| 1. |
- Kumar, S., et al.
(författare)
-
Band structures in Rh-99
- 2014
-
Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 41:10
-
Tidskriftsartikel (refereegranskat)abstract
- Excited states in the Rh-99 nucleus were populated using the fusion-evaporation reaction As-75(Si-28,2p2n) at E-lab = 120 MeV and the de-excitations were investigated through in-beam gamma-ray spectroscopic techniques using the INGA spectrometer consisting of 18 clover detectors. The observed band structures are discussed in the framework of tilted axis cranking shell-model calculations. Level structures at low energies are identified as resulting from the rotational bands based on the pi p(1/2) and pi g(9/2) configurations. The Delta I = 1 coupled bands are observed at higher excitation energies and have been interpreted as based on the pi g(9/2) circle times nu g(7/2) circle times nu d(5/2), pi p(1/2) circle times nu h(11/2) circle times nu d(5/2) and pi g(9/2) circle times nu h(11/2) circle times nu g(7/2) configurations. Calculations based on cranked Nilsson- Strutinsky (CNS) formalism have been performed to interpret the favoured states with I-pi = (41/2(-), 43/2(-)) and (51/2(-), 53/2(-)) as maximal spin aligned states built on the valence space nu(d(5/2)g(7/2))(15/2)(3), (17/2)(h(11/2))(11/2)(1) configuration combined with the fully-aligned pi(g(9/2))(25/2)(5) configuration and the pi(g(9/2))(15/2)(5) configuration with one anti-aligned g(9/2) proton, respectively.
|
|
| 3. |
- Ramakrishna, Sarayu, et al.
(författare)
-
APOE4 affects basal and NMDAR mediated protein synthesis in neurons by perturbing calcium homeostasis
- 2021
-
Ingår i: The Journal of Neuroscience. - 1529-2401. ; 41:42, s. 8686-8709
-
Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E (APOE), one of the primary lipoproteins in the brain has three isoforms in humans - APOE2, APOE3, and APOE4. APOE4 is the most well-established risk factor increasing the pre-disposition for Alzheimer's disease. The presence of the APOE4 allele alone is shown to cause synaptic defects in neurons and recent studies have identified multiple pathways directly influenced by APOE4. However, the mechanisms underlying APOE4 induced synaptic dysfunction remain elusive. Here, we report that the acute exposure of primary cortical neurons or synaptoneurosomes to APOE4 leads to a significant decrease in global protein synthesis. Primary cortical neurons were derived from male and female embryos of Sprague-Dawley rats or C57BL/6J mice. Synaptoneurosomes were prepared from P30 male Sprague-Dawley rats. APOE4 treatment also abrogates the NMDA mediated translation response indicating an alteration of synaptic signaling. Importantly, we demonstrate that both APOE3 and APOE4 generate a distinct translation response which is closely linked to their respective calcium signature. Acute exposure of neurons to APOE3 causes a short burst of calcium through NMDARs leading to an initial decrease in protein synthesis which quickly recovers. Contrarily, APOE4 leads to a sustained increase in calcium levels by activating both NMDARs and L-VGCCs, thereby causing sustained translation inhibition through eEF2 phosphorylation, which in turn disrupts the NMDAR response. Thus, we show that APOE4 affects basal and activity mediated protein synthesis responses in neurons by affecting calcium homeostasis.SIGNIFICANCE STATEMENTDefective protein synthesis has been shown as an early defect in familial Alzheimer's disease. However, this has not been studied in the context of sporadic Alzheimer's disease, which constitutes the majority of cases. In our study, we show that APOE4, the predominant risk factor for Alzheimer's disease, inhibits global protein synthesis in neurons. APOE4 also affects NMDA activity mediated protein synthesis response, thus inhibiting synaptic translation. We also show that the defective protein synthesis mediated by APOE4 is closely linked to the perturbation of calcium homeostasis caused by APOE4 in neurons. Thus, we propose the dysregulation of protein synthesis as one of the possible molecular mechanisms to explain APOE4 mediated synaptic and cognitive defects. Hence, the study not only suggests an explanation for the APOE4 mediated pre-disposition to Alzheimer's disease, it also bridges the gap in understanding APOE4 mediated pathology.
|
|
