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Molecular determinants of health and disease.

Stephan Ludwig, Sabine Blass-Kampmann, Frank Ulrich Müller,

Biol Chem (Biological chemistry)
[2021, :]

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Tumor cell lysis and synergistically enhanced antibody-dependent cell-mediated cytotoxicity by NKG2D engagement with a bispecific immunoligand targeting the HER2 antigen.

Christian Kellner, Sebastian Lutz, Hans-Heinrich Oberg, Daniela Wesch, Anna Otte, Katarina J Diemer, Hauke Wilcken, Dirk Bauerschlag, Claus-Christian Glüer, Christian Wichmann, Dieter Kabelitz, Jeanette H W Leusen, Katja Klausz, Andreas Humpe, Martin Gramatzki, Matthias Peipp,

Natural killer group 2 member D (NKG2D) plays an important role in the regulation of natural killer (NK) cell cytotoxicity in cancer immune surveillance. With the aim of redirecting NK cell cytotoxicity against tumors, the NKG2D ligand UL-16 binding protein 2 (ULBP2) was fused to a single-chain fragment variable (scFv) ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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Corrigendum to: Emerging mechanisms of drug-induced phospholipidosis.

Bernadette Breiden, Konrad Sandhoff,

Biol Chem (Biological chemistry)
[2021, :]

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Molecular determinants of therapy response of venetoclax-based combinations in acute myeloid leukemia.

Philipp Makowka, Verena Stolp, Karoline Stoschek, Hubert Serve,

Acute myeloid leukemia (AML) is a heterogeneous, highly malignant disease of the bone marrow. After decades of slow progress, recent years saw a surge of novel agents for its treatment. The most recent advancement is the registration of the Bcl-2 inhibitor ventoclax in combination with a hypomethylating agent (HMA) in ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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Functional characterisation of two receptor interaction determinants in human thymic stromal lymphopoietin.

Iva Marković, Therese Wolfrum, Andreas Wohlmann, Kritan Gautam, Karlheinz Friedrich,

Thymic stromal lymphopoietin (TSLP) is a pro-inflammatory cytokine with important pathological roles in <i>Asthma bronchiale</i>, malignant tumours and other diseases. The heterodimeric human TSLP receptor (hTSLPR) consists of the TSLP-binding subunit (TSLPRα) and the IL-7Rα-subunit. We studied the properties of hTSLP variants with mutations in their bipartite interaction interface towards ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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Artificial metalloenzymes in a nutshell: the quartet for efficient catalysis.

Paul Ebensperger, Claudia Jessen-Trefzer,

Artificial metalloenzymes combine the inherent reactivity of transition metal catalysis with the sophisticated reaction control of natural enzymes. By providing new opportunities in bioorthogonal chemistry and biocatalysis, artificial metalloenzymes have the potential to overcome certain limitations in both drug discovery and green chemistry or related research fields. Ongoing advances in ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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Molecular mechanisms of vasculopathy and coagulopathy in COVID-19.

Suzan Al-Gburi, Stefan Beissert, Claudia Günther,

COVID-19 primarily affects the respiratory system and may lead to severe systemic complications, such as acute respiratory distress syndrome (ARDS), multiple organ failure, cytokine storm, and thromboembolic events. Depending on the immune status of the affected individual early disease control can be reached by a robust type-I-interferon (type-I-IFN) response restricting viral ... Read more >>

Biol Chem (Biological chemistry)
[2021, 402(12):1505-1518]

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Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells.

Kanagaraj Gomathi, Muthukumar Rohini, Nicola C Partridge, Nagarajan Selvamurugan,

Transforming growth factor beta 1 (TGF-β1) functions as a coupling factor between bone development and resorption. Matrix metalloproteinase 13 (MMP13) is important in bone remodeling, and skeletal dysplasia is caused by a deficiency in MMP13 expre-ssion. Runx2, a transcription factor is essential for bone development, and MMP13 is one of ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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Inhibitory effect of mitoquinone against the α-synuclein fibrillation and relevant neurotoxicity: possible role in inhibition of Parkinson's disease.

Gege Yu, Yonghui Wang, Jinhua Zhao,

Extensive studies have reported that interaction of <i>α</i>-synuclein amyloid species with neurons is a crucial mechanistic characteristic of Parkinson's disease (PD) and small molecules can downregulate the neurotoxic effects induced by protein aggregation. However, the exact mechanism(s) of these neuroprotective effects by small molecules remain widely unknown. In the present ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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Epitranscriptomic modifications in acute myeloid leukemia: m6A and 2'-O-methylation as targets for novel therapeutic strategies.

Cornelius Pauli, Michael Kienhöfer, Stefanie Göllner, Carsten Müller-Tidow,

Modifications of RNA commonly occur in all species. Multiple enzymes are involved as writers, erasers and readers of these modifications. Many RNA modifications or the respective enzymes are associated with human disease and especially cancer. Currently, the mechanisms how RNA modifications impact on a large number of intracellular processes are ... Read more >>

Biol Chem (Biological chemistry)
[2021, 402(12):1531-1546]

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Brothers in arms: proBDNF/BDNF and sAPPα/Aβ-signaling and their common interplay with ADAM10, TrkB, p75NTR, sortilin, and sorLA in the progression of Alzheimer's disease.

Simone Eggert, Stefan Kins, Kristina Endres, Tanja Brigadski,

Brain-derived neurotrophic factor (BDNF) is an important modulator for a variety of functions in the central nervous system (CNS). A wealth of evidence, such as reduced mRNA and protein level in the brain, cerebrospinal fluid (CSF), and blood samples of Alzheimer's disease (AD) patients implicates a crucial role of BDNF ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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Characterization of hepatic zonation in mice by mass-spectrometric and antibody-based proteomics approaches.

Simon Kling, Benedikt Lang, Helen S Hammer, Wael Naboulsi, Heike Sprenger, Falko Frenzel, Oliver Pötz, Michael Schwarz, Albert Braeuning, Markus F Templin,

Periportal and perivenous hepatocytes show zonal heterogeneity in metabolism and signaling. Here, hepatic zonation in mouse liver was analyzed by non-targeted mass spectrometry (MS) and by the antibody-based DigiWest technique, yielding a comprehensive overview of protein expression in periportal and perivenous hepatocytes. Targeted immunoaffinity-based proteomics were used to substantiate findings ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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Life sciences and mass spectrometry: some personal reflections.

Jasna Peter-Katalinic,

Molecular analysis of biological systems by mass spectrometry was in focus of technological developments in the second half of the 20th century, in which the issues of chemical identification of high molecular diversity by biophysical instrumental methods appeared as a mission impossible. By developing dialogs between researchers dealing with life ... Read more >>

Biol Chem (Biological chemistry)
[2021, 402(12):1603-1607]

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Role of the gut microbiota in airway immunity and host defense against respiratory infections.

Maike Willers, Dorothee Viemann,

Colonization of the intestine with commensal bacteria is known to play a major role in the maintenance of human health. An altered gut microbiome is associated with various ensuing diseases including respiratory diseases. Here, we summarize current knowledge on the impact of the gut microbiota on airway immunity with a ... Read more >>

Biol Chem (Biological chemistry)
[2021, 402(12):1481-1491]

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The antioxidant Rutin counteracts the pathological impact of α-synuclein on the enteric nervous system in vitro.

Anne Christmann, Manuela Gries, Patrik Scholz, Pascal L Stahr, Jessica Ka Yan Law, Steven Schulte, Monika Martin, Rainer Lilischkis, Sven Ingebrandt, Cornelia M Keck, Karl-Herbert Schäfer,

Motoric disturbances in Parkinson's disease (PD) derive from the loss of dopaminergic neurons in the substantia nigra. Intestinal dysfunctions often appear long before manifestation of neuronal symptoms, suggesting a strong correlation between gut and brain in PD. Oxidative stress is a key player in neurodegeneration causing neuronal cell death. Using ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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High cellulose diet promotes intestinal motility through regulating intestinal immune homeostasis and serotonin biosynthesis.

Tao Xie, Fa Jin, Xiaokun Jia, Hengxu Mao, Yuting Xu, Shizhong Zhang,

It is widely accepted dietary fiber intimately linked to inflammatory and nervous diseases, which often been described with altered gastrointestinal (GI) motility. However, how dose dietary fiber modulate inflammation and crosstalk influence GI function has not been explained in detail. We found fiber-free diet reduced intestinal motility, accompanied by upregulated ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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A liquid-culture-based screening approach to study compounds affecting inflammatory processes in Caenorhabditis elegans.

Vu Thu Thuy Nguyen, Sarah Christina Meyer, Hanna Rieger, Kristina Endres,

Discovery of biomedical drugs makes use of novel biological sources of limited availability and is often in need of fast, small-scale initial screening approaches. Here, we present a screening, based on the reporter <i>Caenorhabditis elegans</i> strain IG692, for identification of anti- and pro-inflammatory properties. The elaborated workflow is based on ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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EGFR binding Fc domain-drug conjugates: stable and highly potent cytotoxic molecules mediate selective cell killing.

Sebastian Jäger, Stephan Dickgiesser, Jason Tonillo, Stefan Hecht, Harald Kolmar, Christian Schröter,

The exposition of cancer cells to cytotoxic doses of payload is fundamental for the therapeutic efficacy of antibody drug conjugates (ADCs) in solid cancers. To maximize payload exposure, tissue penetration can be increased by utilizing smaller-sized drug conjugates which distribute deeper into the tumor. Our group recently explored small human ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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Emerging contributions of formyl peptide receptors to neurodegenerative diseases.

Lukas Busch, Stefan Vieten, Susan Brödel, Kristina Endres, Bernd Bufe,

Inflammation is a central element of many neurodegenerative diseases. Formyl peptide receptors (FPRs) can trigger several receptor-dependent signal transduction pathways that play a key role in neuroinflammation and neurodegeneration. They are chemotactic receptors that help to regulate pro- and anti-inflammatory responses in most mammals. FPRs are primarily expressed in the ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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Two-photon fluorescent turn-on probes for highly efficient detection and profiling of thiols in live cells and tissues.

Congzhen Shen, Duoteng Zhang, Fang Xu, Yang Yang, Yi Tan, Qian Zhao, Lin Li, Ke Ding, Zhengqiu Li,

Thiols are important units in amino acids such as cysteine and peptides like glutathione. Development of chemical sensors capable of precise detection of thiols is important in cancer diagnosis and therapy. We have developed novel two-photon fluorescent turn-on probes for selective detection of thiols. The probes displayed excellent sensitivity and ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

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Controllers of cutaneous regulatory T cells: ultraviolet radiation and the skin microbiome.

Thomas Schwarz, Agatha Schwarz,

For the maintenance of homeostasis termination of immune reactions is as equally important as their induction. In this scenario regulatory T cells (Treg) play an important role. Accordingly a variety of inflammatory diseases are caused by an impairment of Treg. Hence, it is important to identify triggers by which Treg can ... Read more >>

Biol Chem (Biological chemistry)
[2021, 402(12):1575-1581]

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12 years more than just skin and bones: the CRC Transregio 67.

Jan-Christoph Simon, Carsten Werner,

Biol Chem (Biological chemistry)
[2021, 402(11):1269-1270]

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Pseudomonas aeruginosa and Staphylococcus aureus virulence factors as biomarkers of infection.

Artur J Sabat, Daniele Pantano, Viktoria Akkerboom, Erik Bathoorn, Alexander W Friedrich,

The gold standard for the diagnosis of bacterial infections in clinical samples is based on culture tests that are time-consuming and labor-intense. For these reasons, an extraordinary effort has been made to identify biomarkers as the tools for sensitive, rapid and accurate identification of pathogenic microorganisms. Moreover, biomarkers have been ... Read more >>

Biol Chem (Biological chemistry)
[2021, 402(12):1565-1573]

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Quantifying salt sensitivity.

Hans Oberleithner,

Inner surfaces of blood vessels and outer surfaces of erythrocytes are coated with a negatively charged protective film of proteoglycans, which serves as an effective buffer system for the positively charged sodium ions. If this protective coating is poorly developed or impaired, it loses its buffering capacity. As a consequence, ... Read more >>

Biol Chem (Biological chemistry)
[2021, 402(12):1597-1602]

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Identification of intracellular glycosaminoglycan-interacting proteins by affinity purification mass spectrometry.

Henning Großkopf, Sarah Vogel, Claudia Damaris Müller, Sebastian Köhling, Jan-Niklas Dürig, Stephanie Möller, Matthias Schnabelrauch, Jörg Rademann, Ute Hempel, Martin von Bergen, Kristin Schubert,

Glycosaminoglycans (GAGs) are essential functional components of the extracellular matrix (ECM). Artificial GAGs like sulfated hyaluronan (sHA) exhibit pro-osteogenic properties and boost healing processes. Hence, they are of high interest for supporting bone regeneration and wound healing. Although sulfated GAGs (sGAGs) appear intracellularly, the knowledge about intracellular effects and putative ... Read more >>

Biol Chem (Biological chemistry)
[2021, 402(11):1427-1440]

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