@article{12157,
abstract = {Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on the effect sizes of loci that contribute to variance in the trait, and characterize the allele dynamics at these loci. Notably, we describe the two phases of the allele dynamics: The first is a rapid phase, in which directional selection introduces small frequency differences between alleles whose effects are aligned with or opposed to the shift, ultimately leading to small differences in their probability of fixation during a second, longer phase, governed by stabilizing selection. As we discuss, key results should hold in more general settings and have important implications for efforts to identify the genetic basis of adaptation in humans and other species.},
author = {Hayward, Laura and Sella, Guy},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Polygenic adaptation after a sudden change in environment}},
doi = {10.7554/elife.66697},
volume = {11},
year = {2022},
}
@article{12208,
abstract = {The inadequate understanding of the mechanisms that reversibly convert molecular sulfur (S) into lithium sulfide (Li2S) via soluble polysulfides (PSs) formation impedes the development of high-performance lithium-sulfur (Li-S) batteries with non-aqueous electrolyte solutions. Here, we use operando small and wide angle X-ray scattering and operando small angle neutron scattering (SANS) measurements to track the nucleation, growth and dissolution of solid deposits from atomic to sub-micron scales during real-time Li-S cell operation. In particular, stochastic modelling based on the SANS data allows quantifying the nanoscale phase evolution during battery cycling. We show that next to nano-crystalline Li2S the deposit comprises solid short-chain PSs particles. The analysis of the experimental data suggests that initially, Li2S2 precipitates from the solution and then is partially converted via solid-state electroreduction to Li2S. We further demonstrate that mass transport, rather than electron transport through a thin passivating film, limits the discharge capacity and rate performance in Li-S cells.},
author = {Prehal, Christian and von Mentlen, Jean-Marc and Drvarič Talian, Sara and Vizintin, Alen and Dominko, Robert and Amenitsch, Heinz and Porcar, Lionel and Freunberger, Stefan Alexander and Wood, Vanessa},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
publisher = {Springer Nature},
title = {{On the nanoscale structural evolution of solid discharge products in lithium-sulfur batteries using operando scattering}},
doi = {10.1038/s41467-022-33931-4},
volume = {13},
year = {2022},
}
@article{12217,
abstract = {The development dynamics and self-organization of glandular branched epithelia is of utmost importance for our understanding of diverse processes ranging from normal tissue growth to the growth of cancerous tissues. Using single primary murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix and adapted media supplementation, we generate organoids that self-organize into highly branched structures displaying a seamless lumen connecting terminal end buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis phases, each characterized by a unique pattern of cell invasion, matrix deformation, protein expression, and respective molecular dependencies. We propose a minimal theoretical model of a branching and proliferating tissue, capturing the dynamics of the first phases. Observing the interaction of morphogenesis, mechanical environment and gene expression in vitro sets a benchmark for the understanding of self-organization processes governing complex organoid structure formation processes and branching morphogenesis.},
author = {Randriamanantsoa, S. and Papargyriou, A. and Maurer, H. C. and Peschke, K. and Schuster, M. and Zecchin, G. and Steiger, K. and Öllinger, R. and Saur, D. and Scheel, C. and Rad, R. and Hannezo, Edouard B and Reichert, M. and Bausch, A. R.},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
publisher = {Springer Nature},
title = {{Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids}},
doi = {10.1038/s41467-022-32806-y},
volume = {13},
year = {2022},
}
@article{12224,
abstract = {Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine Mkln1 knockout causes non-habituating locomotor activity, increased exploratory drive, and decreased locomotor response to amphetamine. Muskelin deficiency impairs social novelty detection while promoting the retention of spatial reference memory and fear extinction recall. This is strongly mirrored in either weaker or stronger resting-state functional connectivity between critical circuits mediating locomotor exploration and cognition. We show that Mkln1 deletion alters dendrite branching and spine structure, coinciding with enhanced AMPAR-mediated synaptic transmission but selective impairment in synaptic potentiation maintenance. We identify muskelin at excitatory synapses and highlight its role in regulating dendritic spine actin stability. Our findings point to aberrant spine actin modulation and changes in glutamatergic synaptic function as critical mechanisms that contribute to the neurobehavioral phenotype arising from Mkln1 ablation.},
author = {Muhia, Mary W and YuanXiang, PingAn and Sedlacik, Jan and Schwarz, Jürgen R. and Heisler, Frank F. and Gromova, Kira V. and Thies, Edda and Breiden, Petra and Pechmann, Yvonne and Kreutz, Michael R. and Kneussel, Matthias},
issn = {2399-3642},
journal = {Communications Biology},
keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Medicine (miscellaneous)},
publisher = {Springer Nature},
title = {{Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes}},
doi = {10.1038/s42003-022-03446-1},
volume = {5},
year = {2022},
}
@article{12238,
abstract = {Upon the initiation of collective cell migration, the cells at the free edge are specified as leader cells; however, the mechanism underlying the leader cell specification remains elusive. Here, we show that lamellipodial extension after the release from mechanical confinement causes sustained extracellular signal-regulated kinase (ERK) activation and underlies the leader cell specification. Live-imaging of Madin-Darby canine kidney (MDCK) cells and mouse epidermis through the use of Förster resonance energy transfer (FRET)-based biosensors showed that leader cells exhibit sustained ERK activation in a hepatocyte growth factor (HGF)-dependent manner. Meanwhile, follower cells exhibit oscillatory ERK activation waves in an epidermal growth factor (EGF) signaling-dependent manner. Lamellipodial extension at the free edge increases the cellular sensitivity to HGF. The HGF-dependent ERK activation, in turn, promotes lamellipodial extension, thereby forming a positive feedback loop between cell extension and ERK activation and specifying the cells at the free edge as the leader cells. Our findings show that the integration of physical and biochemical cues underlies the leader cell specification during collective cell migration.},
author = {Hino, Naoya and Matsuda, Kimiya and Jikko, Yuya and Maryu, Gembu and Sakai, Katsuya and Imamura, Ryu and Tsukiji, Shinya and Aoki, Kazuhiro and Terai, Kenta and Hirashima, Tsuyoshi and Trepat, Xavier and Matsuda, Michiyuki},
issn = {1534-5807},
journal = {Developmental Cell},
keywords = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology},
number = {19},
pages = {2290--2304.e7},
publisher = {Elsevier},
title = {{A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration}},
doi = {10.1016/j.devcel.2022.09.003},
volume = {57},
year = {2022},
}
@article{12261,
abstract = {Dose–response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole-cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose–response curves. The shape of the dose–response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose–response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose–response curve of the antibiotic trimethoprim is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose–response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth-mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance.},
author = {Angermayr, Andreas and Pang, Tin Yau and Chevereau, Guillaume and Mitosch, Karin and Lercher, Martin J and Bollenbach, Mark Tobias},
issn = {1744-4292},
journal = {Molecular Systems Biology},
keywords = {Applied Mathematics, Computational Theory and Mathematics, General Agricultural and Biological Sciences, General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, Information Systems},
number = {9},
publisher = {Embo Press},
title = {{Growth‐mediated negative feedback shapes quantitative antibiotic response}},
doi = {10.15252/msb.202110490},
volume = {18},
year = {2022},
}
@article{12288,
abstract = {To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo.},
author = {Sumser, Anton L and Jösch, Maximilian A and Jonas, Peter M and Ben Simon, Yoav},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling}},
doi = {10.7554/elife.79848},
volume = {11},
year = {2022},
}
@article{12670,
abstract = {DNA methylation plays essential homeostatic functions in eukaryotic genomes. In animals, DNA methylation is also developmentally regulated and, in turn, regulates development. In the past two decades, huge research effort has endorsed the understanding that DNA methylation plays a similar role in plant development, especially during sexual reproduction. The power of whole-genome sequencing and cell isolation techniques, as well as bioinformatics tools, have enabled recent studies to reveal dynamic changes in DNA methylation during germline development. Furthermore, the combination of these technological advances with genetics, developmental biology and cell biology tools has revealed functional methylation reprogramming events that control gene and transposon activities in flowering plant germlines. In this review, we discuss the major advances in our knowledge of DNA methylation dynamics during male and female germline development in flowering plants.},
author = {He, Shengbo and Feng, Xiaoqi},
issn = {1744-7909},
journal = {Journal of Integrative Plant Biology},
keywords = {Plant Science, General Biochemistry, Genetics and Molecular Biology, Biochemistry},
number = {12},
pages = {2240--2251},
publisher = {Wiley},
title = {{DNA methylation dynamics during germline development}},
doi = {10.1111/jipb.13422},
volume = {64},
year = {2022},
}
@article{10834,
abstract = {Hematopoietic-specific protein 1 (Hem1) is an essential subunit of the WAVE regulatory complex (WRC) in immune cells. WRC is crucial for Arp2/3 complex activation and the protrusion of branched actin filament networks. Moreover, Hem1 loss of function in immune cells causes autoimmune diseases in humans. Here, we show that genetic removal of Hem1 in macrophages diminishes frequency and efficacy of phagocytosis as well as phagocytic cup formation in addition to defects in lamellipodial protrusion and migration. Moreover, Hem1-null macrophages displayed strong defects in cell adhesion despite unaltered podosome formation and concomitant extracellular matrix degradation. Specifically, dynamics of both adhesion and de-adhesion as well as concomitant phosphorylation of paxillin and focal adhesion kinase (FAK) were significantly compromised. Accordingly, disruption of WRC function in non-hematopoietic cells coincided with both defects in adhesion turnover and altered FAK and paxillin phosphorylation. Consistently, platelets exhibited reduced adhesion and diminished integrin αIIbβ3 activation upon WRC removal. Interestingly, adhesion phenotypes, but not lamellipodia formation, were partially rescued by small molecule activation of FAK. A full rescue of the phenotype, including lamellipodia formation, required not only the presence of WRCs but also their binding to and activation by Rac. Collectively, our results uncover that WRC impacts on integrin-dependent processes in a FAK-dependent manner, controlling formation and dismantling of adhesions, relevant for properly grabbing onto extracellular surfaces and particles during cell edge expansion, like in migration or phagocytosis.},
author = {Stahnke, Stephanie and Döring, Hermann and Kusch, Charly and de Gorter, David J.J. and Dütting, Sebastian and Guledani, Aleks and Pleines, Irina and Schnoor, Michael and Sixt, Michael K and Geffers, Robert and Rohde, Manfred and Müsken, Mathias and Kage, Frieda and Steffen, Anika and Faix, Jan and Nieswandt, Bernhard and Rottner, Klemens and Stradal, Theresia E.B.},
issn = {0960-9822},
journal = {Current Biology},
keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology},
number = {10},
pages = {2051--2064.e8},
publisher = {Elsevier},
title = {{Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion}},
doi = {10.1016/j.cub.2021.02.043},
volume = {31},
year = {2021},
}
@article{11052,
abstract = {In order to combat molecular damage, most cellular proteins undergo rapid turnover. We have previously identified large nuclear protein assemblies that can persist for years in post-mitotic tissues and are subject to age-related decline. Here, we report that mitochondria can be long lived in the mouse brain and reveal that specific mitochondrial proteins have half-lives longer than the average proteome. These mitochondrial long-lived proteins (mitoLLPs) are core components of the electron transport chain (ETC) and display increased longevity in respiratory supercomplexes. We find that COX7C, a mitoLLP that forms a stable contact site between complexes I and IV, is required for complex IV and supercomplex assembly. Remarkably, even upon depletion of COX7C transcripts, ETC function is maintained for days, effectively uncoupling mitochondrial function from ongoing transcription of its mitoLLPs. Our results suggest that modulating protein longevity within the ETC is critical for mitochondrial proteome maintenance and the robustness of mitochondrial function.},
author = {Krishna, Shefali and Arrojo e Drigo, Rafael and Capitanio, Juliana S. and Ramachandra, Ranjan and Ellisman, Mark and HETZER, Martin W},
issn = {1534-5807},
journal = {Developmental Cell},
keywords = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology},
number = {21},
pages = {P2952--2965.e9},
publisher = {Elsevier},
title = {{Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain}},
doi = {10.1016/j.devcel.2021.10.008},
volume = {56},
year = {2021},
}
@article{13356,
abstract = {Self-assembly of nanoparticles can be mediated by polymers, but has so far led almost exclusively to nanoparticle aggregates that are amorphous. Here, we employed Coulombic interactions to generate a range of composite materials from mixtures of charged nanoparticles and oppositely charged polymers. The assembly behavior of these nanoparticle/polymer composites depends on their order of addition: polymers added to nanoparticles give rise to stable aggregates, but nanoparticles added to polymers disassemble the initially formed aggregates. The amorphous aggregates were transformed into crystalline ones by transiently increasing the ionic strength of the solution. The morphology of the resulting crystals depended on the length of the polymer: short polymer chains mediated the self-assembly of nanoparticles into strongly faceted crystals, whereas long chains led to pseudospherical nanoparticle/polymer assemblies, within which the crystalline order of nanoparticles was retained.},
author = {Bian, Tong and Klajn, Rafal},
issn = {1749-6632},
journal = {Annals of the New York Academy of Sciences},
keywords = {History and Philosophy of Science, General Biochemistry, Genetics and Molecular Biology, General Neuroscience},
number = {1},
pages = {191--201},
publisher = {Wiley},
title = {{Morphology control in crystalline nanoparticle–polymer aggregates}},
doi = {10.1111/nyas.14674},
volume = {1505},
year = {2021},
}
@article{9387,
abstract = {We report the complete analysis of a deterministic model of deleterious mutations and negative selection against them at two haploid loci without recombination. As long as mutation is a weaker force than selection, mutant alleles remain rare at the only stable equilibrium, and otherwise, a variety of dynamics are possible. If the mutation-free genotype is absent, generally the only stable equilibrium is the one that corresponds to fixation of the mutant allele at the locus where it is less deleterious. This result suggests that fixation of a deleterious allele that follows a click of the Muller’s ratchet is governed by natural selection, instead of random drift.},
author = {Khudiakova, Kseniia and Neretina, Tatiana Yu. and Kondrashov, Alexey S.},
issn = {0022-5193},
journal = {Journal of Theoretical Biology},
keywords = {General Biochemistry, Genetics and Molecular Biology, Modelling and Simulation, Statistics and Probability, General Immunology and Microbiology, Applied Mathematics, General Agricultural and Biological Sciences, General Medicine},
publisher = {Elsevier },
title = {{Two linked loci under mutation-selection balance and Muller’s ratchet}},
doi = {10.1016/j.jtbi.2021.110729},
volume = {524},
year = {2021},
}
@article{9429,
abstract = {De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs.},
author = {Morandell, Jasmin and Schwarz, Lena A and Basilico, Bernadette and Tasciyan, Saren and Dimchev, Georgi A and Nicolas, Armel and Sommer, Christoph M and Kreuzinger, Caroline and Dotter, Christoph and Knaus, Lisa and Dobler, Zoe and Cacci, Emanuele and Schur, Florian KM and Danzl, Johann G and Novarino, Gaia},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {1},
publisher = {Springer Nature},
title = {{Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development}},
doi = {10.1038/s41467-021-23123-x},
volume = {12},
year = {2021},
}
@article{9431,
abstract = {Inositol hexakisphosphate (IP6) is an assembly cofactor for HIV-1. We report here that IP6 is also used for assembly of Rous sarcoma virus (RSV), a retrovirus from a different genus. IP6 is ~100-fold more potent at promoting RSV mature capsid protein (CA) assembly than observed for HIV-1 and removal of IP6 in cells reduces infectivity by 100-fold. Here, visualized by cryo-electron tomography and subtomogram averaging, mature capsid-like particles show an IP6-like density in the CA hexamer, coordinated by rings of six lysines and six arginines. Phosphate and IP6 have opposing effects on CA in vitro assembly, inducing formation of T = 1 icosahedrons and tubes, respectively, implying that phosphate promotes pentamer and IP6 hexamer formation. Subtomogram averaging and classification optimized for analysis of pleomorphic retrovirus particles reveal that the heterogeneity of mature RSV CA polyhedrons results from an unexpected, intrinsic CA hexamer flexibility. In contrast, the CA pentamer forms rigid units organizing the local architecture. These different features of hexamers and pentamers determine the structural mechanism to form CA polyhedrons of variable shape in mature RSV particles.},
author = {Obr, Martin and Ricana, Clifton L. and Nikulin, Nadia and Feathers, Jon-Philip R. and Klanschnig, Marco and Thader, Andreas and Johnson, Marc C. and Vogt, Volker M. and Schur, Florian KM and Dick, Robert A.},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry},
number = {1},
publisher = {Nature Research},
title = {{Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer}},
doi = {10.1038/s41467-021-23506-0},
volume = {12},
year = {2021},
}
@article{9540,
abstract = {The hexameric AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis and initiates cytoplasmic maturation of the large ribosomal subunit by releasing the shuttling maturation factor Rlp24. Drg1 monomers contain two AAA-domains (D1 and D2) that act in a concerted manner. Rlp24 release is inhibited by the drug diazaborine which blocks ATP hydrolysis in D2. The mode of inhibition was unknown. Here we show the first cryo-EM structure of Drg1 revealing the inhibitory mechanism. Diazaborine forms a covalent bond to the 2′-OH of the nucleotide in D2, explaining its specificity for this site. As a consequence, the D2 domain is locked in a rigid, inactive state, stalling the whole Drg1 hexamer. Resistance mechanisms identified include abolished drug binding and altered positioning of the nucleotide. Our results suggest nucleotide-modifying compounds as potential novel inhibitors for AAA-ATPases.},
author = {Prattes, Michael and Grishkovskaya, Irina and Hodirnau, Victor-Valentin and Rössler, Ingrid and Klein, Isabella and Hetzmannseder, Christina and Zisser, Gertrude and Gruber, Christian C. and Gruber, Karl and Haselbach, David and Bergler, Helmut},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry},
number = {1},
publisher = {Springer Nature},
title = {{Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine}},
doi = {10.1038/s41467-021-23854-x},
volume = {12},
year = {2021},
}
@article{10163,
abstract = {The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay.},
author = {Appel, Lisa-Marie and Franke, Vedran and Bruno, Melania and Grishkovskaya, Irina and Kasiliauskaite, Aiste and Kaufmann, Tanja and Schoeberl, Ursula E. and Puchinger, Martin G. and Kostrhon, Sebastian and Ebenwaldner, Carmen and Sebesta, Marek and Beltzung, Etienne and Mechtler, Karl and Lin, Gen and Vlasova, Anna and Leeb, Martin and Pavri, Rushad and Stark, Alexander and Akalin, Altuna and Stefl, Richard and Bernecky, Carrie A and Djinovic-Carugo, Kristina and Slade, Dea},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {general physics and astronomy, general biochemistry, genetics and molecular biology, general chemistry},
number = {1},
publisher = {Springer Nature},
title = {{PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC}},
doi = {10.1038/s41467-021-26360-2},
volume = {12},
year = {2021},
}
@article{10301,
abstract = {De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement.},
author = {Conde-Dusman, María J and Dey, Partha N and Elía-Zudaire, Óscar and Garcia Rabaneda, Luis E and García-Lira, Carmen and Grand, Teddy and Briz, Victor and Velasco, Eric R and Andero Galí, Raül and Niñerola, Sergio and Barco, Angel and Paoletti, Pierre and Wesseling, John F and Gardoni, Fabrizio and Tavalin, Steven J and Perez-Otaño, Isabel},
issn = {2050-084X},
journal = {eLife},
keywords = {general immunology and microbiology, general biochemistry, genetics and molecular biology, general medicine, general neuroscience},
publisher = {eLife Sciences Publications},
title = {{Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly}},
doi = {10.7554/elife.71575},
volume = {10},
year = {2021},
}
@article{10310,
abstract = {A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700.},
author = {Çoruh, Mehmet Orkun and Frank, Anna and Tanaka, Hideaki and Kawamoto, Akihiro and El-Mohsnawy, Eithar and Kato, Takayuki and Namba, Keiichi and Gerle, Christoph and Nowaczyk, Marc M. and Kurisu, Genji},
issn = {2399-3642},
journal = {Communications Biology},
keywords = {general agricultural and biological Sciences, general biochemistry, genetics and molecular biology, medicine (miscellaneous)},
number = {1},
publisher = {Springer },
title = {{Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster}},
doi = {10.1038/s42003-021-01808-9},
volume = {4},
year = {2021},
}
@article{12585,
abstract = {Glaciers in High Mountain Asia generate meltwater that supports the water needs of 250 million people, but current knowledge of annual accumulation and ablation is limited to sparse field measurements biased in location and glacier size. Here, we present altitudinally-resolved specific mass balances (surface, internal, and basal combined) for 5527 glaciers in High Mountain Asia for 2000–2016, derived by correcting observed glacier thinning patterns for mass redistribution due to ice flow. We find that 41% of glaciers accumulated mass over less than 20% of their area, and only 60% ± 10% of regional annual ablation was compensated by accumulation. Even without 21st century warming, 21% ± 1% of ice volume will be lost by 2100 due to current climatic-geometric imbalance, representing a reduction in glacier ablation into rivers of 28% ± 1%. The ablation of glaciers in the Himalayas and Tien Shan was mostly unsustainable and ice volume in these regions will reduce by at least 30% by 2100. The most important and vulnerable glacier-fed river basins (Amu Darya, Indus, Syr Darya, Tarim Interior) were supplied with >50% sustainable glacier ablation but will see long-term reductions in ice mass and glacier meltwater supply regardless of the Karakoram Anomaly.},
author = {Miles, Evan and McCarthy, Michael and Dehecq, Amaury and Kneib, Marin and Fugger, Stefan and Pellicciotti, Francesca},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
publisher = {Springer Nature},
title = {{Health and sustainability of glaciers in High Mountain Asia}},
doi = {10.1038/s41467-021-23073-4},
volume = {12},
year = {2021},
}
@article{9778,
abstract = {The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses.},
author = {Vandael, David H and Okamoto, Yuji and Jonas, Peter M},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {general physics and astronomy, general biochemistry, genetics and molecular biology, general chemistry},
number = {1},
publisher = {Springer},
title = {{Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses}},
doi = {10.1038/s41467-021-23153-5},
volume = {12},
year = {2021},
}