Publications by authors named "Huber O"

There is no doubt that the proper development of the heart is important for its correct function, in addition, maturation processes of the heart are crucial as well. The actin-binding protein nexilin seems to take over central roles in the latter processes, as nexilin-deficient mice are phenotypically inconspicuous at birth but die within short time thereafter. Recently, it has been proposed that nexilin plays a role in the formation and function of transverse tubules (T-tubules), which are essential for excitation-contraction coupling in the hearts of mature animals.

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This study reveals that Fc-enhanced anti-CTLA-4 harnesses novel mechanisms to overcome the limitations of conventional anti-CTLA-4, effectively treating poorly immunogenic and treatment-refractory cancers. Our findings support the development of a new class of immuno-oncology agents, capable of extending clinical benefit to patients with cancers resistant to current immunotherapies.

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Article Synopsis
  • Glioblastoma is a challenging brain cancer that often resists standard immunotherapy, but Botensilimab, a specialized antibody, has shown potential in treating this type of cancer.
  • In preclinical studies, a mouse version of Botensilimab demonstrated effectiveness when used alone or with doxorubicin combined with ultrasound techniques, leading to significant immune responses in treatment-resistant glioblastoma.
  • Results indicated that this combination therapy not only effectively targeted and reduced tumor-associated immune cells but also fostered a strong infiltration of harmful T cells, achieving a remarkable cure rate in mice and suggesting promising implications for human treatments.
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GDP-mannose pyrophosphorylase B (GMPPB) loss-of-function is associated with muscular dystrophy and variable additional neurological symptoms. GMPPB facilitates the catalytic conversion of mannose-1-phosphate and GTP to GDP-mannose, which serves as a mannose donor for glycosylation. The activity of GMPPB is regulated by its non-catalytic paralogue GMPPA, which can bind GDP-mannose and interact with GMPPB, thereby acting as an allosteric feedback inhibitor of GMPPB.

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Additive manufacturing enables the production of lattice structures, which have been proven to be a superior class of lightweight mechanical metamaterials whose specific stiffness can reach the theoretical limit of the upper Hashin-Shtrikman bound for isotropic cellular materials. To achieve isotropy, complex structures are required, which can be challenging in powder bed additive manufacturing, especially with regard to subsequent powder removal. The present study focuses on the Finite Element Method simulation of 2.

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Abnormal expression of ACSL members 1, 3, 4, 5, and 6 is frequently seen in human cancer; however, their clinical relevance is unclear. In this study, we analyzed the expression of ACSLs and investigated the effects of the ACSL inhibitor Triacsin C (TC) in lung cancer. We found that, compared to normal human bronchial epithelial (NHBE) cells, ACSL1, ACSL4, and ACSL6 were highly expressed, while ACSL3 and ACSL5 were lost in the majority of lung cancer cell lines.

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Epigenetic modulation of the cell-intrinsic immune response holds promise as a therapeutic approach for leukemia. However, current strategies designed for transcriptional activation of endogenous transposons and subsequent interferon type-I (IFN-I) response, show limited clinical efficacy. Histone lysine methylation is an epigenetic signature in IFN-I response associated with suppression of IFN-I and IFN-stimulated genes, suggesting histone demethylation as key mechanism of reactivation.

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Article Synopsis
  • Altered protein phosphorylation in cancer cells can create neoantigens, but their role in cancer immunity is not well understood.
  • This study explores how a specific phosphoneoantigen, pMLL, is recognized by a T cell receptor (TCR27), which may be useful for cancer immunotherapy.
  • Findings indicate that substituting phosphoserine affects TCR27’s ability to activate T cells, underscoring the importance of phosphate interactions for TCR specificity and potential new treatment strategies.
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Estrogen-dependent breast cancers rely on a constant supply of estrogens and expression of estrogen receptors. Local biosynthesis, by aromatase in breast adipose fibroblasts (BAFs), is their most important source for estrogens. Triple-negative breast cancers (TNBC) rely on other growth-promoting signals, including those from the Wnt pathway.

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In previous studies, we have identified the tumor suppressor proteins Fhit (fragile histidine triad) and Nit1 (Nitrilase1) as interaction partners of β-catenin both acting as repressors of the canonical Wnt pathway. Interestingly, in and these proteins are expressed as NitFhit fusion proteins. According to the Rosetta Stone hypothesis, if proteins are expressed as fusion proteins in one organism and as single proteins in others, the latter should interact physically and show common signaling function.

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Article Synopsis
  • Tight junctions (TJs) are crucial for controlling ion and molecule movement in epithelial cells, and the protein hZO-2 plays a significant role in this process.
  • Research identified specific lysine residues (K759 and K992) in hZO-2 that are essential for its ubiquitination and subsequent degradation, while a mutation at K730 resulted in increased ubiquitination and reduced protein stability.
  • The study demonstrated that alterations in these lysine residues impact the integrity of TJs, as MDCK cells with mutated hZO-2 showed reduced trans-epithelial resistance (TER), indicating compromised junction function.
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Programmed death ligand 1 (PD-L1) strongly inhibits T cell activation, thereby aiding tumors in escaping the immune response. PD-L1 inhibitors have proven to be effective in the treatment of different types of cancer, including non-small cell lung cancer (NSCLC). Yet, the knowledge regarding the biological function of tumor-intrinsic PD-L1 in lung cancer remains obscure.

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Phosphoinositide 3-kinases (PI3Ks) are a family of enzymes phosphorylating phospholipids in the membrane, thereby, promoting the PI3K/AKT signaling cascade. PI3Ks are involved in a variety of fundamental cellular functions, including tumor necrosis factor α (TNFα)-induced tight junction (TJ) impairment-a hallmark of inflammatory bowel diseases. Most of the studies analyzing the role of class I PI3K signaling in epithelial barrier maintenance did not decipher which of the isoforms are responsible for the observed effects.

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Podocyte damage is a major pathological lesion leading to focal segmental glomerulosclerosis (FSGS). Podocytes damaged by cellular stress undergo hypertrophy to compensate for podocytopenia. It is known that cyclin-dependent kinase inhibitors induced by p53 ensure podocytes hypertrophy; however, its precise mechanism remains to be further investigated.

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The therapeutic activities of natural plant extracts have been well known for centuries. Many of them, in addition to antiviral and antibiotic effects, turned out to have anti-tumor activities by targeting different signaling pathways. The canonical Wnt pathway represents a major tumorigenic pathway deregulated in numerous tumor entities, including colon cancer.

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GDP-mannose-pyrophosphorylase-B (GMPPB) facilitates the generation of GDP-mannose, a sugar donor required for glycosylation. GMPPB defects cause muscle disease due to hypoglycosylation of α-dystroglycan (α-DG). Alpha-DG is part of a protein complex, which links the extracellular matrix with the cytoskeleton, thus stabilizing myofibers.

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Post-translational modifications (PTMs) such as phosphorylation, ubiquitination or glycosylation are processes affecting the conformation, stability, localization and function of proteins. There is clear evidence that PTMs can act upon tight junction (TJ) proteins, thus modulating epithelial barrier function. Compared to transcriptional or translational regulation, PTMs are rapid and more dynamic processes so in the context of barrier maintenance they might be essential for coping with changing environmental or external impacts.

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Molecular alterations within the hematopoietic system influence cellular longevity and development of age-related myeloid stem-cell disorders like acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). A reduced SIRT7-expression in aged murine hematopoietic stem cells (HSC) resulted in reduced longevity and increased proliferation. In this study we investigated age-related changes of SIRT7-expression in healthy humans and relevant pathomechanisms in AML and CML.

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Paracrine interactions between malignant estrogen receptor positive (ER) breast cancer cells and breast adipose fibroblasts (BAFs) stimulate estrogen biosynthesis by aromatase in BAFs. In breast cancer, mainly the cAMP-responsive promoter I.3/II-region mediates excessive aromatase expression.

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Unlabelled: Glycation occurs as a non-enzymatic reaction between amino and thiol groups of proteins, lipids, and nucleotides with reducing sugars or α-dicarbonyl metabolites. The chemical reaction underlying is the Maillard reaction leading to the formation of a heterogeneous group of compounds named advanced glycation end products (AGEs). Deleterious effects have been observed to accompany glycation such as alterations of protein structure and function resulting in crosslinking and accumulation of insoluble protein aggregates.

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Unlabelled: Apoptotic extrusion of cells from epithelial cell layers is of central importance for epithelial homeostasis. As a prerequisite cell-cell contacts between apoptotic cells and their neighbors have to be dissociated. Tricellular tight junctions (tTJs) represent specialized structures that seal polarized epithelial cells at sites where three cells meet and are characterized by the specific expression of tricellulin and angulins.

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Alterations of the microbial composition in the gut and the concomitant dysregulation of the mucosal immune response are associated with the pathogenesis of opportunistic infections, chronic inflammation, and inflammatory bowel disease. To create a platform for the investigation of the underlying mechanisms, we established a three-dimensional microphysiological model of the human intestine. This model resembles organotypic microanatomical structures and includes tissue resident innate immune cells exhibiting features of mucosal macrophages and dendritic cells.

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