Role of Membrane GM1 on Early Neuronal Membrane Actions of Aβ During Onset of Alzheimer\u27s Disease

The ability of beta-amyloid peptide (Aβ) to disrupt the plasma membrane through formation of pores and membrane breakage has been previously described. However, the molecular determinants for these effects are largely unknown. In this study, we examined if the association and subsequent membrane perforation induced by Aβ was dependent on GM1levels. Pretreatment of hippocampal neurons with D-PDMP decreased GM1 and Aβ clustering at the membrane (Aβ fluorescent-punctas/20 μm, control = 16.2 ± 1.1 vs. D-PDMP = 6.4 ± 0.4, p \u3c 0.001). Interestingly, membrane perforation with Aβ occurred with a slower time course when the GM1 content was diminished (time to establish perforated configuration (TEPC) (min): control = 7.8 ± 2 vs. low GM1 = 12.1 ± 0.5, p \u3c 0.01), suggesting that the presence of GM1 in the membrane can modulate the distribution and the membrane perforation by Aβ. On the other hand, increasing GM1 facilitated the membrane perforation (TEPC: control = 7.8 ± 2 vs. GM1 = 6.2 ± 1 min, p \u3c 0.05). Additionally, using Cholera Toxin Subunit-B (CTB) to block the interaction of Aβ with GM1 attenuated membrane perforation significantly. Furthermore, pretreatment with CTB decreased the membrane association of Aβ (fluorescent-punctas/20 μm, Aβ: control = 14.8 ± 2.5 vs. CTB = 8 ± 1.4, p \u3c 0.05), suggesting that GM1 also plays a role in both association of Aβ with the membrane and in perforation. In addition, blockade of the Aβ association with CTB inhibited synaptotoxicity. Taken together, our results strongly suggest that membrane lipid composition can affect the ability of Aβ to associate and subsequently perforate the plasma membrane thereby modulating its neurotoxicity in hippocampal neurons

Molecular Requirements for Ethanol Differential Allosteric Modulation of Ligand-Gated Ion Channels Based on Selective G Beta Gamma Modulation

It is now believed that the allosteric modulation produced by ethanol in glycine receptors (GlyRs) depends on alcohol binding to discrete sites within the protein structure. Thus, the differential ethanol sensitivity of diverse GlyR isoforms and mutants was explained by the presence of specific residues in putative alcohol pockets. Here, we demonstrate that ethanol sensitivity in two LGIC members, the GlyR adult alpha1 and embryonic alpha2 subunits, can be modified through selective mutations that rescued or impaired Gbetagamma modulation. Even though that both isoforms were able to physically interact with Gbetagamma, only the alpha1 GlyR was functionally modulated by Gbetagamma and pharmacological ethanol concentrations. Remarkably, the simultaneous switching of two transmembrane and a single extracellular residue in alpha2 GlyRs was enough to generate GlyRs modulated by Gbetagamma and low ethanol concentrations. Interestingly, while we found that these TM residues were different to those in the alcohol binding site, the extracellular residue was recently implicated in conformational changes important to generate a pre-open activated state that precedes ion channel gating. Thus, these results support the idea that the differential ethanol sensitivity of these two GlyR isoforms rests on conformational changes in transmembrane and extracellular residues within the ion channel structure rather than in differences in alcohol binding pockets. Our results describe the molecular basis for the differential ethanol sensitivity of two LGIC members based on selective Gbetagamma modulation and provide a new mechanistic framework for allosteric modulations of abuse drugs

Vegetarian nutrition - Comparing physical performance of omnivorous and vegetarian athletes

Abstract of a conference presentation

The Acute Physiological Responses of Eccentric Cycling During the Recovery Periods of a High Intensity Concentric Cycling Interval Session

Eccentric and concentric exercise is associated with disparate acute and chronic responses. We uniquely interspersed workload equivalent eccentric cycling during each recovery period of a high intensity interval training (HIIT) cycling trial to determine acute cardiopulmonary, thermal and psycho-physiological responses. Twelve males [age 28 years (SD 6), peak oxygen consumption 48 mL ⋅ kg-1 ⋅ min-1 (SD 6)] completed two high intensity interval cycling trials [4 x 5 min, 60% peak power output (PPO)] separated by 7-10 days. The CONR trial required participants to cycle concentrically during each recovery period (5 min, 30% PPO). The ECCR trial modified the recovery to be eccentric cycling (5 min, 60% PPO). High intensity workload (CONR: 187 ± 17; ECCR: 187 ± 21 W), oxygen consumption (CONR: 2.55 ± 0.17; ECCR: 2.68 ± 0.20 L ⋅ min-1), heart rate (CONR: 165 ± 7; ECCR: 171 ± 10 beats ⋅ min-1) and RPE legs (CONR: 15 ± 3; ECCR: 15 ± 3) were equivalent between trials. Eccentric cycling recovery significantly increased external workload (CONR: 93 ± 18; ECCR: 196 ± 24 W, P \u3c 0.01) yet lowered oxygen consumption (CONR: 1.51 ± 0.18; ECCR: 1.20 ± 0.20 L ⋅ min-1, P \u3c 0.05) while heart rate (CONR: 132 ± 13; ECCR: 137 ± 12 beats ⋅ min-1) and RPE of the legs (CONR: 11 ± 7; ECCR: 12 ± 7) remained equivalent. There was no significant difference in the aural temperature between the trials (ECCR: 37.3 ± 0.1°C; CONR: 37.4 ± 0.1°C, P \u3e 0.05), yet during recovery periods mean skin temperature was significantly elevated in the ECCR (ECCR: 33.9 ± 0.2°C; CONR: 33.3 ± 0.2°C, P \u3c 0.05). Participants preferred ECCR (10/12) and rated the ECCR as more achievable (82.8 ± 11.4 mm) than CONR (79.4 ± 15.9 mm, P \u3c 0.01). In conclusion, eccentric cycling during the recovery period of a HIIT training session, offers a novel approach to concurrent training methodology. The unique cardiopulmonary and skeletal muscle responses facilitate the achievement of both training stimuli within a single exercise bout

Relationship between long-chain omega-3 polyunsaturated fatty acid intake and ankle brachial index, pulse wave velocity and resting heart rate in a sample of overweight adults: A secondary analysis of baseline data in the HealthTrack study

Aim: The present study aimed to explore the association between dietary long-chain omega-3 polyunsaturated fatty acid (LCn3PUFA) intake and cardiovascular risk indicators (ankle brachial index, resting heart rate and brachial-ankle pulse wave velocity) in a clinical sample of overweight and obese participants volunteering for a weight loss trial. Methods: This was a secondary analysis of baseline data from the HealthTrack study (n = 351). LCn3PUFA intake was calculated via a diet history and the association with ankle brachial index, resting heart rate and brachio-ankle pulse wave velocity was explored using linear regression after controlling for covariates. Results: LCn3PUFA intake was inversely associated with ankle brachial index (R2change = 0.021, F change (1, 339) = 8.864, P \u3c 0.05) and resting heart rate (R2change = 0.014, F change (1, 342) = 5.337, P \u3c 0.05) but not with brachio-ankle pulse wave velocity (R2change = 0.001, F change (1, 339) = 0.725, P \u3e 0.05). Conclusions: In this clinical sample of overweight adults, LCn3PUFA consumption was significantly associated with a lower resting heart rate, adding to the current evidence on the potential benefits of LCn3PUFA consumption. It also supports the value of targeting a diet rich in this nutrient when planning future dietetic approaches. Relationships with ankle brachial index and pulse wave velocity require further investigation. Future research should assess the effect of changes in dietary LCn3PUFA intake on novel cardiovascular risk indicators

Why are fish oil supplements apparently failing to reproduce fish consumption epidemiology in RCT for cardiovascular disease?

Abstract of a presentation

Spin-polarized transport in a lateral two-dimensional diluted magnetic semiconductor electron gas

The transport property of a lateral two-dimensional diluted magnetic semiconductor electron gas under a spatially periodic magnetic field is investigated theoretically. We find that the electron Fermi velocity along the modulation direction is highly spin-dependent even if the spin polarization of the carrier population is negligibly small. It turns out that this spin-polarized Fermi velocity alone can lead to a strong spin polarization of the current, which is still robust against the energy broadening effect induced by the impurity scattering.Comment: 3 pages, 3 figures, submitted to Appl. Phys. Let

Survival of Dopaminergic Amacrine Cells after Near-Infrared Light Treatment in MPTP-Treated Mice

We examined whether near-infrared light (NIr) treatment (photobiomodulation) saves dopaminergic amacrine cells of the retina in an acute and a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease. For the acute model, BALB/c mice had MPTP (100 mg/kg) or saline injections over 30 hours, followed by a six-day-survival period. For the chronic model, mice had MPTP (200 mg/kg) or saline injections over five weeks, followed by a three-week-survival period. NIr treatment was applied either at the same time (simultaneous series) or well after (posttreatment series) the MPTP insult. There were four groups within each series: Saline, Saline-NIr, MPTP, and MPTP-NIr. Retinae were processed for tyrosine hydroxylase (TH) immunochemistry, and cell number was analysed. In the MPTP groups, there was a significant reduction in TH+ cell number compared to the saline controls; this reduction was greater in the acute (~50%) compared to the chronic (~30%) cases. In the MPTP-NIr groups, there were significantly more TH+ cells than in the MPTP groups of both series (~30%). In summary, we showed that NIr treatment was able to both protect (simultaneous series) and rescue (posttreatment series) TH+ cells of the retina from parkinsonian insult

Spin Hall effect in the kagome lattice with Rashba spin-orbit interaction

We study the spin Hall effect in the kagom\'{e} lattice with Rashba spin-orbit coupling. The conserved spin Hall conductance $\sigma_{xy}^{s}$ (see text) and its two components, i.e., the conventional term $\sigma_{xy}^{s0}$ and the spin-torque-dipole term $\sigma_{xy}^{s\tau}$, are numerically calculated, which show a series of plateaus as a function of the electron Fermi energy $\epsilon_{F}$. A consistent two-band analysis, as well as a Berry-phase interpretation, is also given. We show that these plateaus are a consequence of the various Fermi-surface topologies when tuning $\epsilon_{F}$. In particular, we predict that compared to the case with the Fermi surface encircling the $\mathbf{\Gamma}$ point in the Brillouin zone, the amplitude of the spin Hall conductance with the Fermi surface encircling the $\mathbf{K}$ points is twice enhanced, which makes it highly meaningful in the future to systematically carry out studies of the $\mathbf{K}$-valley spintronics.Comment: 7 pages, 3 figures. Phys. Rev. B (in press

Status and specifications of a Project X front-end accelerator test facility at Fermilab

This paper describes the construction and operational status of an accelerator test facility for Project X. The purpose of this facility is for Project X component development activities that benefit from beam tests and any development activities that require 325 MHz or 650 MHz RF power. It presently includes an H- beam line, a 325 MHz superconducting cavity test facility, a 325 MHz (pulsed) RF power source, and a 650 MHz (CW) RF power source. The paper also discusses some specific Project X components that will be tested in the facility.Comment: 3 pp. Particle Accelerator, 24th Conference (PAC'11) 2011. 28 Mar - 1 Apr 2011. New York, US