Song, Catrin S. S. Mueller, Jeannine Engelke, Swadha Mishra, Christoph Martensson, Lars Ellenrieder, Chantal Priesnitz, Sebastian P. P. Straub, Kim Nguyen Doan, Bogusz Kulawiak, Wolfgang Bildl, Heike Rampelt, Nils Wiedemann, Nikolaus Pfanner, Bernd Fakler, Thomas Becker
Summary: This study presents a quantitative mapping of mitochondrial protein assemblies using high-resolution complexome profiling. The results reveal the complex organization of mitochondrial protein assemblies involved in various cellular processes. It also identifies quality-control factors and elucidates a constitutive pathway for preprotein removal.
Article
Immunology
Maria Ghaly, Jessica Proulx, Kathleen Borgmann, In-Woo Park
Summary: Our recent data reveal that HIV-1 Nef plays a crucial role in determining the fate of cellular proteins by modulating ubiquitination. Through proteomic analysis, we identified 93 proteins upregulated and 232 proteins downregulated in ubiquitination status by Nef. These proteins were classified based on molecular function, biological process, subcellular localization, and biological pathway. Among the ubiquitinated proteins, six directly interacted with Nef, and 14 were involved in protein stability through the Ubiquitin Proteasome System (UPS)-mediated proteasomal degradation pathway. The molecular mechanisms underlying Nef-triggered regulation of cellular protein ubiquitination are currently being investigated.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Pauline Elisabeth Kolkwitz, Jeannine Mohrlueder, Dieter Willbold
Summary: Stabilizing protein conformation with D-enantiomeric peptide ligands may offer a promising therapeutic approach for heritable polyglutamine diseases by preventing aggregation and promoting monomerization. A specific D-enantiomeric peptide, QF2D-2, showed potential for inhibiting aggregation of polyglutamine-containing proteins, suggesting a possible treatment option for spinal and bulbar muscular atrophy and other related diseases.
Article
Chemistry, Medicinal
Raphael J. Eberle, Ian Gering, Markus Tusche, Philipp N. Ostermann, Lisa Muller, Ortwin Adams, Heiner Schaal, Danilo S. Olivier, Marcos S. Amaral, Raghuvir K. Arni, Dieter Willbold, Monika A. Coronado
Summary: The C30 endopeptidase is crucial for the life cycle of SARS-CoV-2 and is a potential drug target. Crotamine, a peptide isolated from rattlesnake venom, has shown promising activities and derivatives such as L-peptides have exhibited inhibitory effects on 3CL protease. D-peptides have shown potential as a prototype for peptide-based drugs targeting viral protease 3CL(pro).
Article
Biochemistry & Molecular Biology
Niloufar Mosaddeghzadeh, Silke Pudewell, Farhad Bazgir, Neda S. Kazemein Jasemi, Oliver H. F. Krumbach, Lothar Gremer, Dieter Willbold, Radovan Dvorsky, Mohammad R. Ahmadian
Summary: This study provides evidence for the mechanistic framework model that IQGAP GRD might act as a 'scaffolding domain' by binding CDC42 irrespective of its nucleotide-bound forms. The study found that the binding affinity of GRD1 and GRD2 to CDC42 is lower compared to C794/C795, and mutation of the switch regions of CDC42 greatly affected the binding of C794/C795 but had little effect on GRD1 and no effect on GRD2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Marc Sevenich, Joop van den Heuvel, Ian Gering, Jeannine Mohrlueder, Dieter Willbold
Summary: The binding between the spike protein of SARS-CoV-2 and hACE2 is a two-step interaction, which enhances the stability of the complex. This interaction is not only present in the wild type strain but also in the B.1.1.7 variant, with an increased transition rate. These findings are important for understanding the infectivity and characterizing emerging variants of SARS-CoV-2 spike proteins.
JOURNAL OF VIROLOGY
(2022)
Article
Microbiology
Raphael J. Eberle, Danilo S. Olivier, Marcos S. Amaral, Carolina C. Pacca, Mauricio L. Nogueira, Raghuvir K. Arni, Dieter Willbold, Monika A. Coronado
Summary: This study demonstrates the inhibitory potential of the water-soluble vitamin riboflavin against NS2B/NS3(pro) of ZIKV and YFV and nsP2(pro) of CHIKV, and its ability to inhibit the viral entry of CHIKV. Molecular dynamics simulations validate the repurposing of riboflavin as a promising molecule in drug development against these viruses.
Article
Biochemistry & Molecular Biology
Thomas Pauly, Najoua Bolakhrif, Jesko Kaiser, Luitgard Nagel-Steger, Lothar Gremer, Holger Gohlke, Dieter Willbold
Summary: The polymorphism of Methionine/valine at position 129 in the human prion protein (huPrP) is closely associated with the pathogenic phenotype, disease progression, and onset age of neurodegenerative diseases. This study investigates the influence of the amino acid type at position 129 on the structural properties of huPrP using various biophysical techniques. The results reveal differences in aggregation propensity and oligomer content between the 129M and 129V variants, leading to divergent pathways for amyloid formation. The study also identifies intramolecular interactions responsible for the enhanced monomer stability of the 129M variant.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Oliver H. Weiergraeber, Dusan Petrovic, Andreas Kislat, Martin Pattky, Judith Fabig, Renu Batra-Safferling, Jan Schulte Am Esch, Karen Haenel, Carolin Huhn, Birgit Strodel, Bernhard Homey, Dieter Willbold
Summary: CCL16 is primarily synthesized by hepatocytes, circulates in the blood as a full-length protein, and the C-terminal extension may impair its biological activity modulation.
Article
Biochemistry & Molecular Biology
Raphael J. Eberle, Marc Sevenich, Ian Gering, Lara Scharbert, Birgit Strodel, Nils A. . Lakomek, Karoline Santur, Jeannine Mohrlueder, Monika A. . Coronado, Dieter Willbold
Summary: A novel and efficient next-generation sequencing (NGS) supported phage display selection strategy was used to identify a set of peptide ligands that inhibit the SARS-CoV-2 3CL protease. These ligands have the potential to be lead compounds for therapeutic development and address limitations associated with current L-peptide inhibitors.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tim Altendorf, Ian Gering, Beatrix Santiago-Schuebel, Selma Aghabashlou Saisan, Gueltekin Tamgueney, Markus Tusche, Dominik Honold, Sarah Schemmert, Wolfgang Hoyer, Jeannine Mohrlueder, Dieter Willbold
Summary: Alzheimer's disease and other tauopathies are caused by the misfolding and aggregation of the tau protein, leading to neurodegeneration. In this study, two all D-enantiomeric peptides were developed, which bind to monomeric tau protein and inhibit its aggregation into amyloid fibrils. These peptides show promise as potential therapeutic agents for Alzheimer's disease and other tauopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Lea Sundermeyer, Graziella Bosco, Srushti Gujar, Melanie Brocker, Meike Baumgart, Dieter Willbold, Oliver H. Weiergraeber, Marco Bellinzoni, Michael Bott
Summary: In this study, we investigated the roles of GlnH and GlnX in the GlnH-GlnX-PknG-OdhI-OdhA signal transduction cascade in C. glutamicum, and confirmed their involvement through genetic, biochemical, and structural modeling approaches.
MICROBIOLOGY SPECTRUM
(2022)
Article
Pharmacology & Pharmacy
Monika A. Coronado, Ian Gering, Marc Sevenich, Danilo S. Olivier, Mohammadamin Mastalipour, Marcos S. Amaral, Dieter Willbold, Raphael J. Eberle
Summary: Epigallocatechin molecules, found in green tea, have shown great potential in inhibiting flaviviruses such as Dengue, yellow fever, West Nile, and Zika. This discovery could lead to the development of more effective antiviral drugs.
Article
Medicine, General & Internal
Marlene Pils, Alexandra Dybala, Fabian Rehn, Lara Bloemeke, Tuyen Bujnicki, Victoria Kraemer-Schulien, Wolfgang Hoyer, Detlev Riesner, Dieter Willbold, Oliver Bannach
Summary: Protein misfolding and aggregation are key factors in neurodegenerative diseases. In this study, a synthetic β-amyloid oligomer sample was developed for quality control and standardization of diagnostic methods. The combination of atomic force microscopy and fluorescence analysis showed promising results for the detection of Aβ oligomers in bodily fluids.
Article
Biochemistry & Molecular Biology
Katharina Wintz, Julia Post, Karl-Josef Langen, Dieter Willbold, Antje Willuweit, Janine Kutzsche
Summary: Amyotrophic lateral sclerosis (ALS) is a deadly disease with no cure, causing complete muscle loss and respiratory arrest. Only three symptomatic drugs have been approved by the FDA so far. RD2RD2, a new drug candidate, has shown the ability to delay symptom onset in mouse models of ALS.
Article
Biochemistry & Molecular Biology
Alexandra Albus, Yannick Kronimus, Monika Burg-Roderfeld, Hendrik van der Wurp, Dieter Willbold, Tamar Ziehm, Richard Dodel, Jean Alexander Ross
Summary: The accumulation and aggregation of alpha-synuclein are crucial mechanisms in the development of Parkinson's disease. This study investigated the levels and binding characteristics of naturally occurring autoantibodies against alpha-synuclein in patients with Parkinson's disease and healthy controls. The results showed no significant differences in the levels or affinities of these autoantibodies between the two groups, regardless of the presence of LRRK2 gene mutations.
Article
Cell Biology
Bettina Kass, Sarah Schemmert, Christian Zafiu, Marlene Pils, Oliver Bannach, Janine Kutzsche, Tuyen Bujnicki, Dieter Willbold
Summary: In this study, we analyzed the concentration and size distribution of AD oligomers in different transgenic mouse models and in human brain samples. We demonstrated that the compound RD2 eliminated oligomers in mouse and human AD brain tissue, providing potential translational value from pre-clinical studies to clinical trials.
CELL REPORTS MEDICINE
(2022)