Regional increase in the expression of the BCAT proteins in Alzheimer's disease brain: Implications in glutamate toxicity

BACKGROUNDThe human branched chain aminotransferases (hBCATm, mitochondrial and hBCATc, cytosolic) are major contributors to brain glutamate production. This excitatory neurotransmitter is thought to contribute to neurotoxicity in neurodegenerative conditions such as Alzheimer's disease (AD) but the expression of hBCAT in this disease has not previously been investigated.OBJECTIVEThe objective of investigating hBCAT expression is to gain insight into potential metabolic pathways that may be dysregulated in AD brain, which would contribute to glutamate toxicity.METHODSWestern blot analysis and immunohistochemistry were used to determine the expression and localization of hBCAT in postmortem frontal and temporal cortex from AD and matched control brains.RESULTSWestern blot analysis demonstrated a significant regional increase in hBCATc expression in the hippocampus (↑ 36%; p-values of 0.012), with an increase of ↑ 160% reported for hBCATm in the frontal and temporal cortex (p-values = 4.22 × 10-4 and 2.79 × 10-5, respectively) in AD relative to matched controls, with evidence of post-translational modifications to hBCATm, more prominent in AD samples. Using immunohistochemistry, a significant increase in immunopositive labelling of hBCATc was observed in the CA1 and CA4 region of the hippocampus (p-values = 0.011 and 0.026, respectively) correlating with western blot analysis. Moreover, the level of hBCATm in the frontal and temporal cortex correlated significantly with disease severity, as indicated by Braak staging (p-values = 5.63 × 10-6 and 9.29 × 10-5, respectively).CONCLUSIONThe expression of the hBCAT proteins is significantly elevated in AD brain. This may modulate glutamate production and toxicity, and thereby play a role in the pathogenesis of the disease

The branched-chain aminotransferase proteins: Novel redox chaperones for protein disulfide isomerase-implications in Alzheimer's disease

Aims: The human branched-chain aminotransferase proteins (hBCATm and hBCATc) are regulated through oxidation and S-nitrosation. However, it remains unknown whether they share common redox characteristics to enzymes such as protein disulfide isomerase (PDI) in terms of regulating cellular repair and protein misfolding. Results: Here, similar to PDI, the hBCAT proteins showed dithiol-disulfide isomerase activity that was mediated through an S-glutathionylated mechanism. Site-directed mutagenesis of the active thiols of the CXXC motif demonstrates that they are fundamental to optimal protein folding. Far Western analysis indicated that both hBCAT proteins can associate with PDI. Co-immunoprecipitation studies demonstrated that hBCATm directly binds to PDI in IMR-32 cells and the human brain. Electron and confocal microscopy validated the expression of PDI in mitochondria (using Mia40 as a mitochondrial control), where both PDI and Mia40 were found to be co-localized with hBCATm. Under conditions of oxidative stress, this interaction is decreased, suggesting that the proposed chaperone role for hBCATm may be perturbed. Moreover, immunohistochemistry studies show that PDI and hBCAT are expressed in the same neuronal and endothelial cells of the vasculature of the human brain, supporting a physiological role for this binding. Innovation: This study identifies a novel redox role for hBCAT and confirms that hBCATm differentially binds to PDI under cellular stress. Conclusion: These studies indicate that hBCAT may play a role in the stress response of the cell as a novel redox chaperone, which, if compromised, may result in protein misfolding, creating aggregates as a key feature in neurodegenerative conditions such as Alzheimer's disease. © 2014 Mary Ann Liebert, Inc

Measurement strategies for remote sensing applications

Remote sensing has grown to encompass many instruments and observations, with concomitant data from a huge number of targets. As evidenced by the impressive growth in the number of published papers and presentations in this field, there is a great deal of interest in applying these capabilities. The true challenge is to transition from directly observed data sets to obtaining meaningful and robust information about remotely sensed targets. We use physics-based end-to-end modeling and analysis techniques as a framework for such a transition. Our technique starts with quantified observables and signatures of a target. The signatures are propagated through representative atmospheres to realistically modeled sensors. Simulated data are then propagated through analysis routines, yielding measurements that are directly compared to the original target attributes. We use this approach to develop measurement strategies which ensure that our efforts provide a balanced approach to obtaining substantive information on our targets

Controlling gold nanoparticle assembly on electron beam-reduced nitrophenyl self-assembled monolayers <i>via</i> electron dose

Electron beam lithography is a well-established tool suitable for the modification of substrate surface chemistry. It therefore follows that the deposition and self-assembly of nanoparticles on a surface can be directed using this method. This work explores the effect of electron dose on the electron beam lithographic patterning of self-assembled monolayers (SAMs) on gold surfaces. Electron beam irradiation of the sample induces conversion of the SAM terminal functional aromatic nitro (NO2) moieties to aromatic amino (NH2) moieties. The cationic NH2 functionalised regions direct the site-specific assembly of anionic citrate-passivated gold nanoparticles in aqueous solution at pH 4.5. Control of nanoparticle attachment to the SAM is demonstrated over the exposure range 5000–125,000 uC/cm2. Overexposure led to significant numbers of secondary electrons reaching the surface, causing conversion of functional aromatic moieties outside of the regions irradiated, which reduced feature quality and regional selectivity of adsorption

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

Demonstration of the temporal matter-wave Talbot effect for trapped matter waves

We demonstrate the temporal Talbot effect for trapped matter waves using ultracold atoms in an optical lattice. We investigate the phase evolution of an array of essentially non-interacting matter waves and observe matter-wave collapse and revival in the form of a Talbot interference pattern. By using long expansion times, we image momentum space with sub-recoil resolution, allowing us to observe fractional Talbot fringes up to 10th order.Comment: 17 pages, 7 figure

Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV

We report a measurement of the longitudinal double-spin asymmetry A_LL and the differential cross section for inclusive Pi0 production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV. The cross section was measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be in good agreement with a next-to-leading order perturbative QCD calculation. The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T < 11 GeV/c and excludes a maximal positive gluon polarization in the proton. The mean transverse momentum fraction of Pi0's in their parent jets was found to be around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC

Kaon Production and Kaon to Pion Ratio in Au+Au Collisions at \snn=130 GeV

Mid-rapidity transverse mass spectra and multiplicity densities of charged and neutral kaons are reported for Au+Au collisions at \snn=130 GeV at RHIC. The spectra are exponential in transverse mass, with an inverse slope of about 280 MeV in central collisions. The multiplicity densities for these particles scale with the negative hadron pseudo-rapidity density. The charged kaon to pion ratios are $K^+/\pi^- = 0.161 \pm 0.002 {\rm (stat)} \pm 0.024 {\rm (syst)}$ and $K^-/\pi^- = 0.146 \pm 0.002 {\rm (stat)} \pm 0.022 {\rm (syst)}$ for the most central collisions. The $K^+/\pi^-$ ratio is lower than the same ratio observed at the SPS while the $K^-/\pi^-$ is higher than the SPS result. Both ratios are enhanced by about 50% relative to p+p and $\bar{\rm p}$+p collision data at similar energies.Comment: 6 pages, 3 figures, 1 tabl

Azimuthal anisotropy and correlations in p+p, d+Au and Au+Au collisions at 200 GeV

We present the first measurement of directed flow ($v_1$) at RHIC. $v_1$ is found to be consistent with zero at pseudorapidities $\eta$ from -1.2 to 1.2, then rises to the level of a couple of percent over the range $2.4 < |\eta| < 4$. The latter observation is similar to data from NA49 if the SPS rapidities are shifted by the difference in beam rapidity between RHIC and SPS. Back-to-back jets emitted out-of-plane are found to be suppressed more if compared to those emitted in-plane, which is consistent with {\it jet quenching}. Using the scalar product method, we systematically compared azimuthal correlations from p+p, d+Au and Au+Au collisions. Flow and non-flow from these three different collision systems are discussed.Comment: Quark Matter 2004 proceeding, 4 pages, 3 figure