515 research outputs found
Temporally divergent regulatory mechanisms govern neuronal diversification and maturation in the mouse and marmoset neocortex
Mammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. Cortical neurons are born during embryonic development, and their maturation extends into postnatal life. The regulatory strategies underlying progressive neuronal development and maturation remain unclear. Here we present an integrated single-cell epigenomic and transcriptional analysis of individual mouse and marmoset cortical neuron classes, spanning both early postmitotic stages of identity acquisition and later stages of neuronal plasticity and circuit integration. We found that, in both species, the regulatory strategies controlling early and late stages of pan-neuronal development diverge. Early postmitotic neurons use more widely shared and evolutionarily conserved molecular regulatory programs. In contrast, programs active during later neuronal maturation are more brain- and neuron-specific and more evolutionarily divergent. Our work uncovers a temporal shift in regulatory choices during neuronal diversification and maturation in both mice and marmosets, which likely reflects unique evolutionary constraints on distinct events of neuronal development in the neocortex. The mechanisms underlying neuron specification and maturation are unclear. Here the authors provide an integrated epigenomic and transcriptomic analysis of mouse and marmoset neocortical neuronal classes. Pan-neuronal programs active during early development are more evolutionary conserved but not neuron-specific, whereas pan-neuronal programs active during later stages of maturation are more neuron- and species-specific
Direct Formation of Supermassive Black Holes via Multi-Scale Gas Inflows in Galaxy Mergers
Observations of distant bright quasars suggest that billion solar mass
supermassive black holes (SMBHs) were already in place less than a billion
years after the Big Bang. Models in which light black hole seeds form by the
collapse of primordial metal-free stars cannot explain their rapid appearance
due to inefficient gas accretion. Alternatively, these black holes may form by
direct collapse of gas at the center of protogalaxies. However, this requires
metal-free gas that does not cool efficiently and thus is not turned into
stars, in contrast with the rapid metal enrichment of protogalaxies. Here we
use a numerical simulation to show that mergers between massive protogalaxies
naturally produce the required central gas accumulation with no need to
suppress star formation. Merger-driven gas inflows produce an unstable, massive
nuclear gas disk. Within the disk a second gas inflow accumulates more than 100
million solar masses of gas in a sub-parsec scale cloud in one hundred thousand
years. The cloud undergoes gravitational collapse, which eventually leads to
the formation of a massive black hole. The black hole can grow to a billion
solar masses in less than a billion years by accreting gas from the surrounding
disk.Comment: 26 pages, 4 Figures, submitted to Nature (includes Supplementary
Information
Accreting Black Holes
This chapter provides a general overview of the theory and observations of
black holes in the Universe and on their interpretation. We briefly review the
black hole classes, accretion disk models, spectral state classification, the
AGN classification, and the leading techniques for measuring black hole spins.
We also introduce quasi-periodic oscillations, the shadow of black holes, and
the observations and the theoretical models of jets.Comment: 41 pages, 18 figures. To appear in "Tutorial Guide to X-ray and
Gamma-ray Astronomy: Data Reduction and Analysis" (Ed. C. Bambi, Springer
Singapore, 2020). v3: fixed some typos and updated some parts. arXiv admin
note: substantial text overlap with arXiv:1711.1025
Formation of Supermassive Black Holes
Evidence shows that massive black holes reside in most local galaxies.
Studies have also established a number of relations between the MBH mass and
properties of the host galaxy such as bulge mass and velocity dispersion. These
results suggest that central MBHs, while much less massive than the host (~
0.1%), are linked to the evolution of galactic structure. In hierarchical
cosmologies, a single big galaxy today can be traced back to the stage when it
was split up in hundreds of smaller components. Did MBH seeds form with the
same efficiency in small proto-galaxies, or did their formation had to await
the buildup of substantial galaxies with deeper potential wells? I briefly
review here some of the physical processes that are conducive to the evolution
of the massive black hole population. I will discuss black hole formation
processes for `seed' black holes that are likely to place at early cosmic
epochs, and possible observational tests of these scenarios.Comment: To appear in The Astronomy and Astrophysics Review. The final
publication is available at http://www.springerlink.co
The Formation of the First Massive Black Holes
Supermassive black holes (SMBHs) are common in local galactic nuclei, and
SMBHs as massive as several billion solar masses already exist at redshift z=6.
These earliest SMBHs may grow by the combination of radiation-pressure-limited
accretion and mergers of stellar-mass seed BHs, left behind by the first
generation of metal-free stars, or may be formed by more rapid direct collapse
of gas in rare special environments where dense gas can accumulate without
first fragmenting into stars. This chapter offers a review of these two
competing scenarios, as well as some more exotic alternative ideas. It also
briefly discusses how the different models may be distinguished in the future
by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First
Galaxies - Theoretical Predictions and Observational Clues", Springer
Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B.
Mobasher, in pres
Gene co-regulation by Fezf2 selects neurotransmitter identity and connectivity of corticospinal neurons
The neocortex contains an unparalleled diversity of neuronal subtypes, each defined by distinct traits that are developmentally acquired under the control of subtype-specific and pan-neuronal genes. The regulatory logic that orchestrates the expression of these unique combinations of genes is unknown for any class of cortical neuron. Here, we report that Fezf2 is a selector gene able to regulate the expression of gene sets that collectively define mouse corticospinal motor neurons (CSMN). We find that Fezf2 directly induces the glutamatergic identity of CSMN via activation of Vglut1 (Slc17a7) and inhibits a GABAergic fate by repressing transcription of Gad1. In addition, we identify the axon guidance receptor EphB1 as a target of Fezf2 necessary to execute the ipsilateral extension of the corticospinal tract. Our data indicate that co-regulated expression of neuron subtypeâspecific and pan-neuronal gene batteries by a single transcription factor is one component of the regulatory logic responsible for the establishment of CSMN identity
Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at = 5.02 TeV
Two-particle angular correlations between unidentified charged trigger and
associated particles are measured by the ALICE detector in p-Pb collisions at a
nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum
range 0.7 5.0 GeV/ is examined,
to include correlations induced by jets originating from low
momen\-tum-transfer scatterings (minijets). The correlations expressed as
associated yield per trigger particle are obtained in the pseudorapidity range
. The near-side long-range pseudorapidity correlations observed in
high-multiplicity p-Pb collisions are subtracted from both near-side
short-range and away-side correlations in order to remove the non-jet-like
components. The yields in the jet-like peaks are found to be invariant with
event multiplicity with the exception of events with low multiplicity. This
invariance is consistent with the particles being produced via the incoherent
fragmentation of multiple parton--parton scatterings, while the yield related
to the previously observed ridge structures is not jet-related. The number of
uncorrelated sources of particle production is found to increase linearly with
multiplicity, suggesting no saturation of the number of multi-parton
interactions even in the highest multiplicity p-Pb collisions. Further, the
number scales in the intermediate multiplicity region with the number of binary
nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/161
Multi-particle azimuthal correlations in p-Pb and Pb-Pb collisions at the CERN Large Hadron Collider
Measurements of multi-particle azimuthal correlations (cumulants) for charged
particles in p-Pb and Pb-Pb collisions are presented. They help address the
question of whether there is evidence for global, flow-like, azimuthal
correlations in the p-Pb system. Comparisons are made to measurements from the
larger Pb-Pb system, where such evidence is established. In particular, the
second harmonic two-particle cumulants are found to decrease with multiplicity,
characteristic of a dominance of few-particle correlations in p-Pb collisions.
However, when a gap is placed to suppress such correlations,
the two-particle cumulants begin to rise at high-multiplicity, indicating the
presence of global azimuthal correlations. The Pb-Pb values are higher than the
p-Pb values at similar multiplicities. In both systems, the second harmonic
four-particle cumulants exhibit a transition from positive to negative values
when the multiplicity increases. The negative values allow for a measurement of
to be made, which is found to be higher in Pb-Pb collisions at
similar multiplicities. The second harmonic six-particle cumulants are also
found to be higher in Pb-Pb collisions. In Pb-Pb collisions, we generally find
which is indicative of a Bessel-Gaussian
function for the distribution. For very high-multiplicity Pb-Pb
collisions, we observe that the four- and six-particle cumulants become
consistent with 0. Finally, third harmonic two-particle cumulants in p-Pb and
Pb-Pb are measured. These are found to be similar for overlapping
multiplicities, when a gap is placed.Comment: 25 pages, 11 captioned figures, 3 tables, authors from page 20,
published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/87
Synthetic recording and in situ readout of lineage information in single cells
Reconstructing the lineage relationships and dynamic event histories of individual cells within their native spatial context is a long-standing challenge in biology. Many biological processes of interest occur in optically opaque or physically inaccessible contexts, necessitating approaches other than direct imaging. Here, we describe a new synthetic system that enables cells to record lineage information and event histories in the genome in a format that can be subsequently read out in single cells in situ. This system, termed Memory by Engineered Mutagenesis with Optical In situ Readout (MEMOIR), is based on a set of barcoded recording elements termed scratchpads. The state of a given scratchpad can be irreversibly altered by Cas9-based targeted mutagenesis, and read out in single cells through multiplexed single-molecule RNA fluorescence hybridization (smFISH). To demonstrate a proof of principle of MEMOIR, we engineered mouse embryonic stem (ES) cells to contain multiple scratchpads and other recording components. In these cells, scratchpads were altered in a progressive and stochastic fashion as cells proliferated. Analysis of the final states of scratchpads in single cells in situ enabled reconstruction of the lineage trees of cell colonies. Combining analysis of endogenous gene expression with lineage reconstruction in the same cells further allowed inference of the dynamic rates at which ES cells switch between two gene expression states. Finally, using simulations, we showed how parallel MEMOIR systems operating in the same cell can enable recording and readout of dynamic cellular event histories. MEMOIR thus provides a versatile platform for information recording and in situ, single cell readout across diverse biological systems
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