5,579 research outputs found
Conformational dynamics of the Hop1 HORMA domain reveal a common mechanism with the spindle checkpoint protein Mad2.
The HORMA domain is a highly conserved protein-protein interaction module found in eukaryotic signaling proteins including the spindle assembly checkpoint protein Mad2 and the meiotic HORMAD proteins. HORMA domain proteins interact with short 'closure motifs' in partner proteins by wrapping their C-terminal 'safety belt' region entirely around these motifs, forming topologically-closed complexes. Closure motif binding and release requires large-scale conformational changes in the HORMA domain, but such changes have only been observed in Mad2. Here, we show that Saccharomyces cerevisiae Hop1, a master regulator of meiotic recombination, possesses conformational dynamics similar to Mad2. We identify closure motifs in the Hop1 binding partner Red1 and in Hop1 itself, revealing that HORMA domain-closure motif interactions underlie both Hop1's initial recruitment to the chromosome axis and its self-assembly on the axis. We further show that Hop1 adopts two distinct folded states in solution, one corresponding to the previously-observed 'closed' conformation, and a second more extended state in which the safety belt region has disengaged from the HORMA domain core. These data reveal strong mechanistic similarities between meiotic HORMADs and Mad2, and provide a mechanistic basis for understanding both meiotic chromosome axis assembly and its remodeling by the AAA+ ATPase Pch2/TRIP13
Recent transformation of intertidal environments under a sea-level rise scenario: Examples from northern Spain
The transformation of two intertidal environments from northern Spain during the last 150 years shows an evolution from a tidal flat into a salt marsh environment, with an intermediate transitional stage. The environment of deposition was reconstructed based on benthic foraminifera and sand content. Sediments were put into a temporal framework using short-lived radioisotope activities and heavy metal concentrations. The observed natural evolution responds to the availability of abundant sediment and the current sea-level rise scenario, where intertidal environments are trying to adapt to increasing flooding periods by accreting sediment rapidly. © 2019 Sociedad Geologica de Espana. All rights reserved.This research was funded by the Mi nistry of Economy and Competitiveness of Spain (CGL2013-41083-P), the University of the Basque Country UPV/EHU (UFI11/09), and the Basque Government (IT976-16). Ane GarcĂa-Artola was funded by the Basque Government (BFI08.180). Miriam Torrontegui Aguado carried out the micropalaeontological analysis of the PR core and Eduardo Leorri (East Carolina University, USA) helped in the field. We thank Juan Usera (Universitat de ValĂšn-cia), an anonymous reviewer, and Manuel DĂaz Azpiroz (Assistant Editor) for their valuable comments. This work represents contribution #29 of the Geo-Q Zentroa Research Unit (JoaquĂn GĂłmez de Llarena Laboratory)
TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching.
The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active 'closed' conformer to an inactive 'open' conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination
A Spectropolarimetric Atlas of Seyfert 1 Galaxies
We present optical spectropolarimetry of the nuclei of 36 Seyfert 1 galaxies,
obtained with the William Herschel and the Anglo-Australian Telescopes from
1996 to 1999. In 20 of these, the optical emission from the active nucleus is
intrinsically polarized. We have measured a significant level of polarization
in a further 7 objects but these may be heavily contaminated by Galactic
interstellar polarization. The intrinsically polarized Seyfert 1s exhibit a
variety of characteristics, with the average polarization ranging from < 0.5 to
5 per cent and many showing variations in both the degree and position angle of
polarization across the broad H alpha emission line. We identify a small group
of Seyfert 1s that exhibit polarization properties similar to those of Seyfert
2 galaxies in which polarized broad-lines have been discovered. These objects
represent direct observational evidence that a Seyfert 2-like far-field polar
scattering region is also present in Seyfert 1s. Several other objects have
features that can be explained in terms of equatorial scattering of line
emission from a rotating disk. We propose that much of the diversity in the
polarization properties of Seyfert galaxies can be understood in terms of a
model involving both equatorial and polar scattering, the relative importance
of the two geometries as sources of polarized light being determined
principally by the inclination of the system axis to the line-of-sight.Comment: Accepted for publication in MNRAS (28 pages, 25 figures
Who Pays a Price on Carbon?
We use the 2003 Consumer Expenditure Survey and emissions estimates from an input-output model to estimate the incidence of a price on carbon induced by a cap-and-trade program or carbon tax in the US context. We present results on how much difference income deciles pay for a carbon tax as well as which industries see the largest increase in costs due to a carbon tax. We illustrate the main determinant of the regressivity: consumption patterns for energy-intensive goods. We find that a policy targeting CO2 from energy consumption is more regressive than a price on all emissions. Furthermore, on a per-capita basis a carbon price is much more regressive than calculations at the household level. We discuss policy options to offset the adverse distributional effects of a carbon emissions policy.
Proton Cyclotron Features in Thermal Spectra of Ultra-magnetized Neutron Stars
A great deal of interest has been recently raised in connection with the
possibility that soft -ray repeaters (SGRs) and anomalous X-ray pulsars
(AXPs) contain {\em magnetars}, young neutron stars endowed with magnetic
fields G. In this paper we calculate thermal spectra from
ultra-magnetized neutron stars for values of the luminosity and magnetic field
believed to be relevant to SGRs and AXPs. Emergent spectra are found to be very
close to a blackbody at the star effective temperature and exhibit a
distinctive absorption feature at the proton cyclotron energy keV. The proton cyclotron features (PCFs) are
conspicuous (equivalent width of up to many hundreds eV) and relatively broad
(). The detection of the PCFs is well within the
capabilities of present X-ray spectrometers, like the HETGS and METGS on board
Chandra. Their observation might provide decisive evidence in favor of the
existence of magnetars.Comment: 7 pages, 4 figures, minor changes included, typos corrected. Accepted
for publication in Ap
mGlu5 Inhibition in the Basolateral Amygdala Prevents Estrous Cycle-Dependent Changes in Cue-Induced Cocaine Seeking
Drug associated cues are a common relapse trigger for individuals recovering from cocaine use disorder. Sex and ovarian hormones influence patterns of cocaine use and relapse vulnerability, with studies indicating that females show increased cue-induced craving and relapse vulnerability compared to males. In a rodent model of cocaine craving and relapse vulnerability, cue-induced cocaine seeking behavior following weeks of withdrawal from extended-access cocaine self-administration is higher in females in the estrus stage of the reproductive (estrous) cycle (Estrus Females) compared to both Males and females in all other stages (Non-Estrus Females). However, the neuronal substrates and cellular mechanisms underlying these sex differences is not fully understood. One region that contributes to both sex differences in behavioral responding and cue-induced cocaine seeking is the basolateral amygdala (BLA), while one receptor known to play a critical role in mediating cocaine seeking behavior is metabotropic glutamate receptor 5 (mGlu5). Here we assessed the effects of BLA mGlu5 inhibition following prolonged withdrawal from cocaine self-administration on observed estrous cycle-dependent changes in cue-induced cocaine seeking behavior. We found that BLA microinjections of the mGlu5 antagonist MTEP selectively reduced the enhanced cue-induced cocaine seeking normally observed in Estrus Females while having no effect on cocaine seeking in Males and Non-Estrus Females. These findings identify a unique interaction between cocaine-exposure, estrous cycle fluctuations and BLA mGlu5-dependent transmission on cue-induced cocaine seeking behavior
Examining the reversibility of long-term behavioral disruptions in progeny of maternal SSRI exposure
Serotonergic dysregulation is implicated in numerous psychiatric disorders. Serotonin plays widespread trophic roles during neurodevelopment; thus perturbations to this system during development may increase risk for neurodevelopmental disorders. Epidemiological studies have examined association between selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy and increased autism spectrum disorder (ASD) risk in offspring. It is unclear from these studies whether ASD susceptibility is purely related to maternal psychiatric diagnosis, or if treatment poses additional risk. We sought to determine whether maternal SSRI treatment alone or in combination with genetically vulnerable background was sufficient to induce offspring behavior disruptions relevant to ASD. We exposed C57BL/6J or Celf6(+/-) mouse dams to fluoxetine (FLX) during different periods of gestation and lactation and characterized offspring on tasks assessing social communicative interaction and repetitive behavior patterns including sensory sensitivities. We demonstrate robust reductions in pup ultrasonic vocalizations (USVs) and alterations in social hierarchy behaviors, as well as perseverative behaviors and tactile hypersensitivity. Celf6 mutant mice demonstrate social communicative deficits and perseverative behaviors, without further interaction with FLX. FLX re-exposure in adulthood ameliorates the tactile hypersensitivity yet exacerbates the dominance phenotype. This suggests acute deficiencies in serotonin levels likely underlie the abnormal responses to sensory stimuli, while the social alterations are instead due to altered development of social circuits. These findings indicate maternal FLX treatment, independent of maternal stress, can induce behavioral disruptions in mammalian offspring, thus contributing to our understanding of the developmental role of the serotonin system and the possible risks to offspring of SSRI treatment during pregnancy
Analyzing the Multiwavelength Spectrum and Variability of BL Lacertae During the July 1997 Outburst
The multiwavelength spectrum of BL Lacertae during its July 1997 outburst is
analyzed in terms of different variations of the homogeneous leptonic jet model
for the production of high-energy radiation from blazars. We find that a
two-component gamma-ray spectrum, consisting of a synchrotron self-Compton and
an external Compton component, is required in order to yield an acceptable fit
to the broadband spectrum. Our analysis indicates that in BL Lac, unlike other
BL Lac objects, the broad emission line region plays an important role for the
high-energy emission. Several alternative blazar jet models are briefly
discussed. In the appendix, we describe the formalism in which the process of
Comptonization of reprocessed accretion disk photons is treated in the
previously developed blazar jet simulation code which we use.Comment: Now accepted for publication in The Astronomical Journal.
Significantly extended discussion w.r.t. original version. 3 Figures included
using epsf.sty, rotate.st
The Accretion Rates and Spectral Energy Distributions of BL Lacertae Objects
We investigate the relationship between accretion rates and the spectral
energy distributions (SEDs) of BL Lac objects, using a sample of objects for
which published information on the host galaxies, emission-line luminosities,
and peak frequencies and luminosities of their SEDs are available. The sample
is composed of 43 BL Lac objects which have a relatively continuous
distribution of peak frequencies. Under the assumption that the observed
emission lines are photoionized by the central accretion disk, we use the line
luminosities to estimate the accretion luminosities and hence accretion rates.
We find that low frequency-peaked BL Lac objects (LBLs) span a wide range of
accretion rates, whereas high frequency-peaked BL Lac objects (HBLs) cover a
more restricted range of lower values. There appears to be a continuous
distribution of accretion rates between the two subclasses of BL Lac objects.
We find that the peak frequency of the SED, \pknu, correlates with the
accretion rate, approximately with the form \pknu\propto \Lambda^{-3} in HBLs
and \pknu \propto \Lambda^{-0.25} in LBLs, where . The peak luminosity of the SED is also correlated with .
These results suggest that the accretion rate influences the shape of the SED
in BL Lac objects. They also support models which couple the jet and the
accretion disk. We present a physical scenario to account for the empirical
trends.Comment: 6 pages in emulateapj.sty, 3 figures 1 table. The Astrophysical
Journal (in press
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