TY  - JOUR
A1  - Sherif, Mohammad A.
A1  - Herold, Joerg
A1  - Voelker, Wolfram
A1  - Maniuc, Octavian
A1  - Ertl, Georg
A1  - Praast, Christian
A1  - Braun-Dullaeus, Ruediger Christian
T1  - Feasibility of a new method using two-dimensional transesophageal echocardiography for aortic annular sizing in patients undergoing transcatheter aortic valve implantation; a case-control study
JF  - BMC Cardiovascular Disorders
N2  - Background: 
Accurate preoperative assessment of the aortic annulus dimension is crucial for successful transcatheter aortic valve implantation (TAVI). In this study we validated a new method using two-dimensional transesophageal echocardiography (2D-TEE) for measurement of the aortic annulus prior to TAVI. 

Methods: 
We analysed 124 patients who underwent successful TAVI using a self-expandable prosthesis, divided equally into two groups; in the study group we used the cross sectional short axis 2D-TEE for measurement of the aortic annulus and in the control group we used the long axis 2D-TEE. 

Results: 
Both groups were comparable regarding the clinical parameters. On the other hand, patients in the study group had less left ventricular ejection fraction (38.9 % versus 45.6 %, p = 0.01). The aortic valve annulus was, although not statistically significant, smaller in the study group (21.58 versus 23.28 mm, p = 0.25). Post procedural quantification of the aortic regurgitation revealed that only one patient in both groups had severe aortic regurgitation (AR), in this patient the valve was implanted deep. The incidence of significant AR was higher in the control group (29.0 % versus 12.9 %, p = 0.027). 

Conclusions: 
Sizing of the aortic valve annulus using cross-sectional 2D-TEE offers a safe and plausible method for patients undergoing TAVI using the self-expandable prosthesis and is significantly superior to using long axis 2D-TEE.
KW  - paravalvular regurgitation
KW  - multicenter
KW  - management
KW  - sizing
KW  - echocardiography
KW  - replacement
KW  - tomography
KW  - guidelines
KW  - outcomes
KW  - impact
KW  - recommendations
KW  - stenosis
KW  - TAVI
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148328
VL  - 15
IS  - 78
ER  - 
TY  - JOUR
A1  - Lisinetskaya, Polina
A1  - Braun, Christian
A1  - Proch, Sebastian
A1  - Kim, Young Dok
A1  - Ganteför, Gerd
A1  - Mitrić, Roland
T1  - Excited state nonadiabatic dynamics of bare and hydrated anionic gold clusters Au\(^−_3\)[H\(_2\)O]\(_n\) (n=0-2)
JF  - Physical Chemistry Chemical Physics
N2  - We present a joint theoretical and experimental study of excited state dynamics in pure and hydrated anionic gold clusters Au\(^-_3\)[H\(_2\)O]\(_n\) (n = 0-2). We employ mixed quantum-classical dynamics combined with femtosecond time-resolved photoelectron spectroscopy in order to investigate the influence of hydration on excited state lifetimes and photo-dissociation dynamics. A gradual decrease of the excited state lifetime with the number of adsorbed water molecules as well as gold cluster fragmentation quenching by two or more water molecules are observed both in experiment and in simulations. Non-radiative relaxation and dissociation in excited states are found to be responsible for the excited state population depletion. Time constants of these two processes strongly depend on the number of water molecules leading to the possibility to modulate excited state dynamics and fragmentation of the anionic cluster by adsorption of water molecules.
KW  - nonadiabatic dynamics
KW  - metal cluster
KW  - time-resolved photoelectron spectroscopy
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159176
UR  - https://doi.org/10.1039/C5CP04297F
SN  - 1463-9076
N1  - Accepted version
VL  - 18
IS  - 9
ER  - 
TY  - JOUR
A1  - Chubanov, Vladimir
A1  - Ferioli, Silvia
A1  - Wisnowsky, Annika
A1  - Simmons, David G.
A1  - Leitzinger, Christin
A1  - Einer, Claudia
A1  - Jonas, Wenke
A1  - Shymkiv, Yuriy
A1  - Gudermann, Thomas
A1  - Bartsch, Harald
A1  - Braun, Attila
A1  - Akdogan, Banu
A1  - Mittermeier, Lorenz
A1  - Sytik, Ludmila
A1  - Torben, Friedrich
A1  - Jurinovic, Vindi
A1  - van der Vorst, Emiel P. C.
A1  - Weber, Christian
A1  - Yildirim, Önder A.
A1  - Sotlar, Karl
A1  - Schürmann, Annette
A1  - Zierler, Susanna
A1  - Zischka, Hans
A1  - Ryazanov, Alexey G.
T1  - Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival
JF  - eLife
N2  - Mg2+ regulates many physiological processes and signalling pathways. However, little is known about the mechanisms underlying the organismal balance of Mg2+. Capitalizing on a set of newly generated mouse models, we provide an integrated mechanistic model of the regulation of organismal Mg2+ balance during prenatal development and in adult mice by the ion channel TRPM6. We show that TRPM6 activity in the placenta and yolk sac is essential for embryonic development. In adult mice, TRPM6 is required in the intestine to maintain organismal Mg2+ balance, but is dispensable in the kidney. Trpm6 inactivation in adult mice leads to a shortened lifespan, growth deficit and metabolic alterations indicative of impaired energy balance. Dietary Mg2+ supplementation not only rescues all phenotypes displayed by Trpm6-deficient adult mice, but also may extend the lifespan of wildtype mice. Hence, maintenance of organismal Mg2+ balance by TRPM6 is crucial for prenatal development and survival to adulthood.
KW  - signalling pathways
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164987
VL  - 5
ER  - 
TY  - JOUR
A1  - Marenholz, Ingo
A1  - Esparza-Gordillo, Jorge
A1  - Rüschendorf, Franz
A1  - Bauerfeind, Anja
A1  - Strachan, David P.
A1  - Spycher, Ben D.
A1  - Baurecht, Hansjörg
A1  - Magaritte-Jeannin, Patricia
A1  - Sääf, Annika
A1  - Kerkhof, Marjan
A1  - Ege, Markus
A1  - Baltic, Svetlana
A1  - Matheson, Melanie C.
A1  - Li, Jin
A1  - Michel, Sven
A1  - Ang, Wei Q.
A1  - McArdle, Wendy
A1  - Arnold, Andreas
A1  - Homuth, Georg
A1  - Demenais, Florence
A1  - Bouzigon, Emmanuelle
A1  - Söderhäll, Cilla
A1  - Pershagen, Göran
A1  - de Jongste, Johan C.
A1  - Postma, Dirkje S.
A1  - Braun-Fahrländer, Charlotte
A1  - Horak, Elisabeth
A1  - Ogorodova, Ludmila M.
A1  - Puzyrev, Valery P.
A1  - Bragina, Elena Yu
A1  - Hudson, Thomas J.
A1  - Morin, Charles
A1  - Duffy, David L.
A1  - Marks, Guy B.
A1  - Robertson, Colin F.
A1  - Montgomery, Grant W.
A1  - Musk, Bill
A1  - Thompson, Philip J.
A1  - Martin, Nicholas G.
A1  - James, Alan
A1  - Sleiman, Patrick
A1  - Toskala, Elina
A1  - Rodriguez, Elke
A1  - Fölster-Holst, Regina
A1  - Franke, Andre
A1  - Lieb, Wolfgang
A1  - Gieger, Christian
A1  - Heinzmann, Andrea
A1  - Rietschel, Ernst
A1  - Keil, Thomas
A1  - Cichon, Sven
A1  - Nöthen, Markus M.
A1  - Pennel, Craig E.
A1  - Sly, Peter D.
A1  - Schmidt, Carsten O.
A1  - Matanovic, Anja
A1  - Schneider, Valentin
A1  - Heinig, Matthias
A1  - Hübner, Norbert
A1  - Holt, Patrick G.
A1  - Lau, Susanne
A1  - Kabesch, Michael
A1  - Weidinger, Stefan
A1  - Hakonarson, Hakon
A1  - Ferreira, Manuel A. R.
A1  - Laprise, Catherine
A1  - Freidin, Maxim B.
A1  - Genuneit, Jon
A1  - Koppelman, Gerard H.
A1  - Melén, Erik
A1  - Dizier, Marie-Hélène
A1  - Henderson, A. John
A1  - Lee, Young Ae
T1  - Meta-analysis identifies seven susceptibility loci involved in the atopic march
JF  - Nature Communications
N2  - Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.
KW  - chromosome 11Q13
KW  - risk
KW  - genomewide association
KW  - hay fever
KW  - birth cohort
KW  - filaggrin mutations
KW  - food allergy
KW  - juvenile myoclonic epilepsy
KW  - childhood asthma
KW  - dermatitis
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139835
VL  - 6
IS  - 8804
ER  - 
TY  - JOUR
A1  - Rau, Markus
A1  - Heindel, Tobias
A1  - Unsleber, Sebastian
A1  - Braun, Tristan
A1  - Fischer, Julian
A1  - Frick, Stefan
A1  - Nauerth, Sebastian
A1  - Schneider, Christian
A1  - Vest, Gwenaelle
A1  - Reitzenstein, Stephan
A1  - Kamp, Martin
A1  - Forchel, Alfred
A1  - Höfling, Sven
A1  - Weinfurter, Harald
T1  - Free space quantum key distribution over 500 meters using electrically driven quantum dot single-photon sources-a proof of principle experiment
JF  - New Journal of Physics
N2  - Highly efficient single-photon sources (SPS) can increase the secure key rate of quantum key distribution (QKD) systems compared to conventional attenuated laser systems. Here we report on a free space QKD test using an electrically driven quantum dot single-photon source (QD SPS) that does not require a separate laser setup for optical pumping and thus allows for a simple and compact SPS QKD system. We describe its implementation in our 500 m free space QKD system in downtown Munich. Emulating a BB84 protocol operating at a repetition rate of 125 MHz, we could achieve sifted key rates of 5-17 kHz with error ratios of 6-9% and g((2))(0)-values of 0.39-0.76.
KW  - QKD
KW  - electrically driven
KW  - free space
KW  - quantum dots
KW  - quantum key distribution
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116760
VL  - 16
IS  - 043003
ER  - 
TY  - JOUR
A1  - Surat, Güzin
A1  - Meyer-Sautter, Pascal
A1  - Rüsch, Jan
A1  - Braun-Feldweg, Johannes
A1  - Markus, Christian Karl
A1  - Germer, Christoph-Thomas
A1  - Lock, Johan Friso
T1  - Cefazolin might be adequate for perioperative antibiotic prophylaxis in intra-abdominal infections without sepsis: a quality improvement study
JF  - Antibiotics
N2  - Background: The adequate choice of perioperative antibiotic prophylaxis (PAP) could influence the risk of surgical site infections (SSIs) in general surgery. A new local PAP guideline was implemented in May 2017 and set the first-generation cefazolin (CFZ) instead the second-generation cefuroxime (CXM) as the new standard prophylactic antibiotic. The aim of this study was to compare the risk of SSIs after this implementation in intra-abdominal infections (IAIs) without sepsis. Methods: We performed a single center-quality improvement study at a 1500 bed sized university hospital in Germany analyzing patients after emergency surgery during 2016 to 2019 (n = 985), of which patients receiving CXM or CFZ were selected (n = 587). Propensity score matching was performed to ensure a comparable risk of SSIs in both groups. None-inferiority margin for SSIs was defined as 8% vs. 4%. Results: Two matched cohorts with respectively 196 patients were compared. The rate of SSIs was higher in the CFZ group (7.1% vs. 3.6%, p = 0.117) below the non-inferiority margin. The rate of other postoperative infections was significantly higher in the CFZ group (2.0% vs. 8.7%, p = 0.004). No other differences including postoperative morbidity, mortality or length-of-stay were observed. Conclusion: Perioperative antibiotic prophylaxis might be safely maintained by CFZ even in the treatment of intra-abdominal infections.
KW  - antimicrobial stewardship
KW  - antibiotic prescribing quality
KW  - low-risk intra-abdominal infections
KW  - perioperative antibiotic prophylaxis
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270816
SN  - 2079-6382
VL  - 11
IS  - 4
ER  - 
TY  - JOUR
A1  - Prieto-Garcia, Cristian
A1  - Hartmann, Oliver
A1  - Reissland, Michaela
A1  - Braun, Fabian
A1  - Bozkurt, Süleyman
A1  - Pahor, Nikolett
A1  - Fuss, Carmina
A1  - Schirbel, Andreas
A1  - Schülein-Völk, Christina
A1  - Buchberger, Alexander
A1  - Calzado Canale, Marco A.
A1  - Rosenfeldt, Mathias
A1  - Dikic, Ivan
A1  - Münch, Christian
A1  - Diefenbacher, Markus E.
T1  - USP28 enables oncogenic transformation of respiratory cells, and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K
JF  - Molecular Oncology
N2  - Oncogenic transformation of lung epithelial cells is a multistep process, frequently starting with the inactivation of tumour suppressors and subsequent development of activating mutations in proto-oncogenes, such as members of the PI3K or MAPK families. Cells undergoing transformation have to adjust to changes, including altered metabolic requirements. This is achieved, in part, by modulating the protein abundance of transcription factors. Here, we report that the ubiquitin carboxyl-terminal hydrolase 28 (USP28) enables oncogenic reprogramming by regulating the protein abundance of proto-oncogenes such as c-JUN, c-MYC, NOTCH and ∆NP63 at early stages of malignant transformation. USP28 levels are increased in cancer compared with in normal cells due to a feed-forward loop, driven by increased amounts of oncogenic transcription factors such as c-MYC and c-JUN. Irrespective of oncogenic driver, interference with USP28 abundance or activity suppresses growth and survival of transformed lung cells. Furthermore, inhibition of USP28 via a small-molecule inhibitor resets the proteome of transformed cells towards a ‘premalignant’ state, and its inhibition synergizes with clinically established compounds used to target EGFR\(^{L858R}\)-, BRAF\(^{V600E}\)- or PI3K\(^{H1047R}\)-driven tumour cells. Targeting USP28 protein abundance at an early stage via inhibition of its activity is therefore a feasible strategy for the treatment of early-stage lung tumours, and the observed synergism with current standard-of-care inhibitors holds the potential for improved targeting of established tumours.
KW  - buparlisib
KW  - c-MYC
KW  - gefitinib
KW  - lung cancer
KW  - USP28
KW  - vemurafenib
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312777
VL  - 16
IS  - 17
ER  - 
TY  - JOUR
A1  - Prieto‐Garcia, Cristian
A1  - Hartmann, Oliver
A1  - Reissland, Michaela
A1  - Braun, Fabian
A1  - Fischer, Thomas
A1  - Walz, Susanne
A1  - Schülein‐Völk, Christina
A1  - Eilers, Ursula
A1  - Ade, Carsten P.
A1  - Calzado, Marco A.
A1  - Orian, Amir
A1  - Maric, Hans M.
A1  - Münch, Christian
A1  - Rosenfeldt, Mathias
A1  - Eilers, Martin
A1  - Diefenbacher, Markus E.
T1  - Maintaining protein stability of ∆Np63 via USP28 is required by squamous cancer cells
JF  - EMBO Molecular Medicine
N2  - The transcription factor ∆Np63 is a master regulator of epithelial cell identity and essential for the survival of squamous cell carcinoma (SCC) of lung, head and neck, oesophagus, cervix and skin. Here, we report that the deubiquitylase USP28 stabilizes ∆Np63 and maintains elevated ∆NP63 levels in SCC by counteracting its proteasome‐mediated degradation. Impaired USP28 activity, either genetically or pharmacologically, abrogates the transcriptional identity and suppresses growth and survival of human SCC cells. CRISPR/Cas9‐engineered in vivo mouse models establish that endogenous USP28 is strictly required for both induction and maintenance of lung SCC. Our data strongly suggest that targeting ∆Np63 abundance via inhibition of USP28 is a promising strategy for the treatment of SCC tumours.
KW  - ∆Np63
KW  - NOTCH
KW  - squamous cell carcinoma
KW  - 28
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218303
VL  - 12
IS  - 4
ER  - 
TY  - JOUR
A1  - Adolf, Christian
A1  - Braun, Leah T.
A1  - Fuss, Carmina T.
A1  - Hahner, Stefanie
A1  - Künzel, Heike
A1  - Handgriff, Laura
A1  - Sturm, Lisa
A1  - Heinrich, Daniel A.
A1  - Schneider, Holger
A1  - Bidlingmaier, Martin
A1  - Reincke, Martin
T1  - Spironolactone reduces biochemical markers of bone turnover in postmenopausal women with primary aldosteronism
JF  - Endocrine
N2  - Context
Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis.

Patients and methods
We assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment.

Study design
Observational longitudinal cohort study.

Setting
Tertiary care hospital.

Results
Compared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers.

Conclusion
This study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy.
KW  - aldosterone
KW  - osteocalcin
KW  - osteoporosis
KW  - hyperparathyroidism
KW  - cortisol
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-315966
SN  - 1355-008X
SN  - 1559-0100
VL  - 69
IS  - 3
ER  - 
TY  - JOUR
A1  - Gotru, Sanjeev Kiran
A1  - van Geffen, Johanna P.
A1  - Nagy, Magdolna
A1  - Mammadova-Bach, Elmina
A1  - Eilenberger, Julia
A1  - Volz, Julia
A1  - Manukjan, Georgi
A1  - Schulze, Harald
A1  - Wagner, Leonard
A1  - Eber, Stefan
A1  - Schambeck, Christian
A1  - Deppermann, Carsten
A1  - Brouns, Sanne
A1  - Nurden, Paquita
A1  - Greinacher, Andreas
A1  - Sachs, Ulrich
A1  - Nieswandt, Bernhard
A1  - Hermanns, Heike M.
A1  - Heemskerk, Johan W. M.
A1  - Braun, Attila
T1  - Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases
JF  - Scientific Reports
N2  - Zinc (Zn2+) can modulate platelet and coagulation activation pathways, including fibrin formation. Here, we studied the (patho)physiological consequences of abnormal platelet Zn2+ storage and release. To visualize Zn2+ storage in human and mouse platelets, the Zn2+ specific fluorescent dye FluoZin3 was used. In resting platelets, the dye transiently accumulated into distinct cytosolic puncta, which were lost upon platelet activation. Platelets isolated from Unc13d−/− mice, characterized by combined defects of α/δ granular release, showed a markedly impaired Zn2+ release upon activation. Platelets from Nbeal2−/− mice mimicking Gray platelet syndrome (GPS), characterized by primarily loss of the α-granule content, had strongly reduced Zn2+ levels, which was also confirmed in primary megakaryocytes. In human platelets isolated from patients with GPS, Hermansky-Pudlak Syndrome (HPS) and Storage Pool Disease (SPD) altered Zn2+ homeostasis was detected. In turbidity and flow based assays, platelet-dependent fibrin formation was impaired in both Nbeal2−/− and Unc13d−/− mice, and the impairment could be partially restored by extracellular Zn2+. Altogether, we conclude that the release of ionic Zn2+ store from secretory granules upon platelet activation contributes to the procoagulant role of Zn2+ in platelet-dependent fibrin formation.
KW  - coagulation system
KW  - metals
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227455
VL  - 9
ER  -