72 research outputs found
Overshoot inwards from the bottom of the intershell convective zone in (S)AGB stars
We estimate the extent of overshooting inwards from the bottom of the
intershell convective zone in thermal pulses in (S)AGB stars. We find that the
buoyancy is so strong that any overshooting should be negligible. The
temperature inversion at the bottom of the convective zone adds to the
stability of the region. Any mixing that occurs in this region is highly
unlikely to be due to convective overshooting, and so must be due to another
process
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On the discovery of K-enhanced and possibly Mg-depleted stars throughout the Milky Way
Stars with unusual elemental abundances offer clues about rare astrophysical
events or nucleosynthetic pathways. Stars with significantly depleted magnesium
and enhanced potassium ([Mg/Fe] 1) have to date only been
found in the massive globular cluster NGC 2419 and, to a lesser extent, NGC
2808. The origin of this abundance signature remains unknown, as does the
reason for its apparent exclusivity to these two globular clusters. Here we
present 112 field stars, identified from 454,180 LAMOST giants, that show
significantly enhanced [K/Fe] and possibly depleted [Mg/Fe] abundance ratios.
Our sample spans a wide range of metallicities (-1.5 < [Fe/H] < 0.3), yet none
show abundance ratios of [K/Fe] or [Mg/Fe] that are as extreme as those
observed in NGC 2419. If confirmed, the identified sample of stars represents
evidence that the nucleosynthetic process producing the anomalous abundances
ratios of [K/Fe] and [Mg/Fe] probably occurs at a wide range of metallicities.
This would suggest that pollution scenarios that are limited to early epochs
(such as Population III supernovae) are an unlikely explanation, although they
cannot be ruled out entirely. This sample is expected to help guide modelling
attempts to explain the origin of the Mg-K abundance signature
Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule
N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system
An Alternating GluN1-2-1-2 Subunit Arrangement in Mature NMDA Receptors
NMDA receptors (NMDARs) form glutamate-gated ion channels that play a critical role in CNS physiology and pathology. Together with AMPA and kainate receptors, NMDARs are known to operate as tetrameric complexes with four membrane-embedded subunits associating to form a single central ion-conducting pore. While AMPA and some kainate receptors can function as homomers, NMDARs are obligatory heteromers composed of homologous but distinct subunits, most usually of the GluN1 and GluN2 types. A fundamental structural feature of NMDARs, that of the subunit arrangement around the ion pore, is still controversial. Thus, in a typical NMDAR associating two GluN1 and two GluN2 subunits, there is evidence for both alternating 1/2/1/2 and non-alternating 1/1/2/2 arrangements. Here, using a combination of electrophysiological and cross-linking experiments, we provide evidence that functional GluN1/GluN2A receptors adopt the 1/2/1/2 arrangement in which like subunits are diagonal to one another. Moreover, based on the recent crystal structure of an AMPA receptor, we show that in the agonist-binding and pore regions, the GluN1 subunits occupy a “proximal” position, closer to the central axis of the channel pore than that of GluN2 subunits. Finally, results obtained with reducing agents that differ in their membrane permeability indicate that immature (intracellular) and functional (plasma-membrane inserted) pools of NMDARs can adopt different subunit arrangements, thus stressing the importance of discriminating between the two receptor pools in assembly studies. Elucidating the quaternary arrangement of NMDARs helps to define the interface between the subunits and to understand the mechanism and pharmacology of these key signaling receptors
The origin of dust in galaxies revisited: the mechanism determining dust content
The origin of cosmic dust is a fundamental issue in planetary science. This
paper revisits the origin of dust in galaxies, in particular, in the Milky Way,
by using a chemical evolution model of a galaxy composed of stars, interstellar
medium, metals (elements heavier than helium), and dust. We start from a review
of time-evolutionary equations of the four components, and then, we present
simple recipes for the stellar remnant mass and yields of metal and dust based
on models of stellar nucleosynthesis and dust formation. After calibrating some
model parameters with the data from the solar neighborhood, we have confirmed a
shortage of the stellar dust production rate relative to the dust destruction
rate by supernovae if the destruction efficiency suggested by theoretical works
is correct. If the dust mass growth by material accretion in molecular clouds
is active, the observed dust amount in the solar neighborhood is reproduced. We
present a clear analytic explanation of the mechanism for determining dust
content in galaxies after the activation of accretion growth: a balance between
accretion growth and supernova destruction. Thus, the dust content is
independent of the uncertainty of the stellar dust yield after the growth
activation. The timing of the activation is determined by a critical metal mass
fraction which depends on the growth and destruction efficiencies. The solar
system formation seems to have occurred well after the activation and plenty of
dust would have existed in the proto-solar nebula.Comment: 12 pages, 11 figure
Amino Terminal Domains of the NMDA Receptor Are Organized as Local Heterodimers
The N-methyl-D-aspartate (NMDA) receptor, an obligate heterotetrameric assembly organized as a dimer of dimers, is typically composed of two glycine-binding GluN1 subunits and two glutamate-binding GluN2 subunits. Despite the crucial role that the NMDA receptor plays in the nervous system, the specific arrangement of subunits within the dimer-of-dimer assemblage is not conclusively known. Here we studied the organization of the amino terminal domain (ATD) of the rat GluN1/GluN2A and GluN1/GluN2B NMDA receptors by cysteine-directed, disulfide bond-mediated cross-linking. We found that GluN1 ATDs and GluN2 ATDs spontaneously formed disulfide bond-mediated dimers after introducing cysteines into the L1 interface of GluN2A or GluN2B ATD. The formation of dimer could be prevented by knocking out endogenous cysteines located near the L1 interface of GluN1. These results indicate that GluN1 and GluN2 ATDs form local heterodimers through the interactions in the L1-L1 interface and further demonstrate a dimer-of-heterodimer arrangement in GluN1/GluN2A and GluN1/GluN2B NMDA receptors
Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters
Recent progress in studies of globular clusters has shown that they are not
simple stellar populations, being rather made of multiple generations. Evidence
stems both from photometry and spectroscopy. A new paradigm is then arising for
the formation of massive star clusters, which includes several episodes of star
formation. While this provides an explanation for several features of globular
clusters, including the second parameter problem, it also opens new
perspectives about the relation between globular clusters and the halo of our
Galaxy, and by extension of all populations with a high specific frequency of
globular clusters, such as, e.g., giant elliptical galaxies. We review progress
in this area, focusing on the most recent studies. Several points remain to be
properly understood, in particular those concerning the nature of the polluters
producing the abundance pattern in the clusters and the typical timescale, the
range of cluster masses where this phenomenon is active, and the relation
between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review
The Evolution of Compact Binary Star Systems
We review the formation and evolution of compact binary stars consisting of
white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and
BHs are thought to be the primary astrophysical sources of gravitational waves
(GWs) within the frequency band of ground-based detectors, while compact
binaries of WDs are important sources of GWs at lower frequencies to be covered
by space interferometers (LISA). Major uncertainties in the current
understanding of properties of NSs and BHs most relevant to the GW studies are
discussed, including the treatment of the natal kicks which compact stellar
remnants acquire during the core collapse of massive stars and the common
envelope phase of binary evolution. We discuss the coalescence rates of binary
NSs and BHs and prospects for their detections, the formation and evolution of
binary WDs and their observational manifestations. Special attention is given
to AM CVn-stars -- compact binaries in which the Roche lobe is filled by
another WD or a low-mass partially degenerate helium-star, as these stars are
thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure
Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties.
Genetic and bioinformatic analyses have identified missense mutations in GRIN2B encoding the NMDA receptor GluN2B subunit in autism, intellectual disability, Lennox Gastaut and West Syndromes. Here, we investigated several such mutations using a near-complete, hybrid 3D model of the human NMDAR and studied their consequences with kinetic modelling and electrophysiology. The mutants revealed reductions in glutamate potency; increased receptor desensitisation; and ablation of voltage-dependent Mg block. In addition, we provide new views on Mg and NMDA channel blocker binding sites. We demonstrate that these mutants have significant impact on excitatory transmission in developing neurons, revealing profound changes that could underlie their associated neurological disorders. Of note, the NMDAR channel mutant GluN2B unusually allowed Mg permeation, whereas nearby N615I reduced Ca permeability. By identifying the binding site for an NMDAR antagonist that is used in the clinic to rescue gain-of-function phenotypes, we show that drug binding may be modified by some GluN2B disease-causing mutations
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