Article
Cell Biology
Tobias Heib, Heike M. Hermanns, Georgi Manukjan, Maximilian Englert, Charly Kusch, Isabelle Carlotta Becker, Annika Gerber, Lou Martha Wackerbarth, Philipp Burkard, Thomas Dandekar, Johannes Balkenhol, Daniel Jahn, Sarah Beck, Mara Meub, Sebastian Dutting, Christian Stigloher, Markus Sauer, Deya Cherpokova, Harald Schulze, Cord Brakebusch, Bernhard Nieswandt, Zoltan Nagy, Irina Pleines
Summary: The study demonstrates that RhoA/Cdc42 signaling is crucial for platelet precursor formation, and that the polyploidization and cytoplasmic maturation of MKs are separately regulated processes.
Article
Biochemistry & Molecular Biology
Hiroshi Senoo, Daisuke Murata, May Wai, Kenta Arai, Wakiko Iwata, Hiromi Sesaki, Miho Iijima
Summary: AKT, a serine/threonine kinase, plays a crucial role in metabolism, cell growth, and cytoskeletal dynamics, and is activated by PDK1 and mTORC2. Research has uncovered that insulin activates mTORC2 towards AKT by forming a supercomplex KARATE with KRAS4B and RHOA GTPases, revealing a fundamental mechanism in insulin-regulated glucose homeostasis.
Article
Biology
Simon Stilling, Theodoros Kalliakoudas, Hannah Benninghoven-Frey, Takanari Inoue, Bjorn H. Falkenburger
Summary: The level of PIP2 in the ciliary membrane determines the length of primary cilia. Various pathways converge on PIP2 to induce ciliary fission, which is dependent on actin, AurkA and HDAC6. This study reveals the importance of PIP2 in the stability and turnover of ciliary membrane.
COMMUNICATIONS BIOLOGY
(2022)
Article
Immunology
Eric Malmhall-Bah, Karin M. E. Andersson, Malin C. Erlandsson, Murali K. Akula, Mikael Brisslert, Clotilde Wiel, Ahmed E. El Zowalaty, Volkan I. Sayin, Martin O. Bergo, Maria I. Bokarewa
Summary: This study discovers an unexpected role of macrophages in stimulating the development of pro-inflammatory thymic Tregs and reveals that the activation of Rho-GTPases is behind their arthritogenic phenotype.
JOURNAL OF AUTOIMMUNITY
(2022)
Article
Rheumatology
Huixian Hong, Fatima Alduraibi, David Ponder, Wayne L. Duck, Casey D. Morrow, Jeremy B. Foote, Trenton R. Schoeb, Huma Fatima, Charles O. Elson, Hui-Chen Hsu, John D. Mountz
Summary: The study aims to determine the influence of the gut microbiome on systemic autoimmunity in a mouse model of lupus. The findings suggest that the gut microbiome may regulate certain aspects of systemic autoimmunity.
ARTHRITIS & RHEUMATOLOGY
(2022)
Article
Biology
Ariel Pradipta, Miwa Sasai, Kou Motani, Ji Su Ma, Youngae Lee, Hidetaka Kosako, Masahiro Yamamoto
Summary: The interferon-inducible GTPase Irgm2 plays a crucial role in controlling parasite killing through recruitment of Gbp1 and Irgb6, regardless of its localization at the parasitophorous vacuole membranes (PVM) of Toxoplasma. Ubiquitination of Irgm2 in the cytosol is important for parasite killing by recruiting Gbp1 to the PVM. Meanwhile, PVM ubiquitination and loading of p62/Sqstm1 at later time points post-Toxoplasma infection require Irgm2 localization at the PVM.
LIFE SCIENCE ALLIANCE
(2021)
Review
Cell Biology
Rashmita Pradhan, Phuong A. Ngo, Luz d. C. Martinez-Sanchez, Markus F. Neurath, Rocio Lopez-Posadas
Summary: Rho proteins are crucial regulators of the cytoskeleton, cell morphology, and trafficking. Their function is determined by GTP/GDP exchange and prenylation, allowing binding to cell membranes and interaction with downstream effector proteins. In the context of the GI tract, Rho GTPases play important roles in maintaining tissue homeostasis.
Article
Biochemistry & Molecular Biology
Ammon B. Peck, Cuong Q. Nguyen, Julian L. Ambrus
Summary: The C57BL/6.NOD-Aec1Aec2 mouse is considered an appropriate model of Sjogren's Syndrome, with B lymphocytes and MZB cells playing important roles in the development of the disease. Transcriptomic analyses have revealed upregulation of genes associated with lymphocyte infiltration in the salivary glands of SS mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Malarvizhi Gurusamy, Denise Tischner, Jingchen Shao, Stephan Klatt, Sven Zukunft, Remy Bonnavion, Stefan Guenther, Kai Siebenbrodt, Roxane-Isabelle Kestner, Tanja Kuhlmann, Ingrid Fleming, Stefan Offermanns, Nina Wettschureck
Summary: The G-protein-coupled receptor P2Y10, expressed in CD4 T cells, mediates RhoA activation and migration in response to lysophosphatidylserine and ATP, which are induced in T cells upon chemokine stimulation through an autocrine/paracrine loop.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Charlotte Boussard, Laure Delage, Tania Gajardo, Alexandre Kauskot, Maxime Batignes, Nicolas Goudin, Marie -Claude Stolzenberg, Camille Brunaud, Patricia Panikulam, Quentin Riller, Maryse Moya-Nilges, Jean Solarz, Christelle Reperant, Beatrice Durel, Jean-Claude Bordet, Olivier Pelle, Corinne Lebreton, Aude Magerus, Vithura Pirabakaran, Pablo Vargas, Sebastien Dupichaud, Marie Jeanpierre, Angelique Vinit, Mohammed Zarhrate, Cecile Masson, Nathalie Aladjidi, Peter D. Arkwright, Brigitte Bader-Meunier, Sandrine Baron Joly, Joy Benadiba, Elise Bernard, Dominique Berrebi, Christine Bodemer, Martin Castelle, Fabienne Charbit-Henrion, Marwa Chbihi, Agathe Debray, Philippe Drabent, Sylvie Fraitag, Miguel Hie, Judith Landman-Parker, Ludovic Lhermitte, Despina Moshous, Pierre Rohrlich, Frank Ruemmele, Anne Welfringer-Morin, Maud Tusseau, Alexandre Belot, Nadine Cerf-Bensussan, Marie Roelens, Capucine Picard, Benedicte Neven, Alain Fischer, Isabelle Callebaut, Mickael Menager, Fernando E. Sepulveda, Frederic Adam, Frederic Rieux-Laucat
Summary: DOCK11 deficiency leads to impaired cellular function and immune dysregulation, resulting in autoimmune disorders.
Article
Chemistry, Physical
Simge Senyuz, Hyunbum Jang, Ruth Nussinov, Ozlem Keskin, Attila Gursoy
Summary: Rac1 is a key GTPase protein involved in cellular biology and diseases, with mutations like P29S and A159V associated with melanoma and head and neck cancer, respectively. These mutations activate Rac1 through different mechanisms, affecting the conformation of Switch I in GTP-bound states.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Multidisciplinary Sciences
Sharon A. Sagan, Zahra Moinfar, Carson E. Moseley, Ravi Dandekar, Collin M. Spencer, Alan S. Verkman, Ole Petter Ottersen, Raymond A. Sobel, John Sidney, Alessandro Sette, Mark S. Anderson, Lawrence Steinman, Michael R. Wilson, Joseph J. Sabatino, Scott S. Zamvil
Summary: This study investigates the role of AQP4-specific Th17 cells in the pathogenesis of neuromyelitis optica (NMO). The research shows that AQP4-specific T cells have a high affinity for binding to MHC II, and their clonal expansion is observed in AQP4-deficient mice. Thymic negative selection alone does not account for the tolerance to AQP4 in wild-type (WT) mice. AQP4-specific Th17 cells can cause paralysis followed by recovery, associated with apoptosis of donor T cells. However, these cells can persist and cause persistent paralysis in mice deficient in both T and B cells or lacking T cells only. In contrast, MOG-specific T cells survive and cause sustained disease in WT mice.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Jordan E. Jones, Gregory D. D. Hurst
Summary: The presence of defensive microbial symbionts within insects can affect the outcome of natural enemy attacks. The thermal environment is known to influence symbiont-mediated traits in insects. This study examined the effect of temperature on Spiroplasma-mediated protection against Leptopilina boulardi in Drosophila melanogaster and found that the developmental temperature of the mothers plays a stronger role in determining the protective influence of Spiroplasma than the temperature during or after wasp attack.
Article
Multidisciplinary Sciences
Carmen Ranftler, Dietmar Nagl, Andreas Sparer, Andreas Roehrich, Michael Freissmuth, Ali El-Kasaby, Shahrooz Nasrollahi Shirazi, Florian Koban, Cornelius Tschegg, Stephane Nizet
Summary: The study demonstrated that G-PUR (R) could effectively adsorb clinically relevant amounts of C. difficile toxins A and B, neutralizing their effects in vitro. Furthermore, the use of G-PUR (R) did not cause damage to the epithelial monolayer, indicating its potential safety for the treatment and prevention of C. difficile-associated diarrhea.
Article
Chemistry, Physical
Kiryl Zhaliazka, Stanislav Rizevsky, Mikhail Matveyenka, Valeryia Serada, Dmitry Kurouski
Summary: The charge of phospholipids determines the aggregation rate and morphology of lysozyme on the plasma membrane, while the secondary structure and toxicity of the protein depend on its chemical nature.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Paula Ramos Delgado, Andre Kuehne, Mariya Aravina, Jason M. Millward, Alonso Vazquez, Ludger Starke, Helmar Waiczies, Andreas Pohlmann, Thoralf Niendorf, Sonia Waiczies
Summary: A model-based correction method was proposed and validated to quantify F-19 signals in inflamed mouse brains using F-19-CRP technology. The study showed significant improvements in signal quantification and concentration uncertainty maps, paving the way for future low-SNR F-19-MRI applications in vivo.
MAGNETIC RESONANCE IN MEDICINE
(2022)
Article
Clinical Neurology
Markus Bock, Falk Steffen, Frauke Zipp, Stefan Bittner
Summary: This study investigated the impact of adapted ketogenic diet (AKD) and caloric restriction (CR) on neuroaxonal damage in patients with multiple sclerosis (MS), and found that AKD significantly reduced serum neurofilament light chain (sNfL) levels.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2022)
Article
Endocrinology & Metabolism
Lisa Middendorf, Alexandra Gellhaus, Antonella Iannaccone, Angela Koeninger, Anne-Kathrin Dathe, Ivo Bendix, Beatrix Reisch, Ursula Felderhoff-Mueser, Britta Huening
Summary: The sFlt-1/PlGF ratio does not predict the motor optimality score (MOS-R) in preterm infants, but low birth weight, which is correlated with an elevated ratio, has a negative effect on MOS-R outcome.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Physiology
Kathleen Cantow, Thomas Gladytz, Jason M. Millward, Sonia Waiczies, Thoralf Niendorf, Erdmann Seeliger
Summary: This study used dynamic MRI to monitor kidney size and provided physiological interpretation of changes in renal oxygenation. The results showed correlations between changes in kidney size and T-2* and T-2. Monitoring kidney size allows for a better understanding of renal pathophysiology.
Article
Immunology
Susann Hetze, Lennart Barthel, Laura Luckemann, Hauke S. Gunther, Clemens Wulfing, Yasmin Salem, Marie Jakobs, Tina Horbelt-Grunheidt, Jasmin Petschulat, Ivo Bendix, Ulrike Weber-Stadlbauer, Ulrich Sure, Manfred Schedlowski, Martin Hadamitzky
Summary: This study confirms the efficacy of using taste-immune associative learning with rapamycin in inhibiting GBM tumor growth while promoting the development of an anti-inflammatory anti-tumor microenvironment. These findings can serve as a reference for implementing learning protocols as alternative or supportive treatment strategies in clinical settings.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Medicine, General & Internal
Muriel Schraad, Timo Uphaus, Stefan Runkel, Walter Hitzler, Stefan Bittner, Frauke Zipp
Summary: This study aimed to investigate the response of multiple sclerosis (MS) patients to SARS-CoV-2 vaccination after disease-modifying therapy (DMT). The findings suggest that anti-CD20 treatment, decreased CD8 levels, and non-selective S1P treatment may lead to an insufficient response to SARS-CoV-2 vaccination. Close monitoring of anti-spike antibodies is recommended to customize vaccination regimens for these patients.
Article
Clinical Neurology
Falk Steffen, Timo Uphaus, Nina Ripfel, Vinzenz Fleischer, Muriel Schraad, Gabriel Gonzalez-Escamilla, Sinah Engel, Sergiu Groppa, Frauke Zipp, Stefan Bittner
Summary: Measuring serum neurofilament light chain (sNfL) levels can predict disease severity and future evidence of disease activity in patients with multiple sclerosis (MS). sNfL levels are also associated with the development of neurodegenerative damage.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2023)
Article
Biochemistry & Molecular Biology
Rebekka Vogtmann, Mian Bao, Monia Vanessa Dewan, Alina Riedel, Rainer Kimmig, Ursula Felderhoff-Mueser, Ivo Bendix, Torsten Ploesch, Alexandra Gellhaus
Summary: Fetal adaptations to harmful intrauterine environments due to pregnancy disorders such as preeclampsia (PE) can negatively program the offspring's metabolism, resulting in long-term metabolic changes. In this study, researchers examined the consequences of sFLT1 overexpression in transgenic mice with PE/FGR on the offspring's metabolic phenotype. The results showed that sFLT1 overexpression led to growth-restricted fetuses with altered liver development and metabolic gene expression. The postnatal follow-up revealed increased weight gain and abnormal hormone levels in male PE offspring, suggesting adverse metabolic pre-programming specifically targeting males.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Nandita Saha, Andre Kuehne, Jason M. Millward, Thomas Wilhelm Eigentler, Ludger Starke, Sonia Waiczies, Thoralf Niendorf
Summary: This study designed circular and elliptical thermal magnetic resonance (ThermalMR) RF applicator arrays that combine loop antennas and self-grounded bow-tie (SGBT) dipole antennas for targeted radiofrequency (RF) induced heating and diagnostic magnetic resonance imaging (MRI) transmission. These hybrid designs showed superior MRI performance and targeted RF heating inside the tumor, while preserving healthy tissue. The results provide technical support for diagnostic and therapeutic interventions in brain tumors.
Article
Immunology
Nicole Labusek, Yanis Mouloud, Christian Koester, Eva Diesterbeck, Tobias Tertel, Constanze Wiek, Helmut Hanenberg, Peter A. Horn, Ursula Felderhoff-Mueser, Ivo Bendix, Bernd Giebel, Josephine Herz
Summary: By comparing the neuroprotective effects of EVs derived from primary MSCs and ciMSCs in a mouse model of brain injury, we found that ciMSC-EVs can effectively reduce neuroinflammation and promote neuroregeneration, showing similar neuroprotective effects as primary MSC-EVs. This suggests that ciMSCs are an ideal cell source for the scaled manufacturing of EV-based therapeutics to treat neonatal and possibly also adult brain injury, overcoming the heterogeneity issue of MSCs.
INFLAMMATION AND REGENERATION
(2023)
Article
Clinical Neurology
Vinzenz Fleischer, Gabriel Gonzalez-Escamilla, Deborah Pareto, Alex Rovira, Jaume Sastre-Garriga, Piotr Sowa, Einar A. Hogestol, Hanne F. Harbo, Barbara Bellenberg, Carsten Lukas, Serena Ruggieri, Claudio Gasperini, Tomas Uher, Manuela Vaneckova, Stefan Bittner, Ahmed E. Othman, Sara Collorone, Ahmed T. Toosy, Sven G. Meuth, Frauke Zipp, Frederik Barkhof, Olga Ciccarelli, Sergiu Groppa
Summary: This study investigated the prognostic value of longitudinal structural networks in predicting 5-year Expanded Disability Status Scale (EDSS) progression in relapsing-remitting multiple sclerosis (RRMS) patients. The study found that changes in network degree and global efficiency can predict disability accumulation independent of disease activity, and these network measures outperform conventional MRI predictors in predicting EDSS worsening.
Editorial Material
Immunology
Stefan Bittner, Frauke Zipp
Summary: IL-17-blocking antibodies have limited clinical effect in certain autoimmune diseases. This study demonstrates that SHP2-Act1 complexes can mediate IL-17R signaling autonomously, even in the absence of the IL-17 ligand itself.
Review
Clinical Neurology
Stefan Bittner, Katrin Pape, Luisa Klotz, Frauke Zipp
Summary: Worsening clinical symptoms in patients with multiple sclerosis (MS) are caused by inflammation specifically occurring within the CNS. This chronic and non-relapsing immune-mediated mechanism of disease progression, called "smouldering inflammation," is sustained by local factors in the CNS and explains why current MS treatments do not adequately target it. This review summarizes the current understanding of the local inflammatory microenvironment in smouldering inflammation, its interaction with immune cell metabolism, and potential treatments for preventing neurodegenerative damage.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Medicine, Research & Experimental
Ludger Starke, Jason M. Millward, Christian Prinz, Fatima Sherazi, Helmar Waiczies, Christoph Lippert, Marc Nazare, Friedemann Paul, Thoralf Niendorf, Sonia Waiczies
Summary: The study demonstrates that siponimod can be imaged non-invasively using 19F UTE MRI, laying the foundation for further preclinical and clinical investigations. This technique provides an accurate understanding of the distribution of CNS-acting drugs in individual patients, which can contribute to personalized therapy.
Article
Clinical Neurology
Tobias Brummer, Muthuraman Muthuraman, Falk Steffen, Timo Uphaus, Lena Minch, Maren Person, Frauke Zipp, Sergiu Groppa, Stefan Bittner, Vinzenz Fleischer
Summary: This study demonstrates that combining blood and imaging measures improves the accuracy of predicting cognitive impairment in early multiple sclerosis. The findings highlight the clinical utility of cross-modal biomarkers in multiple sclerosis patients who are likely to experience cognitive decline.
BRAIN COMMUNICATIONS
(2022)