Solitary waves and supersonic reaction front in metastable solids

Motivated by an increasing number of remarkable experimental observations on the role of pressure and shear stress in solid reactions, explosions and detonations, we present a simple toy model that embodies nonlinear elasticity and dispersion as well as chemical or phase transformation. This generalization of the Toda Lattice provides an effective model for the description of the organization during an abrupt transformation in a solid. One of the challenges is to capture both the equilibrium degrees of freedom as well as to quantify the possible role of out-of-equilibrium perturbations. In the Toda Lattice, we verify that the particle velocities converge in distribution towards the Maxwell-Boltzmann distribution, thus allowing us to define a bona-fide temperature. In addition, the balance between nonlinearity and wave dispersion may create solitary waves that act as energy traps. In the presence of reactive chemistry, we show that the trapping of the released chemical energy in solitary waves that are excited by an initial perturbation provides a positive feedback that enhances the reaction rate and leads to supersonic explosion front propagation. These modes of rupture observed in our model may provide a first-order description of ultrafast reactions of heterogeneous mixtures under mechanical loading

What’s Sex (Composition) Got to Do with It? The Importance of Sex Composition of Gangs for Female and Male Members’ Offending and Victimization

Sex composition of groups has been theorized in organizational sociology and found in prior work to structure female and male members’ behaviors and experiences. Peer group and gang literature similarly finds that the sex gap in offending varies across groups of differing sex ratios. Drawing on this and other research linking gang membership, offending, and victimization, we examine whether sex composition of gangs is linked to sex differences in offending in this sample, further assess whether sex composition similarly structures females’ and males’ victimization experiences, and if so, why. Self-report data from gang members in a multi-site, longitudinal study of 3,820 youths are employed. Results support previous findings about variations in member delinquency by both sex and sex composition of the gang and also indicate parallel variations in members’ victimization. These results are further considered within the context of facilitating effects such as gender dynamics, gang characteristics, and normative orientation

Conformational Altered p53 as an Early Marker of Oxidative Stress in Alzheimer's Disease

In order to study oxidative stress in peripheral cells of Alzheimer's disease (AD) patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD) and subjects harboured AD related mutation (ADmut), were used. Oxidative stress was evaluated measuring i) the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii) and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRD). We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut but not in EOSAD patients. However, oxidative imbalance in EOSAD as well as ADmut lymphocytes was underlined by a reduced SOD activity and GRD activity in both pathological groups in comparison with cells derived from healthy subjects. Furthermore, a redox modulated p53 protein was found conformational altered in both EOSAD and ADmut B lymphocytes in comparison with control cells. This conformational altered p53 isoform, named “unfolded p53”, was recognized by the use of two specific conformational anti-p53 antibodies. Immunoprecipitation experiments, performed with the monoclonal antibodies PAb1620 (that recognizes p53wt) and PAb240 (that is direct towards unfolded p53), and followed by the immunoblotting with anti-4-hydroxynonenal (HNE) and anti- 3-nitrotyrosine (3NT) antibodies, showed a preferential increase of nitrated tyrosine residues in unfolded p53 isoform comparing to p53 wt protein, in both ADmut and EOSAD. In addition, a correlation between unfolded p53 and SOD activity was further found. Thus this study suggests that ROS/RNS contributed to change of p53 tertiary structure and that unfolded p53 can be considered as an early marker of oxidative imbalance in these patients

Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death

Amyloid β-peptide [Aβ(1-42)] is central to the pathogenesis of Alzheimer's disease (AD), and the AD brain is under intense oxidative stress, including membrane lipid peroxidation. Aβ(1-42) causes oxidative stress in and neurotoxicity to neurons in mechanisms that are inhibited by Vitamin E and involve the single methionine residue of this peptide. In particular, Aβ induces lipid peroxidation in ways that are inhibited by free radical antioxidants. Two reactive products of lipid peroxidation are the alkenals, 4-hydroxynonenal (HNE) and 2-propenal (acrolein). These alkenals covalently bind to synaptosomal protein cysteine, histidine, and lysine residues by Michael addition to change protein conformation and function. HNE or acrolein binding to proteins introduces a carbonyl to the protein, making the protein oxidatively modified as a consequence of lipid peroxidation. Immunoprecipitation of proteins from AD and control brain, obtained no longer than 4h PMI, showed selective proteins are oxidatively modified in the AD brain. Creatine kinase (CK) and β-actin have increased carbonyl groups, and Glt-1, a glutamate transporter, has increased binding of HNE in AD. Aβ(1-42) addition to synaptosomes also results in HNE binding to Glt-1, thereby coupling increased Aβ(1-42) in AD brain to increased lipid peroxidation and its sequelae and possibly explaining the mechanism of glutatmate transport inhibition known in AD brain. Aβ also inhibits CK. Implications of these findings relate to decreased energy utilization, altered assembly of cytoskeletal proteins, and increased excitotoxicity to neurons by glutamate, all reported for AD. The epsilon-4 allele of the lipid carrier protein apolipoprotein E (APOE) allele is a risk factor for AD. Synaptosomes from APOE knock-out mice are more vulnerable to Aβ-induced oxidative stress (protein oxidation, lipid peroxidation, and ROS generation) than are those from wild-type mice. Further, synaptosomes from allele-specific APOE knock-in mice have tiered vulnerability to Aβ(1-42)-induced oxidative stress, with APOE4 more vulnerable to Aβ(1-42) than are those from APOE2 or APOE3 mice. These results are consistent with the notion of a coupling of the oxidative environment in AD brain and increased risk of developing this disorder. Taken together, the findings from in-vitro studies of lipid peroxidation induced by Aβ(1-42) and postmortem studies of lipid peroxidation (and its sequelae) in AD brain may help explain the APOE allele-related risk for AD, some of the functional and structural alterations in AD brain, and strongly support a causative role of Aβ(1-42)-induced oxidative stress in AD neurodegeneration

Modulation of phospholipid asymmetry in synaptosomal membranes by the lipid peroxidation products, 4-hydroxynonenal and acrolein: implications for Alzheimer's disease

Membrane lipid bilayer asymmetry is maintained by the ATP-dependent enzyme flippase. An early signal of synaptosomal apoptosis is the loss of phospholipid asymmetry and the appearance of phosphatidylserine (PS) in the outer leaflet of the membrane. Two highly reactive products of lipid peroxidation, 4-hydroxynonenal (HNE) and acrolein, both elevated in Alzheimer's disease (AD) brain, have been shown to induce apoptosis and disrupt cellular ion homeostasis. These reactive aldehydes can structurally modify proteins by covalent interaction and inhibit enzyme function. Phospholipid asymmetry of PS is maintained by the ATP-requiring enzyme flippase. We have investigated the inactivation of the transmembrane enzyme aminophospholipid-translocase (or flippase) by HNE and acrolein. Flippase activity depends on a critical cysteine residue, a possible site of covalent modification by HNE or acrolein. The present study demonstrates that these alkenals induce the appearance of PS on the outer bilayer lamellae and suggests that increases in intracellular Ca(2+) might not be the sole cause for loss of flippase activity. Rather, other mechanisms that could modulate the function of flippase might be important in phospholipid asymmetry disruption. These results are discussed with potential relevance to neuronal loss in Alzheimer's disease brain

Evidence that Amyloid Beta-Peptide-Induced Lipid Peroxidation and Its Sequelae in Alzheimer's Disease Brain Contributes to Neuronal Death

Amyloid beta-peptide [Abeta(1-42)] is central to the pathogenesis of Alzheimer's disease (AD), and the AD brain is under intense oxidative stress, including membrane lipid peroxidation. Abeta(1-42) causes oxidative stress in and neurotoxicity to neurons in mechanisms that are inhibited by Vitamin E and involve the single methionine residue of this peptide. In particular, Abeta induces lipid peroxidation in ways that are inhibited by free radical antioxidants. Two reactive products of lipid peroxidation are the alkenals, 4-hydroxynonenal (HNE) and 2-propenal (acrolein). These alkenals covalently bind to synaptosomal protein cysteine, histidine, and lysine residues by Michael addition to change protein conformation and function. HNE or acrolein binding to proteins introduces a carbonyl to the protein, making the protein oxidatively modified as a consequence of lipid peroxidation. Immunoprecipitation of proteins from AD and control brain, obtained no longer than 4 h PMI, showed selective proteins are oxidatively modified in the AD brain. Creatine kinase (CK) and beta-actin have increased carbonyl groups, and Glt-1, a glutamate transporter, has increased binding of HNE in AD. Abeta(1-42) addition to synaptosomes also results in HNE binding to Glt-1, thereby coupling increased Abeta(1-42) in AD brain; to increased lipid peroxidation and its sequelae and possibly explaining the mechanism of glutatmate transport inhibition known in AD brain. Ap also inhibits CK. Implications of these findings relate to decreased energy utilization, altered assembly of cytoskeletal proteins, and increased excitotoxicity to neurons by glutamate, all reported for AD. The epsilon-4 allele of the lipid carrier protein apolipoprotein E (APOE) allele is a risk factor for AD. Synaptosomes from APOE knock-out mice are more vulnerable to Abeta-induced oxidative stress (protein oxidation, lipid peroxidation, and ROS generation) than are those from wild-type mice. Further, synaptosomes from allele-specific APOE knock-in mice have tiered vulnerability to Abeta(1-42)-induced oxidative stress, with APOE4 more vulnerable to Abeta(1-42) than are those from APOE2 or APOE3 mice. These results are consistent with the notion of a coupling of the oxidative environment in AD brain and increased risk of developing this disorder. Taken together, the findings from in-vitro studies of lipid peroxidation induced by Abeta(1-42) and postmortem studies of lipid peroxidation (and its sequelae) in AD brain may help explain the APOE allele-related risk for AD, some of the functional and structural alterations in AD brain, and strongly support a causative role of Abeta(1-42)-induced oxidative stress in AD neurodegeneratio