@article{17597, abstract = {Deep Neural Networks (DNNs) are powerful algorithms that have been proven capable of extracting non-Gaussian information from weak lensing (WL) data sets. Understanding which features in the data determine the output of these nested, non-linear algorithms is an important but challenging task. We analyze a DNN that has been found in previous work to accurately recover cosmological parameters in simulated maps of the WL convergence (κ). We derive constraints on the cosmological parameter pair (Ωm,σ8) from a combination of three commonly used WL statistics (power spectrum, lensing peaks, and Minkowski functionals), using ray-traced simulated κ maps. We show that the network can improve the inferred parameter constraints relative to this combination by 20% even in the presence of realistic levels of shape noise. We apply a series of well established saliency methods to interpret the DNN and find that the most relevant pixels are those with extreme κ values. For noiseless maps, regions with negative κ account for 86−69% of the attribution of the DNN output, defined as the square of the saliency in input space. In the presence of shape nose, the attribution concentrates in high convergence regions, with 36−68% of the attribution in regions with κ>3σκ.}, author = {Matilla, José Manuel Zorrilla and Sharma, Manasi and Hsu, Daniel and Haiman, Zoltán}, issn = {2470-0010}, journal = {Physical Review D}, number = {12}, publisher = {American Physical Society}, title = {{Interpreting deep learning models for weak lensing}}, doi = {10.1103/physrevd.102.123506}, volume = {102}, year = {2020}, } @article{17600, abstract = {The quest for binary and dual supermassive black holes (SMBHs) at the dawn of the multi-messenger era is compelling. Detecting dual active galactic nuclei (AGN) – active SMBHs at projected separations larger than several parsecs – and binary AGN – probing the scale where SMBHs are bound in a Keplerian binary – is an observational challenge. The study of AGN pairs (either dual or binary) also represents an overarching theoretical problem in cosmology and astrophysics. The AGN triggering calls for detailed knowledge of the hydrodynamical conditions of gas in the imminent surroundings of the SMBHs and, at the same time, their duality calls for detailed knowledge on how galaxies assemble through major and minor mergers and grow fed by matter along the filaments of the cosmic web. This review describes the techniques used across the electromagnetic spectrum to detect dual and binary AGN candidates and proposes new avenues for their search. The current observational status is compared with the state-of-the-art numerical simulations and models for formation of dual and binary AGN. Binary SMBHs are among the loudest sources of gravitational waves (GWs) in the Universe. The search for a background of GWs at nHz frequencies from inspiralling SMBHs at low redshifts, and the direct detection of signals from their coalescence by the Laser Interferometer Space Antenna in the next decade, make this a theme of major interest for multi-messenger astrophysics. This review discusses the future facilities and observational strategies that are likely to significantly advance this fascinating field.}, author = {De Rosa, Alessandra and Vignali, Cristian and Bogdanović, Tamara and Capelo, Pedro R. and Charisi, Maria and Dotti, Massimo and Husemann, Bernd and Lusso, Elisabeta and Mayer, Lucio and Paragi, Zsolt and Runnoe, Jessie and Sesana, Alberto and Steinborn, Lisa and Bianchi, Stefano and Colpi, Monica and del Valle, Luciano and Frey, Sándor and Gabányi, Krisztina É. and Giustini, Margherita and Guainazzi, Matteo and Haiman, Zoltán and Herrera Ruiz, Noelia and Herrero-Illana, Rubén and Iwasawa, Kazushi and Komossa, S. and Lena, Davide and Loiseau, Nora and Perez-Torres, Miguel and Piconcelli, Enrico and Volonteri, Marta}, issn = {1387-6473}, journal = {New Astronomy Reviews}, publisher = {Elsevier BV}, title = {{The quest for dual and binary supermassive black holes: A multi-messenger view}}, doi = {10.1016/j.newar.2020.101525}, volume = {86}, year = {2020}, } @article{17601, abstract = {Using numerical hydrodynamics calculations and a novel method for densely sampling parameter space, we measure the accretion and torque on a binary system from a circumbinary disk. In agreement with some earlier studies, we find that the net torque on the binary is positive for mass ratios close to unity, and that accretion always drives the binary toward equal mass. Accretion variability depends sensitively on the numerical sink prescription, but the torque and relative accretion onto each component do not depend on the sink timescale. Positive torque and highly variable accretion occurs only for mass ratios greater than around 0.05. This means that for mass ratios below 0.05, the binary would migrate inward until the secondary accreted sufficient mass, after which it would execute a U-turn and migrate outward. We explore a range of viscosities, from α = 0.03 to α = 0.15, and find that this outward torque is proportional to the viscous torque, so that torque per unit accreted mass is independent of α. Dependence of accretion and torque on mass ratio is explored in detail, densely sampling mass ratios between 0.01 and unity. For mass ratio q > 0.2, accretion variability is found to exhibit a distinct sawtooth pattern, typically with a five-orbit cycle that provides a smoking gun prediction for variable quasars observed over long periods, as a potential means to confirm the presence of a binary.}, author = {Duffell, Paul C. and D’Orazio, Daniel and Derdzinski, Andrea and Haiman, Zoltán and MacFadyen, Andrew and Rosen, Anna L. and Zrake, Jonathan}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {1}, publisher = {American Astronomical Society}, title = {{Circumbinary disks: Accretion and torque as a function of mass ratio and disk viscosity}}, doi = {10.3847/1538-4357/abab95}, volume = {901}, year = {2020}, } @article{17604, abstract = {Numerical studies of gas accretion onto supermassive black hole binaries (SMBHBs) have generally been limited to conditions where the circumbinary disk (CBD) is 10-100 times thicker than expected for disks in active galactic nuclei (AGN). This discrepancy arises from technical limitations, and also from publication bias toward replicating fiducial numerical models. Here we present the first systematic study of how the binary's orbital evolution varies with disk scale height. We report three key results: (1) Binary orbital evolution switches from outspiralling for warm disks (aspect ratio ~0.1), to inspiralling for more realistic cooler, thinner disks at a critical aspect ratio ~0.04, corresponding to orbital Mach number ~25. (2) The net torque on the binary arises from a competition between positive torque from gas orbiting close to the black holes, and negative torque from the inner edge of the CBD, which is denser for thinner disks. This leads to increasingly negative net torques on the binary for increasingly thin disks. (3) The accretion rate is modestly suppressed with increasing Mach number. We discuss how our results may influence modeling of the nano-Hz gravitational wave background, as well as estimates of the LISA merger event rate.}, author = {Tiede, Christopher and Zrake, Jonathan and MacFadyen, Andrew and Haiman, Zoltán}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {1}, publisher = {American Astronomical Society}, title = {{Gas-driven inspiral of binaries in thin accretion disks}}, doi = {10.3847/1538-4357/aba432}, volume = {900}, year = {2020}, } @article{17605, abstract = {Despite the rapidly growing number of stellar-mass binary black hole mergers discovered through gravitational waves, the origin of these binaries is still not known. In galactic centers, black holes can be brought to each others' proximity by dynamical processes, resulting in mergers. It is also possible that black holes formed in previous mergers encounter new black holes, resulting in so-called hierarchical mergers. Hierarchical events carry signatures such as higher-than-usual black hole mass and spin. Here we show that the recently reported gravitational-wave candidate, GW170817A, could be the result of such a hierarchical merger. In particular, its chirp mass ∼40 M⊙ and effective spin of χeff ∼ 0.5 are the typically expected values from hierarchical mergers within the disks of active galactic nuclei. We find that the reconstructed parameters of GW170817A strongly favor a hierarchical merger origin over having been produced by an isolated binary origin (with an odds ratio of > 10^3).}, author = {Gayathri, V. and Bartos, I. and Haiman, Zoltán and Klimenko, S. and Kocsis, B. and Márka, S. and Yang, Y.}, issn = {2041-8205}, journal = {The Astrophysical Journal Letters}, number = {2}, publisher = {American Astronomical Society}, title = {{GW170817A as a hierarchical black hole merger}}, doi = {10.3847/2041-8213/ab745d}, volume = {890}, year = {2020}, } @article{17607, abstract = {The heaviest neutron stars and lightest black holes expected to be produced by stellar evolution leave the mass-range 2.2 M⊙≲m≲5 M⊙ largely unpopulated. Objects found in this so-called lower mass gap likely originate from a distinct astrophysical process. Such an object, with mass 2.6 M⊙ was recently detected in the binary merger GW190814 through gravitational waves by LIGO/Virgo. Here we show that black holes in the mass gap are naturally assembled through mergers and accretion in AGN disks, and can subsequently participate in additional mergers. We compute the properties of AGN-assisted mergers involving neutron stars and black holes, accounting for accretion. We find that mergers in which one of the objects is in the lower mass gap represent up to 4% of AGN-assisted mergers detectable by LIGO/Virgo. The lighter object of GW190814, with mass 2.6 M⊙, could have grown in an AGN disk through accretion. We find that the unexpectedly high total mass of 3.4 M⊙ observed in the neutron star merger GW190425 may also be due to accretion in an AGN disk.}, author = {Yang, Y. and Gayathri, V. and Bartos, I. and Haiman, Zoltán and Safarzadeh, M. and Tagawa, H.}, issn = {2041-8205}, journal = {The Astrophysical Journal Letters}, number = {2}, publisher = {American Astronomical Society}, title = {{Black hole formation in the lower mass gap through mergers and accretion in AGN disks}}, doi = {10.3847/2041-8213/abb940}, volume = {901}, year = {2020}, } @article{177, abstract = {We develop a geometric version of the circle method and use it to compute the compactly supported cohomology of the space of rational curves through a point on a smooth affine hypersurface of sufficiently low degree.}, author = {Browning, Timothy D and Sawin, Will}, journal = {Annals of Mathematics}, number = {3}, pages = {893--948}, publisher = {Princeton University}, title = {{A geometric version of the circle method}}, doi = {10.4007/annals.2020.191.3.4}, volume = {191}, year = {2020}, } @article{7665, abstract = {Acute brain slice preparation is a powerful experimental model for investigating the characteristics of synaptic function in the brain. Although brain tissue is usually cut at ice-cold temperature (CT) to facilitate slicing and avoid neuronal damage, exposure to CT causes molecular and architectural changes of synapses. To address these issues, we investigated ultrastructural and electrophysiological features of synapses in mouse acute cerebellar slices prepared at ice-cold and physiological temperature (PT). In the slices prepared at CT, we found significant spine loss and reconstruction, synaptic vesicle rearrangement and decrease in synaptic proteins, all of which were not detected in slices prepared at PT. Consistent with these structural findings, slices prepared at PT showed higher release probability. Furthermore, preparation at PT allows electrophysiological recording immediately after slicing resulting in higher detectability of long-term depression (LTD) after motor learning compared with that at CT. These results indicate substantial advantages of the slice preparation at PT for investigating synaptic functions in different physiological conditions.}, author = {Eguchi, Kohgaku and Velicky, Philipp and Hollergschwandtner, Elena and Itakura, Makoto and Fukazawa, Yugo and Danzl, Johann G and Shigemoto, Ryuichi}, issn = {1662-5102}, journal = {Frontiers in Cellular Neuroscience}, publisher = {Frontiers Media}, title = {{Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions}}, doi = {10.3389/fncel.2020.00063}, volume = {14}, year = {2020}, } @article{7666, abstract = {Generalizing the decomposition of a connected planar graph into a tree and a dual tree, we prove a combinatorial analog of the classic Helmholtz–Hodge decomposition of a smooth vector field. Specifically, we show that for every polyhedral complex, K, and every dimension, p, there is a partition of the set of p-cells into a maximal p-tree, a maximal p-cotree, and a collection of p-cells whose cardinality is the p-th reduced Betti number of K. Given an ordering of the p-cells, this tri-partition is unique, and it can be computed by a matrix reduction algorithm that also constructs canonical bases of cycle and boundary groups.}, author = {Edelsbrunner, Herbert and Ölsböck, Katharina}, issn = {14320444}, journal = {Discrete and Computational Geometry}, pages = {759--775}, publisher = {Springer Nature}, title = {{Tri-partitions and bases of an ordered complex}}, doi = {10.1007/s00454-020-00188-x}, volume = {64}, year = {2020}, } @article{7672, abstract = {Large overpotentials upon discharge and charge of Li-O2 cells have motivated extensive research into heterogeneous solid electrocatalysts or non-carbon electrodes with the aim to improve rate capability, round-trip efficiency and cycle life. These features are equally governed by parasitic reactions, which are now recognized to be caused by the highly reactive singlet oxygen (1O2). However, the link between the presence of electrocatalysts and 1O2 formation in metal-O2 cells is unknown. Here, we show that, compared to pristine carbon black electrodes, a representative selection of electrocatalysts or non-carbon electrodes (noble metal, transition metal compounds) may both slightly reduce or severely increase the 1O2 formation. The individual reaction steps, where the surfaces impact the 1O2 yield are deciphered, showing that 1O2 yield from superoxide disproportionation as well as the decomposition of trace H2O2 are sensitive to catalysts. Transition metal compounds in general are prone to increase 1O2.}, author = {Samojlov, Aleksej and Schuster, David and Kahr, Jürgen and Freunberger, Stefan Alexander}, journal = {Electrochimica Acta}, number = {12}, publisher = {Elsevier}, title = {{Surface and catalyst driven singlet oxygen formation in Li-O2 cells}}, doi = {10.1016/j.electacta.2020.137175}, volume = {362}, year = {2020}, } @article{7683, abstract = {For any free oriented Borel–Moore homology theory A, we construct an associative product on the A-theory of the stack of Higgs torsion sheaves over a projective curve C. We show that the resulting algebra AHa0C admits a natural shuffle presentation, and prove it is faithful when A is replaced with usual Borel–Moore homology groups. We also introduce moduli spaces of stable triples, heavily inspired by Nakajima quiver varieties, whose A-theory admits an AHa0C-action. These triples can be interpreted as certain sheaves on PC(ωC⊕OC). In particular, we obtain an action of AHa0C on the cohomology of Hilbert schemes of points on T∗C.}, author = {Minets, Sasha}, issn = {1420-9020}, journal = {Selecta Mathematica, New Series}, number = {2}, publisher = {Springer Nature}, title = {{Cohomological Hall algebras for Higgs torsion sheaves, moduli of triples and sheaves on surfaces}}, doi = {10.1007/s00029-020-00553-x}, volume = {26}, year = {2020}, } @article{7684, author = {Gridchyn, Igor and Schönenberger, Philipp and O'Neill, Joseph and Csicsvari, Jozsef L}, issn = {10974199}, journal = {Neuron}, number = {2}, pages = {291--300.e6}, publisher = {Elsevier}, title = {{Assembly-specific disruption of hippocampal replay leads to selective memory deficit}}, doi = {10.1016/j.neuron.2020.01.021}, volume = {106}, year = {2020}, } @article{7686, abstract = {The agricultural green revolution spectacularly enhanced crop yield and lodging resistance with modified DELLA-mediated gibberellin signaling. However, this was achieved at the expense of reduced nitrogen-use efficiency (NUE). Recently, Wu et al. revealed novel gibberellin signaling that provides a blueprint for improving tillering and NUE in Green Revolution varieties (GRVs). }, author = {Xue, Huidan and Zhang, Yuzhou and Xiao, Guanghui}, issn = {1360-1385}, journal = {Trends in Plant Science}, number = {6}, pages = {520--522}, publisher = {Elsevier}, title = {{Neo-gibberellin signaling: Guiding the next generation of the green revolution}}, doi = {10.1016/j.tplants.2020.04.001}, volume = {25}, year = {2020}, } @misc{7689, abstract = {These are the supplementary research data to the publication "Zero field splitting of heavy-hole states in quantum dots". All matrix files have the same format. Within each column the bias voltage is changed. Each column corresponds to either a different gate voltage or magnetic field. The voltage values are given in mV, the current values in pA. Find a specific description in the included Readme file. }, author = {Katsaros, Georgios}, publisher = {Institute of Science and Technology Austria}, title = {{Supplementary data for "Zero field splitting of heavy-hole states in quantum dots"}}, doi = {10.15479/AT:ISTA:7689}, year = {2020}, } @article{7695, abstract = {The TPLATE complex (TPC) is a key endocytic adaptor protein complex in plants. TPC in Arabidopsis (Arabidopsis thaliana) contains six evolutionarily conserved subunits and two plant-specific subunits, AtEH1/Pan1 and AtEH2/Pan1, although cytoplasmic proteins are not associated with the hexameric subcomplex in the cytoplasm. To investigate the dynamic assembly of the octameric TPC at the plasma membrane (PM), we performed state-of-the-art dual-color live cell imaging at physiological and lowered temperatures. Lowering the temperature slowed down endocytosis, thereby enhancing the temporal resolution of the differential recruitment of endocytic components. Under both normal and lowered temperature conditions, the core TPC subunit TPLATE and the AtEH/Pan1 proteins exhibited simultaneous recruitment at the PM. These results, together with co-localization analysis of different TPC subunits, allow us to conclude that TPC in plant cells is not recruited to the PM sequentially but as an octameric complex.}, author = {Wang, J and Mylle, E and Johnson, Alexander J and Besbrugge, N and De Jaeger, G and Friml, Jiří and Pleskot, R and van Damme, D}, issn = {1532-2548}, journal = {Plant Physiology}, number = {3}, pages = {986--997}, publisher = {American Society of Plant Biologists}, title = {{High temporal resolution reveals simultaneous plasma membrane recruitment of TPLATE complex subunits}}, doi = {10.1104/pp.20.00178}, volume = {183}, year = {2020}, } @article{7697, abstract = {* Morphogenesis and adaptive tropic growth in plants depend on gradients of the phytohormone auxin, mediated by the membrane‐based PIN‐FORMED (PIN) auxin transporters. PINs localize to a particular side of the plasma membrane (PM) or to the endoplasmic reticulum (ER) to directionally transport auxin and maintain intercellular and intracellular auxin homeostasis, respectively. However, the molecular cues that confer their diverse cellular localizations remain largely unknown. * In this study, we systematically swapped the domains between ER‐ and PM‐localized PIN proteins, as well as between apical and basal PM‐localized PINs from Arabidopsis thaliana , to shed light on why PIN family members with similar topological structures reside at different membrane compartments within cells. * Our results show that not only do the N‐ and C‐terminal transmembrane domains (TMDs) and central hydrophilic loop contribute to their differential subcellular localizations and cellular polarity, but that the pairwise‐matched N‐ and C‐terminal TMDs resulting from intramolecular domain–domain coevolution are also crucial for their divergent patterns of localization. * These findings illustrate the complexity of the evolutionary path of PIN proteins in acquiring their plethora of developmental functions and adaptive growth in plants.}, author = {Zhang, Yuzhou and Hartinger, Corinna and Wang, Xiaojuan and Friml, Jiří}, issn = {1469-8137}, journal = {New Phytologist}, number = {5}, pages = {1406--1416}, publisher = {Wiley}, title = {{Directional auxin fluxes in plants by intramolecular domain‐domain co‐evolution of PIN auxin transporters}}, doi = {10.1111/nph.16629}, volume = {227}, year = {2020}, } @article{7707, abstract = {The growing sample size of genome-wide association studies has facilitated the discovery of gene-environment interactions (GxE). Here we propose a maximum likelihood method to estimate the contribution of GxE to continuous traits taking into account all interacting environmental variables, without the need to measure any. Extensive simulations demonstrate that our method provides unbiased interaction estimates and excellent coverage. We also offer strategies to distinguish specific GxE from general scale effects. Applying our method to 32 traits in the UK Biobank reveals that while the genetic risk score (GRS) of 376 variants explains 5.2% of body mass index (BMI) variance, GRSxE explains an additional 1.9%. Nevertheless, this interaction holds for any variable with identical correlation to BMI as the GRS, hence may not be GRS-specific. Still, we observe that the global contribution of specific GRSxE to complex traits is substantial for nine obesity-related measures (including leg impedance and trunk fat-free mass).}, author = {Sulc, Jonathan and Mounier, Ninon and Günther, Felix and Winkler, Thomas and Wood, Andrew R. and Frayling, Timothy M. and Heid, Iris M. and Robinson, Matthew Richard and Kutalik, Zoltán}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Quantification of the overall contribution of gene-environment interaction for obesity-related traits}}, doi = {10.1038/s41467-020-15107-0}, volume = {11}, year = {2020}, } @article{7708, abstract = {We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor.}, author = {Nabais, Marta F. and Lin, Tian and Benyamin, Beben and Williams, Kelly L. and Garton, Fleur C. and Vinkhuyzen, Anna A. E. and Zhang, Futao and Vallerga, Costanza L. and Restuadi, Restuadi and Freydenzon, Anna and Zwamborn, Ramona A. J. and Hop, Paul J. and Robinson, Matthew Richard and Gratten, Jacob and Visscher, Peter M. and Hannon, Eilis and Mill, Jonathan and Brown, Matthew A. and Laing, Nigel G. and Mather, Karen A. and Sachdev, Perminder S. and Ngo, Shyuan T. and Steyn, Frederik J. and Wallace, Leanne and Henders, Anjali K. and Needham, Merrilee and Veldink, Jan H. and Mathers, Susan and Nicholson, Garth and Rowe, Dominic B. and Henderson, Robert D. and McCombe, Pamela A. and Pamphlett, Roger and Yang, Jian and Blair, Ian P. and McRae, Allan F. and Wray, Naomi R.}, issn = {2056-7944}, journal = {npj Genomic Medicine}, publisher = {Springer Nature}, title = {{Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis}}, doi = {10.1038/s41525-020-0118-3}, volume = {5}, year = {2020}, } @article{7778, abstract = {Recent advances in synthetic posttranslational protein circuits are substantially impacting the landscape of cellular engineering and offer several advantages compared to traditional gene circuits. However, engineering dynamic phenomena such as oscillations in protein-level circuits remains an outstanding challenge. Few examples of biological posttranslational oscillators are known, necessitating theoretical progress to determine realizable oscillators. We construct mathematical models for two posttranslational oscillators, using few components that interact only through reversible binding and phosphorylation/dephosphorylation reactions. Our designed oscillators rely on the self-assembly of two protein species into multimeric functional enzymes that respectively inhibit and enhance this self-assembly. We limit our analysis to within experimental constraints, finding (i) significant portions of the restricted parameter space yielding oscillations and (ii) that oscillation periods can be tuned by several orders of magnitude using recent advances in computational protein design. Our work paves the way for the rational design and realization of protein-based dynamic systems.}, author = {Kimchi, Ofer and Goodrich, Carl Peter and Courbet, Alexis and Curatolo, Agnese I. and Woodall, Nicholas B. and Baker, David and Brenner, Michael P.}, journal = {Science Advances}, number = {51}, title = {{Self-assembly-based posttranslational protein oscillators}}, doi = {10.1126/sciadv.abc1939}, volume = {6}, year = {2020}, } @article{7788, abstract = {Mutations in NDUFS4, which encodes an accessory subunit of mitochondrial oxidative phosphorylation (OXPHOS) complex I (CI), induce Leigh syndrome (LS). LS is a poorly understood pediatric disorder featuring brain-specific anomalies and early death. To study the LS pathomechanism, we here compared OXPHOS proteomes between various Ndufs4−/− mouse tissues. Ndufs4−/− animals displayed significantly lower CI subunit levels in brain/diaphragm relative to other tissues (liver/heart/kidney/skeletal muscle), whereas other OXPHOS subunit levels were not reduced. Absence of NDUFS4 induced near complete absence of the NDUFA12 accessory subunit, a 50% reduction in other CI subunit levels, and an increase in specific CI assembly factors. Among the latter, NDUFAF2 was most highly increased. Regarding NDUFS4, NDUFA12 and NDUFAF2, identical results were obtained in Ndufs4−/− mouse embryonic fibroblasts (MEFs) and NDUFS4-mutated LS patient cells. Ndufs4−/− MEFs contained active CI in situ but blue-native-PAGE highlighted that NDUFAF2 attached to an inactive CI subcomplex (CI-830) and inactive assemblies of higher MW. In NDUFA12-mutated LS patient cells, NDUFA12 absence did not reduce NDUFS4 levels but triggered NDUFAF2 association to active CI. BN-PAGE revealed no such association in LS patient fibroblasts with mutations in other CI subunit-encoding genes where NDUFAF2 was attached to CI-830 (NDUFS1, NDUFV1 mutation) or not detected (NDUFS7 mutation). Supported by enzymological and CI in silico structural analysis, we conclude that absence of NDUFS4 induces near complete absence of NDUFA12 but not vice versa, and that NDUFAF2 stabilizes active CI in Ndufs4−/− mice and LS patient cells, perhaps in concert with mitochondrial inner membrane lipids.}, author = {Adjobo-Hermans, Merel J.W. and De Haas, Ria and Willems, Peter H.G.M. and Wojtala, Aleksandra and Van Emst-De Vries, Sjenet E. and Wagenaars, Jori A. and Van Den Brand, Mariel and Rodenburg, Richard J. and Smeitink, Jan A.M. and Nijtmans, Leo G. and Sazanov, Leonid A and Wieckowski, Mariusz R. and Koopman, Werner J.H.}, issn = {1879-2650}, journal = {Biochimica et Biophysica Acta - Bioenergetics}, number = {8}, publisher = {Elsevier}, title = {{NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4−/− mice and Leigh syndrome patients: A stabilizing role for NDUFAF2}}, doi = {10.1016/j.bbabio.2020.148213}, volume = {1861}, year = {2020}, }