2,053 research outputs found
Human variants in the Neuronal Basic Helix-Loop-Helix/ Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function
Neuronal Per-Arnt-Sim homology (PAS) Factor 4 (NPAS4) is a neuronal activity-dependent transcription factor which heterodimerises with ARNT2 to regulate genes involved in inhibitory synapse formation. NPAS4 functions to maintain excitatory/inhibitory balance in neurons, while mouse models have shown it to play roles in memory formation, social interaction and neurodegeneration. NPAS4 has therefore been implicated in a number of neuropsychiatric or neurodegenerative diseases which are underpinned by defects in excitatory/inhibitory balance. Here we have explored a broad set of non-synonymous human variants in NPAS4 and ARNT2 for disruption of NPAS4 function. We found two variants in NPAS4 (F147S and E257K) and two variants in ARNT2 (R46W and R107H) which significantly reduced transcriptional activity of the heterodimer on a luciferase reporter gene. Furthermore, we found that NPAS4.F147S was unable to activate expression of the NPAS4 target gene BDNF due to reduced dimerisation with ARNT2. Homology modelling predicts F147 in NPAS4 to lie at the dimer interface, where it appears to directly contribute to protein/protein interaction. We also found that reduced transcriptional activation by ARNT2 R46W was due to disruption of nuclear localisation. These results provide insight into the mechanisms of NPAS4/ARNT dimerisation and transcriptional activation and have potential implications for cognitive phenotypic variation and diseases such as autism, schizophrenia and dementia.David C. Bersten, John B. Bruning, Daniel J. Peet, Murray L. Whitela
Stationary axisymmetric solutions of five dimensional gravity
We consider stationary axisymmetric solutions of general relativity that
asymptote to five dimensional Minkowski space. It is known that this system has
a hidden SL(3,R) symmetry. We identify an SO(2,1) subgroup of this symmetry
group that preserves the asymptotic boundary conditions. We show that the
action of this subgroup on a static solution generates a one-parameter family
of stationary solutions carrying angular momentum. We conjecture that by
repeated applications of this procedure one can generate all stationary
axisymmetric solutions starting from static ones. As an example, we derive the
Myers-Perry black hole starting from the Schwarzschild solution in five
dimensions.Comment: 31 pages, LaTeX; references adde
Effect of Scalar Mass in the Absorption and Emission Spectra of Schwarzschild Black Hole
Following Sanchez's approach we investigate the effect of scalar mass in the
absorption and emission problems of 4d Schwarzschild black hole. The absorption
cross sections for arbitrary angular momentum of the scalar field are computed
numerically in the full range of energy by making use of the analytic
near-horizon and asymptotic solutions and their analytic continuations. The
scalar mass makes an interesting effect in the low-energy absorption cross
section for S-wave. Unlike the massless case, the cross section decreases with
increasing energy in the extremely low-energy regime. As a result the
universality, {\it i.e.} low-energy cross section for S-wave is equal to the
horizon area, is broken in the presence of mass. If the scalar mass is larger
than a critical mass, the absorption cross section becomes monotonically
decreasing function in the entire range of energy. The Hawking emission is also
calculated numerically. It turns out that the Planck factor generally
suppresses the contribution of higher partial waves except S-wave. The scalar
mass in general tends to reduce the emission rate.Comment: 20 pages, 8 figures, V2: few comments are added. version to appear in
Classical and Quantum Gravit
Brane Baldness vs. Superselection Sectors
The search for intersecting brane solutions in supergravity is a large and
profitable industry. Recently, attention has focused on finding localized forms
of known `delocalized' solutions. However, in some cases, a localized version
of the delocalized solution simply does not exist. Instead, localized separated
branes necessarily delocalize as the separation is removed. This phenomenon is
related to black hole no-hair theorems, i.e. `baldness.' We continue the
discussion of this effect and describe how it can be understood, in the case of
Dirichlet branes, in terms of the corresponding intersection field theory. When
it occurs, it is associated with the quantum mixing of phases and lack of
superselection sectors in low dimensional field theories. We find surprisingly
wide agreement between the field theory and supergravity both with respect to
which examples delocalize and with respect to the rate at which this occurs.Comment: 26 pages, ReVTeX, 2 figures, reference added, version to appear in
PR
D-brane dynamics near compactified NS5-branes
We examine the dynamics of a -brane in the background of coincident,
parallel 5-branes which have had one of their common transverse directions
compactified. We find that for small energy, bound orbits can exist at
sufficiently large distances where there will be no stringy effects. The orbits
are dependent upon the energy density, angular momentum and electric field. The
analysis breaks down at radial distances comparable with the compactification
radius and we must resort to using a modified form of the harmonic function in
this region.Comment: Latex, 20 pages, 6 figs, references adde
Black Holes and Five-brane Thermodynamics
The phase diagram for Dp-branes in M-theory compactified on , ,
, and is constructed. As for the lower-dimensional tori considered
in our previous work (hep-th/9810224), the black brane phase at high entropy
connects onto matrix theory at low entropy; we thus recover all known instances
of matrix theory as consequences of the Maldacena conjecture. The difficulties
that arise for are reviewed. We also analyze the D1-D5 system on ;
we exhibit its relation to matrix models of M5-branes, and use spectral flow as
a tool to investigate the dependence of the phase structure on angular
momentum.Comment: 57 pages, 6 eps figures, latex. v2: DLCQ limit of 5-brane corrected;
typos corrected, references added. v3: reference added, typos corrected v4:
comments on DLCQ limit of 5-brane corrected one last time. Final version, to
appear in Phys. Rev.
Hard Scattering and Gauge/String Duality
We consider high-energy fixed-angle scattering of glueballs in confining
gauge theories that have supergravity duals. Although the effective description
is in terms of the scattering of strings, we find that the amplitudes are hard
(power law). This is a consequence of the warped geometry of the dual theory,
which has the effect that in an inertial frame the string process is never in
the soft regime. At small angle we find hard and Regge behaviors in different
kinematic regions.Comment: 4 page
Wilson Loops and Minimal Surfaces
The AdS/CFT correspondence suggests that the Wilson loop of the large N gauge
theory with N=4 supersymmetry in 4 dimensions is described by a minimal surface
in AdS_5 x S^5. We examine various aspects of this proposal, comparing gauge
theory expectations with computations of minimal surfaces. There is a
distinguished class of loops, which we call BPS loops, whose expectation values
are free from ultra-violet divergence. We formulate the loop equation for such
loops. To the extent that we have checked, the minimal surface in AdS_5 x S^5
gives a solution of the equation. We also discuss the zig-zag symmetry of the
loop operator. In the N=4 gauge theory, we expect the zig-zag symmetry to hold
when the loop does not couple the scalar fields in the supermultiplet. We will
show how this is realized for the minimal surface.Comment: 51 pages, 7 figure
Entropy and Action of Dilaton Black Holes
We present a detailed calculation of the entropy and action of
dilaton black holes, and show that both quantities coincide with one quarter of
the area of the event horizon. Our methods of calculation make it possible to
find an explanation of the rule for all static, spherically symmetric
black holes studied so far. We show that the only contribution to the entropy
comes from the extrinsic curvature term at the horizon, which gives
independently of the charge(s) of the black hole, presence of scalar fields,
etc. Previously, this result did not have a general explanation, but was
established on a case-by-case basis. The on-shell Lagrangian for maximally
supersymmetric extreme dilaton black holes is also calculated and shown to
vanish, in agreement with the result obtained by taking the limit of the
expression obtained for black holes with regular horizon.The physical meaning
of the entropy is discussed in relation to the issue of splitting of extreme
black holes.Comment: 15 p., SU-ITP-92-2
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