Amyloid β peptides modify the expression of antioxidant repair enzymes and a potassium channel in the septohippocampal system

Alzheimer\u27s disease (AD) is a progressive, neurodegenerative brain disorder characterized by extracellular accumulations of amyloid β (Aβ) peptides, intracellular accumulation of abnormal proteins, and early loss of basal forebrain neurons. Recent studies have indicated that the conformation of Aβ is crucial for neuronal toxicity, with intermediate misfolded forms such as oligomers being more toxic than the final fibrillar forms. Our previous work shows that Aβ blocks the potassium (K(+)) currents IM and IA in septal neurons, increasing firing rates, diminishing rhythmicity and firing coherence. Evidence also suggests that oxidative stress (OS) plays a role in AD pathogenesis. Thus we wished to determine the effect of oligomeric and fibrillar forms of Aβ₁₋₄₂ on septohippocampal damage, oxidative damage, and dysfunction in AD. Oligomeric and fibrillar forms of Aβ₁₋₄₂ were injected into the CA1 region of the hippocampus in live rats. The rats were sacrificed 24 hours and 1 month after Aβ or sham injection to additionally evaluate the temporal effects. The expression levels of the K(+) voltage-gated channel, KQT-like subfamily, member 2 (KCNQ₂) and the OS-related genes superoxide dismutase 1, 8-oxoguanine DNA glycosylase, and monamine oxidase A, were analyzed in the hippocampus, medial, and lateral septum. Our results show that both forms of Aβ exhibit time-dependent differential modulation of OS and K(+) channel genes in the analyzed regions. Importantly, we demonstrate that Aβ injected into the hippocampus triggered changes in gene expression in anatomical regions distant from the injection site. Thus the Aβ effect was transmitted to anatomically separate sites, because of the functional coupling of the brain structures

Ultraviolet-Optical observations of the Seyfert 2 Galaxies NGC 7130, NGC 5135 and IC 3639: Implications for the Starburst-AGN Connection

We present and discuss HST (WFPC2 and FOC) images and UV GHRS spectra plus ground-based near UV through to near IR spectra of three Seyfert 2 nuclei (NGC 7130, NGC 5135 and IC 3639). These galaxies, together to Mrk 477, were selected from a bigger sample that comprises the 20 brightest Seyfert 2 nuclei, with the goal to study the origin of the UV-optical-near IR featureless continuum in Seyfert 2 nuclei. These four galaxies have bolometric luminosities, as computed with the four IRAS bands, of 10^11 Lsol. They are close enough to be resolved with HST the nuclear zone. This makes these Seyfert 2 galaxies benchmarks to study the Starburst-AGN connection in more distant galaxies. The data provide direct evidence of the existence of a central nuclear starburst that dominates the UV light, and that seem to be responsible for the origin of the so called featureless continuum. These starbursts are dusty and compact. They have sizes (from less than 100 pc to a few hundred pc) much smaller and closer to the nucleus than that seen in the prototype Seyfert 2 galaxy NGC 1068. The bolometric luminosity of these starbursts is similar to the estimated bolometric luminosities of their obscured Seyfert 1 nuclei, and thus they contribute in the same amount to the overall energetics of these galaxies.Comment: to be published in ApJ 505, September issue. The figures are in a tar files at: http://www.iaa.es/~rosa/Seyfert

Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates

In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological conditions associated with mitochondrial deficiency. With the goal to decipher the role of the ATPase inhibitory factor 1 (IF1) in brain development, we employed the zebrafish as elected model reporting that the Atpif1a−/− zebrafish mutant, pinotage (pnttq209), which lacks one of the two IF1 paralogous, exhibits visual impairment alongside increased apoptotic bodies and neuroinflammation in both brain and retina. This associates with increased processing of the dynamin-like GTPase optic atrophy 1 (OPA1), whose ablation is a direct cause of inherited optic atrophy. Defects in vision associated with the processing of OPA1 are specular in Atpif1−/− mice thus confirming a regulatory axis, which interlinks IF1 and OPA1 in the definition of mitochondrial fitness and specialised brain functions. This study unveils a functional relay between IF1 and OPA1 in central nervous system besides representing an example of how the zebrafish model could be harnessed to infer the activity of mitochondrial proteins during development

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum