Phenomenological model for the remanent magnetization of dilute quasi-one-dimensional antiferromagnets

We present a phenomenological model for the remanent magnetization at low temperatures in the quasi-one-dimensional dilute antiferromagnets CH_{3}NH_{3}Mn_{1-x}Cd_{x} Cl_{3}\cdot 2H_{2}O and (CH_{3})_{2}NH_{2}Mn_{1-x}Cd_{x}Cl_{3}\cdot 2H_{2}O. The model assumes the existence of uncompensated magnetic moments induced in the odd-sized segments generated along the Mn(^{2+}) chains upon dilution. These moments are further assumed to correlate ferromagnetically after removal of a cooling field. Using a (mean-field) linear-chain approximation and reasonable set of model parameters, we are able to reproduce the approximate linear temperature dependence observed for the remanent magnetization in the real compounds.Comment: 5 pages, 2 figures; final version to appear in Physical Review

Evidence for structural and electronic instabilities at intermediate temperatures in κ\kappa-(BEDT-TTF)2_{2}X for X=Cu[N(CN)2_{2}]Cl, Cu[N(CN)2_{2}]Br and Cu(NCS)2_{2}: Implications for the phase diagram of these quasi-2D organic superconductors

We present high-resolution measurements of the coefficient of thermal expansion $\alpha (T)=\partial \ln l(T)/\partial T$ of the quasi-twodimensional (quasi-2D) salts $\kappa$-(BEDT-TTF)$_2$X with X = Cu(NCS)$_2$, Cu[N(CN)$_2$]Br and Cu[N(CN)$_2$]Cl. At intermediate temperatures (B), distinct anomalies reminiscent of second-order phase transitions have been found at $T^\ast = 38$ K and 45 K for the superconducting X = Cu(NCS)$_2$ and Cu[N(CN)$_2$]Br salts, respectively. Most interestingly, we find that the signs of the uniaxial pressure coefficients of $T^\ast$ are strictly anticorrelated with those of $T_c$. We propose that $T^\ast$ marks the transition to a spin-density-wave (SDW) state forming on minor, quasi-1D parts of the Fermi surface. Our results are compatible with two competing order parameters that form on disjunct portions of the Fermi surface. At elevated temperatures (C), all compounds show $\alpha (T)$ anomalies that can be identified with a kinetic, glass-like transition where, below a characteristic temperature $T_g$, disorder in the orientational degrees of freedom of the terminal ethylene groups becomes frozen in. We argue that the degree of disorder increases on going from the X = Cu(NCS)$_2$ to Cu[N(CN)$_2$]Br and the Cu[N(CN)$_2$]Cl salt. Our results provide a natural explanation for the unusual time- and cooling-rate dependencies of the ground-state properties in the hydrogenated and deuterated Cu[N(CN)$_2$]Br salts reported in the literature.Comment: 22 pages, 7 figure

Dose-dependent study of the effects of acute lindane administration on rat liver superoxide anion production, antiooidant enzyme activities and lipid peroxidation

The administration of single i.p. doses of lindane (20, 40, 60 and 80 mg/kg) to rats produced a progressive increase in the liver microsomal content of cytochrome P-450 and in the rate of superoxide anion generation, as measured by adrenochrome formation. A dose-dependent increase in lipid peroxidation of liver homogenates, assessed by measuring thiobarbituric acid reactants, was also found. Lindane treatment did not alter the activity of liver glucose-6-phosphate dehydrogenase, glutathione reductase or glutathione peroxidase, while that of superoxide dismutase and catalase was significantly reduced. These changes were accompanied by a progressive liver steatosis. The collected metabolic data were interpreted in terms of a causal relationship between an increase in superoxide radical generation, secondary to cytochrome P-450 induction and a resulting increase in lipid peroxidation. The decrease in superoxide dismutase and catalase activities is likely to contribute to the increased le

Heparanase Levels Are Elevated in the Urine and Plasma of Type 2 Diabetes Patients and Associate with Blood Glucose Levels

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains of heparan sulfate proteoglycans. Utilizing an ELISA method capable of detection and quantification of heparanase, we examined heparanase levels in the plasma and urine of a cohort of 29 patients diagnosed with type 2 diabetes mellitus (T2DM), 14 T2DM patients who underwent kidney transplantation, and 47 healthy volunteers. We provide evidence that heparanase levels in the urine of T2DM patients are markedly elevated compared to healthy controls (1162±181 vs. 156±29.6 pg/ml for T2DM and healthy controls, respectively), increase that is statistically highly significant (P<0.0001). Notably, heparanase levels were appreciably decreased in the urine of T2DM patients who underwent kidney transplantation, albeit remained still higher than healthy individuals (P<0.0001). Increased heparanase levels were also found in the plasma of T2DM patients. Importantly, urine heparanase was associated with elevated blood glucose levels, implying that glucose mediates heparanase upregulation and secretion into the urine and blood. Utilizing an in vitro system, we show that insulin stimulates heparanase secretion by kidney 293 cells, and even higher secretion is observed when insulin is added to cells maintained under high glucose conditions. These results provide evidence for a significant involvement of heparanase in diabetic complications

Firefly Luciferase and Rluc8 Exhibit Differential Sensitivity to Oxidative Stress in Apoptotic Cells

Over the past decade, firefly Luciferase (fLuc) has been used in a wide range of biological assays, providing insight into gene regulation, protein-protein interactions, cell proliferation, and cell migration. However, it has also been well established that fLuc activity can be highly sensitive to its surrounding environment. In this study, we found that when various cancer cell lines (HeLa, MCF-7, and 293T) stably expressing fLuc were treated with staurosporine (STS), there was a rapid loss in bioluminescence. In contrast, a stable variant of Renilla luciferase (RLuc), RLuc8, exhibited significantly prolonged functionality under the same conditions. To identify the specific underlying mechanism(s) responsible for the disparate sensitivity of RLuc8 and fLuc to cellular stress, we conducted a series of inhibition studies that targeted known intracellular protein degradation/modification pathways associated with cell death. Interestingly, these studies suggested that reactive oxygen species, particularly hydrogen peroxide (H2O2), was responsible for the diminution of fLuc activity. Consistent with these findings, the direct application of H2O2 to HeLa cells also led to a reduction in fLuc bioluminescence, while H2O2 scavengers stabilized fLuc activity. Comparatively, RLuc8 was far less sensitive to ROS. These observations suggest that fLuc activity can be substantially altered in studies where ROS levels become elevated and can potentially lead to ambiguous or misleading findings

Cell Survival from Chemotherapy Depends on NF-κB Transcriptional Up-Regulation of Coenzyme Q Biosynthesis

9 pages and 6 figures.[Background] Coenzyme Q (CoQ) is a lipophilic antioxidant that is synthesized by a mitochondrial complex integrated by at least ten nuclear encoded COQ gene products. CoQ increases cell survival under different stress conditions, including mitochondrial DNA (mtDNA) depletion and treatment with cancer drugs such as camptothecin (CPT). We have previously demonstrated that CPT induces CoQ biosynthesis in mammal cells.[Methodology/Principal Findings] CPT activates NF-κB that binds specifically to two κB binding sites present in the 5′-flanking region of the COQ7 gene. This binding is functional and induces both the COQ7 expression and CoQ biosynthesis. The inhibition of NF-κB activation increases cell death and decreases both, CoQ levels and COQ7 expression induced by CPT. In addition, using a cell line expressing very low of NF-κB, we demonstrate that CPT was incapable of enhancing enhance both CoQ biosynthesis and COQ7 expression in these cells.[Conclusions/Significance] We demonstrate here, for the first time, that a transcriptional mechanism mediated by NF-κB regulates CoQ biosynthesis. This finding contributes new data for the understanding of the regulation of the CoQ biosynthesis pathway.This work was supported by spanish Ministerio de Educacion y Ciencia Grant BFU2005-03017.Peer reviewe

Chikungunya Virus Neutralization Antigens and Direct Cell-to-Cell Transmission Are Revealed by Human Antibody-Escape Mutants

Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop “groove” as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis

High-Content, High-Throughput Analysis of Cell Cycle Perturbations Induced by the HSP90 Inhibitor XL888

BACKGROUND: Many proteins that are dysregulated or mutated in cancer cells rely on the molecular chaperone HSP90 for their proper folding and activity, which has led to considerable interest in HSP90 as a cancer drug target. The diverse array of HSP90 client proteins encompasses oncogenic drivers, cell cycle components, and a variety of regulatory factors, so inhibition of HSP90 perturbs multiple cellular processes, including mitogenic signaling and cell cycle control. Although many reports have investigated HSP90 inhibition in the context of the cell cycle, no large-scale studies have examined potential correlations between cell genotype and the cell cycle phenotypes of HSP90 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: To address this question, we developed a novel high-content, high-throughput cell cycle assay and profiled the effects of two distinct small molecule HSP90 inhibitors (XL888 and 17-AAG [17-allylamino-17-demethoxygeldanamycin]) in a large, genetically diverse panel of cancer cell lines. The cell cycle phenotypes of both inhibitors were strikingly similar and fell into three classes: accumulation in M-phase, G2-phase, or G1-phase. Accumulation in M-phase was the most prominent phenotype and notably, was also correlated with TP53 mutant status. We additionally observed unexpected complexity in the response of the cell cycle-associated client PLK1 to HSP90 inhibition, and we suggest that inhibitor-induced PLK1 depletion may contribute to the striking metaphase arrest phenotype seen in many of the M-arrested cell lines. CONCLUSIONS/SIGNIFICANCE: Our analysis of the cell cycle phenotypes induced by HSP90 inhibition in 25 cancer cell lines revealed that the phenotypic response was highly dependent on cellular genotype as well as on the concentration of HSP90 inhibitor and the time of treatment. M-phase arrest correlated with the presence of TP53 mutations, while G2 or G1 arrest was more commonly seen in cells bearing wt TP53. We draw upon previous literature to suggest an integrated model that accounts for these varying observations

Thermal conductivity of high- T c superconductors

This paper reviews existing data on the thermal conductivity of high- T c superconductors. Included are discussions of pristine polycrystalline high- T c ceramics, single crystal specimens, and high- T c materials structurally modified by substitution or by radiation damage. The thermal conductivity of high- T c superconductors is compared with that of conventional superconductors, and dramatic differences are found between the two families. Mechanisms of thermal conductivity applicable to high- T c perovskites are discussed and implications for theories of high- T c superconductivity are noted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45121/1/10948_2004_Article_BF00617463.pd

Purification of the envelope glycoproteins of western equine encephalitis virus by glass wool column chromatography

Glass wool column chromatography was used for separation of the two glycoproteins of western equine encephalitis virus. Cross-contamination of each protein separated was confirmed to be negligible by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.</jats:p