Publications by authors named "Christoph Schmidt"

Dorsal closure is a process that occurs during embryogenesis of . During dorsal closure, the amnioserosa (AS), a one-cell thick epithelial tissue that fills the dorsal opening, shrinks as the lateral epidermis sheets converge and eventually merge. During this process, both shape index and aspect ratio of amnioserosa cells increase markedly.

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  • Sepsis is a serious condition that poses risks to human health and has significant economic implications; recent research highlights various factors, including cellular senescence, that contribute to this issue.
  • In an experimental study on male mice, sepsis was induced via cecal ligation and puncture, leading to noticeable pulmonary damage and increased markers associated with acute lung injury and cellular senescence.
  • The results revealed complex changes in senescence-related pathways, suggesting that while some markers decrease, others may increase during the early stages, pointing to the need for further research on the long-term impacts of sepsis on multiple organ systems.
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  • Schistosomes are skilled at evading human immunity, particularly the complement system, allowing them to survive in human blood for years; this study explores how they interact with this immune response.
  • The research shows that newly formed schistosomula are initially very vulnerable to complement attack, but they can rapidly boost their survival rate, especially when they recruit complement regulator factor H to avoid destruction.
  • The use of the drug praziquantel increases the susceptibility of schistosomula to complement-mediated killing, suggesting that further investigation into factor H's role could help develop new treatments against schistosomes.
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The sinus lift procedure has become the most common method for maxillary bone augmentation. The most frequently observed intraoperative complication is the perforation of the Schneiderian membrane. Various treatment options have been proposed for managing these perforations, including the use of resorbable membranes, centrifugated blood products as PRF, or PRGF, suturing, and fibrin glue application.

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Inert gas washout methods have been shown to detect pathological changes in the small airways that occur in the early stages of obstructive lung diseases such as asthma and COPD. Numerical lung models support the analysis of characteristic washout curves, but are limited in their ability to simulate the complexity of lung anatomy over an appropriate time period. Therefore, the interpretation of patient-specific washout data remains a challenge.

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Venous thromboembolism (VTE) is a common, deadly disease with an increasing incidence despite preventive efforts. Clinical observations have associated elevated antibody concentrations or antibody-based therapies with thrombotic events. However, how antibodies contribute to thrombosis is unknown.

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  • This text discusses paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder caused by complement-mediated intravascular hemolysis, leading to conditions like anemia and thrombosis.
  • The first complement inhibitor, eculizumab, was approved in 2007, significantly improving patient outcomes but still leaving some patients with inadequate responses due to issues like breakthrough hemolysis.
  • Researchers are now exploring new complement therapies and mechanisms to tackle these problems, with several drugs currently available and many more in the pipeline for clinical trials.
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The introduction of a therapeutic anti-C5 antibody into clinical practice in 2007 inspired a surge into the development of complement-targeted therapies. This has led to the recent approval of a C3 inhibitory peptide, an antibody directed against C1s and a full pipeline of several complement inhibitors in preclinical and clinical development. However, no inhibitor is available that efficiently inhibits all three complement initiation pathways and targets host cell surface markers as well as complement opsonins.

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Inherited, age-related, and acute retinal diseases are often exacerbated by an aberrant or excessive activity of the complement system. Consequently, cells not directly affected by an acute event or genetic variants may degenerate, resulting in enhanced visual impairment. The therapeutic potential of supplementation of complement factor H (FH), a key regulator of the complement cascade, is therefore particularly promising in the context of retinal diseases caused by complement activation.

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Dorsal closure is a process that occurs during embryogenesis of . During dorsal closure, the amnioserosa (AS), a one-cell thick epithelial tissue that fills the dorsal opening, shrinks as the lateral epidermis sheets converge and eventually merge. During this process, the aspect ratio of amnioserosa cells increases markedly.

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  • Dorsal closure is an embryonic process where a tissue called the amnioserosa shrinks and the lateral epidermis merges to close the dorsal opening, resulting in changes to cell shape and aspect ratio.
  • Contrary to expectations based on the standard 2D vertex model—which suggests the tissue should become fluid by changing cell neighbors—the amnioserosa behaves as a solid during this process.
  • A modified vertex model, which takes into account the gradual reduction of cell perimeter and differing cell sizes, successfully explains the amnioserosa's solid state, accurately predicts cell shape changes and junction tension, and aligns with experimental findings.
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  • Haemostasis is the process by which the body stops bleeding, primarily through the formation of a platelet plug and a fibrin mesh, but interactions with the complement system can complicate this in certain conditions.
  • This study investigated how complement components affect haemostasis during mechanical vessel injury using a model that simulates this injury with human blood and endothelial cells.
  • Results showed that while some complement inhibitors did not significantly impact fibrin formation, inhibitors targeting common pathways like C3 and C5 greatly reduced both fibrin formation and platelet activation, particularly when using a novel triple inhibitor.
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KIF20A is a critical kinesin for cell division and a promising anti-cancer drug target. The mechanisms underlying its cellular roles remain elusive. Interestingly, unusual coupling between the nucleotide- and microtubule-binding sites of this kinesin-6 has been reported, but little is known about how its divergent sequence leads to atypical motility properties.

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  • Systemic AA amyloidosis is a disease caused by the misfolding of serum amyloid A (SAA) protein, leading to harmful deposits in various organs.
  • The study aimed to discover new substances that can inhibit the formation of amyloid fibrils from SAA protein and to understand how they work.
  • Researchers identified lysozyme as an effective inhibitor of SAA fibril formation, which seems to function by directly binding to SAA and preventing its aggregation, similar to how molecular chaperones operate.
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Complement activation in the diseases paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) results in cytolysis and fatal thrombotic events, which are largely refractory to anticoagulation and/or antiplatelet therapy. Anticomplement therapy, however, efficiently prevents thrombotic events in PNH and aHUS, but the underlying mechanisms remain unresolved. We show that complement-mediated hemolysis in whole blood induces platelet activation similarly to activation by adenosine 5'-diphosphate (ADP).

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A minimized version of complement factor H (FH), designated mini-FH, was previously engineered combining the N-terminal regulatory domains (short consensus repeat [SCR]1-4) and C-terminal host-surface recognition domains (SCR19-20) of the parent molecule. Mini-FH conferred enhanced protection, as compared with FH, in an ex vivo model of paroxysmal nocturnal hemoglobinuria driven by alternative pathway dysregulation. In the current study, we tested whether and how mini-FH could block another complement-mediated disease, namely periodontitis.

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Factor H is a pivotal complement regulatory protein that is preferentially produced by the liver and circulates in high concentrations in serum. There has been an increasing interest in the extrahepatic production of complement factors, including by cells of the immune system, since this contributes to non-canonical functions of local complement activation and regulation. Here we investigated the production and regulation of factor H and its splice variant factor H-like protein 1 (FHL-1) by human myeloid cells.

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The complement system plays a crucial role in host defense, homeostasis, and tissue regeneration and bridges the innate and the adaptive immune systems. Although the genetic variants in complement C2 (c.839_849+17del; p.

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The COVID-19 pandemic requires firms to adequately respond. In this study, we first explore in our empirical data how firms responded to the COVID-19 crisis and identify five tactical response , operational, digitalization, financial, supportive, and organizational responses. Furthermore, our findings indicate that responses vary in ; Some firms act on their own, while others engage in collaborations.

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Over a century after the discovery of the complement system, the first complement therapeutic was approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). It was a long-acting monoclonal antibody (aka 5G1-1, 5G1.1, h5G1.

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  • The use of biomaterials in medicine has improved drug delivery and decreased complications in procedures like transplantations and hemodialysis, but immune reactions remain a challenge.
  • Factor H (FH), a protein that regulates the complement system and dampens immune responses, can be recruited to biomedical surfaces using a cyclic peptide called 5C6, which helps reduce immune activation.
  • This research identifies the key structural elements of 5C6 necessary for effective binding to FH, enhancing its potential application as a therapeutic tool to minimize complement activation on biomaterials.
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The cellular and fluid phase-innate immune responses of many diseases predominantly involve activated neutrophil granulocytes and complement factors. However, a comparative systematic analysis of the early impact of key soluble complement cleavage products, including anaphylatoxins, on neutrophil granulocyte function is lacking. Neutrophil activity was monitored by flow cytometry regarding cellular (electro-)physiology, cellular activity, and changes in the surface expression of activation markers.

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The efficient extraction of image data from curved tissue sheets embedded in volumetric imaging data remains a serious and unsolved problem in quantitative studies of embryogenesis. Here, we present DeepProjection (DP), a trainable projection algorithm based on deep learning. This algorithm is trained on user-generated training data to locally classify 3D stack content, and to rapidly and robustly predict binary masks containing the target content, e.

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