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Book ; Thesis: Über die Pathogenität der mitochondrialen Punktmutation m.5789T>C

Hippen, Marius Emil Friedrich

2023

Author's details	Marius Emil Friedrich Hippen
Subject code	610
Language	German
Size	89 Seiten, Illustrationen, 22 cm
Publishing place	Bonn
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn, 2023
HBZ-ID	HT030727496
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Twisted [C

Spahr, Dominik / Bayarjargal, Lkhamsuren / Haussühl, Eiken / Luchitskaia, Rita / Friedrich, Alexandra / Milman, Victor / Fedotenko, Timofey / Winkler, Björn

Chemical communications (Cambridge, England)

2023 Volume 59, Issue 80, Page(s) 11951–11954

Abstract: The inorganic pyrocarbonate salt Ba[C ...

Abstract	The inorganic pyrocarbonate salt Ba[C
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Journal Article
ZDB-ID	1472881-3
ISSN	1364-548X ; 1359-7345 ; 0009-241X
ISSN (online)	1364-548X
ISSN	1359-7345 ; 0009-241X
DOI	10.1039/d3cc03324d
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Article ; Online: Supramolecular Double Helices from Small C

Lafleur, René P M / Herziger, Svenja / Schoenmakers, Sandra M C / Keizer, Arthur D A / Jahzerah, Jahaziel / Thota, Bala N S / Su, Lu / Bomans, Paul H H / Sommerdijk, Nico A J M / Palmans, Anja R A / Haag, Rainer / Friedrich, Heiner / Böttcher, Christoph / Meijer, E W

Journal of the American Chemical Society

2020 Volume 142, Issue 41, Page(s) 17644–17652

Abstract: Supramolecular fibers in water, micrometers long and several nanometers in width, are among the most studied nanostructures for biomedical applications. These supramolecular polymers are formed through a spontaneous self-assembly process of small ... ...

Abstract	Supramolecular fibers in water, micrometers long and several nanometers in width, are among the most studied nanostructures for biomedical applications. These supramolecular polymers are formed through a spontaneous self-assembly process of small amphiphilic molecules by specific secondary interactions. Although many compounds do not possess a stereocenter, recent studies suggest the (co)existence of helical structures, albeit in racemic form. Here, we disclose a series of supramolecular (co)polymers based on water-soluble benzene-1,3,5-tricarboxamides (BTAs) that form double helices, fibers that were long thought to be chains of single molecules stacked in one dimension (1D). Detailed cryogenic transmission electron microscopy (cryo-TEM) studies and subsequent three-dimensional-volume reconstructions unveiled helical repeats, ranging from 15 to 30 nm. Most remarkable, the pitch can be tuned through the composition of the copolymers, where two different monomers with the same core but different peripheries are mixed in various ratios. Like in lipid bilayers, the hydrophobic shielding in the aggregates of these disc-shaped molecules is proposed to be best obtained by dimer formation, promoting supramolecular double helices. It is anticipated that many of the supramolecular polymers in water will have a thermodynamic stable structure, such as a double helix, although small structural changes can yield single stacks as well. Hence, it is essential to perform detailed analyses prior to sketching a molecular picture of these 1D fibers.
Language	English
Publishing date	2020-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.0c08179
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Article ; Online: Elements of the C-terminal tail of a C-terminal domain homolog of the Orange Carotenoid Protein determining xanthophyll uptake from liposomes.

Likkei, Kristina / Moldenhauer, Marcus / Tavraz, Neslihan N / Egorkin, Nikita A / Slonimskiy, Yury B / Maksimov, Eugene G / Sluchanko, Nikolai N / Friedrich, Thomas

Biochimica et biophysica acta. Bioenergetics

2024 Volume 1865, Issue 3, Page(s) 149043

Abstract: ... from membranes, or accepts it from homologs of its C-terminal domain (CTDH). The CTDH from Anabaena (AnaCTDH) was ... shown to be important for carotenoid transfer and delivery from/to membranes. The C-terminal tail ...

Abstract	Carotenoids perform multifaceted roles in life ranging from coloration over light harvesting to photoprotection. The Orange Carotenoid Protein (OCP), a light-driven photoswitch involved in cyanobacterial photoprotection, accommodates a ketocarotenoid vital for its function. OCP extracts its ketocarotenoid directly from membranes, or accepts it from homologs of its C-terminal domain (CTDH). The CTDH from Anabaena (AnaCTDH) was shown to be important for carotenoid transfer and delivery from/to membranes. The C-terminal tail of AnaCTDH is a critical structural element likely serving as a gatekeeper and facilitator of carotenoid uptake from membranes. We investigated the impact of amino acid substitutions within the AnaCTDH-CTT on echinenone and canthaxanthin uptake from DOPC and DMPG liposomes. The transfer rate was uniformly reduced for substitutions of Arg-137 and Arg-138 to Gln or Ala, and depended on the lipid type, indicating a weaker interaction particularly with the lipid head group. Our results further suggest that Glu-132 has a membrane-anchoring effect on the PC lipids, specifically at the choline motif as inferred from the strongly different effects of the CTT variants on the extraction from the two liposome types. The substitution of Pro-130 by Gly suggests that the CTT is perpendicular to both the membrane and the main AnaCTDH protein during carotenoid extraction. Finally, the simultaneous mutation of Leu-133, Leu-134 and Leu-136 for alanines showed that the hydrophobicity of the CTT is crucial for carotenoid uptake. Since some substitutions accelerated carotenoid transfer into AnaCTDH while others slowed it down, carotenoprotein properties can be engineered toward the requirements of applications.
Language	English
Publishing date	2024-03-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	60-7
ISSN	1879-2650 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2650 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbabio.2024.149043
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Article ; Online: C-terminal variants in CDC42 drive type I interferon-dependent autoinflammation in NOCARH syndrome reversible by ruxolitinib.

Kapp, Friedrich G / Kretschmer, Stefanie / Beckmann, Cora C A / Wäsch, Lena / Molitor, Anne / Carapito, Raphaël / Schubert, Mario / Lucas, Nadja / Conrad, Solène / Poignant, Sylvaine / Isidor, Bertrand / Rohlfs, Meino / Kisaarslan, Ayşenur Paç / Schanze, Denny / Zenker, Martin / Schmitt-Graeff, Annette / Strahm, Brigitte / Peters, Anke / Yoshimi, Ayami /

Driever, Wolfgang / Zillinger, Thomas / Günther, Claudia / Maharana, Shovamayee / Guan, Kaomei / Klein, Christoph / Ehl, Stephan / Niemeyer, Charlotte M / Unal, Ekrem / Bahram, Seiamak / Hauck, Fabian / Lee-Kirsch, Min Ae / Speckmann, Carsten

Clinical immunology (Orlando, Fla.)

2023 Volume 256, Page(s) 109777

Abstract: C-terminal variants in CDC42 encoding cell division control protein 42 homolog underlie neonatal ...

Abstract	C-terminal variants in CDC42 encoding cell division control protein 42 homolog underlie neonatal-onset cytopenia, autoinflammation, rash, and hemophagocytic lymphohistiocytosis (NOCARH). Pyrin inflammasome hyperactivation has been shown to contribute to disease pathophysiology. However, mortality of NOCARH patients remains high despite inflammasome-focused treatments. Here, we demonstrate in four NOCARH patients from three families that cell-intrinsic activation of type I interferon (IFN) is a previously unrecognized driver of autoinflammation in NOCARH. Our data show that aberrant innate immune activation is caused by sensing of cytosolic nucleic acids released from mitochondria, which exhibit disturbances in integrity and dynamics due to CDC42 dysfunction. In one of our patients, treatment with the Janus kinase inhibitor ruxolitinib led to complete remission, indicating that inhibition of type I IFN signaling may have an important role in the management of autoinflammation in patients with NOCARH.
MeSH term(s)	Humans ; Infant, Newborn ; cdc42 GTP-Binding Protein ; Inflammasomes/genetics ; Interferon Type I ; Lymphohistiocytosis, Hemophagocytic/etiology ; Nitriles ; Syndrome
Chemical Substances	cdc42 GTP-Binding Protein (EC 3.6.5.2) ; Inflammasomes ; Interferon Type I ; Nitriles ; ruxolitinib (82S8X8XX8H) ; CDC42 protein, human (EC 3.6.5.2)
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2023.109777
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Book ; Online: HoLLiE C -- A Multifunctional Bimanual Mobile Robot Supporting Versatile Care Applications

Steffen, Lea / Schulze, Martin / Eichmann, Christian / Koch, Robin / Hermann, Andreas / Mussulin, Rosa Frietsch / Graaf, Friedrich / Wilbrandt, Robert / Besselmann, Marvin Große / Roennau, Arne / Dillmann, Rüdiger

2023

Abstract: Care robotics as a research field has developed a lot in recent years, driven by the rapidly increasing need for it. However, these technologies are mostly limited to a very concrete and usually relatively simple use case. The bimanual robot House of ... ...

Abstract	Care robotics as a research field has developed a lot in recent years, driven by the rapidly increasing need for it. However, these technologies are mostly limited to a very concrete and usually relatively simple use case. The bimanual robot House of Living Labs intelligent Escort (HoLLiE) includes an omnidirectional mobile platform. This paper presents how HoLLiE is adapted, by flexible software and hardware modules, for different care applications. The design goal of HoLLiE was to be human-like but abstract enough to ensure a high level of acceptance, which is very advantageous for its use in hospitals. After a short retrospect of previous generations of HoLLiE, it is highlighted how the current version is equipped with a variety of additional sensors and actuators to allow a wide range of possible applications. Then, the software stack of HoLLiE is depicted, with the focus on navigation and force sensitive intention recognition. Comment: 18th international conference on Intelligent Autonomous Systems (IAS18 - 2023)
Keywords	Computer Science - Robotics
Subject code	629
Publishing date	2023-12-11
Publishing country	us
Document type	Book ; Online
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Article ; Online: Missense variant c.1460 T > C (p.L487P) enhances protein degradation of ER mannosyltransferase ALG9 in two new ALG9-CDG patients presenting with West syndrome and review of the literature.

Himmelreich, Nastassja / Dimitrov, Bianca / Zielonka, Matthias / Hüllen, Andreas / Hoffmann, Georg Friedrich / Juenger, Hendrik / Müller, Herbert / Lorenz, Imke / Busse, Birgit / Marschall, Christoph / Schlüter, Gregor / Thiel, Christian

Molecular genetics and metabolism

2022 Volume 136, Issue 4, Page(s) 274–281

Abstract: ... homozygous missense variant c.1460 T > C (p.L487P) in the ALG9 gene which led to global developmental delay ...

Abstract	ALG9-CDG is a CDG-I defect within the group of Congenital Disorders of Glycosylation (CDG). We here describe the clinical symptoms of two new and unrelated ALG9-CDG patients, both carrying the novel homozygous missense variant c.1460 T > C (p.L487P) in the ALG9 gene which led to global developmental delay, psychomotor disability, facial dysmorphisms, brain and heart defects, hearing loss, hypotonia, as well as feeding problems. New clinical symptoms comprised West syndrome with hypsarrhythmia. Quantitative RT-PCR analysis revealed a significantly enhanced ALG9 mRNA transcript level, whereas the protein amount in fibroblasts was significantly reduced. This could be ascribed to a stronger degradation of the mutated ALG9 protein in patient fibroblasts. Lipid-linked oligosaccharide analysis showed an ALG9-CDG characteristic accumulation of Man
MeSH term(s)	Congenital Disorders of Glycosylation/genetics ; Humans ; Infant ; Male ; Mannosyltransferases/genetics ; Membrane Proteins/genetics ; Proteolysis ; Spasms, Infantile/genetics
Chemical Substances	Membrane Proteins ; ALG9 protein, human (EC 2.4.1.-) ; Mannosyltransferases (EC 2.4.1.-)
Language	English
Publishing date	2022-06-26
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1418518-0
ISSN	1096-7206 ; 1096-7192
ISSN (online)	1096-7206
ISSN	1096-7192
DOI	10.1016/j.ymgme.2022.06.005
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Article: The addition of arginine deiminase potentiates Mithramycin A-induced cell death in patient-derived glioblastoma cells via ATF4 and cytochrome C.

Linke, Charlotte / Freitag, Thomas / Riess, Christin / Scheffler, Jana Vanessa / Del Moral, Katharina / Schoenwaelder, Nina / Fiedler, Tomas / Fiebig, Adina / Kaps, Philipp / Dubinski, Daniel / Schneider, Björn / Bergmann, Wendy / Classen, Carl Friedrich / Maletzki, Claudia

Cancer cell international

2023 Volume 23, Issue 1, Page(s) 38

Abstract: ... swollen and had a more pronounced cortically formed cytoskeleton. Also, cytochrome C and ...

Abstract	Background: Arginine auxotrophy constitutes a shortcoming for ~ 30% of glioblastoma multiforme (GBM). Indeed, arginine-depleting therapy using arginine deiminase from Streptococcus pyogenes (SpyADI) has proven activity against GBM in preclinical studies. The good safety profile of SpyADI renders this agent an ideal combination partner for cytostatic therapy. Methods: In this study, we combined the antineoplastic antibiotic Mithramycin A (MitA) with SpyADI to boost single-agent activity and analyzed underlying response mechanisms in-depth. Results: MitA monotherapy induced a time- and dose-dependent cytotoxicity in eight patient-derived GBM cell lines and had a radiosensitizing effect in all but one cell line. Combination treatment boosted the effects of the monotherapy in 2D- and 3D models. The simultaneous approach was superior to the sequential application and significantly impaired colony formation after repetitive treatment. MitA monotherapy significantly inhibited GBM invasiveness. However, this effect was not enhanced in the combination. Functional analysis identified SpyADI-triggered senescence induction accompanied by increased mitochondrial membrane polarization upon mono- and combination therapy. In HROG63, induction of lysosomes was seen after both monotherapies, indicative of autophagy. These cells seemed swollen and had a more pronounced cortically formed cytoskeleton. Also, cytochrome C and endoplasmatic reticulum-stress-associated proteins ATF4 and Calnexin were enhanced in the combination, contributing to apoptosis. Notably, no significant increases in glioma-stemness marker were seen. Conclusions: Therapeutic utilization of a metabolic defect in GBM along with cytostatic therapy provides a novel combination approach. Whether this SpyADI/MitA regimen will provide a safe alternative to combat GBM, will have to be addressed in subsequent (pre-)clinical trials.
Language	English
Publishing date	2023-02-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2091573-1
ISSN	1475-2867
ISSN	1475-2867
DOI	10.1186/s12935-023-02873-2
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Article ; Online: Histopathology-validated lesion detection rates of clinically significant prostate cancer with mpMRI, [ 68 Ga]PSMA-11-PET and [ 11 C]Acetate-PET.

Sandgren, Kristina / Strandberg, Sara N / Jonsson, Joakim H / Grefve, Josefine / Keeratijarut Lindberg, Angsana / Nilsson, Erik / Bergh, Anders / Söderkvist, Karin / Thellenberg Karlsson, Camilla / Friedrich, Bengt / Widmark, Anders / Blomqvist, Lennart / Berg Loegager, Vibeke / Axelsson, Jan / Ögren, Mattias / Ögren, Margareta / Nyholm, Tufve / Riklund, Katrine

Nuclear medicine communications

2023 Volume 44, Issue 11, Page(s) 997–1004

Abstract: ... PSMA-11-PET (PSMA)-PET, [ 11 C]Acetate (ACE)-PET, and mpMRI with histopathology as reference ...

Abstract	Objective: PET/CT and multiparametric MRI (mpMRI) are important diagnostic tools in clinically significant prostate cancer (csPC). The aim of this study was to compare csPC detection rates with [ 68 Ga]PSMA-11-PET (PSMA)-PET, [ 11 C]Acetate (ACE)-PET, and mpMRI with histopathology as reference, to identify the most suitable imaging modalities for subsequent hybrid imaging. An additional aim was to compare inter-reader variability to assess reproducibility. Methods: During 2016-2019, all study participants were examined with PSMA-PET/mpMRI and ACE-PET/CT prior to radical prostatectomy. PSMA-PET, ACE-PET and mpMRI were evaluated separately by two observers, and were compared with histopathology-defined csPC. Statistical analyses included two-sided McNemar test and index of specific agreement. Results: Fifty-five study participants were included, with 130 histopathological intraprostatic lesions >0.05 cc. Of these, 32% (42/130) were classified as csPC with ISUP grade ≥2 and volume >0.5 cc. PSMA-PET and mpMRI showed no difference in performance ( P = 0.48), with mean csPC detection rate of 70% (29.5/42) and 74% (31/42), respectively, while with ACE-PET the mean csPC detection rate was 37% (15.5/42). Interobserver agreement was higher with PSMA-PET compared to mpMRI [79% (26/33) vs 67% (24/38)]. Including all detected lesions from each pair of observers, the detection rate increased to 90% (38/42) with mpMRI, and 79% (33/42) with PSMA-PET. Conclusion: PSMA-PET and mpMRI showed high csPC detection rates and superior performance compared to ACE-PET. The interobserver agreement indicates higher reproducibility with PSMA-PET. The combined result of all observers in both PSMA-PET and mpMRI showed the highest detection rate, suggesting an added value of a hybrid imaging approach.
Language	English
Publishing date	2023-08-24
Publishing country	England
Document type	Journal Article
ZDB-ID	758141-5
ISSN	1473-5628 ; 0143-3636
ISSN (online)	1473-5628
ISSN	0143-3636
DOI	10.1097/MNM.0000000000001743
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Article ; Online: 13 C-Methacetin Breath Test Predicts Survival in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

Clinical and translational gastroenterology

2022 Volume 13, Issue 10, Page(s) e00529

Abstract: Introduction: The 13 C-methacetin breath test ( 13 C-MBT) is a dynamic method for assessing liver ... function. This proof-of-concept study aimed to investigate the association between 13 C-MBT values and ... in baseline and 20 in longitudinal analysis. 13 C-MBTs were performed before the first and second TACE session ...

Abstract	Introduction: The 13 C-methacetin breath test ( 13 C-MBT) is a dynamic method for assessing liver function. This proof-of-concept study aimed to investigate the association between 13 C-MBT values and outcomes in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Methods: A total of 30 patients with HCC were prospectively recruited. Of these, 25 were included in baseline and 20 in longitudinal analysis. 13 C-MBTs were performed before the first and second TACE session. Patients were followed for at least 1 year. Results: At baseline, the median 13 C-MBT value was 261 μg/kg/hr (interquartile range 159-387). 13 C-MBT, albumin-bilirubin, Child-Pugh, and Model for End-Stage Liver Disease scores were associated with overall survival in extended univariable Cox regression ( 13 C-MBT: standardized hazard ratio [sHR] 0.297, 95% confidence interval [CI] 0.111-0.796; albumin-bilirubin score: sHR 4.051, 95% CI 1.813-9.052; Child-Pugh score: sHR 2.616, 95% CI 1.450-4.719; Model for End-Stage Liver Disease score: sHR 2.781, 95% CI 1.356-5.703). Using a cutoff of 140 μg/kg/hr at baseline, 13 C-MBT was associated with prognosis (median overall survival 28.5 months [95% CI 0.0-57.1] vs 3.5 months [95% CI 0.0-8.1], log-rank P < 0.001). Regarding prediction of 90-day mortality after second 13 C-MBT, the relative change in 13 C-MBT values yielded an area under the receiver-operating characteristic curve of 1.000 ( P = 0.007). Discussion: Baseline and longitudinal 13 C-MBT values predict survival of patients with HCC undergoing TACE. The relative change in 13 C-MBT values predicts short-term mortality and may assist in identifying patients who will not benefit from further TACE treatment.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Hepatocellular/therapy ; Chemoembolization, Therapeutic/methods ; End Stage Liver Disease ; Liver Neoplasms/diagnosis ; Liver Neoplasms/therapy ; Treatment Outcome ; Severity of Illness Index ; Bilirubin ; Albumins ; Breath Tests
Chemical Substances	methacetin (13E468TFHP) ; Bilirubin (RFM9X3LJ49) ; Albumins
Language	English
Publishing date	2022-10-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2581516-7
ISSN	2155-384X ; 2155-384X
ISSN (online)	2155-384X
ISSN	2155-384X
DOI	10.14309/ctg.0000000000000529
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