@unpublished{7673, abstract = {Combining drugs can improve the efficacy of treatments. However, predicting the effect of drug combinations is still challenging. The combined potency of drugs determines the drug interaction, which is classified as synergistic, additive, antagonistic, or suppressive. While probabilistic, non-mechanistic models exist, there is currently no biophysical model that can predict antibiotic interactions. Here, we present a physiologically relevant model of the combined action of antibiotics that inhibit protein synthesis by targeting the ribosome. This model captures the kinetics of antibiotic binding and transport, and uses bacterial growth laws to predict growth in the presence of antibiotic combinations. We find that this biophysical model can produce all drug interaction types except suppression. We show analytically that antibiotics which cannot bind to the ribosome simultaneously generally act as substitutes for one another, leading to additive drug interactions. Previously proposed null expectations for higher-order drug interactions follow as a limiting case of our model. We further extend the model to include the effects of direct physical or allosteric interactions between individual drugs on the ribosome. Notably, such direct interactions profoundly change the combined drug effect, depending on the kinetic parameters of the drugs used. The model makes additional predictions for the effects of resistance genes on drug interactions and for interactions between ribosome-targeting antibiotics and antibiotics with other targets. These findings enhance our understanding of the interplay between drug action and cell physiology and are a key step toward a general framework for predicting drug interactions.}, author = {Kavcic, Bor and Tkačik, Gašper and Bollenbach, Tobias}, booktitle = {bioRxiv}, title = {{A minimal biophysical model of combined antibiotic action}}, doi = {10.1101/2020.04.18.047886}, year = {2020}, } @article{8532, abstract = {The molecular anatomy of synapses defines their characteristics in transmission and plasticity. Precise measurements of the number and distribution of synaptic proteins are important for our understanding of synapse heterogeneity within and between brain regions. Freeze–fracture replica immunogold electron microscopy enables us to analyze them quantitatively on a two-dimensional membrane surface. Here, we introduce Darea software, which utilizes deep learning for analysis of replica images and demonstrate its usefulness for quick measurements of the pre- and postsynaptic areas, density and distribution of gold particles at synapses in a reproducible manner. We used Darea for comparing glutamate receptor and calcium channel distributions between hippocampal CA3-CA1 spine synapses on apical and basal dendrites, which differ in signaling pathways involved in synaptic plasticity. We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA) receptors with size. Interestingly, AMPA and NMDA receptors are segregated within postsynaptic sites and negatively correlated in density among both apical and basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels show similar densities in apical and basal synapses with distributions consistent with an exclusion zone model of calcium channel-release site topography.}, author = {Kleindienst, David and Montanaro-Punzengruber, Jacqueline-Claire and Bhandari, Pradeep and Case, Matthew J and Fukazawa, Yugo and Shigemoto, Ryuichi}, issn = {1422-0067}, journal = {International Journal of Molecular Sciences}, number = {18}, publisher = {MDPI}, title = {{Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses}}, doi = {10.3390/ijms21186737}, volume = {21}, year = {2020}, } @article{7426, abstract = {This paper presents a novel abstraction technique for analyzing Lyapunov and asymptotic stability of polyhedral switched systems. A polyhedral switched system is a hybrid system in which the continuous dynamics is specified by polyhedral differential inclusions, the invariants and guards are specified by polyhedral sets and the switching between the modes do not involve reset of variables. A finite state weighted graph abstracting the polyhedral switched system is constructed from a finite partition of the state–space, such that the satisfaction of certain graph conditions, such as the absence of cycles with product of weights on the edges greater than (or equal) to 1, implies the stability of the system. However, the graph is in general conservative and hence, the violation of the graph conditions does not imply instability. If the analysis fails to establish stability due to the conservativeness in the approximation, a counterexample (cycle with product of edge weights greater than or equal to 1) indicating a potential reason for the failure is returned. Further, a more precise approximation of the switched system can be constructed by considering a finer partition of the state–space in the construction of the finite weighted graph. We present experimental results on analyzing stability of switched systems using the above method.}, author = {Garcia Soto, Miriam and Prabhakar, Pavithra}, issn = {1751-570X}, journal = {Nonlinear Analysis: Hybrid Systems}, number = {5}, publisher = {Elsevier}, title = {{Abstraction based verification of stability of polyhedral switched systems}}, doi = {10.1016/j.nahs.2020.100856}, volume = {36}, year = {2020}, } @article{8707, abstract = {Dynamic changes in the three-dimensional (3D) organization of chromatin are associated with central biological processes, such as transcription, replication and development. Therefore, the comprehensive identification and quantification of these changes is fundamental to understanding of evolutionary and regulatory mechanisms. Here, we present Comparison of Hi-C Experiments using Structural Similarity (CHESS), an algorithm for the comparison of chromatin contact maps and automatic differential feature extraction. We demonstrate the robustness of CHESS to experimental variability and showcase its biological applications on (1) interspecies comparisons of syntenic regions in human and mouse models; (2) intraspecies identification of conformational changes in Zelda-depleted Drosophila embryos; (3) patient-specific aberrant chromatin conformation in a diffuse large B-cell lymphoma sample; and (4) the systematic identification of chromatin contact differences in high-resolution Capture-C data. In summary, CHESS is a computationally efficient method for the comparison and classification of changes in chromatin contact data.}, author = { Galan, Silvia and Machnik, Nick N and Kruse, Kai and Díaz, Noelia and Marti-Renom, Marc A and Vaquerizas, Juan M}, issn = {1546-1718}, journal = {Nature Genetics}, pages = {1247--1255}, publisher = {Springer Nature}, title = {{CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction}}, doi = {10.1038/s41588-020-00712-y}, volume = {52}, year = {2020}, } @phdthesis{7680, abstract = {Proteins and their complex dynamic interactions regulate cellular mechanisms from sensing and transducing extracellular signals, to mediating genetic responses, and sustaining or changing cell morphology. To manipulate these protein-protein interactions (PPIs) that govern the behavior and fate of cells, synthetically constructed, genetically encoded tools provide the means to precisely target proteins of interest (POIs), and control their subcellular localization and activity in vitro and in vivo. Ideal synthetic tools react to an orthogonal cue, i.e. a trigger that does not activate any other endogenous process, thereby allowing manipulation of the POI alone. In optogenetics, naturally occurring photosensory domain from plants, algae and bacteria are re-purposed and genetically fused to POIs. Illumination with light of a specific wavelength triggers a conformational change that can mediate PPIs, such as dimerization or oligomerization. By using light as a trigger, these tools can be activated with high spatial and temporal precision, on subcellular and millisecond scales. Chemogenetic tools consist of protein domains that recognize and bind small molecules. By genetic fusion to POIs, these domains can mediate PPIs upon addition of their specific ligands, which are often synthetically designed to provide highly specific interactions and exhibit good bioavailability. Most optogenetic tools to mediate PPIs are based on well-studied photoreceptors responding to red, blue or near-UV light, leaving a striking gap in the green band of the visible light spectrum. Among both optogenetic and chemogenetic tools, there is an abundance of methods to induce PPIs, but tools to disrupt them require UV illumination, rely on covalent linkage and subsequent enzymatic cleavage or initially result in protein clustering of unknown stoichiometry. This work describes how the recently structurally and photochemically characterized green-light responsive cobalamin-binding domains (CBDs) from bacterial transcription factors were re-purposed to function as a green-light responsive optogenetic tool. In contrast to previously engineered optogenetic tools, CBDs do not induce PPI, but rather confer a PPI already upon expression, which can be rapidly disrupted by illumination. This was employed to mimic inhibition of constitutive activity of a growth factor receptor, and successfully implement for cell signalling in mammalian cells and in vivo to rescue development in zebrafish. This work further describes the development and application of a chemically induced de-dimerizer (CDD) based on a recently identified and structurally described bacterial oxyreductase. CDD forms a dimer upon expression in absence of its cofactor, the flavin derivative F420. Safety and of domain expression and ligand exposure are demonstrated in vitro and in vivo in zebrafish. The system is further applied to inhibit cell signalling output from a chimeric receptor upon F420 treatment. CBDs and CDD expand the repertoire of synthetic tools by providing novel mechanisms of mediating PPIs, and by recognizing previously not utilized cues. In the future, they can readily be combined with existing synthetic tools to functionally manipulate PPIs in vitro and in vivo.}, author = {Kainrath, Stephanie}, issn = {2663-337X}, pages = {98}, publisher = {Institute of Science and Technology Austria}, title = {{Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals}}, doi = {10.15479/AT:ISTA:7680}, year = {2020}, } @phdthesis{8620, abstract = {The development of the human brain occurs through a tightly regulated series of dynamic and adaptive processes during prenatal and postnatal life. A disruption of this strictly orchestrated series of events can lead to a number of neurodevelopmental conditions, including Autism Spectrum Disorders (ASDs). ASDs are a very common, etiologically and phenotypically heterogeneous group of disorders sharing the core symptoms of social interaction and communication deficits and restrictive and repetitive interests and behaviors. They are estimated to affect one in 59 individuals in the U.S. and, over the last three decades, mutations in more than a hundred genetic loci have been convincingly linked to ASD pathogenesis. Yet, for the vast majority of these ASD-risk genes their role during brain development and precise molecular function still remain elusive. De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin 3 (CUL3) lead to ASD. In the study described here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 heterozygous knockout mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3+/-, Cul3+/fl Emx1-Cre and Cul3fl/fl Emx1-Cre mutant brains display cortical lamination abnormalities due to defective migration of post-mitotic excitatory neurons, as well as reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal cortical organization, Cul3 heterozygous deletion is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level we show that Cul3 regulates cytoskeletal and adhesion protein abundance in the mouse embryonic cortex. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neural cells results in atypical organization of the actin mesh at the cell leading edge. Of note, heterozygous deletion of Cul3 in adult mice does not induce the majority of the behavioral defects observed in constitutive Cul3 haploinsufficient animals, pointing to a critical time-window for Cul3 deficiency. In conclusion, our data indicate that Cul3 plays a critical role in the regulation of cytoskeletal proteins and neuronal migration. ASD-associated defects and behavioral abnormalities are primarily due to dosage sensitive Cul3 functions at early brain developmental stages.}, author = {Morandell, Jasmin}, issn = {2663-337X}, pages = {138}, publisher = {Institute of Science and Technology Austria}, title = {{Illuminating the role of Cul3 in autism spectrum disorder pathogenesis}}, doi = {10.15479/AT:ISTA:8620}, year = {2020}, } @unpublished{7800, abstract = {De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages.}, author = {Morandell, Jasmin and Schwarz, Lena A and Basilico, Bernadette and Tasciyan, Saren and Nicolas, Armel and Sommer, Christoph M and Kreuzinger, Caroline and Knaus, Lisa and Dobler, Zoe and Cacci, Emanuele and Danzl, Johann G and Novarino, Gaia}, booktitle = {bioRxiv}, title = {{Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development}}, doi = {10.1101/2020.01.10.902064 }, year = {2020}, } @article{8131, abstract = {The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes.}, author = {Basilico, Bernadette and Morandell, Jasmin and Novarino, Gaia}, issn = {1879-0380}, journal = {Current Opinion in Genetics & Development}, number = {12}, pages = {126--137}, publisher = {Elsevier}, title = {{Molecular mechanisms for targeted ASD treatments}}, doi = {10.1016/j.gde.2020.06.004}, volume = {65}, year = {2020}, } @article{11059, abstract = {The genome is packaged and organized nonrandomly within the 3D space of the nucleus to promote efficient gene expression and to faithfully maintain silencing of heterochromatin. The genome is enclosed within the nucleus by the nuclear envelope membrane, which contains a set of proteins that actively participate in chromatin organization and gene regulation. Technological advances are providing views of genome organization at unprecedented resolution and are beginning to reveal the ways that cells co-opt the structures of the nuclear periphery for nuclear organization and gene regulation. These genome regulatory roles of proteins of the nuclear periphery have important influences on development, disease and ageing.}, author = {Buchwalter, Abigail and Kaneshiro, Jeanae M. and HETZER, Martin W}, issn = {1471-0064}, journal = {Nature Reviews Genetics}, keywords = {Genetics (clinical), Genetics, Molecular Biology}, number = {1}, pages = {39--50}, publisher = {Springer Nature}, title = {{Coaching from the sidelines: The nuclear periphery in genome regulation}}, doi = {10.1038/s41576-018-0063-5}, volume = {20}, year = {2019}, } @article{11060, abstract = {The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs.}, author = {Buchwalter, Abigail and Schulte, Roberta and Tsai, Hsiao and Capitanio, Juliana and HETZER, Martin W}, 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 = {{Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress}}, doi = {10.7554/elife.49796}, volume = {8}, year = {2019}, } @article{11061, abstract = {Many adult tissues contain postmitotic cells as old as the host organism. The only organelle that does not turn over in these cells is the nucleus, and its maintenance represents a formidable challenge, as it harbors regulatory proteins that persist throughout adulthood. Here we developed strategies to visualize two classes of such long-lived proteins, histones and nucleoporins, to understand the function of protein longevity in nuclear maintenance. Genome-wide mapping of histones revealed specific enrichment of long-lived variants at silent gene loci. Interestingly, nuclear pores are maintained by piecemeal replacement of subunits, resulting in mosaic complexes composed of polypeptides with vastly different ages. In contrast, nondividing quiescent cells remove old nuclear pores in an ESCRT-dependent manner. Our findings reveal distinct molecular strategies of nuclear maintenance, linking lifelong protein persistence to gene regulation and nuclear integrity.}, author = {Toyama, Brandon H. and Arrojo e Drigo, Rafael and Lev-Ram, Varda and Ramachandra, Ranjan and Deerinck, Thomas J. and Lechene, Claude and Ellisman, Mark H. and HETZER, Martin W}, issn = {1540-8140}, journal = {Journal of Cell Biology}, keywords = {Cell Biology}, number = {2}, pages = {433--444}, publisher = {Rockefeller University Press}, title = {{Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells}}, doi = {10.1083/jcb.201809123}, volume = {218}, year = {2019}, } @article{11062, abstract = {Most neurons are not replaced during an animal’s lifetime. This nondividing state is characterized by extreme longevity and age-dependent decline of key regulatory proteins. To study the lifespans of cells and proteins in adult tissues, we combined isotope labeling of mice with a hybrid imaging method (MIMS-EM). Using 15N mapping, we show that liver and pancreas are composed of cells with vastly different ages, many as old as the animal. Strikingly, we also found that a subset of fibroblasts and endothelial cells, both known for their replicative potential, are characterized by the absence of cell division during adulthood. In addition, we show that the primary cilia of beta cells and neurons contains different structural regions with vastly different lifespans. Based on these results, we propose that age mosaicism across multiple scales is a fundamental principle of adult tissue, cell, and protein complex organization.}, author = {Arrojo e Drigo, Rafael and Lev-Ram, Varda and Tyagi, Swati and Ramachandra, Ranjan and Deerinck, Thomas and Bushong, Eric and Phan, Sebastien and Orphan, Victoria and Lechene, Claude and Ellisman, Mark H. and HETZER, Martin W}, issn = {1550-4131}, journal = {Cell Metabolism}, keywords = {Cell Biology, Molecular Biology, Physiology}, number = {2}, pages = {343--351.e3}, publisher = {Elsevier}, title = {{Age mosaicism across multiple scales in adult tissues}}, doi = {10.1016/j.cmet.2019.05.010}, volume = {30}, year = {2019}, } @article{11499, abstract = {Deep optical spectroscopic surveys of galaxies provide a unique opportunity to investigate rest-frame ultra-violet (UV) emission line properties of galaxies at z ∼ 2 − 4.5. Here we combine VLT/MUSE Guaranteed Time Observations of the Hubble Deep Field South, Ultra Deep Field, COSMOS, and several quasar fields with other publicly available data from VLT/VIMOS and VLT/FORS2 to construct a catalogue of He II λ1640 emitters at z ≳ 2. The deepest areas of our MUSE pointings reach a 3σ line flux limit of 3.1 × 10−19 erg s−1 cm−2. After discarding broad-line active galactic nuclei, we find 13 He II λ1640 detections from MUSE with a median MUV = −20.1 and 21 tentative He II λ1640 detections from other public surveys. Excluding Lyα, all except two galaxies in our sample show at least one other rest-UV emission line, with C III] λ1907, λ1909 being the most prominent. We use multi-wavelength data available in the Hubble legacy fields to derive basic galaxy properties of our sample through spectral energy distribution fitting techniques. Taking advantage of the high-quality spectra obtained by MUSE (∼10 − 30 h of exposure time per pointing), we use photo-ionisation models to study the rest-UV emission line diagnostics of the He II λ1640 emitters. Line ratios of our sample can be reproduced by moderately sub-solar photo-ionisation models, however, we find that including effects of binary stars lead to degeneracies in most free parameters. Even after considering extra ionising photons produced by extreme sub-solar metallicity binary stellar models, photo-ionisation models are unable to reproduce rest-frame He II λ1640 equivalent widths (∼0.2 − 10 Å), thus additional mechanisms are necessary in models to match the observed He II λ1640 properties.}, author = {Nanayakkara, Themiya and Brinchmann, Jarle and Boogaard, Leindert and Bouwens, Rychard and Cantalupo, Sebastiano and Feltre, Anna and Kollatschny, Wolfram and Marino, Raffaella Anna and Maseda, Michael and Matthee, Jorryt J and Paalvast, Mieke and Richard, Johan and Verhamme, Anne}, issn = {1432-0746}, journal = {Astronomy & Astrophysics}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: ISM / galaxies: star formation / galaxies: evolution / galaxies: high-redshift}, publisher = {EDP Sciences}, title = {{Exploring He II λ1640 emission line properties at z ∼2−4}}, doi = {10.1051/0004-6361/201834565}, volume = {648}, year = {2019}, } @article{11505, abstract = {Contact. This paper presents the results obtained with the Multi-Unit Spectroscopic Explorer (MUSE) at the ESO Very Large Telescope on the faint end of the Lyman-alpha luminosity function (LF) based on deep observations of four lensing clusters. The goal of our project is to set strong constraints on the relative contribution of the Lyman-alpha emitter (LAE) population to cosmic reionization. Aims. The precise aim of the present study is to further constrain the abundance of LAEs by taking advantage of the magnification provided by lensing clusters to build a blindly selected sample of galaxies which is less biased than current blank field samples in redshift and luminosity. By construction, this sample of LAEs is complementary to those built from deep blank fields, whether observed by MUSE or by other facilities, and makes it possible to determine the shape of the LF at fainter levels, as well as its evolution with redshift. Methods. We selected a sample of 156 LAEs with redshifts between 2.9 ≤ z ≤ 6.7 and magnification-corrected luminosities in the range 39 ≲ log LLyα [erg s−1] ≲43. To properly take into account the individual differences in detection conditions between the LAEs when computing the LF, including lensing configurations, and spatial and spectral morphologies, the non-parametric 1/Vmax method was adopted. The price to pay to benefit from magnification is a reduction of the effective volume of the survey, together with a more complex analysis procedure to properly determine the effective volume Vmax for each galaxy. In this paper we present a complete procedure for the determination of the LF based on IFU detections in lensing clusters. This procedure, including some new methods for masking, effective volume integration and (individual) completeness determinations, has been fully automated when possible, and it can be easily generalized to the analysis of IFU observations in blank fields. Results. As a result of this analysis, the Lyman-alpha LF has been obtained in four different redshift bins: 2.9 <  z <  6, 7, 2.9 <  z <  4.0, 4.0 <  z <  5.0, and 5.0 <  z <  6.7 with constraints down to log LLyα = 40.5. From our data only, no significant evolution of LF mean slope can be found. When performing a Schechter analysis also including data from the literature to complete the present sample towards the brightest luminosities, a steep faint end slope was measured varying from α = −1.69−0.08+0.08 to α = −1.87−0.12+0.12 between the lowest and the highest redshift bins. Conclusions. The contribution of the LAE population to the star formation rate density at z ∼ 6 is ≲50% depending on the luminosity limit considered, which is of the same order as the Lyman-break galaxy (LBG) contribution. The evolution of the LAE contribution with redshift depends on the assumed escape fraction of Lyman-alpha photons, and appears to slightly increase with increasing redshift when this fraction is conservatively set to one. Depending on the intersection between the LAE/LBG populations, the contribution of the observed galaxies to the ionizing flux may suffice to keep the universe ionized at z ∼ 6.}, author = {de La Vieuville, G. and Bina, D. and Pello, R. and Mahler, G. and Richard, J. and Drake, A. B. and Herenz, E. C. and Bauer, F. E. and Clément, B. and Lagattuta, D. and Laporte, N. and Martinez, J. and Patrício, V. and Wisotzki, L. and Zabl, J. and Bouwens, R. J. and Contini, T. and Garel, T. and Guiderdoni, B. and Marino, R. A. and Maseda, M. V. and Matthee, Jorryt J and Schaye, J. and Soucail, G.}, issn = {1432-0746}, journal = {Astronomy & Astrophysics}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, gravitational lensing: strong / galaxies: high-redshift / dark ages, reionization, first stars / galaxies: clusters: general / galaxies: luminosity function, mass function}, publisher = {EDP Sciences}, title = {{Faint end of the z ∼ 3–7 luminosity function of Lyman-alpha emitters behind lensing clusters observed with MUSE}}, doi = {10.1051/0004-6361/201834471}, volume = {628}, year = {2019}, } @article{11507, abstract = {Lyman-α (Lyα) is intrinsically the brightest line emitted from active galaxies. While it originates from many physical processes, for star-forming galaxies the intrinsic Lyα luminosity is a direct tracer of the Lyman-continuum (LyC) radiation produced by the most massive O- and early-type B-stars (M⋆ ≳ 10 M⊙) with lifetimes of a few Myrs. As such, Lyα luminosity should be an excellent instantaneous star formation rate (SFR) indicator. However, its resonant nature and susceptibility to dust as a rest-frame UV photon makes Lyα very hard to interpret due to the uncertain Lyα escape fraction, fesc, Lyα. Here we explore results from the CAlibrating LYMan-α with Hα (CALYMHA) survey at z = 2.2, follow-up of Lyα emitters (LAEs) at z = 2.2 − 2.6 and a z ∼ 0−0.3 compilation of LAEs to directly measure fesc, Lyα with Hα. We derive a simple empirical relation that robustly retrieves fesc, Lyα as a function of Lyα rest-frame EW (EW0): fesc,Lyα = 0.0048 EW0[Å] ± 0.05 and we show that it constrains a well-defined anti-correlation between ionisation efficiency (ξion) and dust extinction in LAEs. Observed Lyα luminosities and EW0 are easy measurable quantities at high redshift, thus making our relation a practical tool to estimate intrinsic Lyα and LyC luminosities under well controlled and simple assumptions. Our results allow observed Lyα luminosities to be used to compute SFRs for LAEs at z ∼ 0−2.6 within ±0.2 dex of the Hα dust corrected SFRs. We apply our empirical SFR(Lyα,EW0) calibration to several sources at z ≥ 2.6 to find that star-forming LAEs have SFRs typically ranging from 0.1 to 20 M⊙ yr−1 and that our calibration might be even applicable for the most luminous LAEs within the epoch of re-ionisation. Our results imply high ionisation efficiencies (log10[ξion/Hz erg−1] = 25.4−25.6) and low dust content in LAEs across cosmic time, and will be easily tested with future observations with JWST which can obtain Hα and Hβ measurements for high-redshift LAEs.}, author = {Sobral, David and Matthee, Jorryt J}, issn = {1432-0746}, journal = {Astronomy & Astrophysics}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: high-redshift / galaxies: star formation / galaxies: statistics / galaxies: evolution / galaxies: formation / galaxies: ISM}, publisher = {EDP Sciences}, title = {{Predicting Lyα escape fractions with a simple observable: Lyα in emission as an empirically calibrated star formation rate indicator}}, doi = {10.1051/0004-6361/201833075}, volume = {623}, year = {2019}, } @article{11514, abstract = {We discuss the nature and physical properties of gas-mass selected galaxies in the ALMA spectroscopic survey (ASPECS) of the Hubble Ultra Deep Field (HUDF). We capitalize on the deep optical integral-field spectroscopy from the Multi Unit Spectroscopic Explorer (MUSE) HUDF Survey and multiwavelength data to uniquely associate all 16 line emitters, detected in the ALMA data without preselection, with rotational transitions of carbon monoxide (CO). We identify 10 as CO(2–1) at 1 < z < 2, 5 as CO(3–2) at 2 < z < 3, and 1 as CO(4–3) at z = 3.6. Using the MUSE data as a prior, we identify two additional CO(2–1) emitters, increasing the total sample size to 18. We infer metallicities consistent with (super-)solar for the CO-detected galaxies at z ≤ 1.5, motivating our choice of a Galactic conversion factor between CO luminosity and molecular gas mass for these galaxies. Using deep Chandra imaging of the HUDF, we determine an X-ray AGN fraction of 20% and 60% among the CO emitters at z ∼ 1.4 and z ∼ 2.6, respectively. Being a CO-flux-limited survey, ASPECS-LP detects molecular gas in galaxies on, above, and below the main sequence (MS) at z ∼ 1.4. For stellar masses ≥1010 (1010.5) ${M}_{\odot }$, we detect about 40% (50%) of all galaxies in the HUDF at 1 < z < 2 (2 < z < 3). The combination of ALMA and MUSE integral-field spectroscopy thus enables an unprecedented view of MS galaxies during the peak of galaxy formation.}, author = {Boogaard, Leindert A. and Decarli, Roberto and González-López, Jorge and van der Werf, Paul and Walter, Fabian and Bouwens, Rychard and Aravena, Manuel and Carilli, Chris and Bauer, Franz Erik and Brinchmann, Jarle and Contini, Thierry and Cox, Pierre and da Cunha, Elisabete and Daddi, Emanuele and Díaz-Santos, Tanio and Hodge, Jacqueline and Inami, Hanae and Ivison, Rob and Maseda, Michael and Matthee, Jorryt J and Oesch, Pascal and Popping, Gergö and Riechers, Dominik and Schaye, Joop and Schouws, Sander and Smail, Ian and Weiss, Axel and Wisotzki, Lutz and Bacon, Roland and Cortes, Paulo C. and Rix, Hans-Walter and Somerville, Rachel S. and Swinbank, Mark and Wagg, Jeff}, issn = {1538-4357}, journal = {The Astrophysical Journal}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {2}, publisher = {IOP Publishing}, title = {{The ALMA spectroscopic survey in the HUDF: Nature and physical properties of gas-mass selected galaxies using MUSE spectroscopy}}, doi = {10.3847/1538-4357/ab3102}, volume = {882}, year = {2019}, } @article{11515, abstract = {We present new deep ALMA and Hubble Space Telescope (HST)/WFC3 observations of MASOSA and VR7, two luminous Lyα emitters (LAEs) at z = 6.5, for which the UV continuum levels differ by a factor of four. No IR dust continuum emission is detected in either, indicating little amounts of obscured star formation and/or high dust temperatures. MASOSA, with a UV luminosity M1500 = −20.9, compact size, and very high Lyα ${\mathrm{EW}}_{0}\approx 145\,\mathring{\rm A} $, is undetected in [C ii] to a limit of L[C ii] < 2.2 × 107 L⊙, implying a metallicity Z ≲ 0.07 Z⊙. Intriguingly, our HST data indicate a red UV slope β = −1.1 ± 0.7, at odds with the low dust content. VR7, which is a bright (M1500 = −22.4) galaxy with moderate color (β = −1.4 ± 0.3) and Lyα EW0 = 34 Å, is clearly detected in [C ii] emission (S/N = 15). VR7's rest-frame UV morphology can be described by two components separated by ≈1.5 kpc and is globally more compact than the [C ii] emission. The global [C ii]/UV ratio indicates Z ≈ 0.2 Z⊙, but there are large variations in the UV/[C ii] ratio on kiloparsec scales. We also identify diffuse, possibly outflowing, [C ii]-emitting gas at ≈100 km s−1 with respect to the peak. VR7 appears to be assembling its components at a slightly more evolved stage than other luminous LAEs, with outflows already shaping its direct environment at z ∼ 7. Our results further indicate that the global [C ii]−UV relation steepens at SFR < 30 M⊙ yr−1, naturally explaining why the [C ii]/UV ratio is anticorrelated with Lyα EW in many, but not all, observed LAEs.}, author = {Matthee, Jorryt J and Sobral, D. and Boogaard, L. A. and Röttgering, H. and Vallini, L. and Ferrara, A. and Paulino-Afonso, A. and Boone, F. and Schaerer, D. and Mobasher, B.}, issn = {1538-4357}, journal = {The Astrophysical Journal}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {2}, publisher = {IOP Publishing}, title = {{Resolved UV and [C ii] structures of luminous galaxies within the epoch of reionization}}, doi = {10.3847/1538-4357/ab2f81}, volume = {881}, year = {2019}, } @article{11516, abstract = {The well-known quasar SDSS J095253.83+011421.9 (J0952+0114) at z = 3.02 has one of the most peculiar spectra discovered so far, showing the presence of narrow Lyα and broad metal emission lines. Although recent studies have suggested that a proximate damped Lyα absorption (PDLA) system causes this peculiar spectrum, the origin of the gas associated with the PDLA is unknown. Here we report the results of observations with the Multi Unit Spectroscopic Explorer (MUSE) that reveal a new giant (≈100 physical kpc) Lyα nebula. The detailed analysis of the Lyα velocity, velocity dispersion, and surface brightness profiles suggests that the J0952+0114 Lyα nebula shares similar properties with other QSO nebulae previously detected with MUSE, implying that the PDLA in J0952+0144 is covering only a small fraction of the solid angle of the QSO emission. We also detected bright and spectrally narrow C iv λ1550 and He ii λ1640 extended emission around J0952+0114 with velocity centroids similar to the peak of the extended and central narrow Lyα emission. The presence of a peculiarly bright, unresolved, and relatively broad He ii λ1640 emission in the central region at exactly the same PDLA redshift hints at the possibility that the PDLA originates in a clumpy outflow with a bulk velocity of about 500 km s−1. The smaller velocity dispersion of the large-scale Lyα emission suggests that the high-speed outflow is confined to the central region. Lastly, the derived spatially resolved He ii/Lyα and C iv/Lyα maps show a positive gradient with the distance to the QSO, hinting at a non-homogeneous distribution of the ionization parameter.}, author = {Marino, Raffaella Anna and Cantalupo, Sebastiano and Pezzulli, Gabriele and Lilly, Simon J. and Gallego, Sofia and Mackenzie, Ruari and Matthee, Jorryt J and Brinchmann, Jarle and Bouché, Nicolas and Feltre, Anna and Muzahid, Sowgat and Schroetter, Ilane and Johnson, Sean D. and Nanayakkara, Themiya}, issn = {1538-4357}, journal = {The Astrophysical Journal}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {1}, publisher = {IOP Publishing}, title = {{A giant Lyα nebula and a small-scale clumpy outflow in the system of the exotic quasar J0952+0114 unveiled by MUSE}}, doi = {10.3847/1538-4357/ab2881}, volume = {880}, year = {2019}, } @article{11517, abstract = {To understand star formation in galaxies, we investigate the star formation rate (SFR) surface density (ΣSFR) profiles for galaxies, based on a well-defined sample of 976 star-forming MaNGA galaxies. We find that the typical ΣSFR profiles within 1.5Re of normal SF galaxies can be well described by an exponential function for different stellar mass intervals, while the sSFR profile shows positive gradients, especially for more massive SF galaxies. This is due to the more pronounced central cores or bulges rather than the onset of a `quenching' process. While galaxies that lie significantly above (or below) the star formation main sequence (SFMS) show overall an elevation (or suppression) of ΣSFR at all radii, this central elevation (or suppression) is more pronounced in more massive galaxies. The degree of central enhancement and suppression is quite symmetric, suggesting that both the elevation and suppression of star formation are following the same physical processes. Furthermore, we find that the dispersion in ΣSFR within and across the population is found to be tightly correlated with the inferred gas depletion time, whether based on the stellar surface mass density or the orbital dynamical time. This suggests that we are seeing the response of a simple gas-regulator system to variations in the accretion rate. This is explored using a heuristic model that can quantitatively explain the dependence of σ(ΣSFR) on gas depletion timescale. Variations in accretion rate are progressively more damped out in regions of low star-formation efficiency leading to a reduced amplitude of variations in star-formation.}, author = {Wang, Enci and Lilly, Simon J. and Pezzulli, Gabriele and Matthee, Jorryt J}, issn = {1538-4357}, journal = {The Astrophysical Journal}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {2}, publisher = {IOP Publishing}, title = {{On the elevation and suppression of star formation within galaxies}}, doi = {10.3847/1538-4357/ab1c5b}, volume = {877}, year = {2019}, } @article{11535, abstract = {We investigate the clustering and halo properties of ∼5000 Ly α-selected emission-line galaxies (LAEs) from the Slicing COSMOS 4K (SC4K) and from archival NB497 imaging of SA22 split in 15 discrete redshift slices between z ∼ 2.5 and 6. We measure clustering lengths of r0 ∼ 3–6 h−1 Mpc and typical halo masses of ∼1011 M⊙ for our narrowband-selected LAEs with typical LLy α ∼ 1042–43 erg s−1. The intermediate-band-selected LAEs are observed to have r0 ∼ 3.5–15 h−1 Mpc with typical halo masses of ∼1011–12 M⊙ and typical LLy α ∼ 1043–43.6 erg s−1. We find a strong, redshift-independent correlation between halo mass and Ly α luminosity normalized by the characteristic Ly α luminosity, L⋆(z). The faintest LAEs (L ∼ 0.1 L⋆(z)) typically identified by deep narrowband surveys are found in 1010 M⊙ haloes and the brightest LAEs (L ∼ 7 L⋆(z)) are found in ∼5 × 1012 M⊙ haloes. A dependency on the rest-frame 1500 Å UV luminosity, MUV, is also observed where the halo masses increase from 1011 to 1013 M⊙ for MUV ∼ −19 to −23.5 mag. Halo mass is also observed to increase from 109.8 to 1012 M⊙ for dust-corrected UV star formation rates from ∼0.6 to 10 M⊙ yr−1 and continues to increase up to 1013 M⊙ in halo mass, where the majority of those sources are active galactic nuclei. All the trends we observe are found to be redshift independent. Our results reveal that LAEs are the likely progenitors of a wide range of galaxies depending on their luminosity, from dwarf-like, to Milky Way-type, to bright cluster galaxies. LAEs therefore provide unique insight into the early formation and evolution of the galaxies we observe in the local Universe.}, author = {Khostovan, A A and Sobral, D and Mobasher, B and Matthee, Jorryt J and Cochrane, R K and Chartab, N and Jafariyazani, M and Paulino-Afonso, A and Santos, S and Calhau, J}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: evolution, galaxies: haloes, galaxies: high-redshift, galaxies: star formation, cosmology: observations, large-scale structure of Universe}, number = {1}, pages = {555--573}, publisher = {Oxford University Press}, title = {{The clustering of typical Ly α emitters from z ∼ 2.5–6: Host halo masses depend on Ly α and UV luminosities}}, doi = {10.1093/mnras/stz2149}, volume = {489}, year = {2019}, }