TY  - JOUR
A1  - Menekse, Kaan
A1  - Mahl, Magnus
A1  - Albert, Julius
A1  - Niyas, M. A.
A1  - Shoyama, Kazutaka
A1  - Stolte, Matthias
A1  - Würthner, Frank
T1  - Supramolecularly Engineered Bulk‐Heterojunction Solar Cells with Self‐Assembled Non‐Fullerene Nanographene Tetraimide Acceptors
JF  - Solar RRL
N2  - A series of novel imide‐functionalized C\(_{64}\) nanographenes is investigated as acceptor components in organic solar cells (OSCs) in combination with donor polymer PM6. These electron‐poor molecules either prevail as a monomer or self‐assemble into dimers in the OSC active layer depending on the chosen imide substituents. This allows for the controlled stacking of electron‐poor and electron‐rich π–scaffolds to establish a novel class of non‐fullerene acceptor materials to tailor the bulk‐heterojunction morphology of the OSCs. The best performance is observed for derivatives that are able to self‐assemble into dimers, reaching power conversion efficiencies of up to 7.1%.
KW  - nanographene
KW  - non-fullerene acceptors
KW  - organic solar cells
KW  - polycyclic aromatic hydrocarbons
KW  - self-assembly
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312099
VL  - 7
IS  - 2
ER  - 
TY  - JOUR
A1  - Dekker, Annelot M.
A1  - Diekstra, Frank P.
A1  - Pulit, Sara L.
A1  - Tazelaar, Gijs H. P.
A1  - van der Spek, Rick A.
A1  - van Rheenen, Wouter
A1  - van Eijk, Kristel R.
A1  - Calvo, Andrea
A1  - Brunetti, Maura
A1  - Van Damme, Philip
A1  - Robberecht, Wim
A1  - Hardiman, Orla
A1  - McLaughlin, Russell
A1  - Chiò, Adriano
A1  - Sendtner, Michael
A1  - Ludolph, Albert C.
A1  - Weishaupt, Jochen H.
A1  - Pardina, Jesus S. Mora
A1  - van den Berg, Leonard H.
A1  - Veldink, Jan H.
T1  - Exome array analysis of rare and low frequency variants in amyotrophic lateral sclerosis
JF  - Scientific Reports
N2  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 1 in ~350 individuals. Genetic association studies have established ALS as a multifactorial disease with heritability estimated at ~61%, and recent studies show a prominent role for rare variation in its genetic architecture. To identify rare variants associated with disease onset we performed exome array genotyping in 4,244 cases and 3,106 controls from European cohorts. In this largest exome-wide study of rare variants in ALS to date, we performed single-variant association testing, gene-based burden, and exome-wide individual set-unique burden (ISUB) testing to identify single or aggregated rare variation that modifies disease risk. In single-variant testing no variants reached exome-wide significance, likely due to limited statistical power. Gene-based burden testing of rare non-synonymous and loss-of-function variants showed NEK1 as the top associated gene. ISUB analysis did not show an increased exome-wide burden of deleterious variants in patients, possibly suggesting a more region-specific role for rare variation. Complete summary statistics are released publicly. This study did not implicate new risk loci, emphasizing the immediate need for future large-scale collaborations in ALS that will expand available sample sizes, increase genome coverage, and improve our ability to detect rare variants associated to ALS.
KW  - amyotrophic lateral sclerosis
KW  - genome-wide association studies
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223686
VL  - 9
ER  - 
TY  - JOUR
A1  - Langhauser, Friederike
A1  - Casas, Ana I.
A1  - Dao, Vu-Thao-Vi
A1  - Guney, Emre
A1  - Menche, Jörg
A1  - Geuss, Eva
A1  - Kleikers, Pamela W. M.
A1  - López, Manuela G.
A1  - Barabási, Albert-L.
A1  - Kleinschnitz, Christoph
A1  - Schmidt, Harald H. H. W.
T1  - A diseasome cluster-based drug repurposing of soluble guanylate cyclase activators from smooth muscle relaxation to direct neuroprotection
JF  - npj Systems Biology and Applications
N2  - Network medicine utilizes common genetic origins, markers and co-morbidities to uncover mechanistic links between diseases. These links can be summarized in the diseasome, a comprehensive network of disease–disease relationships and clusters. The diseasome has been influential during the past decade, although most of its links are not followed up experimentally. Here, we investigate a high prevalence unmet medical need cluster of disease phenotypes linked to cyclic GMP. Hitherto, the central cGMP-forming enzyme, soluble guanylate cyclase (sGC), has been targeted pharmacologically exclusively for smooth muscle modulation in cardiology and pulmonology. Here, we examine the disease associations of sGC in a non-hypothesis based manner in order to identify possibly previously unrecognized clinical indications. Surprisingly, we find that sGC, is closest linked to neurological disorders, an application that has so far not been explored clinically. Indeed, when investigating the neurological indication of this cluster with the highest unmet medical need, ischemic stroke, pre-clinically we find that sGC activity is virtually absent post-stroke. Conversely, a heme-free form of sGC, apo-sGC, was now the predominant isoform suggesting it may be a mechanism-based target in stroke. Indeed, this repurposing hypothesis could be validated experimentally in vivo as specific activators of apo-sGC were directly neuroprotective, reduced infarct size and increased survival. Thus, common mechanism clusters of the diseasome allow direct drug repurposing across previously unrelated disease phenotypes redefining them in a mechanism-based manner. Specifically, our example of repurposing apo-sGC activators for ischemic stroke should be urgently validated clinically as a possible first-in-class neuroprotective therapy.
KW  - neurology
KW  - pharmacology
KW  - systems biology
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236381
VL  - 4
ER  -