55 research outputs found
Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure
27 p.-7 fig.Expansion of the glutamine tract (poly-Q) in the protein huntingtin (HTT) causes the neurodegenerative disorder Huntington's disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered male induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT. The introduction of a 70Q mutation caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of the protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), a transcription factor involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics that was reverted upon overexpression of CHCHD2. Removing the poly-Q tract from HTT normalized CHCHD2 levels and corrected key mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early interventional target for HD.We acknowledge support from the Deutsche Forschungsgemeinschaft (DFG)(PR1527/5-1 to A.P., RTG 2155 ProMoAge to H.O. and L.A.M.K., SFB167 B07 to J.P., RU2795: âSynapses under stressâ: PR-1527/6-1 to A.P. and AN-1440/4-1 to R.A.), the Berlin Institute of Health (BIH) (to S.D., J.P., R.K., and A.P.),the Bundesministerium fĂŒr Bildung und Forschung (BMBF) (AZ. 031L0211 and 01GM2002A to A.P. and 01EE2303B to J.P.), the Medical Faculty of Heinrich Heine University (FoKo grant to A.P. and S.C.), the European Commissionâs Horizon Europe Program (SIMPATHIC #101080249 to A.P.),the National Science Centre, Poland (NCN grant No. 20 16/22/M/NZ2/00548 and 2017/27/B/NZ1/02401 to P.L.), the UK Dementia Research Institute programme grant (to J.P.), the Instituto de Salud Carlos III (ISCIII) grant PI20-00057 (to C.U.), the Berlin School of Integrative Oncology through the GSSP program of the German Academy of Exchange Service (DAAD) and the Joachim Herz Foundation through the Add-on Fellowship program (to T.M.P.), and the Studienstiftung des deutschen Volkes (to Se.Li.). We acknowledge the Center for Advanced Imaging (CAi) at Heinrich Heine University DĂŒsseldorf for providing access to the Perki-
nElmer Operetta CLS (DFG grant number INST 208/760-1 FUGG) and Olympus FV3000 microscope.Peer reviewe
Data from: Sexual selection and population divergence II. divergence in different sexual traits and signal modalities in field crickets (Teleogryllus oceanicus)
Wing morphometric data includes relative warps 1-3 plus mirror and harp surface areas. Data from validations run on a subset of samples are also included. "Unique identifier" cross-references each sample to the CHC analysis in [Pascoal et al. (2016) Sexual selection and population divergence I. The influence of socially flexible cuticular hydrocarbon expression in male field crickets (Teleogryllus oceanicus). Evolution 10:82-97.] "N/A" indicates the n = 13 samples excluded from morphometric analysis as described in the present manuscript
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A progress report on the Berkeley search for distant supernovae to measure. Omega
Over the past two years, in collaboration with the Anglo-Australian Observatory, we have constructed a prototype version of the hardware and software needed to discover distant supernovae for a measurement of {Omega}, the ratio of the average density of the universe to the critical density. To make this measurement, we will use Type Ia supernova, which are now thought to be adequate standard candles for this purpose. 5 refs
Tracing stars of MW dwarf galaxies: Sextans
VizieR online Data Catalogue associated with article published in journal Astronomy & Astrophysics with title 'Tracing the stellar component of low surface brightness Milky Way dwarf galaxies to their outskirts. I: Sextans.' (bibcode: 2018A&A...609A..53C
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