310 research outputs found
Estrogen protects neuronal cells from amyloid beta-induced apoptosis via regulation of mitochondrial proteins and function
BACKGROUND: Neurodegeneration in Alzheimer's disease is associated with increased apoptosis and parallels increased levels of amyloid beta, which can induce neuronal apoptosis. Estrogen exposure prior to neurotoxic insult of hippocampal neurons promotes neuronal defence and survival against neurodegenerative insults including amyloid beta. Although all underlying molecular mechanisms of amyloid beta neurotoxicity remain undetermined, mitochondrial dysfunction, including altered calcium homeostasis and Bcl-2 expression, are involved in neurodegenerative vulnerability. RESULTS: In this study, we investigated the mechanism of 17ÎČ-estradiol-induced prevention of amyloid beta-induced apoptosis of rat hippocampal neuronal cultures. Estradiol treatment prior to amyloid beta exposure significantly reduced the number of apoptotic neurons and the associated rise in resting intracellular calcium levels. Amyloid beta exposure provoked down regulation of a key antiapoptotic protein, Bcl-2, and resulted in mitochondrial translocation of Bax, a protein known to promote cell death, and subsequent release of cytochrome c. E(2 )pretreatment inhibited the amyloid beta-induced decrease in Bcl-2 expression, translocation of Bax to the mitochondria and subsequent release of cytochrome c. Further implicating the mitochondria as a target of estradiol action, in vivo estradiol treatment enhanced the respiratory function of whole brain mitochondria. In addition, estradiol pretreatment protected isolated mitochondria against calcium-induced loss of respiratory function. CONCLUSION: Therefore, we propose that estradiol pretreatment protects against amyloid beta neurotoxicity by limiting mitochondrial dysfunction via activation of antiapoptotic mechanisms
Astrocytic Ca2+ Waves Guide CNS Growth Cones to Remote Regions of Neuronal Activity
Activity plays a critical role in network formation during developmental, experience-dependent, and injury related remodeling. Here we report a mechanism by which axon trajectory can be altered in response to remote neuronal activity. Using photoconductive stimulation to trigger high frequency action potentials in rat hippocampal neurons in vitro, we find that activity functions as an attractive cue for growth cones in the local environment. The underlying guidance mechanism involves astrocyte Ca2+ waves, as the connexin-43 antagonist carbenoxolone abolishes the attraction when activity is initiated at a distance greater than 120 ”m. The asymmetric growth cone filopodia extension that precedes turning can be blocked with CNQX (10 ”M), but not with the ATP and adenosine receptor antagonists suramin (100 ”M) and alloxazine (4 ”M), suggesting non-NMDA glutamate receptors on the growth cone mediate the interaction with astrocytes. These results define a potential long-range signalling pathway for activity-dependent axon guidance in which growth cones turn towards directional, temporally coordinated astrocyte Ca2+ waves that are triggered by neuronal activity. To assess the viability of the guidance effect in an injury paradigm, we performed the assay in the presence of conditioned media from lipopolysaccharide (LPS) activated purified microglial cultures, as well as directly activating the glia present in our co-cultures. Growth cone attraction was not inhibited under these conditions, suggesting this mechanism could be used to guide regeneration following axonal injury
âSub-Primeâ Water, Low-Security Entitlements and Policy Challenges in Over-Allocated River Basins: the Case of the MurrayâDarling Basin
Environmental policy is often implemented using market instruments. In some cases, including carbon taxing, the links
between financial products and the environmental objectives, are transparent. In other cases, including water markets, the
links are less transparent. In Australiaâs MurrayâDarling Basin (MDB), financial water products are known as âentitlementsâ,
and are similar to traditional financial products, such as shares. The Australian water market includes âLow Securityâ
entitlements, which are similar to âsub-primeâ mortgage bonds because they are unlikely to yield an amount equal to their
financial worth. Nearly half the water purchased under the MurrayâDarling Basin Plan for environmental purposes is âLow
Securityâ. We suggest that the current portfolio of water held by the Australian Government for environmental purposes
reflects the mortgage market in the lead-up to the global financial crisis. Banks assumed that the future value of the mortgage
market would reflect past trends. Similarly, it is assumed that the future value of water products will reflect past trends,
without considering climate change. Historic records of allocations to âLow Securityâ entitlements in the MDB suggest that,
in the context of climate change, the Basin Plan water portfolio may fall short of the target annual average yield of 2075 GL
by 511 GL. We recommend adopting finance sector methods including âhedgingâ âLow Securityâ entitlements by purchasing
an additional 322â2755 GL of âLow Securityâ, or 160â511 GL of âHigh Securityâ entitlements. Securing reliable
environmental water is a global problem. Finance economics present opportunities for increasing the reliability of
environmental flows
Bilobalide modulates serotonin-controlled behaviors in the nematode Caenorhabditis elegans
<p>Abstract</p> <p>Background</p> <p>Dysfunctions in the serotonergic system have been implicated in several neurological disorders such as depression. Elderly individuals who have been diagnosed with clinical depression show elevated cases of neurodegenerative diseases. This has led to suggestions that modulating the serotonin (5-HT) system could provide an alternative method to current therapies for alleviating these pathologies. The neuroprotective effects of bilobalide <it>in vitro </it>have been documented. We aim to determine whether bilobalide affects the 5-HT system in the nematode <it>C. elegans</it>. The wild type worms, as well as well-characterized 5-HT mutants, were fed with bilobalide in a range of concentrations, and several 5-HT controlled behaviors were tested.</p> <p>Results</p> <p>We observed that bilobalide significantly inhibited 5-HT-controlled egg-laying behavior in a dose-dependent manner, which was blocked in the 5-HT receptor mutants (<it>ser-4, mod-1</it>), but not in the 5-HT transporter (<it>mod-5</it>) or synthesis (<it>tph-1</it>) mutants. Bilobalide also potentiated a 5-HT-controlled, experience-dependent locomotory behavior, termed the enhanced slowing response in the wild type animals. However, this effect was fully blocked in 5-HT receptor <it>mod-1 </it>and dopamine defective <it>cat-2 </it>mutants, but only partially blocked in <it>ser-4 </it>mutants. We also demonstrated that acetylcholine transmission was inhibited in a transgenic <it>C. elegans </it>strain that constitutively expresses AÎČ, and bilobalide did not significantly affect this inhibition.</p> <p>Conclusion</p> <p>These results suggest that bilobalide may modulate specific 5-HT receptor subtypes, which involves interplay with dopamine transmission. Additional studies for the function of bilobalide in neurotransmitter systems could aid in our understanding of its neuroprotective properties.</p
Extended Longevity of Reproductives Appears to be Common in Fukomys Mole-Rats (Rodentia, Bathyergidae)
African mole-rats (Bathyergidae, Rodentia) contain several social, cooperatively breeding species with low extrinsic mortality and unusually high longevity. All social bathyergids live in multigenerational families where reproduction is skewed towards a few breeding individuals. Most of their offspring remain as reproductively inactive âhelpersâ in their natal families, often for several years. This âreproductive subdivisionâ of mole-rat societies might be of interest for ageing research, as in at least one social bathyergid (Ansell's mole-rats Fukomys anselli), breeders have been shown to age significantly slower than non-breeders. These animals thus provide excellent conditions for studying the epigenetics of senescence by comparing divergent longevities within the same genotypes without the inescapable short-comings of inter-species comparisons. It has been claimed that many if not all social mole-rat species may have evolved similar ageing patterns, too. However, this remains unclear on account of the scarcity of reliable datasets on the subject. We therefore analyzed a 20-year breeding record of Giant mole-rats Fukomys mechowii, another social bathyergid species. We found that breeders indeed lived significantly longer than helpers (ca. 1.5â2.2fold depending on the sex), irrespective of social rank or other potentially confounding factors. Considering the phylogenetic positions of F. mechowii and F. anselli and unpublished data on a third Fukomys-species (F. damarensis) showing essentially the same pattern, it seems probable that the reversal of the classic trade-off between somatic maintenance and sexual reproduction is characteristic of the whole genus and hence of the vast majority of social mole-rats
Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay
We reconstruct the rare decays , , and in a data sample
corresponding to collected in collisions at
by the CDF II detector at the Fermilab Tevatron
Collider. Using and decays we report the branching ratios. In addition, we report
the measurement of the differential branching ratio and the muon
forward-backward asymmetry in the and decay modes, and the
longitudinal polarization in the decay mode with respect to the squared
dimuon mass. These are consistent with the theoretical prediction from the
standard model, and most recent determinations from other experiments and of
comparable accuracy. We also report the first observation of the {\mathcal{B}}(B^0_s \to
\phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}27 \pm 6B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons
We report measurements of the resonance properties of Lambda_c(2595)+ and
Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as
Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+
pi+/- final states. These measurements are performed using data corresponding
to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV,
collected with the CDF II detector at the Fermilab Tevatron. Exploiting the
largest available charmed baryon sample, we measure masses and decay widths
with uncertainties comparable to the world averages for Sigma_c states, and
significantly smaller uncertainties than the world averages for excited
Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17
pages, 15 figure
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV
We present a search for a new heavy charged vector boson decaying
to an electron-neutrino pair in collisions at a center-of-mass
energy of 1.96\unit{TeV}. The data were collected with the CDF II detector
and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No
significant excess above the standard model expectation is observed and we set
upper limits on . Assuming standard
model couplings to fermions and the neutrino from the boson decay to
be light, we exclude a boson with mass less than
1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR
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