News Article | May 1, 2017
The Smart Cincy Summit in Cincinnati last week focused on how the city is working toward becoming a smarter city. The event, held at tech savvy maker space Union Hall in the trendy Over-the-Rhine district of Cincinnati, was the focus of brainstorming sessions on what it takes to become a truly smart city, with attention on security, big data, connectivity, sustainability and transportation. TechRepublic spoke to 11 smart city experts at the one-day event, ranging from Cincinnati city officials, to executives at Cintrifuse, Nexigen, Cincinnati Bell, TransitX and ET3 and more. Here are the videos with their thoughts on what it takes to become a smart city: Find out how the city has changed its focus from internal to external in order to work with businesses to add smart city tech to Cincinnati. SEE: Video: Cincinnati's smart plan to become a smarter city Cincinnati is focused on building a structural backbone for its data analytics infrastructure. Find out how the city is using the data to assess problems and measure progress. Cintrifuse is a network connecting entrepreneurs, enterprises and investors in Cincinnati. Learn how the city has positioned itself in the smart city space and learn more about Union Hall and its role. SEE: Video: How Cincinnati businesses are working together to turn their city into a smart city Cincinnati has an open data portal. Here are the data types that can be downloaded and used for deep dives into smart city analytics. SEE: Video: How open source data is helping Cincinnati Cincinnati Bell has worked to help provide broadband to homes to help low-income families acquire internet access. SEE: Video: Bridging the digital divide with Cincinnati Bell Find out about real-world examples of successes and failures, when it comes to revenue generation in a smart city. SEE: Video: How smart cities can make money for their communities Energy, agricultural, economic and environmental solutions are essential components of a smart city. There is a need for smart cities to be able to build solutions on top of each other. SEE: Video: Sustainability is key in the creation of a smart city TransitX CEO talked about his vision for the future of mass transit, and the role of infrastructure development in smart transportation. SEE: Video: How tech will fundamentally change the future of transportation Tube transport company ET3, similar to Elon Musk's Hyperloop, could reshape how people travel, offering a "freeway" that could reduce labor and fuel costs. SEE: Video: How tech could enable 'space travel on earth' The Smart Cincy Summit will help Cincinnati build on its foundation of four pillars essential to any smart city. SEE: Video: Understanding the four pillars of a smart city Wyzerr creates surveys designed as games to encourage responses. Wyzerr works with city governments to use survey data to improve services for a smarter city. SEE: Video: Wyzerr gets creative with smart city analytics
Kokkola T.,Universitatsklinikum Hamburg Eppendorf |
Kokkola T.,University of Eastern Finland |
Kruse C.,Forschungsinstitut Caesar |
Kruse C.,Nexigen GmbH |
And 7 more authors.
FEBS Letters | Year: 2011
Many G-protein coupled receptors are palmitoylated in their C-terminal, intracellular regions. So far no enzymes responsible for this modification have been described. We identified an interaction of the membrane proximal helix 8 of somatostatin receptor 5 (SSTR5) with the N-terminal region of the putative palmitoyltransferase ZDHHC5 using the Ras recruitment interaction screening system. ZDHHC5 and SSTR5 are colocalized at the plasma membrane and can be efficiently coimmunoprecipitated from transfected cells. Coexpression of ZDHHC5 in HEK293 cells increased palmitoylation of SSTR5 whereas knock-down of endogenous ZDHHC5 by siRNAs decreased it. Our data identify the first palmitoyltransferase for a G-protein coupled receptor. © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
News Article | November 15, 2016
BONN, Germany & MUNICH & CRAMBRIDGE, Mass.--(BUSINESS WIRE)--Rigontec, the leader in RIG-I targeting RNA therapeutics, today announced that Dr. Jörg Vollmer has joined the Company as Chief Scientific Officer. Dr. Vollmer brings to Rigontec more than 17 years of drug discovery and development experience including leadership roles at Nexigen GmbH, Pfizer and Coley Pharmaceutical Group. Dr. Vollmer will be responsible for leading Rigontec’s R&D efforts and advancing the Company’s RIG-I-based p
Hoffmann C.,University of Konstanz |
Berking A.,University of Konstanz |
Agerer F.,University of Würzburg |
Agerer F.,Nexigen GmbH |
And 6 more authors.
Journal of Cell Science | Year: 2010
Staphylococcus aureus, which is a leading cause of hospital-acquired infections, binds via fibronectin to integrin α5β1, a process that can promote host colonization in vivo. Integrin engagement induces actin cytoskeleton rearrangements that result in the uptake of S. aureus by non-professional phagocytic cells. Interestingly, we found that fibronectin-binding S. aureus trigger the redistribution of membrane microdomain components. In particular, ganglioside GM1 and GPI-linked proteins were recruited upon integrin β1 engagement, and disruption of membrane microdomains blocked bacterial internalization. Several membrane-microdomain- associated proteins, such as flotillin-1 and flotillin-2, as well as caveolin, were recruited to sites of bacterial attachment. Whereas dominantnegative versions of flotillin-2 did not affect bacterial attachment or internalization, cells deficient for caveolin-1 (Cav1-/-) showed increased uptake of S. aureus and other Fn-binding pathogens. Recruitment of membrane microdomains to cell-associated bacteria was unaltered in Cav1-/- cells. However, fluorescence recovery after photobleaching (FRAP) revealed an enhanced mobility of membrane-microdomain-associated proteins in the absence of caveolin-1. Enhanced membrane microdomain mobility and increased uptake of S. aureus was repressed by expression of wild-type caveolin-1, but not caveolin-1 G83S, which harbors a point mutation in the caveolin scaffolding domain. Similarly, chemical or physical stimulation of membrane fluidity led to increased uptake of S. aureus. These results highlight a crucial role for caveolin-1 in negative regulation of membrane microdomain mobility, thereby affecting endocytosis of bacteria-engaged integrins. This process might not only limit host cell invasion by integrin-binding bacterial pathogens, but might also be physiologically relevant for integrin-mediated cell adhesion.
PubMed | Miltenyi Biotec GmbH, TU Munich, Adiutide Pharmaceuticals GmbH, Nexigen GmbH and University of Heidelberg
Type: Journal Article | Journal: PloS one | Year: 2015
Activation of TLR7 and TLR9 by endogenous RNA- or DNA-containing ligands, respectively, is thought to contribute to the complicated pathophysiology of systemic lupus erythematosus (SLE). These ligands induce the release of type-I interferons by plasmacytoid dendritic cells and autoreactive antibodies by B-cells, both responses being key events in perpetuating SLE. We recently described the development of inhibitory oligonucleotides (INH-ODN), which are characterized by a phosphorothioate backbone, a CC(T)XXX3-5GGG motif and a chemical modification of the G-quartet to avoid the formation of higher order structures via intermolecular G-tetrads. These INH-ODNs were equally or significantly more efficient to impair TLR7- and TLR9-stimulated murine B-cells, macrophages, conventional and plasmacytoid dendritic cells than the parent INH-ODN 2088, which lacks G-modification. Here, we evaluate the inhibitory/therapeutic potential of our set of G-modified INH-ODN on human immune cells. We report the novel finding that G-modified INH-ODNs efficiently inhibited the release of IFN- by PBMC stimulated either with the TLR7-ligand oligoribonucleotide (ORN) 22075 or the TLR9-ligand CpG-ODN 2216. G-modification of INH-ODNs significantly improved inhibition of IL-6 release by PBMCs and purified human B-cells stimulated with the TLR7-ligand imiquimod or the TLR9-ligand CpG-ODN 2006. Furthermore, inhibition of B-cell activation analyzed by expression of activation markers and intracellular ATP content was significantly improved by G-modification. As observed with murine B-cells, high concentrations of INH-ODN 2088 but not of G-modified INH-ODNs stimulated IL-6 secretion by PBMCs in the absence of TLR-ligands thus limiting its blocking efficacy. In summary, G-modification of INH-ODNs improved their ability to impair TLR7- and TLR9-mediated signaling in those human immune cells which are considered as crucial in the pathophysiology of SLE.
Ries M.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Schuster P.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Thomann S.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Donhauser N.,Friedrich - Alexander - University, Erlangen - Nuremberg |
And 3 more authors.
Journal of Leukocyte Biology | Year: 2013
This study tested the hypothesis that mtDNA fragments carry immunostimulatory motifs that naturally induce immune activation by PDC. Genomic and mtDNA induced similar IFN-α production after transfection into PBMCs using the liposomal transfection reagent DOTAP. Shortening of mtDNA to CpG islands enhanced the immunostimulatory activity, based on the presence of unmethylated CpG DNA. Further fragmentation into mtODN, which exhibited similarities to published CpG ODN, resulted in a strong immunostimulatory activity in addition to PDC maturation and migration. The addition of the human cathelicidin LL-37 to CpG islands induced spontaneous PDC IFN-α production. Notably, one phosphodiester mtODN with a double-palindromic structure induced PDC IFN-α production in the absence of DOTAP. Flow cytometry, life-cell, and confocal imaging revealed attachment and spontaneous uptake into PDC, colocalizing, in part, with TLR9 in early endosomal vesicles. This process was accompanied by a moderate but significant PDC maturation in addition to B cell and NK cell activation (P<0.05). Altogether, our data indicate that fragmented mtDNA, which may be released as a consequence of apoptotic, necrotic, and necroptotic cell death, can act as a DAMP. For the first time, our study provides a mechanism how longer and shorter mtDNA fragments can be taken up naturally by the PDC and thus, may contribute to acute and chronic immune activation. © Society for Leukocyte Biology.
Krebiehl G.,University of Tübingen |
Ruckerbauer S.,University of Tübingen |
Burbulla L.F.,University of Tübingen |
Kieper N.,University of Tübingen |
And 11 more authors.
PLoS ONE | Year: 2010
Background: Mitochondrial dysfunction and degradation takes a central role in current paradigms of neurodegeneration in Parkinson's disease (PD). Loss of DJ-1 function is a rare cause of familial PD. Although a critical role of DJ-1 in oxidative stress response and mitochondrial function has been recognized, the effects on mitochondrial dynamics and downstream consequences remain to be determined. Methodology/Principal Findings: Using DJ-1 loss of function cellular models from knockout (KO) mice and human carriers of the E64D mutation in the DJ-1 gene we define a novel role of DJ-1 in the integrity of both cellular organelles, mitochondria and lysosomes. We show that loss of DJ-1 caused impaired mitochondrial respiration, increased intramitochondrial reactive oxygen species, reduced mitochondrial membrane potential and characteristic alterations of mitochondrial shape as shown by quantitative morphology. Importantly, ultrastructural imaging and subsequent detailed lysosomal activity analyses revealed reduced basal autophagic degradation and the accumulation of defective mitochondria in DJ-1 KO cells, that was linked with decreased levels of phospho-activated ERK2. Conclusions/Significance: We show that loss of DJ-1 leads to impaired autophagy and accumulation of dysfunctional mitochondria that under physiological conditions would be compensated via lysosomal clearance. Our study provides evidence for a critical role of DJ-1 in mitochondrial homeostasis by connecting basal autophagy and mitochondrial integrity in Parkinson's disease. © 2010 Krebiehl et al.
Hennemann H.,Nexigen GmbH |
Wirths S.,Nexigen GmbH |
Carl C.,Nexigen GmbH
European journal of medicinal chemistry | Year: 2015
Only 20-30% of drug target proteins can be accessed by common drug classes, like small molecules or therapeutic antibodies. The vast majority of the remaining proteins are considered "undruggable" and include drug target proteins, like transcription factors, scaffold or adapter proteins, which play important roles in disease. However over the last years innovative compound classes including nucleotide derived drugs (e.g. siRNA, antisense), macrocyclic compounds and cell-permeable peptides matured significantly and hold now the potential to modulate these hard to access target proteins for therapeutic use. This article will focus on the discovery of cell-permeable peptides and discuss intracellular screening systems for peptides, which yield highly relevant peptides, because peptide selection takes place in eukaryotic cells, under conditions, which are very similar to the later therapeutic use. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Nexigen Gmbh | Date: 2010-08-04
The present invention generally relates to a method for identifying and cloning nucleic acid molecules encoding a new class of proteins or fragments thereof, capable of interacting with proteins associated with the Human Hepatitis C virus (HCV) and thus being suitable either alone or in complex with the HCV protein for serving as a target for the development of antiviral drugs. In this context, the present invention provides novel HCV-interacting proteins and complexes as well as antibodies which specifically recognize and bind to the complex or to specific domains of HCV proteins.
PubMed | Nexigen GmbH
Type: | Journal: European journal of medicinal chemistry | Year: 2015
Only 20-30% of drug target proteins can be accessed by common drug classes, like small molecules or therapeutic antibodies. The vast majority of the remaining proteins are considered undruggable and include drug target proteins, like transcription factors, scaffold or adapter proteins, which play important roles in disease. However over the last years innovative compound classes including nucleotide derived drugs (e.g. siRNA, antisense), macrocyclic compounds and cell-permeable peptides matured significantly and hold now the potential to modulate these hard to access target proteins for therapeutic use. This article will focus on the discovery of cell-permeable peptides and discuss intracellular screening systems for peptides, which yield highly relevant peptides, because peptide selection takes place in eukaryotic cells, under conditions, which are very similar to the later therapeutic use.