bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudomonas-SaccharomycesInteractions: Influence of Fungal Metabolism on Bacterial Physiology and Survival
Authors: Romano Julia D. , Kolter Roberto
Published: January 2005

Fungal-bacterial interactions are ubiquitous, yet their molecular basis is only poorly understood. In this study, a novel beneficial interaction between a strain ofPseudomonas putidaand the fungusSaccharomyces cerevisiaewas identified. When the bacteria were incubated alone in grape juice or in synthetic medium containing various concentrations of glucose, they lost viability rapidly during stationary phase. However, when the bacteria were incubated in these media in the presence of the fungus, their stationary phase survival improved dramatically. On agar plates containing glucose, the beneficial effects of the fungus were manifested in robust bacterial growth and exopolysaccharide production that led to visible mucoidy. In contrast, bacteria grew poorly and were nonmucoid in such media in the absence of the fungus. By using the availableS. cerevisiaedeletion library, yeast mutants that were unable to mediate this beneficial interaction were identified. These mutants revealed that the beneficial effect on bacterial physiology and survival was mediated by the ability of the fungus to metabolize the available glucose and consequent effects on the medium's pH. In natural environments where the concentration of glucose is high, it is likely that the presence of fungi has had profound beneficial effects on the physiology and survival of certainP. putidastrains throughout their natural history.
DECOMPOSITIONS OF MODULES SUPPLEMENTED RELATIVE TO A TORSION THEORY
Authors: KOŞAN M. TAMER , HARMANCI ABDULLAH
Published: January 2005

Let R be a ring, M a right R-module and a hereditary torsion theory in Mod-R with associated torsion functor τ for the ring R. Then M is called τ-supplemented when for every submodule N of M there exists a direct summand K of M such that K ≤ N and N/K is τ-torsion module. In [4], M is called almost τ-torsion if every proper submodule of M is τ-torsion. We present here some properties of these classes of modules and look for answers to the following questions posed by the referee of the paper [4]: (1) Let a module M = M′ ⊕ M″ be a direct sum of a semisimple module M′ and τ-supplemented module M″. Is M τ-supplemented? (2) Can one find a non-stable hereditary torsion theory τ and τ-supplemented modules M′ and M″ such that M′ ⊕ M″ is not τ-supplemented? (3) Can one find a stable hereditary torsion theory τ and a τ-supplemented module M such that M/N is not τ-supplemented for some submodule N of M? (4) Let τ be a non-stable hereditary torsion theory and the module M be a finite direct sum of almost τ-torsion submodules. Is M τ-supplemented? (5) Do you know an example of a torsion theory τ and a τ-supplemented module M with τ-torsion submodule τ(M) such that M/τ(M) is not semisimple?
A NOTE ON CONTACT SURGERY DIAGRAMS
Authors: OZBAGCI BURAK
Published: January 2005

We prove that for any positive integer k, the stabilization of a [Formula: see text]-surgery curve in a contact surgery diagram induces an overtwisted contact structure.
ON THE EIGHTEENTH QUESTION OF ALLEN SHIELDS
Authors: YOUSEFI B.
Published: January 2005

We give sufficient conditions for reflexivity of the multiplication operator by the independent variable z, Mz acting on Banach spaces of formal Laurent series. This work presents sufficient conditions to a problem considered by A. L. Shields.
A CLASSIFICATION AND A NON-EXISTENCE THEOREM FOR CONFORMALLY FLAT HYPERSURFACES IN EUCLIDEAN 4-SPACE
Authors: SUYAMA YOSHIHIKO
Published: January 2005

We study generic conformally flat hypersurfaces in the Euclidean 4-space satisfying a certain condition on the conformal class of the first fundamental form. We first classify such hypersurfaces by determining all conformal-equivalence classes of generic conformally flat hypersurfaces satisfying the condition. Next, as an application of the classification theorem, we give some examples of flat Riemannian metrics which are not conformal to the first fundamental form of any generic conformally flat hypersurface. These flat Riemannian metrics seem to provide counter-examples to Hertrich–Jeromin's claim [3, 5].
HOMOGENEOUS AND BLENDED ER FLUIDS WITH POLYETHER DERIVATIVES
Authors: MINAGAWA K. , MASUDA S. , GOHKO N. , KOYAMA K. , TANAKA M.
Published: January 2005

Various ER fluids were prepared based on polyethers such as polypropylene glycol and polytetramethylene glycol. The polyethers were modified with isocyanates to give homogeneous liquids which show a positive or a negative ER effect depending on the molecular structure. The molecular motion of an urea-derivative of the polyether was analyzed with the NMR relaxation method. The modified polyethers were also used as a component of immiscible blends with silicones and suspensions. The immiscible blends showed a positive ER effects even when the polyether showed a negative ER effect. The suspensions tended to show a positive ER effect, which is similar to usual ER suspensions.
SYNTHESIS AND VISCOELASTIC BEHAVIORS OF POLY(ANILINE-CO-O-ETHOXYANILINE) PARTICLES SUSPENDED ELECTRORHEOLOGICAL FLUID
Authors: CHOI H. J. , KIM J. W. , SUH M. S. , SHIN M. J. , TO K.
Published: January 2005

Copolyanilines are synthesized by a chemical oxidation of aniline and o-ethoxyaniline with various molar ratios in an acidic media, and then characteristics of these polymers such as chemical structure, particle size and the particle size distribution were examined by using FT-IR, SEM and particle size analyzer, respectively. Suspensions of copolyaniline containing ethoxy group, namely poly(aniline-co-o-ethoxyaniline), in silicone oil have been investigated as one of many potential candidates for dry-base electrorheological (ER) fluid systems. Rotational rheometer (Physica) equipped with a high voltage generator was used to characterize the rheological properties of ER fluids from both steady shear and dynamic tests. From the steady shear experiment, we obtained flow properties and found that ER fluids exhibited the yield phenomenon. On the other hand, viscoelastic property was also obtained from the dynamic experiment. Since viscoelastic properties for ER fluids are mainly dominated by the particle chain structure, the state at different time scale was analyzed from the rheological parameters such as storage modulus (G'), loss modulus (G'') and tan δ. We conducted a strain amplitude sweep at 1 Hz under an applied electric field to determine a linear viscoelastic region first. The G' and G'' were then measured by a frequency sweep from 0.1 to 100 Hz in the linear viscoelastic region.
THE MECHANISM OF ER EFFECT INDUCED BY ATTACHING FLOCKED FABRICS ON ELECTRODES
Authors: KATO YOSHIKAZU , MASUBUCHI YUICHI , TAKIMOTO JUN-ICHI , KOYAMA KIYOHITO
Published: January 2005

In recent years, it has been found that ER effects can be induced by attaching fabrics on the electrodes. In this paper, the mechanism of this effect is studied in detail. The fluid studied was dimethylsiloxane, which shows no ER effect without the fabric. Velvet fabric was attached on one of the electrodes, and the shear and the normal stresses were measured with various gap distance but only weakly on the shear rate. A simple model which can explain these results are presented and discussed.
REVERSE ELECTRORHEOLOGICAL EFFECT: A SUSPENSION OF COLLOIDAL MOTORS
Authors: LEMAIRE E. , LOBRY L.
Published: January 2005

We present an experimental evidence of a "colloidal motor" behavior of a suspension. Previous attempts to observe such a phenomenon with ferrofluids under alternating magnetic fields have failed. Here, negative viscosity is obtained by making use of Quincke rotation: the spontaneous rotation of insulating particles suspended in a weakly conducting liquid when the system is submitted to a DC electric field. In such a case, particles rotate around any axis perpendicular to the applied field, nevertheless, when a velocity gradient (simple shear rate) is applied along the E field direction, the particles rotation axes will be favored in the vorticity direction (the direction perpendicular to the suspension velocity and the velocity gradient). The collective movement of particles drives the surrounding liquid and then leads to a reduction of the apparent viscosity of the suspension. The decrease in viscosity is sufficiently important for the liquid to flow while no submitted to any mechanical stress.
BROWNIAN DYNAMICS ANALYSIS OF CLUSTER STRUCTURES AND MAGNETIC CHARACTERISTICS OF FERROMAGNETIC PARTICLES SUBJECTED TO A SHEAR FLOW FIELD
Authors: MORIMOTO HISAO , MAEKAWA TORU
Published: January 2005

We carried out Brownian dynamics analysis of a ferromagnetic colloidal system which is subjected to both shear flow and external magnetic fields and investigated the magnetic and rheological characteristics. The effects of the strength of magnetic field, particle interactions and shear rate on the magnetisation, the viscosity and the cluster formations are examined and discussed. The cluster structures in the ferromagnetic colloidal system and rheological characteristics of the system in both low and high shear rate regions are made clear.
STATISTICAL ANALYSIS OF CLUSTER STRUCTURES FORMED BY DIPOLE-DIPOLE INTERACTIONS
Authors: MORIMOTO HISAO , MAEKAWA TORU
Published: January 2005

We developed a statistical model of the cluster formation of ferromagnetic particles and analysed the cluster structures. We investigated the effect of the control parameter λ, that is, the ratio of magnetic dipole moment energy to thermal energy, and external magnetic fields on the fractal dimensions of three-dimensional ferromagnetic clusters. We found that the fractal dimension of clusters, D, changes from 5/3 to 2 as λ increases in the absence of a magnetic field. We also found that when clusters are subjected to a magnetic field, the fractal dimension decreases and the transition region from high fractal dimension to D=1 becomes shorter as λ increases.
SHEARING EFFECTS ON THE ELECTRORHEOLOGICAL RESPONSE
Authors: TANAKA K. , HASHIMOTO S. , TAKENOUCHI T. , SUGIMOTO I. , KUBONO A. , AKIYAMA R.
Published: January 2005

The steady and transient stress responses were investigated from lower shear rates to higher shear rates at a given strength of the electric field, and the individual experimental conditions were reduced to Mason number ( M n). The electro-rheological response was found in the region with higher M n of the order of 10, and the transient response became faster as the shear rate increased. These results show that the effect of chance of collision among the polarized particles would play an important role even in the region.
Behavior of ER Fluids based on Three Variants of a Liquid Crystalline Polysiloxane
Authors: Yamada Hiroyuki , Taniguchi Yumiko , Inoue Akio
Published: January 2005

ER fluids of three types, composed of liquid crystalline polymethylsiloxanes (LCSs) differing in the range of polysiloxane chain length and mesogenic group content diluted by polydimethylsiloxanes (DMSs) with or without phenyl groups, were prepared and the ER effect of each was investigated in terms of its temperature dependence and rise time. Type A fluid exhibited an ER effect with a short rise time but a strong temperature dependence. The ER effect of the Type B fluid showed little temperature dependence but a comparatively long rise time. The Type C fluid exhibited a short rise time, comparable to that of Type A, and a temperature independence similar to that of Type B. For all three types, the decay time of the ER effect was long. Investigation of the decay time for the Type A fluid showed that it was affected particularly by shear rate and DMS dilution ratio and also by temperature and DMS viscosity, and indicated that deformation by shear stress was necessary for a return of the fluid to its original non viscous structure.
HYDRODYNAMIC CHARACTERISTICS OF ELECTRORHEOLOGICAL FLUID IN A PARALLEL DUCT FLOW
Authors: SHIMADA K. , KAMIYAMA S.
Published: January 2005

An experimental investigation is conducted to clarify the hydrodynamic characteristics of ERF with elastic particles of smectite in a two-dimensional parallel duct of various widths. Experimental data on pressure difference to a volumetric flow rate in a supplying D.C. electric field are measured. These data are arranged to obtain the apparent viscosit by using the integral method of rheology. From the data of apparent viscosity, the wall friction coefficient is obtained. The increment of the apparent viscosity caused by the applying electric field is a function of shear rate as well as the electric field strength and the width of the duct. However, the wall friction coefficient is not a function of elecric field strength and the width of the parallel duct, but only of shear rate. The yield stress is a function of the width of the parallel duct as well as of electric field strength. The ratio of Non-Newtonian viscosity in the apparent viscosity is varied by the intensity of the shear rate.
FRACTURE TOUGHNESS OF DIAMOND-LIKE CARBON FILMS
Authors: HOU Q. R. , GAO J.
Published: January 2005

Diamond-like carbon films were deposited on silicon (111) substrates at different temperatures using a pulsed-laser deposition method. Vickers indentation was used to measure the fracture toughness of the deposited diamond-like carbon films. It is found that diamond-like carbon films deposited at low temperature (55°C and 100°C) were very brittle and the fracture toughness was a difficult parameter to measure. The fracture toughness of diamond-like carbon films deposited at 270°C increased with film thickness and the measured values were between 1.0 and 2.3 MPa m 1/2.
Enhanced Ca2+response to AVP in preglomerular vessels from rats with genetic hypertension during different hydration states
Authors: Vagnes Øyvind B. , Hansen Frank H. , Feng Jian J. , Iversen Bjarne M. , Arendshorst William J.
Published: January 2005

Exaggerated arginine vasopressin (AVP)-induced calcium signaling and renal vasoconstriction, characteristic in young spontaneously hypertensive rats (SHR) during euvolemia, are related to greater amounts of V1areceptor mRNA and V1aprotein in preglomerular resistance arterioles. The present study determined whether V1areceptor density and calcium signal transduction in the renal vasculature of young SHR is regulated appropriately during physiological changes in hydration state. [3H]AVP ligand binding documented two- to threefold greater density of V1areceptors in euvolemic SHR vs. Wistar-Kyoto (WKY) rats. Parallel changes in V1areceptor density were observed in both strains during chronic water loading (plus ∼50 fmol/mg) and during dehydration (minus ∼50 fmol/mg). Affinity was unchanged. Real-time RT-PCR demonstrated that V1amRNA in preglomerular arterioles was three times greater in euvolemic SHR. Dehydration decreased expression ∼50% in renal vessels independent of rat strain; water loading increased V1amRNA. Thus V1areceptor regulation correlated with changes in mRNA in a normal manner in response to chronic changes in AVP concentration, albeit set at a higher level in SHR. In dehydrated animals, AVP increased the cytosolic Ca2+concentration ([Ca2+]i) by 60 ± 5 and 112 ± 13 nM cytosolic Ca2+in WKY and SHR, respectively ( P < 0.01), whereas in hydrated animals the [Ca2+]iincrease was 168 ± 10 and 220 ± 18 nM, respectively ( P < 0.05). In all hydration states, calcium signaling was greater in SHR compared with WKY ( P < 0.05). Calcium signaling paralleled changes in the receptor density and mRNA. Mechanisms other than hydration state per se are likely to be responsible for the two- to threefold difference in the V1areceptor density between WKY and SHR in the renal vasculature at the critical age of 6 wk.
PML mediates IFN-α–induced apoptosis in myeloma by regulating TRAIL induction
Authors: Crowder Chun , Dahle Øyvind , Davis R. Eric , Gabrielsen Odd S. , Rudikoff Stuart
Published: January 2005

Interferon (IFN) induces expression of proapoptotic genes and has been used in the clinical treatment of multiple myeloma. The promyelocytic leukemia (PML) gene is an IFN-induced target that encodes a tumor suppressor protein. PML protein is typically localized within discrete speckled nuclear structures termed PML nuclear bodies (NBs). Multiple myeloma cells demonstrate differential responses to IFN treatment, the mechanism of which is largely unknown. Herein, we show that growth inhibition effects of IFN-α in myeloma cells correlate with PML NBs and tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) induction, whereas known IFN targets including signal transducer and activator of transcription-1 (STAT1), STAT3, p38, and Daxx cannot account for these differential responses. RNAi silencing of PML blocks IFN-α–induced apoptosis in myeloma cells and correspondingly down-regulates TRAIL expression. Similarly, stable expression of a dominant negative TRAIL receptor DR5 partially blocks IFN-induced cell death. These results demonstrate that PML and TRAIL play important roles in IFN-induced apoptosis and identify TRAIL as a novel downstream transcriptional target of PML. Identification of PML and PML NBs as effectors of IFN responses provides insights into mechanisms by which tumor cells exhibit resistance to this class of agents and may prove useful in assessing treatment regimens.
Prevention of lethal acute GVHD with an agonistic CD28 antibody and rapamycin
Authors: Albert Michael H. , Yu Xue-Zhong , Martin Paul J. , Anasetti Claudio
Published: January 2005

Successful hematopoietic cell transplantation (HCT) from an allogeneic donor ideally should produce tolerance to recipient alloantigens while preserving anti-infectious and antitumor immunity. Rapamycin together with costimulation blockade can induce tolerance in organ allograft models by inhibiting G1 → S-phase progression and promoting T-cell apoptosis. In contrast to blocking costimulation through CD28, administration of agonistic CD28-specific antibody 37.51 partially prevents lethal graft-versus-host disease (GVHD) by selective depletion of alloreactive T cells in mice. We hypothesized that combining rapamycin with agonistic CD28 treatment would improve GVHD control by tolerizing a small subset of alloreactive T cells that might escape effects of the CD28-specific antibody. A short course of rapamycin plus agonistic CD28 treatment showed synergism at suboptimal doses, was highly effective in preventing lethal GVHD, and was superior to rapamycin plus CD28 blockade in a major histocompatibility complex class I– and II–mismatched HCT model. The combination treatment reduced the number of proliferating, alloreactive cells in the recipient, promoted donor B- and T-cell reconstitution, and reduced inflammatory cytokine levels. Administration of rapamycin plus agonistic CD28 antibodies offers a promising new therapeutic approach to facilitate tolerance after HCT.
Rivastigmine: an open-label, observational study of safety and effectiveness in treating patients with Alzheimer's disease for up to 5 years
Authors: Farlow Martin R , Lilly Mary L ,   for the ENA713 B352 Study Group
Published: January 2005

Background

Rivastigmine, a butyl- and acetylcholinesterase inhibitor, is approved for symptomatic treatment of Alzheimer's disease (AD). Data supporting the safety and efficacy of second-generation cholinesterase inhibitors, such as rivastigmine, are available for treatment up to 1 year, with limited data up to 2 1/2 years. The purpose of this report is to present safety and effectiveness data for rivastigmine therapy in patients with mild to moderately severe AD receiving treatment for up to 5 years.

Methods

An observational approach was used to study 37 patients with originally mild to moderate AD receiving rivastigmine as a therapy for AD in an open-label extension (ENA713, B352 Study Group, 1998).

Results

The initial trial demonstrated rivastigmine was well-tolerated and effective in terms of cognition, global functioning and activities of daily living. In this open label extension, high-dose rivastigmine therapy was safe and well tolerated over a 5-year period. Two thirds of the participants still enrolled at week 234 were in the original high-dose rivastigmine group during the double-blind phase, suggesting that early therapy may confer some benefit in delaying long-term progression of symptoms.

Conclusions

Long-term cholinesterase inhibition therapy with rivastigmine was well tolerated, with no dropouts due to adverse effects past the initial titration period. Early initiation of treatment, with titration to high-dose therapy, may have an advantage in delaying progression of the illness.
Exogenous Tissue Inhibitor of Metalloproteinase‐1 Promotes Endothelial Cell Survival Through Activation of the Phosphatidylinositol 3‐Kinase/Akt Pathway
Authors: BOULDAY GWÉNOLA , FITAU JULIETTE , COUPEL STÉPHANIE , SOULILLOU JEAN‐PAUL , CHARREAU BÉATRICE
Published: January 2005

Abstract: Control of molecular targets and signaling pathways which improve endothelial cell survival may be an attractive concept for interfering with dysregulated vascular injury and remodeling, a key mechanism for transplant arteriosclerosis and chronic allograft rejection. In addition to inhibiting matrix metalloproteinase activity, it has been suggested by recent studies that the tissue inhibitor of metalloproteinase (TIMP)‐1 may inhibit apoptosis in various cell types. The present work examines the possibility that TIMP‐1 belongs to a protective pathway via antiapoptotic properties and investigates the signaling pathway mediated by TIMP‐1 in human ECs. We demonstrate that exogenous, recombinant, TIMP‐1 efficiently prevents apoptosis induced by TNFα in cycloheximide‐sensitized ECs. The antiapoptotic effect of TIMP‐1 was dose‐dependent and a maximal effect of TIMP‐1 (30% protection) was reached using 250 ng/mL of recombinant TIMP‐1. We present evidence that TIMP‐1 induces activation of PI3‐kinase but not NFκB pathway in ECs. Our findings further indicate that TIMP‐1‐induced EC survival is mediated through activation of PI3‐kinase pathway and the downstream phosphorylation of Akt kinase. Blocking the PI3‐kinase pathway with wortmannin or LY294002 restores TNFα‐mediated EC death. In conclusion, our findings suggest that TIMP‐1, generated upon inflammation, acts as an antiapoptotic molecule that can prevent EC apoptosis through activation of the PI3‐kinase and phosphorylation of the Akt kinase.
Alterations in Protein Expression in HL‐60 Cells during Etoposide‐Induced Apoptosis Modulated by the Caspase Inhibitor ZVAD.fmk
Authors: NAVAKAUSKIENE RUTA , TREIGYTE GRAZINA , SAVICKIENE JURATE , GINEITIS ARUNAS , MAGNUSSON KARL‐ERIC
Published: January 2005

Abstract: DNA topoisomerase inhibitors induce a specific signaling cascade that promotes an active apoptotic caspase‐dependent cell death process. However, little is known about the initial signals elicited by these agents. In the present study, we compared apoptosis in HL‐60 cells treated either with the chemotherapeutic drug etoposide (VP16) alone or combined with the broad caspase inhibitor ZVAD.fmk. Apoptosis was assessed by changes in cell morphology and agarose gel electrophoresis of extracted cell DNA. We found that ZVAD.fmk prevents VP16‐induced DNA fragmentation and the appearance of an increased number of apoptotic cells in the culture. We also compared the effects of etoposide alone or together with the pan‐caspase inhibitor ZVAD.fmk on proliferating cell nuclear antigen, Bcl‐2, and actin expression in human promyelocytic leukemia HL‐60 cells. In addition, we screened for proteins that were initially upregulated in a caspase‐dependent manner. Indeed, some proteins were induced in the cytoplasm and subsequently accumulated in the nuclei after etoposide treatment. This process was slightly inhibited by the caspase inhibitor ZVAD.fmk. We suggest that these proteins are associated with the induction of specific signaling cascades that characterize the apoptotic cell death process.
Spontaneous Generation of Reactive Oxygen Species in the Mixture of Cyanide and Glycerol
Authors: CHUN YANG‐SOOK , YEO EUN‐JIN , SUH HWA‐JIN , PARK JONG‐WAN
Published: January 2005

Abstract: Reactive oxygen species are involved in tumor promotion or apoptosis. In assaying prooxidant or antioxidant activities, cyanide has been commonly used as an inhibitor of mitochondrial oxidases, peroxidases, or Cu,Zn‐superoxide dismutase, which have an influence on intracellular levels of reactive oxygen species. It has also been used to chemically mimic hypoxia. On the other hand, glycerol has been widely used as a stabilizer of various enzymes. In particular, glycerol is required to maintain the enzymatic activities of membrane‐bound NAD(P)H oxidases extracted from surrounding phospholipids. Since both cyanide and glycerol are relatively inert, they have been used concomitantly regardless of any mutual interference. In this study, we demonstrate that a mixture of glycerol and cyanide reduced cytochrome c and nitroblue tetrazolium, both of which are superoxide anion indicators. The mixture also enhanced the production of superoxide anion in the presence of redox‐cycling compounds. Superoxide production by the mixture was confirmed by electron spin resonance spectra. Moreover, the mixture induced lipid peroxidation and hemolysis in human erythrocytes. These results suggest that cyanide and glycerol should be used carefully in reaction systems used to measure superoxide production or antioxidant activity. However, sucrose and sodium azide in combination do not produce such artifacts and thus may be used as an alternative.
Low‐Grade Inflammation with Aging Has Consequences for T‐Lymphocyte Signaling
Authors: LARBI ANIS , DUPUIS GILLES , DOUZIECH NADINE , KHALIL ABDELOUAHED , FÜLÖP TAMÀS
Published: January 2005

Abstract: T lymphocytes are key players of immune responses that are associated with immune senescence because their functions are the most affected with aging. Defects in signal delivery to the nucleus have been demonstrated, by our group and others, in human aging and may explain the dysfunctions that occur in T cells with aging. Although aging has been related to a decline in several biological functions, it is also associated with a basal low‐grade proinflammatory state and an increase in oxidative stress that lead to changes and damage. However, there are no clear data concerning the basal state of activation of T lymphocytes and its putative link with the low‐grade inflammation observed with aging. Since membrane microdomains (lipid rafts) are specialized plasma membrane structures involved in T‐lymphocyte activation, we studied the effect of aging on the phosphorylation state of signaling molecules associated with lipid rafts. We found that the signaling molecules in T lymphocytes from elderly donors were hyperphosphorylated and that the high basal state of phosphorylation did not allow activation exposure to a T‐cell stimulus. We found that the cholesterol composition is changed in lipid rafts of resting T cells. We analyzed lipid raft distribution in situ using confocal microscopy and found a disorganization of these microdomains in T cells from aged donors. In conclusion, we show a link between aging, T‐lymphocyte lipid rafts, immune senescence, and low‐grade inflammation.
Supervision of Multiple Signaling Protein Kinases by the CK2‐Cdc37 Couple, a Possible Novel Cancer Therapeutic Target
Authors: MIYATA YOSHIHIKO , NISHID EISUKE
Published: January 2005

Abstract: Overexpression of a pleiotropic Ser/Thr kinase CK2 (casein kinase II), or of a kinase‐targeting molecular chaperone Cdc37, induces neoplastic cell growth in animals. Recent genetic and biochemical evidence from several laboratories has revealed an unexpected direct link between CK2 and Cdc37. In this short review, we describe the basic characteristics of CK2 and Cdc37 and introduce recent findings on the interaction between CK2 and Cdc37. Cdc37 was identified as a multicopy suppressor of a temperature‐sensitive allele of CK2 in Saccharomyces cerevisiae. CK2 phosphorylates a conserved serine residue in the N‐terminal extremity of Cdc37 in vitro and in yeast as well as mammalian cells, and this is the unique phosphorylation site of Cdc37 under normal conditions. Mutations in the CK2‐mediated phosphorylation site abolish the association of Cdc37 with various protein kinases. The same mutations in yeast cause severe growth and morphological defects. Specific inhibition of CK2 activity decreases intracellular levels of Cdc37‐dependent protein kinases. Altogether, this evidence clearly indicates that the CK2‐dependent phosphorylation is essential for the proper function of Cdc37 to bind and stabilize signaling protein kinases. In contrast, CK2 activity is enhanced by Cdc37 both in vitro and in vivo; thus, the CK2‐Cdc37 couple seems to constitute a positive feedback control mechanism that may govern the activity of multiple protein kinases. Cdc37‐dependent protein kinases include important signaling molecules whose disregulations are intimately related to neoplastic cell growth; hence, inhibition of the CK2‐Cdc37 system may simultaneously suppress various cancer‐promoting signal cascades. We propose that the CK2‐Cdc37 couple can be a novel and efficient pharmacological target for cancer chemotherapy.
p38 Is a Key Signaling Molecule for H‐ras‐Induced Inhibition of Gap Junction Intercellular Communication in Rat Liver Epithelial Cells
Authors: LEE KI WON , JUNG JI WON , KANG KYUNG‐SUN , LEE HYONG JOO
Published: January 2005

Abstract: Multiple lines of evidence indicate that inhibition of gap junction intercellular communication (GJIC) is a major carcinogenic process. Several reports suggest that activation of extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) plays a key role in the disrupted GJIC by hydrogen peroxide, 12‐O‐tetradecanoylphorbol‐13‐acetate, and quinones in rat liver epithelial cells. Recently, we reported that p38 mitogen‐activated protein kinase (MAPK) is also involved in the inhibition of GJIC by hydrogen peroxide in WB‐F344 rat liver epithelial cells (WB cells). The present study investigated the role of ERK1/2 and p38 MAPK in H‐ras‐induced inhibition of GJIC in WB cells. H‐ras induces complete inhibition of GJIC and unphosphorylation of connexin 43 (Cx43) in WB cells. SB203580, an inhibitor of p38, restored inhibition of GJIC and blocked unphosphorylation of Cx43 in H‐ras‐transformed WB cells. However, PD98059, an inhibitor of ERK1/2, had no effect. Our results suggest that the disruption of GJIC induced by H‐ras may be strongly related to the unphosphorylation of Cx43 via the activation of p38 but not ERK1/2. Thus, p38 is a key signaling molecule for H‐ras‐induced inhibition of GJIC in WB cells.
Increased Mitochondrial and Nuclear Gene Expression of Cytochrome Oxidase Subunits I and IV in Neuronal Aging
Authors: FATTORETTI PATRIZIA , BERTONI‐FREDDARI CARLO , GIORGETTI BELINDA , BALIETTI MARTA
Published: January 2005

Abstract: To assess the role of mitochondrial metabolic competence (MMC) in neuronal aging, quantitative immunohistochemistry of cytochrome oxidase (COX) subunits I (mitochondrial‐encoded) and IV (nuclear‐encoded) was carried out in the cerebellar cortex of adult and old rats. The optical density (OD) values of the immunostained COX subunits I and IV were measured on an overall area of 75,000 μm2 in the granular and molecular layers of the cerebellar cortex of each animal. In old animals, OD values of subunit I were increased by 35.5 and 34.2% in the molecular and granular layers, respectively, but only the difference found in the latter cerebellar zone was statistically significant (p <, 0.05%). As regards subunit IV, old animals showed higher, not significant, densitometric values in the molecular (120.6%) and granular (126.8%) layers. The present findings sustain that gene expression of COX subunits I and IV appears not to be involved in the well‐documented time‐related mitochondrial decay. The proper functioning of COX depends on several factors that can affect MMC in the aging cell. In the fully assembled holoenzyme, both the subunits I and IV span the inner mitochondrial membrane. On the basis of these molecular biology data, it is reasonable to suppose that any alteration of the physicochemical features and chemical composition of the mitochondrial membranes reported to occur in aging (e.g., decreased membrane fluidity and cardiolipin content, increased cholesterol/phospholipid molar ratio and free‐radical damage, etc.) may significantly affect the proper assembling of the enzyme and, in turn, its activity. Considering the reported significant decline of COX activity with advancing age, our findings further support that an adequate mitochondrial metabolic competence, while including proper nuclear and mitochondrial gene expression of subunits of the respiratory chain, relies on the overall balance among various determinants that can be differently damaged by aging and represent critical causative events responsible for the age‐related functional decline of selected mitochondrial populations.
BACE1 Overexpression Regulates Amyloid Precursor Protein Cleavage and Interaction with the ShcA Adapter
Authors: REPETTO EMANUELA , RUSSO CLAUDIO , VENEZIA VALENTINA , NIZZARI MARIO , NITSCH ROGER M. , SCHETTINI GENNARO
Published: January 2005

Abstract: The amyloid precursor protein (APP) is a cell surface protein with a large extracellular N‐terminal domain, a single transmembrane segment, and a short cytoplasmic tail. Its location and structural features are characteristic of a receptor for signal transduction. Yet, the physiological function of APP is unclear, although it is well documented that APP's proteolytic processing, through the formation of membrane‐bound C‐terminal fragments (CTFs) and of β‐amyloid peptides, likely influences the development of Alzheimer's disease (AD). There is evidence that BACE1 is the enzyme responsible for β‐site cleavage of the APP and for the generation of CTFs. BACE1 expression is upregulated in AD brain, and we have recently shown in human brain and in vitro that BACE product CTFs, when phosphorylated in tyrosine residues, interact with the adaptor proteins ShcA and Grb2, which usually are involved in signal transduction pathways. We investigated the interaction between ShcA, APP, and CTFs in the H4 human cell line that overexpresses BACE1 to clarify the significance of such interactions in vitro and for AD generation. Our result show that the APP, CTF, and ShcA interaction is induced only upon overexpression of BACE1 either transiently or in stable cell lines. In particular, although BACE1 drives the formation of C99 and C89 CTFs, only C99 interacts with the ShcA adaptor protein. Therefore, our data suggest that BACE1 activity influences APP processing and its intracellular signaling through the ShcA adaptor protein.
Plasma Membrane Alteration Is an Early Signaling Event in Doxorubicin‐Induced Apoptosis in the Yeast Candida utilis
Authors: KEYHANI EZZATOLLAH , KEYHANI JACQUELINE
Published: January 2005

Abstract: Signaling pathways such as increased ceramide, mitochondrial dysfunction, and P3 and caspase activation are produced by anticancer drugs and lead to apoptosis. In this research we show that the first event after culturing the yeast Candida utilis in the presence of low doses of doxorubicin (25 μg/mL) is the morphological alteration of the plasma membrane. In the presence of higher doxorubicin doses (≥50 μg/mL), in addition to profound alterations in the plasma membrane, changes in mitochondrial shape and cristae organization were observed. Concomitantly, increases in respiration, substrate oxidation, and cytochrome biosynthesis were observed at low doxorubicin doses (up to 25 μg/mL), whereas a progressive decrease was observed at higher doses. [3H]Leu incorporation into proteins increased by 40% in the mitochondrial fraction and by 19% in the cytosol in the presence of 25 μg/mL doxorubicin; it decreased to 80% of the control in the cytosol in the presence of 1 mg/mL doxorubicin. Morphologically, doxorubicin doses of up to 200 μg/mL produced apoptosis, whereas higher doxorubicin doses produced necrosis.
Suppression of the Nuclear Factor‐κB Activation Pathway by Spice‐Derived Phytochemicals: Reasoning for Seasoning
Authors: AGGARWAL BHARAT B. , SHISHODIA SHISHIR
Published: January 2005

Abstract: The activation of nuclear transcription factor κB has now been linked with a variety of inflammatory diseases, including cancer, atherosclerosis, myocardial infarction, diabetes, allergy, asthma, arthritis, Crohn's disease, multiple sclerosis, Alzheimer's disease, osteoporosis, psoriasis, septic shock, and AIDS. Extensive research in the last few years has shown that the pathway that activates this transcription factor can be interrupted by phytochemicals derived from spices such as turmeric (curcumin), red pepper (capsaicin), cloves (eugenol), ginger (gingerol), cumin, anise, and fennel (anethol), basil and rosemary (ursolic acid), garlic (diallyl sulfide, S‐allylmercaptocysteine, ajoene), and pomegranate (ellagic acid). For the first time, therefore, research provides “reasoning for seasoning.”
Hypoxia/Anoxia as Signaling for Increased Alcohol Dehydrogenase Activity in Saffron (Crocus sativus L.) Corm
Authors: KEYHANI EZZATOLLAH , KEYHANI JACQUELINE
Published: January 2005

Abstract: Alcohol dehydrogenase, NAD‐dependent lactate dehydrogenase, and NAD‐independent lactate dehydrogenase activities were investigated in corms cultivated in normoxic and hypoxic/anoxic conditions. Depending on the developmental stage, hypoxia/anoxia was a signal for increase in either alcohol dehydrogenase or NAD‐dependent lactate dehydrogenase. NAD‐independent lactate dehydrogenase contributed to the recycling of lactate, thus preventing acidosis.
Prevention Against Oxidative Stress of Eukaryotic Cell Membranes by Selenium Compounds of the Rat
Authors: KYRIAKOPOULOS A , BUKALIS K , ROETHLEIN D , HOPPE B , GRAEBERT A , BEHNE D
Published: January 2005

Abstract: By a combination of trace techniques and various biochemical methods, information about the characteristics of a 15‐kDa selenoprotein was obtained. After labeling of rats in vivo with [75Se]selenite, subcellular fractionation of the homogenates of the prostate, lung, brain, thyroid gland, and large intestine, and gel electrophoretic separation of the proteins and subcellular fractionation, 15‐kDa 75Se was found in the cytosols of the tissues prostate > brain > lung > thyroid gland > large intestine after autoradiography. After coelectrophoresis of the separated 15‐kDa labeled band obtained from each cytosolic fraction, the 15‐kDa 75Se band migrated in the same way as the combined bands isolated from the five tissue cytosols. After proteolytic cleavage in the gel of the 15‐kDa labeled band obtained from the cytosol of each tissue and re‐electrophoresis, the same labeled peptide pattern was found in each gel slice after autoradiography. By means of reversed‐phase HPLC, we characterized a selenocysteine‐containing protein that has enzymatic activity like that of glutathione peroxidase.
Effect of Dietary Restriction on DNA Synthesis in Vitamin E‐Deficient Rats
Authors: MORONI FAUSTO , RECCHIONI RINA , MARCHESELLI FIORELLA , FATTORETTI PATRIZIA , BERTONI‐FREDDARI CARLO
Published: January 2005

Abstract: To assess the effect of dietary restriction on increased oxidative stress conditions, we measured the proliferative response of spleen lymphocytes from the following groups of adult rats: (1) control fed ad libitum (14 months of age); (2) vitamin E‐deficient (12 months of age); and (3) vitamin E‐deficient maintained on dietary restricted paradigm, that is, every other day schedule (12 months of age) animals. No significant change was observed among the three groups investigated at 24 h. At 48 h, [3H]thymidine incorporation was significantly lower in vitamin E‐deficient rats vs. the other groups at Con A concentrations of 1 and 5 μg/mL, while at Con A concentration of 10 μg/mL the incorporation of the labeled compound in lymphocytes was significantly lower than only the vitamin E‐deficient rats vs. controls. At 72 h: nonstimulated lymphocytes from ad libitum fed control rats showed significant higher values of [3H]thymidine incorporation vs. the other groups; no significant difference was found among the three groups investigated at 1 and 10 μg/mL Con A concentrations, while at 5 μg/mL Con A concentration, the lymphocytes from vitamin E‐deficient rats showed a significant lower value of [3H]thymidine incorporation vs. the other groups. These data support that vitamin E‐deficiency impairs the proliferative response of spleen lymphocytes from adult rats, while dietary restriction appears to be able to reverse this alteration. Although the mechanism(s) of action of dietary restriction in prolonging the life span and ameliorating health conditions are not know, it is currently supported that a reduced food intake results in a better control of free radical attacks to biological molecules as well as to several cellular and system functions. With specific reference to the present findings, dietary restriction may help the mitotic process dynamics to be accomplished in a condition of low rate of free radical damage, thus representing a physiological intervention capable of modulating positively the proliferative capacity of spleen lymphocytes and, in turn, the immune system, even in adverse conditions such as increased oxidative stress.
Relaxin and Phosphodiesterases Collaborate during Decidualization
Authors: BARTSCHA OLAF , IVELL RICHARD
Published: January 2005

Abstract: During the evolution of mammals, the endometrium has developed for one reason only: to implant an embryo in the uterus. In higher primates, should an oocyte fail to be fertilized, then the endometrial layer is sloughed off during menses and the menstrual cycle starts again with a new round of endometrial differentiation. This stromal differentiation process is called decidualization and is accompanied in vivo by sustained high levels of intracellular cAMP. The present study was conducted to determine whether manipulation of cAMP‐phosphodiesterase (PDE) activities in cultured human endometrial stromal cells could positively influence the decidualization process. The combination of relaxin treatment with inhibition of PDE4 by the specific inhibitor rolipram induced a strong increase in relaxin‐mediated cAMP production, both acutely, after 20 min, and after long‐term treatment for 3 days, to promote a sustained intracellular cAMP concentration. Moreover, there was a dramatic synergistic effect on the decidualization phenotype, characterized both morphologically and by increased production of prolactin and insulin‐like growth factor binding protein‐1 gene transcripts. The observations that expression of PDE4D transcripts were selectively increased by cAMP and that inhibition of protein kinase A by H89 to potentially block negative feedback regulation enhanced the relaxin/rolipram‐mediated cAMP accumulation lead to a complex picture of cAMP regulation in these cells. There appears to be a coordinated contribution by relaxin and PDE4 at different levels to promote a sustained increased cAMP concentration during decidualization, and thus to provide an adequate maternal interface for the implanting blastocyst.
Effects of Cyclopentenone Prostaglandins on the Expression of Heme Oxygenase‐1 in MCF‐7 Cells
Authors: KIM EUN‐HEE , KIM DO‐HEE , NA HYE‐KYUNG , SURH YOUNG‐JOON
Published: January 2005

Abstract: Cyclopentenone prostaglandins (cyPGs) are produced by dehydration of precursor molecules. The cyPGs are reported to have proapoptotic effects in a variety of cell types. However, cyPGs, particularly 15‐deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2), can also exert cytoprotective effects at relatively low concentrations. The cytoprotective activity of cyPGs appears to be mediated by the reactive α,β‐unsaturated carbonyl group located in the cyclopentene ring. In this study, we investigated the effect of cyPGs on the expression of heme oxygenase‐1 (HO‐1), a ubiquitous stress‐responsive enzyme that catalyzes oxidative cleavage of heme to form iron, carbon monoxide, and biliverdin. Treatment of the human breast cancer cell line (MCF‐7) with 15d‐PGJ2 resulted in a concentration‐ and time‐dependent increase in the expression of HO‐1, whereas prostaglandin A2 (PGA2) and the non‐PG derivative 2‐cyclopenten‐1‐one failed to induce HO‐1 expression at the protein level. RT‐PCR revealed that the expression of HO‐1 mRNA was induced at 6 h by 15d‐PGJ2 at 10 μM. However, PGA2 induced HO‐1 mRNA expression at a higher concentration (30 μM). 2‐Cyclopenten‐1‐one did not induce the expression of HO‐1 mRNA at all. Likewise, 15d‐PGJ2 treatment for 6 h led to phosphorylation of Akt/protein kinase B (PKB) to a greater extent than that achieved with PGA2. Thus, the induction of HO‐1 expression and the activation of Akt/PKB by 15d‐PGJ2 and PGA2 are likely to confer cytoprotective or antiapoptotic effects exerted by these cyPGs.
Comparison of Gene Expression in Intra‐Abdominal and Subcutaneous Fat: A Study of Men with Morbid Obesity and Nonobese Men Using Microarray and Proteomics
Authors:   ABDOMINAL OBESITY STUDY GROUP, VON EYBEN FINN EDLER , KROUSTRUP JENS PETER , LARSEN JENS FROMHOLT , CELIS JULIO
Published: January 2005

Abstract:Extent of intra‐abdominal fat had significant linear relations with six metabolic coronary risk factors: systolic and diastolic blood pressure, fasting blood concentrations of glucose, high density lipoprotein (HDL) cholesterol, triglyceride, and plasminogen activator inhibitor‐1. Tumor necrosis factor‐α and adiponectin can be biological mediators from the intra‐abdominal fat to the metabolic coronary risk factors. Complementarily, we describe a new study that will analyze the gene expression in intra‐abdominal and subcutaneous fat on mRNA and protein level using high throughput methods. The study will elucidate further whether intra‐abdominal obesity is the common denominator for the different components of the metabolic syndrome.
Thymocyte Apoptosis Induced by Various Compounds Including YO‐2 Is Accompanied by a Change in Chromatin Structure
Authors: ENOMOTO RIYO , SUGAHARA CHIYOKO , TSUDA YUKO , OKADA YOSHIO , LEE EIBAI
Published: January 2005

Abstract: To elucidate the role of chromatin structure in DNA fragmentation during apoptosis, we have examined whether chromatin structural change is observed after treatment with proapoptotic compounds. Analysis of the circular dichroism (CD) spectrum of the soluble chromatin from dexamethasone‐treated thymocytes revealed a decrease in α‐helical content. Mifepristone, an antagonist of glucocorticoid receptor, prevented both the change in chromatin structure and DNA fragmentation induced by dexamethasone. The effect of YO‐2 [trans‐4‐aminomethylcyclohexanecarbonyl‐l‐(O‐picolyl)tyrosine‐n‐octylamide], which possesses proapoptotic action, on chromatin structure was also examined. Judging from the CD spectrum of the soluble chromatin from YO‐2‐treated thymocytes, the structure was changed by this compound as well as by dexamethasone. A decrease in α‐helical content was also observed in cells treated with etoposide, which is used clinically as an anticancer agent. These results suggest that the change in chromatin structure is likely to be an important process in DNA fragmentation of cells undergoing apoptosis.