Cell-cycle control in cell-biomaterial interactions

Current biocompatibility testing involves the demonstration of cell proliferation, which is usually interpreted as a sign of positive biocompatibility when the materials sustain cell proliferation. As the field of biomaterials research is rapidly moving toward tissue-engineered devices and hybrid organs, control of cell function has become a main topic. Cell function, which involves specific differentiation pathways, cannot be separated from cell-cycle control. The study of cell-cycle control is an important extension of routine proliferation assays and has extensive roots in developmental and tumor biology. We studied the expression of the tumour suppressor gene p53 and the proliferation-a…

Die bilanzielle Behandlung der verschiedenen Abtretungsformen

Basierend auf den handels- und steuerrechtlichen Grundlagen der bilanziellen Abbildung von Pensionszusagen (Kapitel 4) soll im Folgenden die bilanzielle Behandlung der verschiedenen Abtretungsformen dargestellt werden. Zu beachten ist hierbei stets, dass eine einmal gebildete Ruckstellung nach § 249 Abs. 2 Satz 2 HGB erst aufgelost werden darf, wenn und soweit der Grund fur ihre Bildung entfallen ist.

A New Structural Motif for an Enantiomerically Pure Metallosupramolecular Pd4L8Aggregate by Anion Templating

An enantiomerically pure BINOL-based bis(3-pyridyl) ligand 1 assembles into a homochiral [Pd4(1)8] complex upon coordination to tetravalent PdII ions. The formation of this aggregate is templated by two tetrafluoroborate counterions that are encapsulated in two peripheral cavities. The resulting structure is a new structural motif for this kind of metallosupramolecular assemblies that arranges the palladium ions in a distorted tetrahedral fashion and forces ligand 1 to adopt two different conformations. Both phenomena are unique and cause an overall three-dimensional structure that has another confined, chiral, and hydrophilic central cavity.

Enantiomerenreine [M6L12]- oder [M12L24]-Polyeder aus flexiblen Bis(pyridin)-Liganden

Enantiomerically pure [M(6)L(12)] or [M(12)L(24)] polyhedra from flexible bis(pyridine) ligands.

Coordination-driven self-assembly is one of the most powerful strategies to prepare nanometer-sized discrete (supra)molecular assemblies. Herein, we report on the use of two constitutionally isomeric BINOL-based bis(pyridine) ligands for this purpose. Upon coordination to Pd(II) ions these self-assemble into enantiomerically pure endo- and exo-functionalized hexa- and dodecanuclear metallosupramolecular spheres with a chiral skeleton depending on the substitution pattern of the BINOL core. These aggregates were characterized by NMR, MS, DLS, TEM, and EELS as well as ECD. Furthermore, experimental ECD data could be compared to those obtained from theoretical simulations using a simplified Ta…

Machine Learning Unveils Proteotypic Mimicry in Genetically Defined SCN Variants

Background Novel computational algorithms for multi-omics analysis bear great potential to highlight pathomechanisms of monogenic diseases. We recently defined the in-depth proteome of primary human neutrophil granulocytes (PMID 30630937). Here, we ask the question whether proteotypic patterns differ between defined genetic subtypes associated with severe congenital neutropenia (SCN). We focus on two novel genetic variants in constituents of the signal recognition particle (SRPRA and SRP19) and previously reported SCN genotypes SRP54, HAX1, and ELANE. Methods We analyzed proteomes of highly purified neutrophil granulocytes from a total of 26 SCN patients, including 5 with homozygous splice …

Formen der Abtretung von Pensionsverpflichtungen

Die unmittelbare Pensionszusage wurde als Mittel der Innenfinanzierung von Seiten der Arbeitgeber in der Nachkriegszeit und bis in die spaten 90er Jahre hinein geschatzt und nicht als finanzielle Bedrohung erachtet. Seit Ende der 90er Jahre ist jedoch zu beobachten, dass insbesondere Grosunternehmen bemuht sind, ihre Pensionsverpflichtungen auszulagern. Die Grunde hierfur sind vielseitig: Zum einen wird damit die direkte Bereinigung der Bilanzen von Pensionslasten bezweckt, was insbesondere bei bevorstehenden Unternehmensverkaufen oder anderen M&A-Deals zu einem „verschonerten“ Bilanzbild fuhren soll.

Defects in Signal Recognition Particle (SRP) Components Reveal an Essential and Non-Redundant Role for Granule Biogenesis and Differentiation of Neutrophil Granulocytes

Neutrophil granulocyte play pivotal roles in inflammatory responses, immune defence, tissue remodeling, and cancer control. Studying rare patients with defects in differentiation and/or function of neutrophil granulocytes highlights genes and pathways orchestrating these important cellular functions. A previously not appreciated role of the signal recognition particle (SRP) has emerged when monoallelic mutations in SRP54 were associated with congenital neutropenia and pancreatic insufficiency. The eukaryotic SRP is composed of six distinct polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) bound to an RNA molecule (the 7SL RNA). SRP and its receptor (SRPRA and SRPRB) cooperatively trans…

Characterization of the Clinical and Immunologic Phenotype and Management of 157 Individuals with 56 Distinct Heterozygous NFKB1 Mutations

Contains fulltext : 229571.pdf (Publisher’s version ) (Closed access) BACKGROUND: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. OBJECTIVE: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. METHODS: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. RESU…

The role of metal corrosion in inflammatory processes: induction of adhesion molecules by heavy metal ions

Prosthetic devices undergo corrosion processes after implantation including the release of certain amounts of metal ions into the adjacent tissues. On reaching the bloodstream, a systemic influence of those ions may be envisaged. Cell adhesion molecules (CAMs) are recognized as an essential component of the mechanisms of endothelial damage. To study the influence of selected heavy metals on human umbilical vein endothelial cells (HUVEC) EIA methods were used to evaluate cellular expression of E-selectin, ICAM-1, VCAM-1 and GMP-140 under the influence of high (cytotoxic) very low (non-cytotoxic) concentrations of Zn, Ni, Co and Cr. The de novo synthesis of CAMs was studied with the help of m…

Die Bilanzierung von Pensionsrückstellungen in Handels- und Steuerbilanz

Anders als in internationalen bzw. auslandischen Rechnungslegungsstandards wird im prinzipienbasierten deutschen Handelsbilanzrecht die Bilanzierung von Pensionsruckstellungen nicht in gesonderten Vorschriften geregelt. Der Ansatz einer Pensionsruckstellung dem Grunde nach leitet sich jedoch aus § 249 HGB ab: Fur die Zusage einer betrieblichen Altersversorgung muss gem. § 249 Abs. 1 Satz 1 HGB eine Ruckstellung gebildet werden, da aufgrund der Unsicherheit uber die Hohe sowie das tatsachliche Eintreten der Zahlungsverpflichtung gegenuber dem Versorgungsberechtigten der Tatbestand der ungewissen Verbindlichkeit erfullt ist.

Grundlagen und rechtliche Definition einer Pensionsverpflichtung

Das System der Alterssicherung in Deutschland basiert auf dem sog. Drei-Saulen-Konzept und ist untergliedert nach den jeweiligen Tragern der Altersvorsorgeleistungen. Im Einzelnen handelt es sich bei den „Saulen“ um die gesetzliche Rentenversicherung, die betriebliche Altersversorgung und die private Eigenvorsorge. Das Ziel der Altersvorsorge ist im Allgemeinen, dem Versicherten im Alter eine Vollversorgung zu ermoglichen, welche dem im Erwerbsleben erreichten Lebensstandard entspricht.

Increased adhesion and activation of polymorphonuclear neutrophil granulocytes to endothelial cells under heavy metal exposure in vitro.

Heavy metals have been implicated in the mechanisms of endothelial damage. Influences of heavy metal ions on diverse cell types have been studied using a variety of in vitro and in vivo methods. Polymorphonuclear neutrophil granulocytes (PMNs) have physiological and pathological functions, including the modulation of adhesion to and destruction of endothelial cells (ECs). PMNs were studied during interaction with human umbilical vein ECs under exposure to zinc, nickel and cobalt using an in vitro model. We studied adhesion processes with the help of a computer-controlled image-analyzing system and examined the activation of PMNs by quantification of leukotriene B4 (LTB4) release. The biphas…

Application of X-ray microanalysis to study of the expression of endothelial adhesion molecules on human umbilical vein endothelial cells in vitro

A semi-quantitative procedure is described, which allows the evaluation of expression levels of endothelial adhesion molecules on cultured human umbilical vein endothelial cells (HUVEC) using energy dispersive X-ray microanalysis (EDX). As a model two adhesion molecules, E-selection (CD62E; ELAM-1/endothelial leukocyte adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1; CD54), were localized by the use of the silver-enhancement colloidal gold method after stimulation of HUVEC with endotoxin lipopolysaccharide (LPS), tumour necrosis factor (TNF) or a phorbol ester (PMA). The analysis was performed in a scanning electron microscope (SEM) at an accelerating voltage of 15 kV wit…

Western blotting as a method for studying cell-biomaterial interactions: The role of protein collection

Research of cell-biomaterial interactions is building on knowledge and methods available in cell and molecular biology. Western blotting is one of the options to characterize protein expression in cell populations. Method transfer to biomaterial model systems is not trivial because of the structure that exists in many biomaterials, preventing the collection of cell lysate by mechanical means. In this technical report, we describe the influence of different protein collection methods in a model system for cell-biomaterial interactions, consisting of endothelial cells exposed to different stimuli. In particular, the influence of trypsinization before lysis, and handling complexity were determ…

Mechanisms of cell activation by heavy metal ions

Heavy metal ions can be released by corroding metallic implants into the surrounding tissue. When they enter blood vessels some of them are carried by proteins like albumin and can be taken up by endothelial cells lining the vessels. To study their involvement in the inflammatory response we investigated heavy metal ion induced effects in cultured human vascular endothelial cells (HUVECs). NiCl2 and CoCl2 upregulate, especially in concentrations of 1 mM, the expression of adhesion molecules (e.g., E-selectin and intercellular adhesion molecule-1), as well as the cytokines IL-6 and IL-8, as shown by enzyme immunoassay and Northern blot analysis. In addition, possible signal transduction mech…

Ein enantiomerenreines metallosupramolekulares Pd4L8-Aggregat mit neuartigem Strukturmotiv: Bildung durch einen Anionen-Templateffekt

Ein enantiomerenreiner Bis(3-pyridyl)-Ligand 1 auf der Basis eines BINOL-Gerusts bildet mit tetravalenten PdII-Ionen einen homochiralen [Pd4(1)8]-Komplex. Zwei Tetrafluoroborationen dienen dabei als Template fur die Bildung dieses Aggegates und werden in zwei periphere Kavitaten eingeschlossen. Die dadurch resultierende Struktur reprasentiert ein neues Strukturmotiv fur diese Sorte von metallosupramolekularen Assemblaten, in dem die vier Palladiumionen in einer verzerrt tetraedrischen Anordnung zu finden sind. Dies zwingt den Liganden 1, zwei verschiedene Konformationen in dem Aggregat einzunehmen. Beide Phanomene sind einzigartig und fuhren uberdies zur Bildung einer dreidimensionalen Stru…

Focal adhesions and assessment of cytotoxicity

Focal adhesions are highly ordered assemblies of transmembrane receptors, extracellular matrix proteins, and a large number of cytoplasmic proteins, including structural proteins, as well as tyrosine kinases, phosphatases, and their substrates. They are now accepted as a prime component of signal transduction. Because focal adhesions also play an important role in cell morphology and migration, it can be argued that their presence is indicative of healthy cells. This has been the reason for several research groups to conclude that biomaterials sustaining focal adhesion assembly are biocompatible. In this study we demonstrate that cells under cytotoxic stress may still be able to retain thei…

Spot compliant neuronal networks by structure optimized micro-contact printing

Neuronal cell growth in vitro can be controlled with micropatterned structures of extracellular matrix proteins such as laminin. This technique is a powerful tool for studying neuronal cell function in order to increase experimental reproducibility and to specifically design innovative experimental setups. In this paper the correlation between the structural dimensions of the ECM pattern and the shape of the resulting cellular network is analyzed. The aim of the present study was to position neuronal cell bodies as precisely as possible and to induce directed cell differentiation. PCC7-MzN cells were cultured on laminin patterns. The line width, node size and gap size in-between cell adhesi…

CCDC 982088: Experimental Crystal Structure Determination

Related Article: Christoph Klein, Christoph Gütz, Maximilian Bogner, Filip Topić, Kari Rissanen, Arne Lützen|2014|Angew.Chem.,Int.Ed.|53|3739|doi:10.1002/anie.201400626