bluuebunny/crossref_metadata_2025 huggingface dataset:
Copper(I) Alkynyl Clusters, [Cux+y(hfac)x(CCR)y], with Cu10–Cu12 Cores
Authors: Baxter Christopher W. , Higgs Timothy C. , Bailey Philip J. , Parsons Simon , McLachlan Fiona , McPartlin Mary , Tasker Peter A.
Published: June 2006

The facile syntheses and the structures of five new CuI alkynyl clusters, [Cu12(hfac)8(CCnPr)4(thf)6]⋅THF (1), [Cu12(hfac)8(CCtBu)4] (2), [Cu12(hfac)8(CCSiMe3)4] (3), [Cu10(hfac)6(CCtBu)4(diethyl ether)]/[Cu10(hfac)6(CCtBu)3(CCnPr)(diethyl ether)] (4) and [Cu10(hfac)6(CCtBu)4(diethyl ether)] (5) are reported, in which hfacH=1,1,1,5,5,5‐hexafluoropentan‐2,4‐dione. The first independent molecule found in the crystals of 4 (4 a) proved to be chemically identical to 5. The Cu10 and Cu12 cores in these clusters are based on a central “square” Cu4C4 unit. Whilst the connectivities of the Cu10 or Cu12 units remain identical the geometries vary considerably and depend on the bulk of the alkynyl group, weak coordination of ether molecules to copper atoms in the core and Cu⋅⋅⋅O intramolecular contacts formed between Cu–hfac units on the periphery of the cluster. Similar intermolecular contacts and interlocking of Cu–hfac units are formed in the simple model complex [Cu2(hfac)2(HCCtBu)] (6). When linear alkynes, CnH2n+1CCH, are used in the synthesis and non‐coordinating solvents are used in the workup, further association of the Cu4C4 cores occurs and clusters with more than eighteen copper atoms are isolated.
Electronic Origin for Enhanced Nonlinear Optical Response of Complexes from Tetraalkylammonium Halide and Carbon Tetrabromide: Electrostatic Potentials of Intermolecular Donor–Acceptor Dyads
Authors: Cheng Wendan , Shen Juan , Wu Dongsheng , Li Xiaodong , Lan Youzhao , Li Feifei , Huang Shuping , Zhang Hao , Gong Yajing
Published: June 2006

Electronic origin for nonresonant enhancement of nonlinear optical response in the complexes formed from tetraalkylammonium halide and carbon tetrabromide is provided in view of electrostatic potentials of intermolecular donor (halide ion)–acceptor (CBr4). The calculated electrostatic potentials of donor–acceptor range from −4.83 to −7.70 kcal mol−1and show a decreasing order of [Et4Cl−⋅⋅⋅Br] > [Et4Br−⋅⋅⋅Br] ≅ [Et4I−⋅⋅⋅Br] > [Bu4Br−⋅⋅⋅Br]. The calculated second‐order susceptibilities of solid complexes are in an increasing order of [NEt4Cl⋅CBr4] < [NEt4Br⋅CBr4] ≅ [NEt4I⋅CBr4] < [NBu4Br⋅CBr4⋅C3H6O]. It has been shown that the donor/acceptor dyads make the exclusive contribution to nonlinear optical response. A large size of halide or tetraalkylammonium ion results in a small electrostatic potential and large nonlinear optical response in these charge‐transfer complexes. It indicates that a small supermolecular interaction will create a large nonlinear optical response, and it gives a clue to design the molecular complexes with large non‐linear optical susceptibility.
Powerful CarbonCarbon Bond Forming Reactions Based on a Novel Radical Exchange Process
Authors: Quiclet‐Sire Béatrice , Zard Samir Z.
Published: June 2006

Xanthates and related derivatives have proved to be extremely useful for both inter‐ and intramolecular radical additions. The broad applicability of the intermolecular addition to un‐activated olefins opens tremendous opportunities for synthesis, since various functional groups can be brought together under mild conditions and complex structures can be rapidly assembled. The presence of the xanthate in the product is also a powerful asset for further modifications, by both radical and non‐radical pathways. Of special importance is the access to highly substituted aromatic and heteroaromatic derivatives and the synthesis of block polymers through a controlled radical polymerisation mediated by various thiocarbonylthio group containing agents (RAFT and MADIX processes).
Guanine Oxidation: One‐ and Two‐Electron Reactions
Authors: Pratviel Geneviève , Meunier Bernard
Published: June 2006

Guanine bases in DNA are the most sensitive to oxidation. A lot of effort has been devoted to the understanding of the chemical modifications of guanine under different oxidizing conditions, the final goal being to know which lesions in DNA can be expected in vivo and their biological consequences. This article analyses the mechanisms underlying guanine oxidation by the comparison between one‐ and two‐electron transfer processes. The different oxidants used in vitro give complementary answers. This overview presents a choice of some key intermediates and the predictive description of G‐oxidation products that can be generated from these intermediates depending on the reaction conditions.
Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents
Authors: Laurent Sophie , Elst Luce Vander , Muller Robert N.
Published: June 2006

This paper compares the physicochemical properties of six low molecular weight clinical complexes of gadolinium studied under identical experimental conditions. Magnevist®, Dotarem®, Omniscan®, ProHance®, MultiHance® and Gadovist® were investigated by oxygen‐17 relaxometry at different temperatures and by proton relaxometry at various magnetic fields, temperatures and media [pure water, zinc(II)‐containing aqueous solutions and HSA‐containing solutions]. Osmolality, viscosity and stability versus transmetallation by zinc(II) ions were added for a more comprehensive description. The relaxivities of the clinical formulations as measured in water are similar in the imaging magnetic field region, with a slightly better performance for MultiHance. This can be explained by a shorter distance between the hydrogen nuclei of the water molecule bound to the Gd3+ ion and this paramagnetic centre. In contrast to the open‐chain complexes, all macrocyclic systems (Dotarem, ProHance and Gadovist) are insensitive to transmetallation by zinc ions. The stability of the open‐chain complexes with respect to transmetallation depends on the chemical structure of the ligand, with a better stability for MultiHance. The presence of human serum albumin has no significant effect on the proton relaxivity of Magnevist, Dotarem, Omniscan, ProHance and Gadovist but markedly increases the relaxivity of MultiHance because of a non‐covalent interaction with the protein. As a result, the relaxivity of MultiHance in HSA‐containing media of fixed concentration decreases with increasing concentration of the contrast agent. Copyright © 2006 John Wiley & Sons, Ltd.
Impact of rigidification on relaxometric properties of a tricyclic tetraazatriacetic gadolinium chelate
Authors: Port Marc , Raynal Isabelle , Vander Elst Luce , Muller Robert N. , Dioury Fabienne , Ferroud Clotilde , Guy Alain
Published: June 2006

A constrained derivative of Gd–PCTA12, Gd–cyclo‐PCTA12, in which one ethylene bridge connecting two nitrogen atoms of the triamine block is replaced by a cyclohexylene bridge, was synthesized and the impact of rigidification was studied by comparing the physicochemical and relaxometric properties of both gadolinium MRI contrast agents, Gd–PCTA12 and Gd–cyclo‐PCTA12. The new complex has higher proton relaxivity than the parent compound (r1 = 6.1 s−1 mM−1 at 20 MHz and 310 K). The rigidification of the PCTA12 scaffold proved to have no impact on the inertness towards transmetallation by endogenous ions such as Zn2+. Moreover, for both contrast agents, the relaxivity was not quenched by endogenous anions. The oxygen‐17 NMR study and the NMRD profile demonstrated that the rigidification of the PCTA scaffold had no impact on the electronic relaxation of Gd–cyclo‐PCTA12. However, the rigidity of this complex induced an acceleration of the exchange rate of the inner‐sphere water molecules as a result of steric crowding around the gadolinium ion. The value of τM310 thus approached the optimal value required to attain high relaxivity once the chelate is immobilized by covalent or non‐covalent binding to macromolecules. Copyright © 2006 John Wiley & Sons, Ltd.
Predictors of mortality after androgen‐deprivation therapy in patients with rapidly rising prostate‐specific antigen levels after local therapy for prostate cancer
Authors: Rodrigues Neesha A. , Chen Ming‐Hui , Catalona William J. , Roehl Kimberly A. , Richie Jerome P. , D'Amico Anthony V.
Published: June 2006

BACKGROUND.

The authors identified biochemical and pathologic factors that were associated significantly with prostate cancer‐specific mortality (PCSM) after androgen deprivation therapy (ADT) in men who had rapidly rising prostate‐specific antigen (PSA) levels after they received local treatment.

METHODS.

The study population consisted of 67 patients who had a PSA doubling time (DT) ≤6 months after radical prostatectomy (n= 50 patients) or external beam radiation therapy (n= 17 patients) for localized prostate cancer. Multivariate Cox proportional hazards regression analysis was used to evaluate whether the interval to PSA failure, pre‐ADT PSA DT, PSA level at the time of ADT initiation, time to PSA nadir, PSA nadir after 8 months on ADT, and Gleason score were associated significantly with the time to PCSM 8 months after the initiation of ADT.

RESULTS.

A PSA nadir >0.2 ng/mL (adjusted hazard ratio [HR], 8.0; 95% confidence interval [95% CI], 1.7–38.7;P= 0.009) and a Gleason score ≥8 (adjusted HR, 5.2; 95% CI, 1.3–20.6;P= 0.02) were associated significantly with a short time to PCSM. The cumulative incidence estimates of 3‐year PCSM were 5.8% versus 50.9% for patients with a PSA nadir ≤0.2 ng/mL versus >0.2 ng/mL, respectively, and 10.8% versus 35.8% for patients who had tumors with a Gleason score ≤7 versus ≥8, respectively.

CONCLUSIONS.

Among men with a PSA DT ≤6 months, both a PSA nadir >0.2 ng/mL after ADT and a Gleason score ≥8 cancer identified men who were at high risk for PCSM. These men would be ideal candidates for Phase III studies that evaluate the impact on survival of new systemic therapies for prostate cancer. Cancer 2006. © 2006 American Cancer Society.
Primary versus radiation‐associated craniofacial osteosarcoma
Authors: McHugh Jonathan B. , Thomas Dafydd G. , Herman Joseph M. , Ray Michael E. , Baker Laurence H. , Adsay N. Volkan , Rabah Raja , Lucas David R.
Published: June 2006

BACKGROUND.

Craniofacial osteosarcoma differs from long bone osteosarcoma in that patients are older, tumors are often low grade, and prognosis is more favorable. Although most are sporadic, some tumors occur in association with prior radiation therapy. The purpose of the current study was to compare clinicopathologic and prognostic features of primary and radiation‐associated osteosarcoma.

METHODS.

The study group consisted of 15 primary and 6 radiation‐associated osteosarcomas. Clinical and follow‐up data were obtained in every case. Tissue microarrays were immunohistochemically stained for p53, pRB, Ki‐67 (MIB‐1), and ezrin. DNA was sequenced for TP53 mutations.

RESULTS.

All radiation‐associated osteosarcomas were high grade and half were fibroblastic. In contrast, 47% of primary craniofacial osteosarcomas were high grade and only 1 was fibroblastic. All radiation‐associated osteosarcomas recurred, half the patients died of disease, 2 were alive with unresectable tumors, whereas only 1 was alive without disease. In contrast, 80% of patients with primary tumors were alive without disease, 33% had local recurrences, and 13% died of disease. Radiation‐associated tumors overexpressed p53 more often (33% vs. 13%), more often had TP53 mutations (33% vs. 8%), had higher proliferative activity (67% vs. 0% showing >50% MIB‐1 staining), and expressed ezrin more frequently (83% vs. 40%) than primary tumors. Compared with a control group of 24 high‐ and 7 low‐grade primary extremity osteosarcomas, radiation‐associated tumors marked as the high‐grade tumors.

CONCLUSIONS.

Craniofacial radiation‐associated osteosarcomas are high‐grade tumors that behave more aggressively than most primary craniofacial osteosarcomas. In addition, they demonstrate higher expression rates of adverse prognostic indicators, further highlighting the distinction. Cancer 2006. © 2006 American Cancer Society.
Oncogenic T‐antigen of JC virus is present frequently in human gastric cancers
Authors: Shin Sung Kwan , Li Mei‐Shu , Fuerst Florentine , Hotchkiss Erin , Meyer Richard , Kim Tae , Goel Ajay , Boland C. Richard
Published: June 2006

BACKGROUND.

JC virus (JCV) is a polyomavirus that commonly infects humans and is the causative agent of progressive multifocal leukoencephalopathy in immune‐compromised patients. An association between JCV and human cancers long has been suspected, because this virus induces brain tumors in several animal models. The oncogenic potential of JCV is mediated by a transforming protein, the T‐antigen (T‐Ag), which is a multifunctional protein that transforms cells through interactions with various growth‐regulatory genes, including p53 and pRb, and by stabilizing β‐catenin. Previously, the laboratory at the authors' institution demonstrated that JCV is present frequently in the human gastrointestinal tract and may play a role in colorectal carcinogenesis. However, to date, no studies have determined whether JCV sequences are present specifically in gastric cancers. The current study was designed to investigate whether JCV sequences and expression are found in human gastric cancers.

METHODS.

DNA was extracted from 23 paraffin embedded and 14 frozen gastric cancer specimens. For the detection of JCV gene sequences, polymerase chain reaction amplifications were performed using gene‐specific primers for T‐Ag, VP‐1 (a JCV capsid gene), and the viral regulatory region (or transcriptional control region). Immunohistochemical staining was performed with an anti‐T‐Ag monoclonal antibody to detect protein expression.

RESULTS.

Twenty‐one of 37 gastric cancers (57%) harbored JCV T‐Ag sequences, and 13 of 37 gastric cancers (30%) contained VP‐1 sequences. T‐Ag sequences also were found in adjacent nonneoplastic mucosa. In addition, JCV regulatory region sequences were present frequently in gastric cancers and adjacent nonneoplastic mucosa. T‐Ag protein expression was found in 9 of 23 gastric cancers (39%), whereas no expression was observed in any of the nonneoplastic tissues.

CONCLUSIONS.

To the authors' knowledge, this is the first demonstration of the presence of JCV T‐Ag expression in human gastric cancers. These findings suggest a possible role for this polyomavirus in gastric carcinogenesis. Cancer 2006. © 2006 American Cancer Society.
Current status of lymph node‐positive prostate cancer
Authors: Swanson Gregory P. , Thompson Ian M. , Basler Joseph
Published: June 2006

In early surgical series, the incidence of positive lymph nodes in patients with prostate cancer was approximately 40%. In the modern era of screening and improved patient selection, the incidence is now <10%, although most series excluded patients with higher risk disease. The risk of having positive lymph nodes is influenced by disease stage, prostate‐specific antigen level, and tumor grade and by the aggressiveness of lymph node dissection. Many of the same factors predict the outcome of these patients. Although the percentage of patients with positive lymph nodes has declined, there remain significant numbers of patients with lymph node‐positive prostate cancer, and it remains a therapeutic dilemma. Cancer 2006. © 2006 American Cancer Society.
The chemokine receptor CCX‐CKR mediates effective scavenging of CCL19 in vitro
Authors: Comerford Iain , Milasta Sandra , Morrow Valerie , Milligan Graeme , Nibbs Robert
Published: June 2006

The chemokines CCL19, CCL21 and CCL25, by signalling through the receptors CCR7 or CCR9, play critical roles in leukocyte homing. They also bind another heptahelical surface protein, CCX‐CKR. CCX‐CKR cannot couple to typical chemokine receptor signalling pathways or mediate chemotaxis, and its function remains unclear. We have proposed that it controls chemokine bioavailability. Here, using transfected HEK293 cells, we have shown that both CCX‐CKR and CCR7 mediate rapid CCL19 internalisation upon initial chemokine exposure. However, internalised CCL19 was more efficiently retained and degraded after uptake via CCX‐CKR. More importantly, CCR7 rapidly became refractory for CCL19 uptake, but the sequestration activity of CCX‐CKR was enhanced. These properties endowed CCX‐CKR with an impressive ability to mediate progressive sequestration and degradation of large quantities of CCL19, and conversely, prevented CCR7‐expressing cells from extensively altering their chemokine environment. These differences may be linked to the routes of endocytosis used by these receptors. CCX‐CKR, unlike CCR7, was not critically dependent on β‐arrestins or clathrin‐coated pits. However, over‐expression of caveolin‐1, which stabilises caveolae, blocked CCL19 uptake by CCX‐CKR while having no impact on other chemokine receptors, including CCR7. These data predict that CCX‐CKR scavenges extracellular chemokines in vivo to modify responses through CCR7.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200636327
Duration of CTL activation regulates IL‐2 production required for autonomous clonal expansion
Authors: Spierings Diana C. J. , Lemmens Edward E. , Grewal Kirpal , Schoenberger Stephen P. , Green Douglas R.
Published: June 2006

The extent and magnitude of CD8+ T lymphocyte (CTL) clonal expansion in vivo depends on the duration of stimulation provided during primary activation, whereas expansion under conventional in vitro conditions fails to reveal this. The molecular details of this differential programming are unclear. We developed a low‐density culture system that recapitulates in vivo conditions and enables analysis of both proliferation and survival/apoptosis during primary expansion. We found that CTL given a prolonged stimulus produced more IL‐2 and for a longer period than briefly activated CTL, and the IL‐2 produced during the expansion phase was essential for cell proliferation and accumulation at low densities. CTL given a short stimulation and plated at low density followed the fate of briefly stimulated cells in vivo and underwent an abortive expansion and apoptosis, unless IL‐2 was exogenously provided. Inhibition of apoptosis did not replace the requirement for IL‐2 to drive clonal expansion. CTL primed for prolonged periods but in the absence of costimulation similarly behaved as though “partially programmed”, undergoing abortive expansion at low densities. These results indicate that the nature and duration of antigenic stimulation regulate the autonomy of CTL expansion via the production of autocrine IL‐2.
Distinct roles for IL‐6 and IL‐12p40 in mediating protection against Leishmania donovani and the expansion of IL‐10+ CD4+ T cells
Authors: Stäger Simona , Maroof Asher , Zubairi Soombul , Sanos Stephanie L. , Kopf Manfred , Kaye Paul M.
Published: June 2006

Adoptive dendritic cell (DC) immunotherapy provides a useful experimental tool to evaluate immunoregulation in vivo and has previously been successfully used to enhance host resistance in a variety of experimental models of leishmaniasis. Here, we used this approach to identify IL‐6 and IL‐12p40 as critical cytokines that cooperate to mediate host protection to Leishmania donovani but which act independently to regulate expansion of IL‐10+ CD4+ T cells, shown here for the first time to be associated with this infection. Adoptive transfer of LPS‐activated bone marrow‐derived DC (BMDC) from wild‐type mice was therapeutically beneficial and led to enhanced resistance as measured by spleen parasite burden. In contrast, IL‐6‐ or IL‐12p40‐deficient BMDC had no protective benefit, indicating that production of both cytokines was essential for the therapeutic efficacy of DC. IL‐10 production by CD25– FoxP3– IL‐10+ CD4+ T cells is a strong correlate of disease progression, and BMDC from wild‐type mice inhibited expansion of these cells. Strikingly, IL‐12‐deficient BMDC could also inhibit the expansion of this T cell population whereas IL‐6‐deficient BMDC could not, indicating that IL‐6 played a key role in this aspect of DC function in vivo. Breadth of cytokine production is thus an important factor when considering strategies for DC‐based interventions.
Src kinase Lyn is crucial for Pseudomonas aeruginosa internalization into lung cells
Authors: Kannan Shibichakravarthy , Audet Aaron , Knittel Jessica , Mullegama Saman , Gao George F. , Wu Min
Published: June 2006

Lyn is an important B cell signaling kinase of the Src tyrosine kinase family with a broad range of functions from cytoskeletal changes to induction of apoptosis. However, the role of Lyn in infectious diseases is not clear. Here, we demonstrate that Lyn activation by phosphorylation significantly impacted invasion of an alveolar epithelial cell line, primary lung cells, and rat lungs by Pseudomonas aeruginosa (PA), a common opportunistic lung pathogen affecting individuals with deficient lung immunity. Our results indicate that activation of Lyn and its interaction with rafts and TLR2, played an important role in the initial stages of PA interaction with host cells. The role of Lyn was further evaluated using the pharmacologic Src‐specific inhibitor PP2, a dominant negative mutant, and finally confirmed with Lyn‐deficient (Lyn–/–) bone marrow‐derived mast cells. Inhibition of Lyn's function by above approaches prevented PA internalization. Moreover, blocking of Lyn also affected downstream events: induction of inflammatory cytokines and apoptosis. This report brings out a new role of Lyn in infectious diseases and indicates potential new targets for prevention and treatment of infections.
Follicular B helper T cell activity is confined to CXCR5hiICOShi CD4 T cells and is independent of CD57 expression
Authors: Rasheed Ata‐Ur , Rahn Hans‐Peter , Sallusto Federica , Lipp Martin , Müller Gerd
Published: June 2006

The generation of high‐affinity antibody‐secreting plasma cells critically depends on the presence of CD4 T cells during the germinal center (GC) reaction. GC T cells are so far incompletely characterized in terms of phenotype and function. Here, we show that human follicular B helper T (TFH) cells are characterized by high expression of the homeostatic chemokine receptor CXCR5 and the costimulatory molecule ICOS, but not CD57 expression. CXCR5hiICOShi CD4 T cells are the most potent inducers of IgG production that also secrete large amounts of the B cell‐attracting chemokine CXCL13. CXCR5hiICOShi CD4 T cells differ from other tonsillar CD4 T cell subsets in their stimulatory activity, proliferative capacity and susceptibility to apoptosis. Large‐scale gene expression analysis revealed that TFH cells are only distantly related to CXCR5– and CXCR5+ central memory T (TCM) as well as effector memory T (TEM) cells present in the periphery. CXCR5hiICOShi CD4 T cells appear to be terminally differentiated T helper cells that express a unique set of transcription factors related to the Notch signaling pathway and thus differentiate independent of other T helper cell populations.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200636334
How T lymphocytes switch between life and death
Authors: Arnold Rüdiger , Brenner Dirk , Becker Mareike , Frey Christian R. , Krammer Peter H.
Published: June 2006

While insufficient cell death of activated T cells can result in autoimmune disorders, elimination of too many T cells can lead to immunodeficiency. Therefore, T lymphocyte fate is highly regulated and requires that cells can switch from an apoptosis‐resistant towards an apoptosis‐sensitive state. This switch is tightly controlled by various effector molecules. Basically, two separate pathways control the fate of antigen‐activated T cells: activation‐induced cell death (AICD) and activated T cell autonomous death (ACAD). Autoreactive T lymphocytes are eliminated by restimulation via their T cell receptor (TCR) and undergo AICD involving death receptors (extrinsic pathway). In contrast, ACAD can lead to T cell deletion without TCR restimulation, and is determined by the ratio between anti‐ and pro‐apoptotic Bcl‐2 family members at the mitochondria (intrinsic pathway). While the extrinsic and the intrinsic pathway lead to caspase activation, non‐caspase proteases (e.g., cathepsins) can be released by the lysosomes and might contribute to AICD as well as to ACAD. Activated T cells posses cell death escape mechanisms which are needed for survival of (memory) T cells, but are deleterious for autoimmune disorders or progression of T cell lymphomas.
DNA damage and acute toxicity caused by the urban air pollutant 3‐nitrobenzanthrone in rats; Characterization of DNA adducts in eight different tissues and organs with synthesized standards
Authors: Nagy Eszter , Adachi Shuichi , Takamura‐Enya Takeji , Zeisig Magnus , Möller Lennart
Published: June 2006

3‐Nitrobenzanthrone (3‐NBA) is an urban air pollutant and rat lung carcinogen that is among the most potent mutagens yet tested in the Salmonella reversion assay. In the present study, 1 mg 3‐NBA was administered orally to female F344 rats and DNA adduct formation was examined in liver, lung, kidney and five sections of the gastrointestinal (GI) tract at 6 hr, and 1, 2, 3, 5, and 10 days after administration. The DNA adduct patterns, analyzed by 32P‐postlabelling followed by HPLC separation, were similar in all tissues and organs. Five of the adduct peaks cochromatographed with synthesized DNA adduct standards. Three of these unequivocally determined standards, dGp‐C8‐N‐ABA, dGp‐N2‐C2‐ABA, and dAp‐N6‐C2‐ABA, were of the nonacetylated type, suggesting that at least part of the pathway for activation of 3‐NBA proceeds through O‐acetylation of the hydroxylamine intermediate. The two other DNA adduct standards, dGp‐C8‐C2‐N‐Ac‐ABA, and dGp‐N2‐C2‐N‐Ac‐ABA, were of the acetylated type, but there was some ambiguity in the characterization of these DNA adducts, since they varied inconsistently between samples and they also aligned with peaks found in controls. At 6 hr after treatment, the level of DNA adducts was highest in glandular stomach (relative adduct labeling (RAL), ∼70 adducts/108 normal nucleotides (NN)); adduct levels in this organ decreased at 24 hr, but increased afterwards. DNA adduct levels in the majority of organs were characterized by an early increase (from 6 hr to 3 days), which was followed by a decrease at 5 days and a maximum level 10 days after administration (RAL ∼120 adducts/108 NN for the lung, kidney and glandular stomach, ∼80 adducts/108 NN for the forestomach and ceacum, and ∼40 adducts/108 NN for the liver, small intestine, and colon). This pattern was consistent with pathological observations during autopsy showing high levels of tissue damage in the GI tract; the tissue damage included hemorrhages, loss of villous surface structure in the small intestine, as well as intestine fragility and oedema of the adipose tissue around the GI‐tract. Tissue damage decreased and DNA adduct levels increased at 10 days after administration. These observations suggest that 3‐NBA not only exerts acute toxic effects, but that the bioavailability is affected by storage in tissues and later becomes available, resulting in the increased DNA adduct levels at the later time points of collection. Environ. Mol. Mutagen., 2006. © 2006 Wiley‐Liss, Inc.
Urinary concentrations of bisphenol A in relation to biomarkers of sensitivity and effect and endocrine‐related health effects
Authors: Yang Mihi , Kim Soo‐Young , Chang Seong‐Sil , Lee In‐Seon , Kawamoto Toshihiro
Published: June 2006

The impact of endocrine‐disrupting chemicals (EDCs) on human health is not yet clear because of difficulties in ascertaining their biological effects. In the present study, we evaluated exposure to the EDC, bisphenol A (BPA), in 172 Koreans in relation to biomarkers of susceptibility and effect. The subjects completed questionnaires, which documented occupation, education, lifestyle factors, potential sources of BPA‐exposure, and the occurrence of self‐diagnosed endocrine disorders. None of the subjects were occupationallay exposed to BPA; however, urinary levels of conjugated BPA, determined by HPLC/FD, ranged from 0.03–62.4 μg/l (median, 7.86). The frequencies of potential susceptibility biomarkers, theUGT1A6‐Arg184Ser and theSULT1A1‐Arg213His polymorphisms, were not associated with urinary BPA levels, either as single genes or in combination. Indirect effects of BPA exposure on the susceptibility to mutagens were evaluated by comparing urinary BPA concentrations with MNNG‐induced sister‐chromatid exchange (SCE) in lymphocytes cultured from the subjects. BPA exposure showed marginal or significant associations with theSCEs induced by the low doses of MNNG (0–0.4 mM). However, there was no overall association between urinary BPA levels and MNNG‐induced frequency at doses ranging from 0.2–0.6 mM. Finally, we did not detect an association between urinary BPA concentration and endocrine‐related disorders. Even though we were unable to find a strong association between BPA exposure and a biological response, possibly because of the limited number of subjects, we observed that most of the subjects were exposed to BPA. Therefore, continuous biological monitoring of BPA is a prudent measure to prevent possible BPA‐related health risks. Environ. Mol. Mutagen., 2006. © 2006 Wiley‐Liss, Inc.
Influence of the SCGE protocol on the amount of basal DNA damage detected in the Mediterranean mussel, Mytilus galloprovincialis
Authors: Machella Nicola , Battino Maurizio , Pisanelli Barbara , Regoli Francesco
Published: June 2006

Genotoxicity studies using the single cell gel electrophoresis (SCGE) assay indicate that basal levels of DNA strand breaks (SBs) in marine invertebrates are higher and more variable than those in marine vertebrates. This elevated level of DNA damage was attributed to a large number of alkali‐labile sites, which are characteristic of the tightly‐packaged DNA in invertebrate cells. To investigate if altering the SCGE protocol can artificially modulate high levels of SBs, SCGE experiments were performed on haemocytes from the Mediterranean mussel (Mytilus galloprovincialis) using proteinase K (PK) digestion in combination with assay buffers containing various concentrations of EDTA. In addition, the effects of Trolox® (soluble antioxidant) and aurintricarboxylic acid (ATA; inhibitor of Ca2+/Mg2+‐dependent nucleases) also were tested. The levels of SBs in M. galloprovicialis cells were compared with SBs in cells from a terrestrial mollusk (the snail Helix aspersa), and a teleost fish (the seabass Dicentrarchus labrax). The integrity of M. galloprovincialis DNA isolated with phenol extractions using EDTA, Trolox, and ATA was further assayed by gel electrophoresis. High SBs in mussel cells were reduced by combining EDTA with PK digestion, or using Trolox® or ATA during cell processing for the SCGE assay. Snails and seabass had lower levels of SBs in the SCGE assay, and the levels were not affected by the protocol modifications. Adding EDTA, Trolox®, or ATA to phenol extractions of M. galloprovincialis genomic DNA also reduced the extent of DNA fragmentation. These results suggest that the internal fluids of M. galloprovincialis may increase the basal levels of DNA SBs through oxidative and/or enzyme‐mediated pathways. M. galloprovincialis is used extensively as a sentinel species for assessing the genotoxic hazard of marine pollutants. Our data suggest that the SCGE protocol should be carefully considered when assessing DNA damage in these species. Environ. Mol. Mutagen., 2006. © 2006 Wiley‐Liss, Inc.
Potential New Solid Oxide Fuel Cell (SOFC) Anode Materials in the La‐Ca‐Cr‐Ti‐Ru‐O System
Authors: Vashook V. , Zosel J. , Müller R. , Shuk P. , Vasylechko L. , Ullmann H. , Guth U.
Published: June 2006

Six single phase La1–xCaxCr1–yTiy–γRuγO3–δ (x = 0.1, 0.2, y = 1.0, 0.8 and γ = 0.0, 0.1, 0.2) compositions are prepared by solid state reaction. Oxygen non‐stoichiometry, electrical conductivity, catalytic activity, and electrochemical efficiency of these compositions is investigated over a wide temperature and oxygen partial pressure range. The compositions with the highest electrical conductivity (50 S cm–1) at reducing conditions and highest catalytic activity for the oxidation of hydrocarbons are found. A combination of highly conductive La1–xCaxTiO3–δ in a reducing atmosphere and an intermediate functional film of catalytically active La0.1Ca0.9Ti1–xRuxO3–δ for the oxidation of hydrocarbons could potentially be very useful in a multilayer SOFC anode.
Overexpression of caveolin‐1 results in increased plasma membrane targeting of glycolytic enzymes: The structural basis for a membrane associated metabolic compartment
Authors: Raikar Leena S. , Vallejo Johana , Lloyd Pamela G. , Hardin Christopher D.
Published: June 2006

Although membrane‐associated glycolysis has been observed in a variety of cell types, the mechanism of localization of glycolytic enzymes to the plasma membrane is not known. We hypothesized that caveolin‐1 (CAV‐1) serves as a scaffolding protein for glycolytic enzymes and may play a role in the organization of cell metabolism. To test this hypothesis, we over‐expressed CAV‐1 in cultured A7r5 (rat aorta vascular smooth muscle; VSM) cells. Confocal immunofluorescence microscopy was used to study the distribution of phosphofructokinase (PFK) and CAV‐1 in the transfected cells. Areas of interest (AOI) were analyzed in a central Z‐plane across the cell transversing the perinuclear region. To quantify any shift in PFK localization resulting from CAV‐1 over‐expression, we calculated a periphery to center (PC) index by taking the average of the two outer AOIs from each membrane region and dividing by the central one or two AOIs. We found the PC index to be 1.92 ± 0.57 (mean ± SEM, N = 8) for transfected cells and 0.59 ± 0.05 (mean ± SEM, N = 11) for control cells. Colocalization analysis demonstrated that the percentage of PFK associated with CAV‐1 increased in transfected cells compared to control cells. The localization of aldolase (ALD) was also shifted towards the plasma membrane (and colocalized with PFK) in CAV‐1 over‐expressing cells. These results demonstrate that CAV‐1 creates binding sites for PFK and ALD that may be of higher affinity than those binding sites localized in the cytoplasm. We conclude that CAV‐1 functions as a scaffolding protein for PFK, ALD and perhaps other glycolytic enzymes, either through direct interaction or accessory proteins, thus contributing to compartmented metabolism in vascular smooth muscle. J. Cell. Biochem. 98: 861–871, 2006. © 2006 Wiley‐Liss, Inc.
Cellular and molecular parameters of mesothelioma
Authors: Ramos‐Nino Maria E. , Testa Joseph R. , Altomare Deborah A. , Pass Harvey I. , Carbone Michele , Bocchetta Maurizio , Mossman Brooke T.
Published: June 2006

Malignant mesotheliomas (MM) are neoplasms arising from mesothelial cells that line the body cavities, most commonly the pleural and peritoneal cavities. Although traditionally recognized as associated with occupational asbestos exposures, MMs can appear in individuals with no documented exposures to asbestos fibers, and emerging data suggest that genetic susceptibility and simian virus 40 (SV40) infections also facilitate the development of MMs. Both asbestos exposure and transfection of human mesothelial cells with SV40 large and small antigens (Tag, tag) cause genetic modifications and cell signaling events, most notably the induction of cell survival pathways and activation of receptors, and other proteins that favor the growth and establishment of MMs as well as their resistance to chemotherapy. Recent advances in high‐throughput technologies documenting gene and protein expression in patients and animal models of MMs can now be validated in human MM tissue arrays. These have revealed expression profiles that allow more accurate diagnosis and prognosis of MMs. More importantly, serum proteomics has revealed two new candidates (osteopontin and serum mesothelin‐related protein or SMRP) potentially useful in screening individuals for MMs. These mechanistic approaches offer new hope for early detection and treatment of these devastating tumors. J. Cell. Biochem. 98: 723–734, 2006. © 2006 Wiley‐Liss, Inc.
Ochnaflavone inhibits TNF‐α‐induced human VSMC proliferation via regulation of cell cycle, ERK1/2, and MMP‐9
Authors: Suh Seok‐Jong , Jin Un‐Ho , Kim Sung‐Hoon , Chang Hyeun‐Wook , Son Jong‐Keun , Ho Lee Seung , Son Kun‐Ho , Kim Cheorl‐Ho
Published: June 2006

Ochnaflavone (c‐3 of apigenin‐0‐c‐4 of apigenin; OC), a biflavonoid present in the human diet, is known to inhibit angiotensin II‐induced hypertrophy and serum‐induced smooth muscle cell proliferation. OC is known to have anti‐fungal and anti‐inflammatory activities. However, it is not known whether OC exerts similar cardioprotective effects in cells treated with tumor necrosis factor (TNF)‐α. In this study, we isolated OC from Lonicera japonica and studied its effect on matrix metalloproteinase‐9 (MMP‐9) gene expression in human aortic smooth muscle cells (HASMC). Furthermore, we investigated whether OC exerts the multiple suppressive effects on cytokine TNF‐α‐induced HASMC. Treatment of OC showed its potent inhibitory effects on DNA synthesis of cultured HASMC in the presence of TNF‐α. These inhibitory effects were associated with reduced extracellular signal‐regulated kinase 1/2 (ERK1/2) activity and G1 cell cycle arrest. Treatment of OC, which induced a cell cycle block in G1‐phase, induced downregulation of cyclins and CDKs and upregulation of the CDK inhibitor p21waf1 expression, whereas upregulation of p27 or p53 by OC was not observed. Because anti‐atherogenic effects need not be limited to anti‐proliferation, we decided to examine whether OC exerts inhibitory effects on MMP‐9 activity in TNF‐α‐induced HASMC. OC inhibited TNF‐α‐induced MMP‐9 secretion on HASMC in a dose‐dependent manner. This inhibition was characterized by downregulation of MMP‐9, which was transcriptionally regulated at nuclear factor (NF)‐κB site and activation protein (AP)‐1 site in the MMP‐9 promoter. These findings indicate the efficacy of OC in inhibiting cell proliferation, G1 to S‐phase cell cycle progress, and MMP‐9 expression through the transcription factors NF‐κB and AP‐1 on TNF‐α‐induced HASMC. The findings of the present study may provide a potential mechanism that explains the anti‐atherogenic activity of OC. J. Cell. Biochem. 99: 1298–1307, 2006. © 2006 Wiley‐Liss, Inc.
Photodynamic cell‐kill analysis of breast tumor cells with a tamoxifen‐pyropheophorbide conjugate
Authors: Gacio Ana Fernandez , Fernandez‐Marcos Carlos , Swamy Narasimha , Dunn Darra , Ray Rahul
Published: June 2006

We hypothesized that estrogen receptor (ER) in hormone‐sensitive breast cancer cells could be targeted for selective photodynamic killing of tumor cell with antiestrogen‐porphyrin conjugates by combining the over‐expression of ER in hormone‐sensitive breast cancer cells and tumor‐retention property of porphyrin photosensitizers. In this study we describe that a tamoxifen (TAM)‐pyropheophorbide conjugate that specifically binds to ERα, caused selective cell‐kill in MCF‐7 breast cancer cells upon light exposure. Therefore, it is a potential candidate for ER‐targeted photodynamic therapy of cancers (PDT) of tissues and organs that respond to estrogens/antiestrogens. J. Cell. Biochem. 99: 665–670, 2006. © 2006 Wiley‐Liss, Inc.
Regulation of osteoblast differentiation by transcription factors
Authors: Komori Toshihisa
Published: June 2006

Runx2, osterix, and β‐catenin are essential for osteoblast differentiation. Runx2 directs multipotent mesenchymal cells to an osteoblastic lineage, and inhibits them from differentiating into the adipocytic and chondrocytic lineages. After differentiating to preosteoblasts, β‐catenin, osterix, and Runx2 direct them to immature osteoblasts, which produce bone matrix proteins, blocking their potential to differentiate into the chondrocytic lineage. Runx2 inhibits osteoblast maturation and the transition into osteocytes, keeping osteoblasts in an immature stage. Other transcription factors including Msx1, Msx2, Dlx5, Dlx6, Twist, AP1(Fos/Jun), Knox‐20, Sp3, and ATF4 are also involved in osteoblast differentiation. To gain an understanding of bone development, it is important to position these transcription factors to the right places in the processes of osteoblast differentiation. J. Cell. Biochem. 99: 1233–1239, 2006. © 2006 Wiley‐Liss, Inc.
Gene expression of human T lymphocytes cell cycle: Experimental and bioinformatic analysis
Authors: Giacomelli Luca , Nicolini Claudio
Published: June 2006

Human lymphocytes gene expression is monitored before and after PHA stimulation over 72 h, using DNA microarray technology. Results are then compared with our previous bioinformatics predictions, which identified six leader genes of highest importance in human T lymphocytes cell cycle. Experimental data are strikingly compatible with bioinformatic predictions of the specific role and interaction of PCNA, CDC2, and CCNA2 at all phases of the cell cycle and of CHEK1 in regulating DNA repair and preservation. It does not escape our notice that the conception and use of ad hoc arrays, based on a bioinformatics prediction which identifies the most important genes involved in a particular biological process, can really be an added value in cell biology and cancer research alternative to massive frequently misleading molecular genomics. J. Cell. Biochem. 99: 1326–1333, 2006. © 2006 Wiley‐Liss, Inc.
Fibronectin enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells via ERK pathway
Authors: Ding Hai‐Tao , Wang Chen‐Guang , Zhang Tian‐Lan , Wang Kui
Published: June 2006

The process of vascular calcification presents several features similar to osteogenesis in which fibronectin (FN) acts as a regulator of osteoblastic differentiation and the ERK signal pathway is involved. In order to find whether FN promotes the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) through the ERK signal pathway, we investigated the effect of FN on the calcification of VSMCs by using an in vitro cell model. VSMCs cultured in plates with FN (0–20 µg/cm2) coating were induced to calcify by 10 mM sodium β‐glycerophosphate (β‐GP). FN exacerbated VSMC calcification in a dose‐ and time‐dependent manner, as indicated by the number of calcifying nodules per slide and the amount of calcium in the deposition. Data from RT‐PCR and immunoblotting assay revealed that FN also enhanced the expression of several phenotypic markers of osteoblasts, including alkaline phosphatase (ALP) activity, osteocalcin (OC), and Osf2/Cbfa1, a key transcription factor in osteoblastic differentiation. Furthermore, a specific inhibitor for ERK, PD98059 (10 µM), significantly suppressed the effect of FN on calcification and phenotypic marker expression. These findings seem to suggest that FN enhanced vascular calcification by promoting the osteoblastic differentiation of VSMCs via ERK signal pathway. J. Cell. Biochem. 99: 1343–1352, 2006. © 2006 Wiley‐Liss, Inc.
From inclusion to exclusion: armenian NGOs participation in the PRSP
Authors: Ishkanian Armine
Published: June 2006

Following the collapse of the Soviet Union, donor agencies embraced the idea of civil society development as critical to democratisation and successful transition. The belief was that stronger civil societies would promote good governance, increased civic participation and social trust. Examining NGOs' participation in Armenia's PRSP process, this paper asks whether NGOs have played or have the potential to play a part in promoting good governance and sustainable development in Armenia through their participation in such initiatives as the PRSP. The paper uses the ‘inclusion’, ‘exclusion’ and ‘hybrid’ stances1 to analyse the diverse approaches that local NGOs have embraced vis a vis the PRSP during the implementation stage. By analysing these stances, the paper demonstrates the diversity of Armenian civil society and considers how these stances affect NGOs ability to influence policy.

Albert Hirschman's (1970) study of exit, voice and loyalty was very useful in examining the stances of the NGOs, but his framework was not entirely applicable given the nature of the organisations under discussion as well as the politics and power dynamics involved. ‘Stance’ is used here to signify both the strategy and political or ideological positions of the NGOs. Michelle Rivkin‐Fish (2004) uses a similar approach in discussing the strategies of global actors engaged in collaborative encounters with Russian health workers.

Copyright © 2006 John Wiley & Sons, Ltd.
The varied and conditional integration of NGOs in the aid system: NGOs and the World Bank
Authors: Nelson Paul
Published: June 2006

This paper proposes a conceptual and methodological understanding of thenature and extentof NGO integration into state and donor systems that is based on a dynamic view of NGOs as multidimensional organisations with financial, political, interpersonal, legal, values a technical dimensions that vary across organisations, and produce a wide variety of interactions with the aid industry. NGOs' engagement with the World Bank is interpreted as a function of the interaction of these six dimensions. Through cooperation in projects, critical advocacy and the rapidly growing consultations on policy issues, NGOs' engagement with the World Bank grew rapidly in the 1980s and 1990s. After identifying some of the factors that appear to affect whether and how an NGO is drawn into the aid system, the paper offers a set of research questions and priorities for scholars exploring the varied and conditional ways that NGOs are integrated into the aid system. Copyright © 2006 John Wiley & Sons, Ltd.
The spatiotemporal climate variability over Senegal and its relationship to global climate
Authors: Fall Souleymane , Semazzi Fredrick H. M. , Niyogi Dev Dutta S. , Anyah Richard O. , Bowden Jared
Published: June 2006

Climate variability over Senegal (West Africa) and its relationship to global climate are examined for the period 1979–1998. Monthly observed rainfall for 20 stations and monthly CPC merged analysis precipitation (CMAP) over Senegal were averaged for the months of June, July, August, and September in order to generate seasonal rainfall totals for the wet season, as well as climate indices averaged over the study period. The spatial distribution patterns are mapped and analyzed using ArcGIS Spatial Analyst. Rainfall distribution over Senegal is dominated by a N–S gradient.

To investigate the climate variability over Senegal, an empirical orthogonal function (EOF) analysis is performed for the 1979–1998 period, using rain‐gauge and CMAP rainfall data over Senegal, and CMAP data only for West Africa. The first West African mode agrees strongly with Lamb's rainfall index. One of our major findings is that EOF2 for West Africa is well correlated with EOF1 for rainfall in Senegal. This relationship is supported by the projection of winds on the EOF2 mode by the National Centers for Environmental Prediction (NCEP), as well as the grid‐point correlation between the time series of EOF2 over West Africa and the Atlantic sea‐surface temperature (SST). The typical circulation associated with positive anomalies over Senegal is a moisture convergence, which takes place over the Guinea Gulf, in conjunction with the warm waters in this area.

The time series for rainfall over Senegal show positive correlations with the South Atlantic SST. Over the Pacific Ocean, the greatest correlation coefficients (up to −0.72) are observed during the April–July period, which provide a modest possibility of predicting Senegal's rainy season.

Given the specificity of coastal West Africa, the traditional indices used by policy makers and end users for the whole Sahel–Sudan region will not work for Senegal.

The CMAP data are robust and suitable for analyses over West Africa. On the basis of its reliability, CMAP data has proven to be a good validation for analyses based on rain‐gauge precipitation. Copyright © 2006 Royal Meteorological Society