156 research outputs found
Elucidating the Role of Endogenous Electric Fields in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System
Endogenous bioelectric fields guide morphogenesis during embryonic development and regeneration by directly regulating the cellular functions responsible for these phenomena. Although this role has been extensively explored in many peripheral tissues, the ability of electric fields to regulate wound repair and stimulate regeneration in the mammalian central nervous system (CNS) has not been convincingly established. This dissertation explores the role of electric fields in regulating the injury response and controlling the regenerative potential of the mammalian CNS. We place particular emphasis on their influence on astrocytes, as specific differences in their injury-induced behaviors have been associated with differences in the regenerative potential demonstrated between mammalian and non-mammalian vertebrates. For example, astrocytes in both mammalian and non- mammalian vertebrates begin migrating towards the lesion within hours and begin to proliferate after an initial delay of two days; subsequently, astrocytes in non-mammalian vertebrates support neurogenesis and assume a bipolar radial glia-like morphology that guides regenerating axons, whereas astrocytes in mammals do not demonstrate robust neurogenesis and undergo a hypertrophic response that inhibits axon sprouting. To test whether injury-induced electric fields drive the astrocytic response to injury, we exposed separate populations of purified astrocytes from the rat cortex and cerebellum to electric field intensities associated with intact and injured mammalian tissues, as well as to those electric field intensities measured in regenerating non-mammalian vertebrate tissues. Upon exposure to electric field intensities associated with uninjured tissue, astrocytes showed little change in their cellular behavior. However, cortical astrocytes responded to electric field intensities associated with injured mammalian tissues by demonstrating dramatic increases in migration and proliferation, behaviors that are associated with their formation of a glial scar in vivo; in contrast, cerebellar astrocytes, which do not organize into a demarcated glial scar, did not respond to these electric fields. At electric field intensities associated with regenerating tissues, both cerebellar and cortical astrocytes demonstrated robust and sustained responses that included morphological changes consistent with a regenerative phenotype. These results support the hypothesis that physiologic electric fields drive the astrocytic response to injury, and that elevated electric fields may induce a more regenerative response among mammalian astrocytes
Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System
Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50â100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair
Recommended from our members
Initial Metabolic Profiles Are Associated with 7-Day Survival among Infants Born at 22-25 Weeks of Gestation.
OBJECTIVE:To evaluate the association between early metabolic profiles combined with infant characteristics and survival past 7 days of age in infants born at 22-25 weeks of gestation. STUDY DESIGN:This nested case-control consisted of 465 singleton live births in California from 2005 to 2011 at 22-25 weeks of gestation. All infants had newborn metabolic screening data available. Data included linked birth certificate and mother and infant hospital discharge records. Mortality was derived from linked death certificates and death discharge information. Each death within 7 days was matched to 4 surviving controls by gestational age and birth weight z score category, leaving 93 cases and 372 controls. The association between explanatory variables and 7-day survival was modeled via stepwise logistic regression. Infant characteristics, 42 metabolites, and 12 metabolite ratios were considered for model inclusion. Model performance was assessed via area under the curve. RESULTS:The final model included 1 characteristic and 11 metabolites. The model demonstrated a strong association between metabolic patterns and infant survival (area under the curve [AUC] 0.885, 95% CI 0.851-0.920). Furthermore, a model with just the selected metabolites performed better (AUC 0.879, 95% CI 0.841-0.916) than a model with multiple clinical characteristics (AUCâ0.685, 95% CIâ0.627-0.742). CONCLUSIONS:Use of metabolomics significantly strengthens the association with 7-day survival in infants born extremely premature. Physicians may be able to use metabolic profiles at birth to refine mortality risks and inform postnatal counseling for infants born at <26 weeks of gestation
Prompt Decays of General Neutralino NLSPs at the Tevatron
Recent theoretical developments have shown that gauge mediation has a much
larger parameter space of possible spectra and mixings than previously
considered. Motivated by this, we explore the collider phenomenology of gauge
mediation models where a general neutralino is the lightest MSSM superpartner
(the NLSP), focusing on the potential reach from existing and future Tevatron
searches. Promptly decaying general neutralino NLSPs can give rise to final
states involving missing energy plus photons, Zs, Ws and/or Higgses. We survey
the final states and determine those where the Tevatron should have the most
sensitivity. We then estimate the reach of existing Tevatron searches in these
final states and discuss new searches (or optimizations of existing ones) that
should improve the reach. Finally we comment on the potential for discovery at
the LHC.Comment: 41 pages, minor changes, added refs and discussion of previous
literatur
Testing the Nambu-Goldstone Hypothesis for Quarks and Leptons at the LHC
The hierarchy of the Yukawa couplings is an outstanding problem of the
standard model. We present a class of models in which the first and second
generation fermions are SUSY partners of pseudo-Nambu-Goldstone bosons that
parameterize a non-compact Kahler manifold, explaining the small values of
these fermion masses relative to those of the third generation. We also provide
an example of such a model. We find that various regions of the parameter space
in this scenario can give the correct dark matter abundance, and that nearly
all of these regions evade other phenomenological constraints. We show that for
gluino mass ~700 GeV, model points from these regions can be easily
distinguished from other mSUGRA points at the LHC with only 7 fb^(-1) of
integrated luminosity at 14 TeV. The most striking signatures are a dearth of
b- and tau-jets, a great number of multi-lepton events, and either an
"inverted" slepton mass hierarchy, narrowed slepton mass hierarchy, or
characteristic small-mu spectrum.Comment: Corresponds to published versio
Diagnosing Spin at the LHC via Vector Boson Fusion
We propose a new technique for determining the spin of new massive particles
that might be discovered at the Large Hadron Collider. The method relies on
pair-production of the new particles in a kinematic regime where the vector
boson fusion production mechanism is enhanced. For this regime, we show that
the distribution of the leading jets as a function of their relative azimuthal
angle can be used to distinguish spin-0 from spin-1/2 particles. We illustrate
this effect by considering the particular cases of (i) strongly-interacting,
stable particles and (ii) supersymmetric particles carrying color charge. We
argue that this method should be applicable in a wide range of new physics
scenarios.Comment: 5 pages, 4 figure
A One-Scale Model of Dynamical Supersymmetry Breaking
A model of gauge-mediated supersymmetry breaking is constructed in which the
low-energy physics depends on a single dynamical scale. Strong coupling
dynamics of gauge theories plays an important role, in particular through its
effects on beta functions and through confinement. The model does not have
distinct messenger and supersymmetry-breaking sectors. The scale of
supersymmetry breaking is of order 10-100 \TeV, implying that the decay of the
next-to-lightest superpartner into the gravitino is prompt. Superoblique
corrections are enhanced. A Dirac fermion and one complex scalar, in a 10 or
\bar{10} of (global) SU(5), are predicted to be relatively light and to satisfy
certain mass relations with the standard model squarks and sleptons.Comment: 28 pages, uses revtex, h-physrev.bs
Determination of Fundamental Supersymmetry Parameters from Chargino Production at Lepii
If accessible at LEP II, chargino production is likely to be one of the few
available supersymmetric signals for many years. We consider the prospects for
the determination of fundamental supersymmetry parameters in such a scenario.
The study is complicated by the dependence of observables on a large number of
these parameters. We propose a straightforward procedure for disentangling
these dependences and demonstrate its effectiveness by presenting a number of
case studies at representative points in parameter space. Working in the
context of the minimal supersymmetric standard model, we find that chargino
production by itself is a fairly sensitive probe of the supersymmetry-breaking
sector. For significant regions of parameter space, it is possible to test the
gaugino mass unification hypothesis and to measure the gaugino contents of the
charginos and neutralinos, thereby testing the predictions of grand unification
and the viability of the lightest supersymmetric particle as a dark matter
candidate. For much of the parameter space, it is also possible to set limits
on the mass of the electron sneutrino, which provide a valuable guide for
future particle searches.Comment: 52pp, Revtex, 30 figures available upon request, SLAC-PUB-6497,
RU-94-67 (text and figures available in ps form by anonymous ftp from
preprint.slac.stanford.edu, directory pub/preprints/hep-ph/9408
Simplified Models for LHC New Physics Searches
This document proposes a collection of simplified models relevant to the
design of new-physics searches at the LHC and the characterization of their
results. Both ATLAS and CMS have already presented some results in terms of
simplified models, and we encourage them to continue and expand this effort,
which supplements both signature-based results and benchmark model
interpretations. A simplified model is defined by an effective Lagrangian
describing the interactions of a small number of new particles. Simplified
models can equally well be described by a small number of masses and
cross-sections. These parameters are directly related to collider physics
observables, making simplified models a particularly effective framework for
evaluating searches and a useful starting point for characterizing positive
signals of new physics. This document serves as an official summary of the
results from the "Topologies for Early LHC Searches" workshop, held at SLAC in
September of 2010, the purpose of which was to develop a set of representative
models that can be used to cover all relevant phase space in experimental
searches. Particular emphasis is placed on searches relevant for the first
~50-500 pb-1 of data and those motivated by supersymmetric models. This note
largely summarizes material posted at http://lhcnewphysics.org/, which includes
simplified model definitions, Monte Carlo material, and supporting contacts
within the theory community. We also comment on future developments that may be
useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results
from "Topologies for Early LHC Searches" workshop (SLAC, September 2010).
Supplementary material can be found at http://lhcnewphysics.or
- âŠ