TY  - JOUR
A1  - Coelho, Catarina
A1  - Mahro, Martin
A1  - Trincao, Jose
A1  - Carvalho, Alexandra T. P.
A1  - Ramos, Maria Joao
A1  - Terao, Mineko
A1  - Garattini, Enrico
A1  - Leimkühler, Silke
A1  - Romao, Maria Joao
T1  - The first mammalian aldehyde oxidase crystal structure insights into substrate specificity
JF  - The journal of biological chemistry
N2  - Aldehyde oxidases (AOXs) are homodimeric proteins belonging to the xanthine oxidase family of molybdenum-containing enzymes. Each 150-kDa monomer contains a FAD redox cofactor, two spectroscopically distinct [2Fe-2S] clusters, and a molybdenum cofactor located within the protein active site. AOXs are characterized by broad range substrate specificity, oxidizing different aldehydes and aromatic N-heterocycles. Despite increasing recognition of its role in the metabolism of drugs and xenobiotics, the physiological function of the protein is still largely unknown. We have crystallized and solved the crystal structure of mouse liver aldehyde oxidase 3 to 2.9 angstrom. This is the first mammalian AOX whose structure has been solved. The structure provides important insights into the protein active center and further evidence on the catalytic differences characterizing AOX and xanthine oxidoreductase. The mouse liver aldehyde oxidase 3 three-dimensional structure combined with kinetic, mutagenesis data, molecular docking, and molecular dynamics studies make a decisive contribution to understand the molecular basis of its rather broad substrate specificity.
Y1  - 2012
U6  - https://doi.org/10.1074/jbc.M112.390419
SN  - 0021-9258
VL  - 287
IS  - 48
SP  - 40690
EP  - 40702
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda
ER  - 
TY  - JOUR
A1  - Janssen, Annette B. G.
A1  - Arhonditsis, George B.
A1  - Beusen, Arthur
A1  - Bolding, Karsten
A1  - Bruce, Louise
A1  - Bruggeman, Jorn
A1  - Couture, Raoul-Marie
A1  - Downing, Andrea S.
A1  - Elliott, J. Alex
A1  - Frassl, Marieke A.
A1  - Gal, Gideon
A1  - Gerla, Daan J.
A1  - Hipsey, Matthew R.
A1  - Hu, Fenjuan
A1  - Ives, Stephen C.
A1  - Janse, Jan H.
A1  - Jeppesen, Erik
A1  - Joehnk, Klaus D.
A1  - Kneis, David
A1  - Kong, Xiangzhen
A1  - Kuiper, Jan J.
A1  - Lehmann, Moritz K.
A1  - Lemmen, Carsten
A1  - Oezkundakci, Deniz
A1  - Petzoldt, Thomas
A1  - Rinke, Karsten
A1  - Robson, Barbara J.
A1  - Sachse, Rene
A1  - Schep, Sebastiaan A.
A1  - Schmid, Martin
A1  - Scholten, Huub
A1  - Teurlincx, Sven
A1  - Trolle, Dennis
A1  - Troost, Tineke A.
A1  - Van Dam, Anne A.
A1  - Van Gerven, Luuk P. A.
A1  - Weijerman, Mariska
A1  - Wells, Scott A.
A1  - Mooij, Wolf M.
T1  - Exploring, exploiting and evolving diversity of aquatic ecosystem models: a community perspective
JF  - Aquatic ecology : the international forum covering research in freshwater and marine environments
N2  - Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality management. In this spirit, numerous models have been developed since the 1970s. We set off to explore model diversity by making an inventory among 42 aquatic ecosystem modellers, by categorizing the resulting set of models and by analysing them for diversity. We then focus on how to exploit model diversity by comparing and combining different aspects of existing models. Finally, we discuss how model diversity came about in the past and could evolve in the future. Throughout our study, we use analogies from biodiversity research to analyse and interpret model diversity. We recommend to make models publicly available through open-source policies, to standardize documentation and technical implementation of models, and to compare models through ensemble modelling and interdisciplinary approaches. We end with our perspective on how the field of aquatic ecosystem modelling might develop in the next 5-10 years. To strive for clarity and to improve readability for non-modellers, we include a glossary.
KW  - Water quality
KW  - Ecology
KW  - Geochemistry
KW  - Hydrology
KW  - Hydraulics
KW  - Hydrodynamics
KW  - Physical environment
KW  - Socio-economics
KW  - Model availability
KW  - Standardization
KW  - Linking
Y1  - 2015
U6  - https://doi.org/10.1007/s10452-015-9544-1
SN  - 1386-2588
SN  - 1573-5125
VL  - 49
IS  - 4
SP  - 513
EP  - 548
PB  - Springer
CY  - Dordrecht
ER  - 
TY  - JOUR
A1  - Achilles, E. I. S.
A1  - Fink, G. R.
A1  - Fischer, Martin H.
A1  - Dovern, A.
A1  - Held, A.
A1  - Timpert, D. C.
A1  - Schroeter, C.
A1  - Schuetz, K.
A1  - Kloetzsch, C.
A1  - Weiss, P. H.
T1  - Effect of meaning on apraxic finger imitation deficits
JF  - Neuropsychologia : an international journal in behavioural and cognitive neuroscience
N2  - Apraxia typically results from left-hemispheric (LH), but also from right-hemispheric (RH) stroke, and often impairs gesture imitation. Especially in LH stroke, it is important to differentiate apraxia-induced gesture imitation deficits from those due to co-morbid aphasia and associated semantic deficits, possibly influencing the imitation of meaningful (MF) gestures. To explore this issue, we first investigated if the 10 supposedly meaningless (ML) gestures of a widely used finger imitation test really carry no meaning, or if the test also contains MF gestures, by asking healthy subjects (n=45) to classify these gestures as MF or ML. Most healthy subjects (98%) classified three of the 10 gestures as clearly MF. Only two gestures were considered predominantly ML. We next assessed how imitation in stroke patients (255 LH, 113 RH stroke) is influenced by gesture meaning and how aphasia influences imitation of LH stroke patients (n=208). All patients and especially patients with imitation deficits (17% of LH, 27% of RH stroke patients) imitated MF gestures significantly better than ML gestures. Importantly, meaningfulness-scores of all 10 gestures significantly predicted imitation scores of patients with imitation deficits. Furthermore, especially in LH stroke patients with imitation deficits, the severity of aphasia significantly influenced the imitation of MF, but not ML gestures. Our findings in a large patient cohort support current cognitive models of imitation and strongly suggest that ML gestures are particularly sensitive to detect imitation deficits while minimising confounding effects of aphasia which affect the imitation of MF gestures in LH stroke patients. (C) 2015 Elsevier Ltd. All rights reserved.
KW  - Apraxia
KW  - Meaning
KW  - Cognitive models of imitation
Y1  - 2016
U6  - https://doi.org/10.1016/j.neuropsychologia.2015.12.022
SN  - 0028-3932
SN  - 1873-3514
VL  - 82
SP  - 74
EP  - 83
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Ostermeyer, Martin
A1  - Klemz, Guido
A1  - Kubina, P.
A1  - Menzel, Ralf
T1  - Quasi-continuous-wave birefringence-compensated single- and double-rod Nd : YAG lasers
Y1  - 2002
ER  - 
TY  - JOUR
A1  - Klemz, Guido
A1  - Kubina, P.
A1  - Ostermeyer, Martin
A1  - Menzel, Ralf
T1  - Diode pumped high power TEM_00 Nd:YAG rod laser with birefringence compensation
Y1  - 2001
ER  - 
TY  - JOUR
A1  - Miedema, P. S.
A1  - Mitzner, Rolf
A1  - Ganschow, S.
A1  - Föhlisch, Alexander
A1  - Beye, Martin
T1  - X-ray spectroscopy on the active ion in laser crystals
JF  - Physical chemistry, chemical physics : a journal of European Chemical Societies
N2  - The active ions in typical laser crystals were studied with Resonant Inelastic X-ray Scattering (RIXS) and Partial Fluorescence Yield X-ray Absorption (PFY-XAS) spectroscopies as solid state model systems for dilute active centers. We analyzed Ti3+ and Cr3+ in alpha-Al2O3:Ti3+ and LiCaAlF6:Cr3+, respectively. The comparison of experimental data with semi-empirical multiplet calculations provides insights into the electronic structure and shows how measured crystal field energies are related across different spectroscopies.
Y1  - 2017
U6  - https://doi.org/10.1039/c7cp03026f
SN  - 1463-9076
SN  - 1463-9084
VL  - 19
SP  - 21800
EP  - 21806
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Sarem, Melika
A1  - Arya, Neha
A1  - Heizmann, Miriam
A1  - Neffe, Axel T.
A1  - Barbero, Andrea
A1  - Gebauer, Tim P.
A1  - Martin, Ivan
A1  - Lendlein, Andreas
A1  - Shastri, V. Prasad
T1  - Interplay between stiffness and degradation of architectured gelatin hydrogels leads to differential modulation of chondrogenesis in vitro and in vivo
JF  - Acta biomaterialia
N2  - The limited capacity of cartilage to heal large lesions through endogenous mechanisms has led to extensive effort to develop materials to facilitate chondrogenesis. Although physical-chemical properties of biomaterials have been shown to impact in vitro chondrogenesis, whether these findings are translatable in vivo is subject of debate. Herein, architectured 3D hydrogel scaffolds (ArcGel) (produced by crosslinking gelatin with ethyl lysine diisocyanate (LDI)) were used as a model system to investigate the interplay between scaffold mechanical properties and degradation on matrix deposition by human articular chondrocytes (HAC) from healthy donors in vitro and in vivo. Using ArcGel scaffolds of different tensile and shear modulus, and degradation behavior; in this study, we compared the fate of ex vivo engineeredArcGels-chondrocytes constructs, i.e. the traditional tissue engineering approach, with the de novo formation of cartilaginous tissue in HAC laden ArcGels in an ectopic nude mouse model. While the softer and fast degrading ArcGel (LNCO3) was more efficient at promoting chondrogenic differentiation in vitro, upon ectopic implantation, the stiffer and slow degrading ArcGel (LNCO8) was superior in maintaining chondrogenic phenotype in HAC and retention of cartilaginous matrix. Furthermore, surprisingly the de novo formation of cartilage tissue was promoted only in LNCO8. Since HAC cultured for only three days in the LNCO8 environment showed upregulation of hypoxia-associated genes, this suggests a potential role for hypoxia in the observed in vivo outcomes. In summary, this study sheds light on how immediate environment (in vivo versus in vitro) can significantly impact the outcomes of cell-laden biomaterials. Statement of Significance In this study, 3D architectured hydrogels (ArcGels) with different mechanical and biodegradation properties were investigated for their potential to promote formation of cartilaginous matrix by human articular chondrocytes in vitro and in vivo. Two paradigms were explored (i) ex vivo engineering followed by in vivo implantation in ectopic site of nude mice and (ii) short in vitro culture (3 days) followed by implantation to induce de novo cartilage formation. Softer and fast degrading ArcGel were better at promoting chondrogenesis in vitro, while stiffer and slow degrading ArcGel were strikingly superior in both maintaining chondrogenesis in vivo and inducing de novo formation of cartilage. Our findings highlight the importance of the interplay between scaffold mechanics and degradation in chondrogenesis.
KW  - Cartilage repair
KW  - Scaffold stiffness
KW  - Scaffold contraction
KW  - Scaffold degradation
KW  - Matrix metalloproteinase
KW  - Hypoxia
Y1  - 2018
U6  - https://doi.org/10.1016/j.actbio.2018.01.025
SN  - 1742-7061
SN  - 1878-7568
VL  - 69
SP  - 83
EP  - 94
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Otten, Cecile
A1  - Knox, Jessica
A1  - Boulday, Gwenola
A1  - Eymery, Mathias
A1  - Haniszewski, Marta
A1  - Neuenschwander, Martin
A1  - Radetzki, Silke
A1  - Vogt, Ingo
A1  - Haehn, Kristina
A1  - De Luca, Coralie
A1  - Cardoso, Cecile
A1  - Hamad, Sabri
A1  - Igual Gil, Carla
A1  - Roy, Peter
A1  - Albiges-Rizo, Corinne
A1  - Faurobert, Eva
A1  - von Kries, Jens P.
A1  - Campillos, Monica
A1  - Tournier-Lasserve, Elisabeth
A1  - Derry, William Brent
A1  - Abdelilah-Seyfried, Salim
T1  - Systematic pharmacological screens uncover novel pathways involved in cerebral cavernous malformations
JF  - EMBO molecular medicine
N2  - Cerebral cavernous malformations (CCMs) are vascular lesions in the central nervous system causing strokes and seizures which currently can only be treated through neurosurgery. The disease arises through changes in the regulatory networks of endothelial cells that must be comprehensively understood to develop alternative, non-invasive pharmacological therapies. Here, we present the results of several unbiased small-molecule suppression screens in which we applied a total of 5,268 unique substances to CCM mutant worm, zebrafish, mouse, or human endothelial cells. We used a systems biology-based target prediction tool to integrate the results with the whole-transcriptome profile of zebrafish CCM2 mutants, revealing signaling pathways relevant to the disease and potential targets for small-molecule-based therapies. We found indirubin-3-monoxime to alleviate the lesion burden in murine preclinical models of CCM2 and CCM3 and suppress the loss-of-CCM phenotypes in human endothelial cells. Our multi-organism-based approach reveals new components of the CCM regulatory network and foreshadows novel small-molecule-based therapeutic applications for suppressing this devastating disease in patients.
KW  - angiogenesis
KW  - CCM
KW  - ERK5
KW  - indirubin-3-monoxime
KW  - KLF2
Y1  - 2018
U6  - https://doi.org/10.15252/emmm.201809155
SN  - 1757-4676
SN  - 1757-4684
VL  - 10
IS  - 10
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Bronner, C.
A1  - Leyssner, F.
A1  - Stremlau, S.
A1  - Utecht, Manuel Martin
A1  - Saalfrank, Peter
A1  - Klamroth, Tillmann
A1  - Tegeder, P.
T1  - Electronic structure of a subnanometer wide bottom-up fabricated graphene nanoribbon: End states, band gap, and dispersion
JF  - Physical review : B, Condensed matter and materials physics
N2  - Angle-resolved two-photon photoemission and high-resolution electron energy loss spectroscopy are employed to derive the electronic structure of a subnanometer atomically precise quasi-one-dimensional graphene nanoribbon (GNR) on Au(111). We resolved occupied and unoccupied electronic bands including their dispersion and determined the band gap, which possesses an unexpectedly large value of 5.1 eV. Supported by density functional theory calculations for the idealized infinite polymer and finite size oligomers, an unoccupied nondispersive electronic state with an energetic position in the middle of the band gap of the GNR could be identified. This state resides at both ends of the ribbon (end state) and is only found in the finite sized systems, i.e., the oligomers.
Y1  - 2012
U6  - https://doi.org/10.1103/PhysRevB.86.085444
SN  - 1098-0121
VL  - 86
IS  - 8
PB  - American Physical Society
CY  - College Park
ER  - 
TY  - GEN
A1  - Doege, N.
A1  - Hoenzke, S.
A1  - Schumacher, Fabian
A1  - Balzus, Benjamin
A1  - Colombo, Miriam
A1  - Hadam, S.
A1  - Rancan, F.
A1  - Blume-Peytavi, Ulrike
A1  - Schindler, A.
A1  - Ruehl, E.
A1  - Skov, P.
A1  - Church, Martin K.
A1  - Hedtrich, Sarah
A1  - Kleuser, Burkhard
A1  - Bodmeier, Roland
A1  - Vogt, A.
T1  - Ex vivo microdialysis used for the preclinical assessment of anti-inflammatory therapy
T2  - Experimental dermatology : the official journal of the European Immunodermatology Society
Y1  - 2016
SN  - 0906-6705
SN  - 1600-0625
VL  - 25
SP  - E32
EP  - E32
PB  - Wiley-Blackwell
CY  - Hoboken
ER  -