Phonon anomalies due to strong electronic correlations in layered organic metals

We show how the coupling between the phonons and electrons in a strongly correlated metal can result in phonon frequencies which have a non-monotonic temperature dependence. Dynamical mean-field theory is used to study the Hubbard-Holstein model that describes the \kappa-(BEDT-TTF)_2 X family of superconducting molecular crystals. The crossover with increasing temperature from a Fermi liquid to a bad metal produces phonon anomalies that are consistent with recent Raman scattering and acoustic experiments.Comment: 6 pages, 3 eps figure

Molecular characterization of microbial communities in fault-bordered aquifers in the Miocene formation of northernmost Japan

We investigated the diversity and distribution of archaeal and bacterial 16S rRNA gene sequences in deep aquifers of mid- to late Miocene hard shale located in the northernmost region of the Japanese archipelago. A major fault in the north-west-south-east (NW-SE) direction runs across the studied area. We collected three groundwater samples from boreholes on the south-west (SW) side of the fault at depths of 296, 374 and 625 m below ground level (m.b.g.l.) and one sample from the north-east (NE) side of the fault at a depth of 458 m.b.g.l. The groundwater samples were observed to be neutral and weakly saline. The total microbial counts after staining with acridine orange were in the order 105-106 cells mL-1 and 103 cells mL-1 in the aquifers to the SW and to the NE of the fault, respectively. A total of 407 archaeal and bacterial 16S rRNA gene sequences (204 and 203 sequences, respectively) were determined for clone libraries constructed from all groundwater samples. Phylogenetic analyses showed that the libraries constructed from the SW aquifers were generally coherent but considerably different from those constructed from the NE aquifer. All of the archaeal clone libraries from the SW aquifers were predominated by a single sequence closely related to the archaeon Methanoculleus chikugoensis, and the corresponding bacterial libraries were mostly predominated by the sequences related to Bacteroidetes, Firmicutes and δ-Proteobacteria. In contrast, the libraries from the NE aquifer were dominated by uncultured environmental archaeal clones with no methanogen sequences and by β-proteobacterial clones with no sequences related to Bacteroidetes and δ-Proteobacteria. Hence, the possible coexistence of methanogens and sulphate reducers in Horonobe deep borehole (HDB) on the SW side is suggested, particularly in HDB-6 (374 m.b.g.l.). Moreover, these organisms might play an important geochemical role in the groundwater obtained from the aquifers

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

Induction of Cytotoxic Oxidative Stress by d-Alanine in Brain Tumor Cells Expressing Rhodotorula gracilis d-Amino Acid Oxidase: A Cancer Gene Therapy Strategy

Overview summary Gene-directed enzyme prodrug therapy (GDEPT) is an antineoplastic treatment strategy designed to overcome the systemic toxicity of chemotherapy by specifically expressing a foreign enzyme in malignant cells that converts a nontoxic prodrug into a cytotoxic metabolite. The relative inefficiency of current in situ gene transfer methodology suggests that enzyme/prodrug combinations that produce membrane permeable metabolites will elicit a more favorable therapeutic response. Ideally, the agent produced by the transduced cell “factories” would be cytotoxic toward both proliferating and quiescent cells. We describe a novel GDEPT approach using d-amino acid oxidase from the red yeast Rhodotorula gracilis and d-alanine as a substrate that generates hydrogen peroxide, a reactive metabolite of oxygen that has both these characteristics. We also demonstrate the ability to sensitize tumor cells to this GDEPT protocol by manipulating cellular antioxidant pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63220/1/hum.1998.9.2-185.pd

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

Order and Stochastic Dynamics in Drosophila Planar Cell Polarity

Cells in the wing blade of Drosophila melanogaster exhibit an in-plane polarization causing distal orientation of hairs. Establishment of the Planar Cell Polarity (PCP) involves intercellular interactions as well as a global orienting signal. Many of the genetic and molecular components underlying this process have been experimentally identified and a recently advanced system-level model has suggested that the observed mutant phenotypes can be understood in terms of intercellular interactions involving asymmetric localization of membrane bound proteins. Among key open questions in understanding the emergence of ordered polarization is the effect of stochasticity and the role of the global orienting signal. These issues relate closely to our understanding of ferromagnetism in physical systems. Here we pursue this analogy to understand the emergence of PCP order. To this end we develop a semi-phenomenological representation of the underlying molecular processes and define a “phase diagram” of the model which provides a global view of the dependence of the phenotype on parameters. We show that the dynamics of PCP has two regimes: rapid growth in the amplitude of local polarization followed by a slower process of alignment which progresses from small to large scales. We discuss the response of the tissue to various types of orienting signals and show that global PCP order can be achieved with a weak orienting signal provided that it acts during the early phase of the process. Finally we define and discuss some of the experimental predictions of the model

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

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

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