60 research outputs found
Dynamical compactification from de Sitter space
We show that D-dimensional de Sitter space is unstable to the nucleation of
non-singular geometries containing spacetime regions with different numbers of
macroscopic dimensions, leading to a dynamical mechanism of compactification.
These and other solutions to Einstein gravity with flux and a cosmological
constant are constructed by performing a dimensional reduction under the
assumption of q-dimensional spherical symmetry in the full D-dimensional
geometry. In addition to the familiar black holes, black branes, and
compactification solutions we identify a number of new geometries, some of
which are completely non-singular. The dynamical compactification mechanism
populates lower-dimensional vacua very differently from false vacuum eternal
inflation, which occurs entirely within the context of four-dimensions. We
outline the phenomenology of the nucleation rates, finding that the
dimensionality of the vacuum plays a key role and that among vacua of the same
dimensionality, the rate is highest for smaller values of the cosmological
constant. We consider the cosmological constant problem and propose a novel
model of slow-roll inflation that is triggered by the compactification process.Comment: Revtex. 41 pages with 24 embedded figures. Minor corrections and
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Altered Microstructural Caudate Integrity in Posttraumatic Stress Disorder but Not Traumatic Brain Injury
Objective: Given the high prevalence and comorbidity of combat-related PTSD and TBI in Veterans, it is often difficult to disentangle the contributions of each disorder. Examining these pathologies separately may help to understand the neurobiological basis of memory impairment in PTSD and TBI independently of each other. Thus, we investigated whether a) PTSD and TBI are characterized by subcortical structural abnormalities by examining diffusion tensor imaging (DTI) metrics and volume and b) if these abnormalities were specific to PTSD versus TBI. Method We investigated whether individuals with PTSD or TBI display subcortical structural abnormalities in memory regions by examining DTI metrics and volume of the hippocampus and caudate in three groups of Veterans: Veterans with PTSD, Veterans with TBI, and Veterans with neither PTSD nor TBI (Veteran controls). Results: While our results demonstrated no macrostructural differences among the groups in these regions, there were significant alterations in microstructural DTI indices in the caudate for the PTSD group but not the TBI group compared to Veteran controls. Conclusions: The result of increased mean, radial, and axial diffusivity, and decreased fractional anisotropy in the caudate in absence of significant volume atrophy in the PTSD group suggests the presence of subtle abnormalities evident only at a microstructural level. The caudate is thought to play a role in the physiopathology of PTSD, and the habit-like behavioral features of the disorder could be due to striatal-dependent habit learning mechanisms. Thus, DTI appears to be a vital tool to investigate subcortical pathology, greatly enhancing the ability to detect subtle brain changes in complex disorders
Wdpcp, a PCP Protein Required for Ciliogenesis, Regulates Directional Cell Migration and Cell Polarity by Direct Modulation of the Actin Cytoskeleton
Planar cell polarity (PCP) regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin cytoskeleton to regulate cell polarity and directional cell migration
GLI1 Confers Profound Phenotypic Changes upon LNCaP Prostate Cancer Cells That Include the Acquisition of a Hormone Independent State
The GLI (GLI1/GLI2) transcription factors have been implicated in the development
and progression of prostate cancer although our understanding of how they
actually contribute to the biology of these common tumours is limited. We
observed that GLI reporter activity was higher in normal (PNT-2) and
tumourigenic (DU145 and PC-3) androgen-independent cells compared to
androgen-dependent LNCaP prostate cancer cells and, accordingly, GLI mRNA levels
were also elevated. Ectopic expression of GLI1 or the constitutively active
ΔNGLI2 mutant induced a distinct cobblestone-like morphology in LNCaP cells
that, regarding the former, correlated with increased GLI2 as well as expression
of the basal/stem-like markers CD44, β1-integrin, ΔNp63 and BMI1, and
decreased expression of the luminal marker AR (androgen receptor). LNCaP-GLI1
cells were viable in the presence of the AR inhibitor bicalutamide and gene
expression profiling revealed that the transcriptome of LNCaP-GLI1 cells was
significantly closer to DU145 and PC-3 cells than to control LNCaP-pBP (empty
vector) cells, as well as identifying LCN2/NGAL as a highly induced transcript
which is associated with hormone independence in breast and prostate cancer.
Functionally, LNCaP-GLI1 cells displayed greater clonal growth and were more
invasive than control cells but they did not form colonies in soft agar or
prostaspheres in suspension suggesting that they do not possess inherent stem
cell properties. Moreover, targeted suppression of GLI1 or GLI2 with siRNA did
not reverse the transformed phenotype of LNCaP-GLI1 cells nor did double
GLI1/GLI2 knockdowns activate AR expression in DU145 or PC-3 cells. As such,
early targeting of the GLI oncoproteins may hinder progression to a hormone
independent state but a more detailed understanding of the mechanisms that
maintain this phenotype is required to determine if their inhibition will
enhance the efficacy of anti-hormonal therapy through the induction of a luminal
phenotype and increased dependency upon AR function
Globetrotting strangles: the unbridled national and international transmission of Streptococcus equi between horses.
The equine disease strangles, which is characterized by the formation of abscesses in the lymph nodes of the head and neck, is one of the most frequently diagnosed infectious diseases of horses around the world. The causal agent, Streptococcus equi subspecies equi, establishes a persistent infection in approximately 10 % of animals that recover from the acute disease. Such 'carrier' animals appear healthy and are rarely identified during routine veterinary examinations pre-purchase or transit, but can transmit S. equi to naïve animals initiating new episodes of disease. Here, we report the analysis and visualization of phylogenomic and epidemiological data for 670 isolates of S. equi recovered from 19 different countries using a new core-genome multilocus sequence typing (cgMLST) web bioresource. Genetic relationships among all 670 S. equi isolates were determined at high resolution, revealing national and international transmission events that drive this endemic disease in horse populations throughout the world. Our data argue for the recognition of the international importance of strangles by the Office International des Épizooties to highlight the health, welfare and economic cost of this disease. The Pathogenwatch cgMLST web bioresource described herein is available for tailored genomic analysis of populations of S. equi and its close relative S. equi subspecies zooepidemicus that are recovered from horses and other animals, including humans, throughout the world. This article contains data hosted by Microreact
QCD and strongly coupled gauge theories : challenges and perspectives
We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe
Distribution of stress state in the Nankai subduction zone, southwest Japan and a comparison with Japan Trench
To better understand the distribution of three dimensional stress states in the Nankai subduction zone, southwest Japan, we review various stress-related investigations carried out in the first and second stage expeditions of the Nankai Trough Seismogenic Zone Experiment (NanTroSEIZE) by the Integrated Ocean Drilling Program (IODP) and compile the stress data. Overall, the maximum principal stress ?1 in the shallower levels (<~1km) is vertical from near the center of forearc basin to near the trench and; the maximum horizontal stress SHmax (interpreted to be the intermediate principal stress ?2) is generally parallel to the plate convergence vector. The exception to this generalization occurs along the shelf edge of the Nankai margin where SHmax is along strike rather than parallel to the plate convergence vector. Reorientation of the principal stresses at deeper levels (e.g., >~1km below seafloor or in underlying accretionary prism) with ?1 becoming horizontal is also suggested at all deeper drilling sites. We also make a comparison of the stress state in the hanging wall of the frontal plate-interface between Site C0006 in the Nankai and Site C0019 in the Japan Trench subduction zone drilled after the 2011 Mw9.0 Tohoku-Oki earthquake. In the Japan Trench, the comparison between stress state before and after the 2011 mega-earthquake shows that the stress changed from compression before the earthquake to extension after the earthquake. As a result of the comparison between the Nankai Trough and Japan Trench, a similar current stress state with trench parallel extension was recognized at both C0006 and C0019 sites. Hypothetically, this may indicate that in Nankai Trough it is still in an early stage of the interseismic cycle of a great earthquake which occurs on the décollement and propagates to the toe (around site C0006)
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