@article{YinBrocherFischeretal.2011,
  author    = {Yin, Jun and Brocher, Jan and Fischer, Utz and Winkler, Christoph},
  title     = {Mutant Prpf31 causes pre-mRNA splicing defects and rod photoreceptor cell degeneration in a zebrafish model for Retinitis pigmentosa},
  series = {Molecular neurodegeneration},
  volume    = {6},
  journal   = {Molecular neurodegeneration},
  number    = {56},
  doi       = {10.1186/1750-1326-6-56},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141090},
  pages     = {1-17},
  year      = {2011},
  abstract  = {Background: Retinitis pigmentosa (RP) is an inherited eye disease characterized by the progressive degeneration of rod photoreceptor cells. Mutations in pre-mRNA splicing factors including PRPF31 have been identified as cause for RP, raising the question how mutations in general factors lead to tissue specific defects. Results: We have recently shown that the zebrafish serves as an excellent model allowing the recapitulation of key events of RP. Here we use this model to investigate two pathogenic mutations in PRPF31, SP117 and AD5, causing the autosomal dominant form of RP. We show that SP117 leads to an unstable protein that is mislocalized to the rod cytoplasm. Importantly, its overexpression does not result in photoreceptor degeneration suggesting haploinsufficiency as the underlying cause in human RP patients carrying SP117. In contrast, overexpression of AD5 results in embryonic lethality, which can be rescued by wild-type Prpf31. Transgenic retina-specific expression of AD5 reveals that stable AD5 protein is initially localized in the nucleus but later found in the cytoplasm concurrent with progressing rod outer segment degeneration and apoptosis. Importantly, we show for the first time in vivo that retinal transcripts are wrongly spliced in adult transgenic retinas expressing AD5 and exhibiting increased apoptosis in rod photoreceptors. Conclusion: Our data suggest that distinct mutations in Prpf31 can lead to photoreceptor degeneration through different mechanisms, by haploinsufficiency or dominant-negative effects. Analyzing the AD5 effects in our animal model in vivo, our data imply that aberrant splicing of distinct retinal transcripts contributes to the observed retina defects.},
  language  = {en}
}
@article{ZhaoZhangBhuripanyoetal.2013,
  author    = {Zhao, Bo and Zhang, Keya and Bhuripanyo, Karan and Choi, Chan Hee J. and Villhauer, Eric B. and Li, Heng and Zheng, Ning and Kiyokawa, Hiroaki and Schindelin, Hermann and Yin, Jun},
  title     = {Profiling the Cross Reactivity of Ubiquitin with the Nedd8 Activating Enzyme by Phage Display},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {e70312},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0070312},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128479},
  year      = {2013},
  abstract  = {The C-terminal peptides of ubiquitin (UB) and UB-like proteins (UBLs) play a key role in their recognition by the specific activating enzymes (E1s) to launch their transfer through the respective enzymatic cascades thus modifying cellular proteins. UB and Nedd8, a UBL regulating the activity of cullin-RING UB ligases, only differ by one residue at their C-termini; yet each has its specific E1 for the activation reaction. It has been reported recently that UAE can cross react with Nedd8 to enable its passage through the UB transfer cascade for protein neddylation. To elucidate differences in UB recognition by UAE and NAE, we carried out phage selection of a UB library with randomized C-terminal sequences based on the catalytic formation of UB similar to NAE thioester conjugates. Our results confirmed the previous finding that residue 72 of UB plays a "gate-keeping" role in E1 selectivity. We also found that diverse sequences flanking residue 72 at the UB C-terminus can be accommodated by NAE for activation. Furthermore heptameric peptides derived from the C-terminal sequences of UB variants selected for NAE activation can function as mimics of Nedd8 to form thioester conjugates with NAE and the downstream E2 enzyme Ubc12 in the Nedd8 transfer cascade. Once the peptides are charged onto the cascade enzymes, the full-length Nedd8 protein is effectively blocked from passing through the cascade for the critical modification of cullin. We have thus identified a new class of inhibitors of protein neddylation based on the profiles of the UB C-terminal sequences recognized by NAE.},
  language  = {en}
}
@article{VaethWangEcksteinetal.2019,
  author    = {Vaeth, Martin and Wang, Yin-Hu and Eckstein, Miriam and Yang, Jun and Silverman, Gregg J. and Lacruz, Rodrigo S. and Kannan, Kasthuri and Feske, Stefan},
  title     = {Tissue resident and follicular Treg cell differentiation is regulated by CRAC channels},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-08959-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232148},
  year      = {2019},
  abstract  = {T regulatory (Treg) cells maintain immunological tolerance and organ homeostasis. Activated Treg cells differentiate into effector Treg subsets that acquire tissue-specific functions. Ca2+ influx via Ca2+ release-activated Ca2+ (CRAC) channels formed by STIM and ORAI proteins is required for the thymic development of Treg cells, but its function in mature Treg cells remains unclear. Here we show that deletion of Stim1 and Stim2 genes in mature Treg cells abolishes Ca2+ signaling and prevents their differentiation into follicular Treg and tissue-resident Treg cells. Transcriptional profiling of STIM1/STIM2-deficient Treg cells reveals that Ca2+ signaling regulates transcription factors and signaling pathways that control the identity and effector differentiation of Treg cells. In the absence of STIM1/STIM2 in Treg cells, mice develop a broad spectrum of autoantibodies and fatal multiorgan inflammation. Our findings establish a critical role of CRAC channels in controlling lineage identity and effector functions of Treg cells.},
  language  = {en}
}
@article{WilsonAmblerLeeetal.2019,
  author    = {Wilson, Duncan and Ambler, Gareth and Lee, Keon-Joo and Lim, Jae-Sung and Shiozawa, Masayuki and Koga, Masatoshi and Li, Linxin and Lovelock, Caroline and Chabriat, Hugues and Hennerici, Michael and Wong, Yuen Kwun and Mak, Henry Ka Fung and Prats-S{\´a}nchez, Luis and Mart{\´i}nez-Dome{\~n}o, Alejandro and Inamura, Shigeru and Yoshifuji, Kazuhisa and Arsava, Ethem Murat and Horstmann, Solveig and Purrucker, Jan and Lam, Bonnie Yin Ka and Wong, Adrian and Kim, Young Dae and Song, Tae-Jin and Schrooten, Maarten and Lemmens, Robin and Eppinger, Sebastian and Gattringer, Thomas and Uysal, Ender and Tanriverdi, Zeynep and Bornstein, Natan M and Ben Assayag, Einor and Hallevi, Hen and Tanaka, Jun and Hara, Hideo and Coutts, Shelagh B and Hert, Lisa and Polymeris, Alexandros and Seiffge, David J and Lyrer, Philippe and Algra, Ale and Kappelle, Jaap and Salman, Rustam Al-Shahi and J{\"a}ger, Hans R and Lip, Gregory Y H and Mattle, Heinrich P and Panos, Leonidas D and Mas, Jean-Louis and Legrand, Laurence and Karayiannis, Christopher and Phan, Thanh and Gunkel, Sarah and Christ, Nicolas and Abrigo, Jill and Leung, Thomas and Chu, Winnie and Chappell, Francesca and Makin, Stephen and Hayden, Derek and Williams, David J and Kooi, M Eline and van Dam-Nolen, Dianne H K and Barbato, Carmen and Browning, Simone and Wiegertjes, Kim and Tuladhar, Anil M and Maaijwee, Noortje and Guevarra, Christine and Yatawara, Chathuri and Mendyk, Anne-Marie and Delmaire, Christine and K{\"o}hler, Sebastian and van Oostenbrugge, Robert and Zhou, Ying and Xu, Chao and Hilal, Saima and Gyanwali, Bibek and Chen, Christopher and Lou, Min and Staals, Julie and Bordet, R{\´e}gis and Kandiah, Nagaendran and de Leeuw, Frank-Erik and Simister, Robert and van der Lugt, Aad and Kelly, Peter J and Wardlaw, Joanna M and Soo, Yannie and Fluri, Felix and Srikanth, Velandai and Calvet, David and Jung, Simon and Kwa, Vincent I H and Engelter, Stefan T and Peters, Nils and Smith, Eric E and Yakushiji, Yusuke and Necioglu Orken, Dilek and Fazekas, Franz and Thijs, Vincent and Heo, Ji Hoe and Mok, Vincent and Veltkamp, Roland and Ay, Hakan and Imaizumi, Toshio and Gomez-Anson, Beatriz and Lau, Kui Kai and Jouvent, Eric and Rothwell, Peter M and Toyoda, Kazunori and Bae, Hee-Yoon and Marti-Fabregas, Joan and Werring, David J},
  title     = {Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies},
  series = {The Lancet Neurology},
  volume    = {18},
  journal   = {The Lancet Neurology},
  organization    = {Microbleeds International Collaborative Network},
  doi       = {10.1016/S1474-4422(19)30197-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233710},
  pages     = {653-665},
  year      = {2019},
  abstract  = {Background Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Findings Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95\% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95\% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-2·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95\% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). Interpretation In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden.},
  language  = {en}
}