TY  - JOUR
A1  - Mikhailyuk, Igor K.
A1  - Knox, Peter P.
A1  - Paschenko, Vladimir Z.
A1  - Razjivin, Andrej P.
A1  - Lokstein, Heiko
T1  - Analysis of absorption spectra of purple bacterial reaction centers in the near infrared region by higher order derivative spectroscopy
N2  - Reaction centers (RCs) of purple bacteria are uniquely suited objects to study the mechanisms of the photosynthetic conversion of light energy into chemical energy. A recently introduced method of higher order derivative spectroscopy [I.K. Mikhailyuk, H. Lokstein, A.P. Razjivin, A method of spectral subband decomposition by simultaneous fitting the initial spectrum and a set of its derivatives, J. Biochem. Biophys. Methods 63 (2005) 10-23] was used to analyze the NIR absorption spectra of RC preparations from Rhodobacter (R.) sphaeroides strain 2R and Blastochloris (B.) viridis strain KH, containing bacteriochlorophyll (BChl) a and b, respectively. Q(y) bands of individual RC porphyrin components (BChls and bacteriopheophytins, BPheo) were identified. The results indicate that the upper exciton level Py+ of the photo-active BChl dimer in RCs of R. sphaeroides has an absorption maximum of 810nm. The blue shift of a complex integral band at approximately 800nm upon oxidation of the RC is caused primarily by bleaching of Py+, rather than by an electrochromic shift of the absorption band(s) of the monomeric BChls. Likewise, the disappearance of a band peaking at 842 nm upon oxidation of RCs from B. viridis indicates that this band has to be assigned to Py+, A blue shift of an absorption band at approximately 830nm upon oxidation of RCs of B. viridis is also essentially caused by the disappearance of Py+, rather than by an electrochromic shift of the absorption bands of monomeric BChls. Absorption maxima of the monomeric BCHls, B-B and B-A are at 802 and 797nm, respectively, in RCs of R. sphaeroides at room temperature. BPheo co-factors H-B and HA peak at 748 and 758 nm, respectively, at room temperature. For B. viridis RCs the spectral positions of HB and HA were found to be 796 and 816nm, respectively, at room temperature.
Y1  - 2006
UR  - http://www.sciencedirect.com/science/journal/03014622
U6  - https://doi.org/10.1016/j.bpc.2006.02.002
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  -