N-Acetylcysteine in Combination with IGF-1 Enhances Neuroprotection against Proteasome Dysfunction-Induced Neurotoxicity in SH-SY5Y Cells

Ubiquitin proteasome system (UPS) dysfunction has been implicated in the development of many neuronal disorders, including Parkinson’s disease (PD). Previous studies focused on individual neuroprotective agents and their respective abilities to prevent neurotoxicity following a variety of toxic insults. However, the effects of the antioxidant N-acetylcysteine (NAC) on proteasome impairment-induced apoptosis have not been well characterized in human neuronal cells. The aim of this study was to determine whether cotreatment of NAC and insulin-like growth factor-1 (IGF-1) efficiently protected against proteasome inhibitor-induced cytotoxicity in SH-SY5Y cells. Our results demonstrate that the proteasome inhibitor, MG132, initiates poly(ADP-ribose) polymerase (PARP) cleavage, caspase 3 activation, and nuclear condensation and fragmentation. In addition, MG132 treatment leads to endoplasmic reticulum (ER) stress and autophagy-mediated cell death. All of these events can be attenuated without obvious reduction of MG132 induced protein ubiquitination by first treating the cells with NAC and IGF-1 separately or simultaneously prior to exposure to MG132. Moreover, our data demonstrated that the combination of the two proved to be significantly more effective for neuronal protection. Therefore, we conclude that the simultaneous use of growth/neurotrophic factors and a free radical scavenger may increase overall protection against UPS dysfunction-mediated cytotoxicity and neurodegeneration

Exploring quantum criticality based on ultracold atoms in optical lattices

Critical behavior developed near a quantum phase transition, interesting in its own right, offers exciting opportunities to explore the universality of strongly-correlated systems near the ground state. Cold atoms in optical lattices, in particular, represent a paradigmatic system, for which the quantum phase transition between the superfluid and Mott insulator states can be externally induced by tuning the microscopic parameters. In this paper, we describe our approach to study quantum criticality of cesium atoms in a two-dimensional lattice based on in situ density measurements. Our research agenda involves testing critical scaling of thermodynamic observables and extracting transport properties in the quantum critical regime. We present and discuss experimental progress on both fronts. In particular, the thermodynamic measurement suggests that the equation of state near the critical point follows the predicted scaling law at low temperatures.Comment: 15 pages, 6 figure

Mechanism of an ATP-independent Protein Disaggregase. II. Distinct Molecular Interactions Drive Multiple Steps During Aggregate Disassembly

The ability of molecular chaperones to overcome the misfolding and aggregation of proteins is essential for the maintenance of proper protein homeostasis in all cells. Thus far, the best studied disaggregase systems are the Clp/Hsp100 family of “ATPases associated with various cellular activities” (AAA^+) ATPases, which use mechanical forces powered by ATP hydrolysis to remodel protein aggregates. An alternative system to disassemble large protein aggregates is provided by the 38-kDa subunit of the chloroplast signal recognition particle (cpSRP43), which uses binding energy with its substrate proteins to drive disaggregation. The mechanism of this novel chaperone remains unclear. Here, molecular genetics and structure-activity analyses show that the action of cpSRP43 can be dissected into two steps with distinct molecular requirements: (i) initial recognition, during which cpSRP43 binds specifically to a recognition motif displayed on the surface of the aggregate; and (ii) aggregate remodeling, during which highly adaptable binding interactions of cpSRP43 with hydrophobic transmembrane domains of the substrate protein compete with the packing interactions within the aggregate. This establishes a useful framework to understand the molecular mechanism by which binding interactions from a molecular chaperone can be used to overcome protein aggregates in the absence of external energy input from ATP

N-Acetylcysteine in Combination with IGF-1 Enhances Neuroprotection against Proteasome Dysfunction-Induced Neurotoxicity in SH-SY5Y Cells

Ubiquitin proteasome system (UPS) dysfunction has been implicated in the development of many neuronal disorders, including Parkinson’s disease (PD). Previous studies focused on individual neuroprotective agents and their respective abilities to prevent neurotoxicity following a variety of toxic insults. However, the effects of the antioxidant N-acetylcysteine (NAC) on proteasome impairment-induced apoptosis have not been well characterized in human neuronal cells. The aim of this study was to determine whether cotreatment of NAC and insulin-like growth factor-1 (IGF-1) efficiently protected against proteasome inhibitor-induced cytotoxicity in SH-SY5Y cells. Our results demonstrate that the proteasome inhibitor, MG132, initiates poly(ADP-ribose) polymerase (PARP) cleavage, caspase 3 activation, and nuclear condensation and fragmentation. In addition, MG132 treatment leads to endoplasmic reticulum (ER) stress and autophagy-mediated cell death. All of these events can be attenuated without obvious reduction of MG132 induced protein ubiquitination by first treating the cells with NAC and IGF-1 separately or simultaneously prior to exposure to MG132. Moreover, our data demonstrated that the combination of the two proved to be significantly more effective for neuronal protection. Therefore, we conclude that the simultaneous use of growth/neurotrophic factors and a free radical scavenger may increase overall protection against UPS dysfunction-mediated cytotoxicity and neurodegeneration

On the number of limit cycles of the Lienard equation

In this paper, we study a Lienard system of the form dot{x}=y-F(x), dot{y}=-x, where F(x) is an odd polynomial. We introduce a method that gives a sequence of algebraic approximations to the equation of each limit cycle of the system. This sequence seems to converge to the exact equation of each limit cycle. We obtain also a sequence of polynomials R_n(x) whose roots of odd multiplicity are related to the number and location of the limit cycles of the system.Comment: 10 pages, 5 figures. Submitted to Physical Review

Extracting density-density correlations from in situ images of atomic quantum gases

We present a complete recipe to extract the density-density correlations and the static structure factor of a two-dimensional (2D) atomic quantum gas from in situ imaging. Using images of non-interacting thermal gases, we characterize and remove the systematic contributions of imaging aberrations to the measured density-density correlations of atomic samples. We determine the static structure factor and report results on weakly interacting 2D Bose gases, as well as strongly interacting gases in a 2D optical lattice. In the strongly interacting regime, we observe a strong suppression of the static structure factor at long wavelengths.Comment: 15 pages, 5 figure

Octet magnetic moments and the Coleman-Glashow sum rule violation in the chiral quark model

Baryon octet magnetic moments when calculated within the chiral quark model, incorporating the orbital angular momentum as well as the quark sea contribution through the Cheng-Li mechanism, not only show improvement over the non relativistic quark model results but also gives a non zero value for the right hand side of Coleman-Glashow sum rule. When effects due to spin-spin forces between constituent quarks as well as `mass adjustments' due to confinement are added, it leads to an excellent fit for the case of p, \Sigma^+, \Xi^o and violation of Coleman-Glashow sum rule, whereas in almost all the other cases the results are within 5% of the data.Comment: 5 RevTeX pages, accepted for publication in PRD(Rapid Communication

Roles of seed components in the growth of barley seedlings under salt stress

The cereal endosperm provides nutrients for seedling growth. The effects of seed components in seedling establishments under salt stress are, however, not yet fully explored. In this study, 60 barley recombinant inbred lines derived from Lewis × Karl cross were grown in four different environments, and the seed contents of starch, total soluble protein, phytate, total phenolics, total flavonoids and total inorganic phosphorus were determined in the harvested grains. Seeds of each line from the four environments were also assayed for seedling growth under saline treatments from 0 to 400 mM NaCl. Root and shoot lengths after 7 days decreased with increasing salt concentration. Correlations between seed components and either root or shoot length were established across the four seed sources. ANOVA showed a significant environment/source effect for both seed components and seedling growth, although the latter was less affected by the seed-production environment. Modeling seedling length across multiple salinities for each seed source showed that the environment with the most saline-tolerant root-growth curve was that associated the highest seed phosphorus content. Correlations between seed components and seedling growth traits highlighted phytate and total inorganic phosphorus as key components for seedling growth under moderate salinities. Seed phytate contents benefited seedling growth, even at high salinities, suggesting an additional role for this seed component under stressful growth conditions, possibly linked to its potential function as an osmolyte source

Exponentially selective molecular sieving through angstrom pores

Two-dimensional crystals with angstrom-scale pores are widely considered as candidates for a next generation of molecular separation technologies aiming to provide extreme, exponentially large selectivity combined with high flow rates. No such pores have been demonstrated experimentally. Here we study gas transport through individual graphene pores created by low intensity exposure to low kV electrons. Helium and hydrogen permeate easily through these pores whereas larger species such as xenon and methane are practically blocked. Permeating gases experience activation barriers that increase quadratically with molecules' kinetic diameter, and the effective diameter of the created pores is estimated as ~2 angstroms, about one missing carbon ring. Our work reveals stringent conditions for achieving the long sought-after exponential selectivity using porous two-dimensional membranes and suggests limits on their possible performance

Intercomparison of methods of coupling between convection and large-scale circulation: 1. Comparison over uniform surface conditions

As part of an international intercomparison project, a set of single column models (SCMs) and cloud-resolving models (CRMs) are run under the weak temperature gradient (WTG) method and the damped gravity wave (DGW) method. For each model, the implementation of the WTG or DGW method involves a simulated column which is coupled to a reference state defined with profiles obtained from the same model in radiative-convective equilibrium. The simulated column has the same surface conditions as the reference state and is initialized with profiles from the reference state. We performed systematic comparison of the behavior of different models under a consistent implementation of the WTG method and the DGW method and systematic comparison of the WTG and DGW methods in models with different physics and numerics. CRMs and SCMs produce a variety of behaviors under both WTG and DGW methods. Some of the models reproduce the reference state while others sustain a large-scale circulation which results in either substantially lower or higher precipitation compared to the value of the reference state. CRMs show a fairly linear relationship between precipitation and circulation strength. SCMs display a wider range of behaviors than CRMs. Some SCMs under the WTG method produce zero precipitation. Within an individual SCM, a DGW simulation and a corresponding WTG simulation can produce different signed circulation. When initialized with a dry troposphere, DGW simulations always result in a precipitating equilibrium state. The greatest sensitivities to the initial moisture conditions occur for multiple stable equilibria in some WTG simulations, corresponding to either a dry equilibrium state when initialized as dry or a precipitating equilibrium state when initialized as moist. Multiple equilibria are seen in more WTG simulations for higher SST. In some models, the existence of multiple equilibria is sensitive to some parameters in the WTG calculations