bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalized stacking fault energies, ductilities, and twinnabilities of Ni and selected Ni alloys
Authors: Siegel Donald J.
Published: September 2005

The generalized stacking fault energies, Rice-criterion ductilities, and twinnabilities of selected Ni-x solid-solution alloys (x=Nb, W, Mn, Fe, Cu) are calculated using density functional theory to elucidate how alloying alters the mechanical properties of pure Ni. Relative to Ni, the alloys have smaller stacking fault energies (γsf), similar ductilities, and a greater tendency to undergo deformation twinning. The results are compared to experimental studies of the mechanical properties of nanocrystalline (nc) Ni alloys from the literature, and it is suggested that the higher strain-hardening rate recently reported for nc-Ni-Cu (relative to nc-Ni-Fe) does not arise from differences in γsf, but from a higher dislocation density caused by more facile dislocation nucleation.
Third-order optical nonlinearity in regio-controlled polythiophene films
Authors: Kishida Hideo , Hirota Keisuke , Wakabayashi Takeru , Okamoto Hiroshi , Kokubo Hisashi , Yamamoto Takakazu
Published: September 2005

We have investigated the third-order optical nonlinearity of poly(3-hexylthiophenes) with various head-to-tail coupling ratios (r), using the third-harmonic generation method. An increase in r leads to a reduction in optical gap energy (Eg) and an increase in the third-order nonlinear susceptibility (χ(3)). For r=0 to 0.80, χ(3) is scaled by Eg as χ(3)∝Eg−6.7, while for r∼1, χ(3) is considerably enhanced beyond this scaling law. We discuss how the behavior of χ(3) is based upon the conjugation-length dependence of the transition dipole moments.
Meyer-Neldel rule and the influence of entropy on capture cross-section determination in Cu(In,Ga)Se2
Authors: AbuShama Jehad A. M. , Johnston S. W. , Crandall R. S. , Noufi R.
Published: September 2005

We use deep-level transient spectroscopy (DLTS) to investigate the electronic properties of ZnO∕CdS∕CuxIn1−yGaySe2∕Mo∕soda-lime glass thin-film solar cells. We deposited films with different x and y values using elemental evaporation. Devices made from these films exhibit more than 40 hole and electron traps, with activation energies ranging from 0.07to1.17eV. Standard DLTS analysis (which assumes that entropy changes can be neglected) gives apparent capture cross sections that vary by 18 orders of magnitude over this energy range. All our data show that the charge-carrier emission rate obeys the Meyer-Neldel rule (MNR) with an isokinetic temperature of 340±30K. By including the MNR relation in detailed balance, we show that there is a single cross section for all the traps.
Chlorophyll-layer-inserted poly(3-hexyl-thiophene) solar cell having a high light-to-current conversion efficiency up to 1.48%
Authors: Yun Je-Jung , Jung Ho-Seok , Kim Sung-Han , Han Eun-Mi , Vaithianathan Veeramuthu , Jenekhe Samson A.
Published: September 2005

We report the fabrication of a chlorophyll-layer-inserted poly(3-hexyl-thiophene) (P3HT) solar cell. A significant enhancement in the light-to-current conversion efficiency of up to 1.48% with a fill factor of 0.32 was achieved in a solar cell with a device structure of indium tin oxide anode/poly (3,4-ethylene dioxy-thiophene):poly(styrene sulfonate)/P3HT/chlorophyll/Al cathode under the standard air mass 1.5 irradiation (20mW∕cm2). These results suggest that the generation of an internal electric field is mainly due to a difference between the highest occupied molecular orbital of the P3HT (donor) and the lowest unoccupied molecular orbital of the chlorophyll (acceptor), which permits the transfer of photoinduced electrons from P3HT to chlorophyll.
The change of electric field and of some other insulating properties during isochronal annealing in thermally poled Ge-doped silica films
Authors: Liu Qiming , Poumellec Bertrand , Braga Delfin , Blaise Guy , Ren Yitao , Kristensen Martin
Published: September 2005

The secondary electron emission contrast between poled and unpoled regions in thermally poled Ge-doped silica films were measured according to different annealing temperatures and electron doses with electron acceleration energy of 5keV. It is used for measuring the change on annealing of poling induced electric field and other insulating properties like electron traps population and conductivity in high field. Concerning the change of the contrast at low dose arising from the poling electric field, we show that this field begins to disappear at around 450°C and is erased completely at 650°C. Using a larger dose allows measuring the change in conductivity contrast. We find a stability similar to the electric field with a disappearance around 450∼650°C. On the contrary, for intermediate dose, the contrast remains for larger annealing temperature. It allows measuring properties of the electron traps. Their number appears to be modified in the poling process.
Engineering stable peptide toxins by means of backbone cyclization: Stabilization of the α-conotoxin MII
Authors: Clark Richard J. , Fischer Harald , Dempster Louise , Daly Norelle L. , Rosengren K. Johan , Nevin Simon T. , Meunier Frederic A. , Adams David J. , Craik David J.
Published: September 2005

Conotoxins (CTXs), with their exquisite specificity and potency, have recently created much excitement as drug leads. However, like most peptides, their beneficial activities may potentially be undermined by susceptibility to proteolysis
in vivo
. By cyclizing the α-CTX MII by using a range of linkers, we have engineered peptides that preserve their full activity but have greatly improved resistance to proteolytic degradation. The cyclic MII analogue containing a seven-residue linker joining the N and C termini was as active and selective as the native peptide for native and recombinant neuronal nicotinic acetylcholine receptor subtypes present in bovine chromaffin cells and expressed in
Xenopus
oocytes, respectively. Furthermore, its resistance to proteolysis against a specific protease and in human plasma was significantly improved. More generally, to our knowledge, this report is the first on the cyclization of disulfide-rich toxins. Cyclization strategies represent an approach for stabilizing bioactive peptides while keeping their full potencies and should boost applications of peptide-based drugs in human medicine.
Inorganic polyphosphate in the social life of
Myxococcus xanthus
: Motility, development, and predation
Authors: Zhang Haiyu , Rao Narayan N. , Shiba Toshikazu , Kornberg Arthur
Published: September 2005

Inorganic polyphosphate (poly P), a polymer of tens or hundreds of phosphate residues linked by high-energy, ATP-like bonds, is found in all organisms and performs a wide variety of functions.
Myxococcus xanthus
, a social bacterium that feeds on other bacteria and forms fruiting bodies and spores, depends on poly P for motility, development, and nutritional predation. Two poly P metabolizing enzymes were studied in
M. xanthus
: poly P kinase 1, which synthesizes poly P reversibly from ATP, and poly P:AMP phosphotransferase, which uses poly P as a donor to also reversibly convert AMP to ADP. The null mutant of
ppk1
is defective in social motility, overproduces pilin protein on the cell surface, is delayed in fruiting body formation, produces fewer spores, is delayed in germination, and forms far smaller plaques on a lawn of
Klebsiella aerogenes
. The
pap
mutant is also impaired in social motility, but shows only slightly reduced abilities in development and predation.
Opposing effects of DNA hypomethylation on intestinal and liver carcinogenesis
Authors: Yamada Yasuhiro , Jackson-Grusby Laurie , Linhart Heinz , Meissner Alex , Eden Amir , Lin Haijiang , Jaenisch Rudolf
Published: September 2005

Genome-wide DNA hypomethylation and concomitant promoter-specific tumor suppressor gene hypermethylation are among the most common molecular alterations in human neoplasia. Consistent with the notion that both promoter hypermethylation and genome-wide hypomethylation are functionally important in tumorigenesis, genetic and/or pharmacologic reduction of DNA methylation levels results in suppression or promotion of tumor incidence, respectively, depending on the tumor cell type. For instance, DNA hypomethylation promotes tumors that rely predominantly on loss of heterozygosity (LOH) or chromosomal instability mechanisms, whereas loss of DNA methylation suppresses tumors that rely on epigenetic silencing. Mutational and epigenetic silencing events in Wnt pathway genes have been identified in human colon tumors. We used
Apc
Min/+
mice to investigate the effect of hypomethylation on intestinal and liver tumor formation. Intestinal carcinogenesis in
Apc
Min/+
mice occurs in two stages, with the formation of microadenomas leading to the development of macroscopic polyps. Using
Dnmt1
hypomorphic alleles to reduce genomic methylation, we observed elevated incidence of microadenomas that were associated with LOH at
Apc
. In contrast, the incidence and growth of macroscopic intestinal tumors in the same animals was strongly suppressed. In contrast to the overall inhibition of intestinal tumorigenesis in hypomethylated
Apc
Min/+
mice, hypomethylation caused development of multifocal liver tumors accompanied by
Apc
LOH. These findings support the notion of a dual role for DNA hypomethylation in suppressing later stages of intestinal tumorigenesis, but promoting early lesions in the colon and liver through an LOH mechanism.
Regulation of SR-BI protein levels by phosphorylation of its associated protein, PDZK1
Authors: Nakamura Toshiyuki , Shibata Norihito , Nishimoto-Shibata Takako , Feng Dongdong , Ikemoto Mamoru , Motojima Kiyoto , Iso-o Naoyuki , Tsukamoto Kazuhisa , Tsujimoto Masafumi , Arai Hiroyuki
Published: September 2005

Scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor that mediates the selective uptake of HDL cholesterol and cholesterol secretion into bile in the liver. Previously, we identified an SR-BI-associated protein, termed PDZK1, from rat liver membrane extracts. PDZK1 contains four PSD-95/Dlg/ZO-1 (PDZ) domains, the first of which in the N-terminal region is responsible for the association with SR-BI. PDZK1 controls hepatic SR-BI expression in a posttranscriptional fashion both in cell culture and
in vivo
. In this study, we demonstrated that the C-terminal region of PDZK1 is crucial for up-regulating SR-BI protein expression. Metabolic labeling experiments and phosphoamino acid analysis revealed that PDZK1 is phosphorylated at Ser residues within this region. Point-mutation analysis demonstrated that PDZK1 is phosphorylated at Ser-509. Interestingly, a mutant PDZK1, in which Ser-509 was replaced with Ala, lost the ability to up-regulate SR-BI protein. We identified Ser-509 of PDZK1 as the residue that is phosphorylated by the cAMP-dependent PKA
in vitro
as well as in cell culture. Ser-509 of PDZK1 in rat liver was also phosphorylated, as shown by an Ab that specifically detects phosphorylated Ser-509. Administration of glucagon to Wistar rats increased PDZK1 phosphorylation as well as hepatic SR-BI and PDZK1 expression while it decreased plasma HDL levels, indicating that PDZK1 phosphorylation is hormonally regulated. These findings suggest that phosphorylation of PDZK1 has an important role in the regulation of hepatic SR-BI expression and, thus, influences plasma HDL levels.
Distinct pathways control recruitment and maintenance of myosin II at the cleavage furrow during cytokinesis
Authors: Dean Sara O. , Rogers Stephen L. , Stuurman Nico , Vale Ronald D. , Spudich James A.
Published: September 2005

The correct localization of myosin II to the equatorial cortex is crucial for proper cell division. Here, we examine a collection of genes that cause defects in cytokinesis and reveal with live cell imaging two distinct phases of myosin II localization. Three genes in the rho1 signaling pathway,
pebble
(a Rho guanidine nucleotide exchange factor),
rho1
, and
rho kinase
, are required for the initial recruitment of myosin II to the equatorial cortex. This initial localization mechanism does not require F-actin or the two components of the centralspindlin complex, the mitotic kinesin pavarotti/MKLP1 and racGAP50c/CYK-4. However, F-actin, the centralspindlin complex, formin (
diaphanous
), and profilin (
chickadee
) are required to stably maintain myosin II at the furrow. In the absence of these latter genes, myosin II delocalizes from the equatorial cortex and undergoes highly dynamic appearances and disappearances around the entire cell cortex, sometimes associated with abnormal contractions or blebbing. Our findings support a model in which a rho kinase-dependent event, possibly myosin II regulatory light chain phosphorylation, is required for the initial recruitment to the furrow, whereas the assembly of parallel, unbranched actin filaments, generated by formin-mediated actin nucleation, is required for maintaining myosin II exclusively at the equatorial cortex.
Perspectives on the role of the human gut microbiota and its modulation by pro- and prebiotics
Authors: Steer Toni , Carpenter Hollie , Tuohy Kieran , Gibson Glenn R.
Published: September 2005

One of the most topical areas of human nutrition is the role of the gut in health and disease. Specifically, this involves interactions between the resident microbiota and dietary ingredients that support their activities. Currently, it is accepted that the gut microflora contains pathogenic, benign and beneficial components. Some microbially induced disease states such as acute gastroenteritis and pseudomembranous colitis have a defined aetiological agent(s). Speculation on the role of microbiota components in disorders such as irritable bowel syndrome, bowel cancer, neonatal necrotising enterocolitis and ulcerative colitis are less well defined, but many studies are convincing. It is evident that the gut microflora composition can be altered through diet. Because of their perceived health-promoting status, bifidobacteria and lactobacilli are the commonest targets. Probiotics involve the use of live micro-organisms in food; prebiotics are carbohydrates selectively metabolized by desirable moieties of the indigenous flora; synbiotics combine the two approaches. Dietary intervention of the human gut microbiota is feasible and has been proven as efficacious in volunteer trials. The health bonuses of such approaches offer the potential to manage many gut disorders prophylactically. However, it is imperative that the best methodologies available are applied to this area of nutritional sciences. This will undoubtedly involve a genomic application to the research and is already under way through molecular tracking of microbiota changes to diet in controlled human trials.
The interactions between selenium and iodine deficiencies in man and animals
Authors: Arthur John R , Beckett Geoffrey J , Mitchell Julie H
Published: September 2005

Up to one billion people live in areas where they may be at risk from I deficiency. Many of the debilitating effects of the deficiency may be irreversible, consequently it is essential to understand the mechanisms whereby lack of I can cause disease through decreased thyroxine and 3, 3',5-triiodothyronine (T3) synthesis. Since Se has an essential role in thyroid hormone metabolism, it has the potential to play a major part in the outcome of I deficiency. These effects of Se derive from two aspects of its biological function. First, three Se-containing deiodinases regulate the synthesis and degradation of the biologically active thyroid hormone, T3. Second, selenoperoxidases and possibly thioredoxin reductase (EC1.6.4.5) protect the thyroid gland from H2O2produced during the synthesis of thyroid hormones. The mechanisms whereby Se deficiency exacerbates the hypothyroidism due to I deficiency have been elucidated in animals. In contrast to these adverse effects, concurrent Se deficiency may also cause changes in deiodinase activities which can protect the brain from low T3concentrations in I deficiency. Animals with Se and I deficiency have changes in serum thyroid hormone concentrations that are similar to those observed in patients with I deficiency disease. However such animal models show no thyroid involution, a feature which is characteristic of myxoedematous cretinism in man. These observations imply that if Se deficiency is involved in the outcome of I deficiency in human populations it is likely that other interacting factors such as goitrogens are also implicated. Nevertheless the protection of the thyroid gland from H2O2and the regulation of tissue T3levels are the functions of Se that are most likely to underlie the interactions of Se and I.
The influence of a fish oil high in docosahexaenoic acid on plasma lipoprotein and vitamin E concentrations and haemostatic function in healthy male volunteers
Authors: Sanders T. A. B. , Hinds Alison
Published: September 2005

Nine healthy male subjects consumed a daily fish oil supplement providing 2.1 g docosahexaenoic acid (22:6n-3; DHA) and 0.8 g eicosapentaenoic acid (20:5n-3; EPA) for 6 weeks. The proportion of EPA and DHA in plasma, erythrocytes, leucocytes and platelet phospholipids was increased by the supplement. Plasma concentration of triacylglycerol and very-low-density-lipoprotein-cholesterol were lowered and those of high-density-lipotrotein (HDL)- and HDL2-cholesterol and apoprotein B were increased. Platelet aggregation and thromboxane B2production induced by collagen were partially inhibited. Both systolic and diastolic blood pressure fell during treatment and rose following withdrawal of the supplement. Statistically significant reductions in erythrocyte counts, packed cell volume and haemoglobin and increases in total leucocyte and monocyte counts occurred with the supplement. Plasma α-tocopherol concentrations fell below the normal range during the period of supplementation. It is suggested that future studies consider components other than EPA in fish oil. Further studies are needed to investigate the extent to which fish oil increases the requirement for antioxidant nutrients.
Nutritional outcome and immunocompetence in mice fed on a diet containing raw field beans (Vicia faba, var. minor) as the source of protein
Authors: Martínez J. Alfredo , Macarulla M. Teresa , Marcos Rafael , Larralde Jesús
Published: September 2005

Feeding growing mice on diets containing raw field beans (Vicia fabavar. minor) as the only source of protein brought about an impairment in growth, muscle mass and liver weight. No changes in food consumption were observed, but the food intake:weight gain ratio was increased in those animals. Plasma protein, triacylglycerols and cholesterol values were not affected by the dietary treatment although serum glucose and zinc levels fell after legume intake as well as the number of circulating erythrocytes. The relative enlargement of thymus and spleen in the legume-fed mice was apparently accompanied by a reduction in the cell number and an increase in cell size, while the protein synthesis capacity followed differentiated patterns in both tissues when assessed through protein, DNA and RNA determinations. The haemagglutination titres and the number of rosette-forming cells were lower in those animals fed on the field bean diet as well as the splenic lymphocyte responses to phytohaemagglutinin, Concanavalin A or lipopolysaccharide mitogens used to evaluate the functional status of T and B lymphocytes. The present study describes, apparently for the first time in mice, the involvement of field bean intake in some immunological disturbances affecting both humoral- and cell-mediated aspects of the immune response
Breastfeeding and introduction of solid foods in Swedish infants: the All Babies in Southeast Sweden study
Authors: Brekke Hilde K. , Ludvigsson Jonas F. , van Odijk Jenny , Ludvigsson Johnny
Published: September 2005

The aim of this report is to describe breastfeeding duration and introduction of foods in Swedish infants born 1997–9, in relation to current recommendations. A secondary aim is to examine breastfeeding duration and introduction of certain allergenic foods in allergy-risk families (for whom allergy-preventive advice has been issued). Out of 21 700 invited infants, screening questionnaires were completed for 16 070 infants after delivery. Parents to 11 081 infants completed a follow-up questionnaire regarding breastfeeding and introduction of foods and 9849 handed in detailed food diaries at 1 year of age. The percentages of infants who were exclusively breast-fed at 3, 6 and ≥9 months of age were 78·4, 10·1 and 3·9, respectively. The corresponding percentages for partial breastfeeding were 87·8, 68·9 and 43·6. Gluten-containing foods were introduced to 66 % of infants between 4 and 6 months, as recommended at the time of the study, and one-quarter had stopped breastfeeding when gluten was introduced. More than 90 % of parents introduced the first sample of solid food during months 4–6, as recommended. Fish and eggs had been introduced during the first year in 43 % and 29 %, respectively, of infants with atopic heredity. Exclusive breastfeeding duration and time of introduction of solid foods, including gluten, seemed to have been in line with Swedish recommendations at the time, although gluten was often introduced late, and not during ongoing breastfeeding as recommended. The adherence to allergy-preventive advice was less than optimal in infants with atopic heredity.
Qualitative and quantitative comparison of the cytotoxic and apoptotic potential of phytosterol oxidation products with their corresponding cholesterol oxidation products
Authors: Ryan Eileen , Chopra Jay , McCarthy Florence , Maguire Anita R. , O'Brien Nora M.
Published: September 2005

Phytosterols contain an unsaturated ring structure and therefore are susceptible to oxidation under certain conditions. Whilst the cytotoxicity of the analogous cholesterol oxidation products (COP) has been well documented, the biological effects of phytosterol oxidation products (POP)have not yet been fully ascertained. The objective of the present study was to examine the cytotoxicity of β-sitosterol oxides and their corresponding COP in a human monocytic cell line (U937), a colonic adenocarcinoma cell line (CaCo-2) and a hepatoma liver cell line (HepG2). 7β-Hydroxysitosterol, 7-ketositosterol, sitosterol-3β,5α,6β-triol and a sitosterol-5α,6α-epoxide–sitosterol-5β,6β-epoxide (6:1) mixture were found to be cytotoxic to all three cell lines employed; the mode of cell death was by apoptosis in the U937 cell line and necrosis in the CaCo-2 and HepG2 cells. 7β-Hydroxysitosterol was the only β-sitosterol oxide to cause depletion in glutathione, indicating that POP-induced apoptosis may not be dependent on the generation of an oxidative stress. A further objective of this study was to assess the ability of the antioxidants α-tocopherol, γ-tocopherol and β-carotene to modulate POP-induced cytotoxicity in U937 cells. Whilst α/γ-tocopherol protected against 7β-hydroxycholesterol-induced apoptosis, they did not confer protection against 7β-hydroxysitosterol-or 7-ketositosterol-induced toxicity, indicating that perhaps COP provoke different apoptotic pathways than POP. β-Carotene did not protect against COP- or POP-induced toxicity. In general, results indicate that POP have qualitatively similar toxic effects to COP. However, higher concentrations of POP are required to elicit comparable levels of toxicity.
Dietary flavonoids as intracellular substrates for an erythrocyte trans-plasma membrane oxidoreductase activity
Authors: Fiorani Mara , Accorsi Augusto
Published: September 2005

The plasma membrane oxidoreductase (PMOR) activity, which mainly utilises ascorbate as intracellular electron donor, represents a major mechanism for cell-dependent reduction of extracellular oxidants and might be an important process used by the erythrocytes to keep a reduced plasma environment. We previously reported that in human erythrocytes, myricetin and quercetin act as intracellular substrates of a PMOR showing a novel mechanism whereby these flavonoids could exert beneficial effects under oxidative stress conditions. Here, we evaluated the ability of different flavonoids (quercetin, myricetin, morin, kaempferol, fisetin, catechin, luteolin, apigenin, acacetin, rutin, taxifolin, naringenin, genistein) and of twoin vivoO-methylated metabolites of quercetin (isorhamnetin and tamarixetin) to be substrates of PMOR, by comparing their antioxidant capacity (i.e. direct interaction with the oxidant ferricyanide or with the free radical 1,1-diphenyl-2-picryl-hydrazil) with their ability to penetrate the erythrocytes and donate electrons to the PMOR. The results obtained indicate that, although most of the flavonoids display significant antioxidant activities, only those (quercetin, myricetin, fisetin) that combine the cathecol structure of the B ring (responsible for the reducing activity) with the 2,3 double bond and 4-oxo function of the C ring (responsible for the uptake by erythrocytes) can act as intracellular substrates for PMOR. It is of note that the metabolites of quercetin enter erythrocytes and donate electrons to the PMOR as the parent compound. The present data show a relationship between the flavonoid structures and their ability to provide electrons to the PMOR, suggesting an additional mechanism whereby dietary flavonoids may exert beneficial effects in man.
Chinese Housing Reform in State-owned Enterprises and Its Impacts on Different Social Groups
Authors: Wang Ya Ping , Wang Yanglin , Bramley Glen
Published: September 2005

Housing change has been a major part of urban social and economic reform in China. Earlier research and literature on housing policy focused largely on changes which affected office workers employed by government departments and professional institutions. Relatively little attention has been given to the examination of housing reform practice in state-owned enterprises. This paper aims to enhance our understanding of the social impacts of housing reform in China. It reports findings from fieldwork carried out in four large cities; highlights the different approaches adopted by state-owned enterprises; and assesses their impacts on different categories of employees.
Reduction of Alachlor-Induced Olfactory Mucosal Neoplasms by the Matrix Metalloproteinase Inhibitor Ro 28-2653
Authors: Genter Mary Beth , Warner Blake M. , Krell Hans-Willi , Bolon Brad
Published: September 2005

Chronic exposure to the chloracetanilide herbicide alachlor has been shown to cause olfactory mucosal neoplasms. Genomic analysis of olfactory mucosa from rats given alachlor (126 mg/kg/d) for from 1 day to 18 mo suggested that matrix metalloproteinases MMP-2 and MMP-9 were upregulated in the month following initiation of treatment. The present studies were designed to confirm this latter finding and to explore the potential role of MMPs in alachlor-induced olfactory carcinogenesis. Zymographic analysis of olfactory mucosal extracts confirmed that MMP-2 activity is higher in the olfactory mucosa of alachlor-treated rats. Therefore, rats were fed alachlor (126 mg/kg/d in the diet for 1 year) either with or without the MMP-2/MMP-9 inhibitor Ro 28-2653 (100 mg/kg daily by gavage for the first 2 months of alachlor treatment). The number of olfactory mucosal neoplasms was reduced by 25% after 1 year of alachlor treatment in rats that received both alachlor and Ro 28-2653. The morphology of alachlor-induced olfactory tumors was similar whether or not Ro 28-2653 had been given; the MMP inhibitor itself had no impact on olfactory mucosal histology. These data confirm that olfactory mucosal MMP-2 activity is increased following short-term alachlor exposure and show that administration of an MMP-2/9 inhibitor reduced the incidence of olfactory neoplasms in alachlor-treated rats, thereby implicating MMP-2 activity as a mediator of alachlor-induced carcinogenicity.
Effects of N-Acetylcysteine, Quercetin, and Phytic Acid on Spontaneous Hepatic and Renal Lesions in LEC Rats
Authors: Kitamura Yasuki , Nishikawa Akiyoshi , Nakamura Hideaki , Furukawa Fumio , Imazawa Takayoshi , Umemura Takashi , Uchida Koji , Hirose Masao
Published: September 2005

The effects of anti-oxidants were examined in Long-Evans Cinnamon (LEC) rats, which develop acute hepatic injury, and subsequent hepatic and renal tumors due to accumulation of excess Cu. The rats, at the age of 15 weeks, were supplied a diet containing either 1% of N-acetylcysteine (NAC), quercetin (QC), or phytic acid (PA), or basal diet alone. At weeks 2 and 6 posttreatment, animals were sacrificed for collection of blood and tissue samples. In the NAC-treated group, the development of hepatic and renal lesions was dramatically reduced. In addition, accumulation of Cu and Fe in the liver was suppressed. Acrolein-modified protein, a new marker for lipid peroxidation, was not detected in the liver or kidney of NAC treated rats, even though deposition was evident in control. Neither QC nor PA affected the development of spontaneous hepatic lesions. These results indicate that oxidative stress was reduced by NAC in the liver and kidney, and suggest that Cu and Fe may be involved in the generation of oxidative stress in the liver. In addition, it was suggested that the different effects of the anti-oxidants on lesion development in LEC rats might be related to different mechanisms of action with regard to oxidative stress.
Life and Times in Biochemical Toxicology
Authors: Guengerich F. Peter
Published: September 2005

The biochemical facets of toxicology have always had a major role in providing insight into mechanisms. Some of the history of the development of this area is summarized, including metabolism, enzymology, and the chemistry of reactive intermediates. Knowledge in these fields has had a major impact in the areas of drug metabolism and safety assessment, which are both critical steps in the development of pharmaceuticals and the rational use of commodity chemicals. The science of toxicology has developed considerably with input from other disciplines and today is poised to emerge as a predictive science with even more dramatic impact. The challenges ahead are considerable but there is renewed excitement in the potential of the field. As in the past, further advances in the field of toxicology will require the input of knowledge from many disciplines.
Influence of Gender on Cocaine Hepatotoxicity in CF-1 Mice
Authors: Visalli Thomas , Turkall Rita , Abdel-Rahman Mohamed S
Published: September 2005

Gender is known to play a role in the bioavailability, metabolism, and lethality of many toxic substances. This study was conducted to investigate the influence of gender on cocaine hepatotoxicity (CH) and lipopolysaccharide (LPS) potentiation of CH. Male and female CF-1 mice were orally administered 20 mg/kg body weight cocaine hydrochloride once daily for 7 days. Four hours after the last cocaine administration, the mice were administered 12 × 106 EU LPS (or equal volume of sterile saline) intraperitoneally. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were evaluated as indices of liver injury. Blood and liver glutathione (GSH), glutathione reductase (GRx), and catalase (CAT) activities were also determined to investigate the extent of oxidative stress induced by the treatments. Serum ALT and AST concentrations were elevated in all males receiving cocaine alone or cocaine + LPS. Furthermore, blood GSH and CAT were decreased and GRx activity was elevated in these same animals. Histological analysis revealed a high degree of hepatic focal necrosis in the male cocaine group, and severe hemorrhagic necrosis in the male cocaine + LPS group. Unlike males, females showed no damage resulting from cocaine or cocaine + LPS exposure, whereas testosterone-supplemented ovariectomized females displayed histological and biochemical profiles statistically similar to males. The results demonstrate that the extent of CH or LPS-potentiated CH is influenced by gender and sex hormones, particularly testosterone.
The End of Print: Digitization and Its Consequence—Revolutionary Changes in Scholarly and Social Communication and in Scientific Research
Authors: Davidson Lloyd A.
Published: September 2005

The transformation from print to digital media for scientific communication, driven in part by the growth of the Internet and the tremendous explosion in the amount of information now available to everybody, is creating fundamental changes in institutions such as publishers, libraries, and universities that primarily exist for the creation, management, and distribution of information and knowledge. Scientific, technological, and medical journals are the first publications to be completely transformed from print to digital format but monographs are beginning to appear in digital format as well and soon all communication and publishing of scientific information will be entirely electronic. In fact, this change is affecting all components of the scientific enterprise, from personal correspondence and laboratory methods to peer reviewing and the quality assessment of scientific research. Along with these radical and rapid changes in information presentation and distribution are coincident changes in the expectations of both the public and other scientists, with both groups demanding ever more rapid, open, and global access to scientific information than has been available in the past. The consequence of this revolution in the mechanics of communications technology is threatening the very existence of a number of highly regarded institutions such as intellectual property, commercial publishers, scientific societies, and academic libraries and might soon begin to threaten even the traditional university.
Skin Sensitization: Modeling Based on Skin Metabolism Simulation and Formation of Protein Conjugates
Authors: Dimitrov Sabcho D. , Low Lawrence K. , Patlewicz Grace Y. , Kern Petra S. , Dimitrova Gergana D. , Comber Mike H. I. , Phillips Richard D. , Niemela Jay , Bailey Paul T. , Mekenyan Ovanes G.
Published: September 2005

A quantitative structure-activity relationship (QSAR) system for estimating skin sensitization potency has been developed that incorporates skin metabolism and considers the potential of parent chemicals and/or their activated metabolites to react with skin proteins. A training set of diverse chemicals was compiled and their skin sensitization potency assigned to one of three classes. These three classes were, significant, weak, or nonsensitizing. Because skin sensitization potential depends upon the ability of chemicals to react with skin proteins either directly or after appropriate metabolism, a metabolic simulator was constructed to mimic the enzyme activation of chemicals in the skin. This simulator contains 203 hierarchically ordered spontaneous and enzyme controlled reactions. Phase I and phase II metabolism were simulated by using 102 and 9 principal transformations, respectively. The covalent interactions of chemicals and their metabolites with skin proteins were described by 83 reactions that fall within 39 alerting groups. The SAR/QSAR system developed was able to correctly classify about 80% of the chemicals with significant sensitizing effect and 72% of nonsensitizing chemicals. For some alerting groups, three-dimensional (3D)-QSARs were developed to describe the multiplicity of physicochemical, steric, and electronic parameters. These 3D-QSARs, so-called pattern recognition-type models, were applied each time a latent alerting group was identified in a parent chemical or its generated metabolite(s). The concept of the mutual influence amongst atoms in a molecule was used to define the structural domain of the skin sensitization model. The utility of the structural model domain and the predictability of the model were evaluated using sensitization potency data for 96 chemicals not used in the model building. The TIssue MEtabolism Simulator (TIMES) software was used to integrate a skin metabolism simulator and 3D-QSARs to evaluate the reactivity of chemicals thus predicting their likely skin sensitization potency.
Risk Assessment and Therapeutic Indices of Artesunate and Artelinate in Plasmodium berghei–Infected and Uninfected Rats
Authors: Xie Lisa H. , Johnson Todd O. , Weina Peter J. , Si Yuanzheng , Haeberle Adam , Upadhyay Ravi , Wong Elaine , Li Qigui
Published: September 2005

Artesunate (AS) is being developed as a potential agent for the treatment of severe and complicated malaria. A risk assessment of the therapeutic index and related hematological changes of AS and artelinate (AL) following daily intravenous injection for 3 days was conducted in Plasmodium berghei–infected and uninfected rats. The minimum doses of AS and AL for parasitemia suppression were 2.3 and 2.5 mg/kg, respectively, and the suppressive doses for half parasitemia (SD50) were 7.4 and 8.6 mg/kg, respectively. The maximum tolerated dose (MTD) for AS was 240 mg/kg with a therapeutic index of 32.6. The MTD for AL was 80 mg/kg with a therapeutic index of 9.3. Hematological changes were studied on days 1 and 8 after the final dosing. In both AS- and AL-treated rats, dose-dependent and rapidly reversible hematological changes (significant reductions in RBC, HCT, Hb, and reticulocyte levels) were seen in the peripheral blood. Bone marrow evaluation revealed a statistically significant reduction in the myeloid/erythroid ratio only at the highest dose of AS (240 mg/kg), albeit still within the normal ratio range (1.0–1.5:1.0). Looking at the respective therapeutic indices the authors have concluded that AS is much safer than AL. Both drugs induced hematological changes in rats that parallel the dose-dependent, reversible anemia and reticulocytopenia previously reported in animals and humans. However, no significant bone marrow depression was seen for either agent.
Recent advances in our understanding of sediment-to-water contaminant fluxes: The soluble release fraction
Authors: Thibodeaux L.J.
Published: September 2005

Flux from the sediment-bed is a key element in chemical fate and transport water quality models used for rivers, lakes, estuaries and coastal oceans. These environmental chemodynamics simulation tools are being used to evaluate the effectiveness of remediating contaminated bed sediments. The options include monitored natural recovery, capping, dredging, in situ treatment and combinations of these. The chemical flux to water based on the particle processes (i.e., resuspension and setting) have traditionally been the focus of attention and it has received much study and re-development in the past decade. The recent availability of large sets of high quality particle and chemical data from several rivers containing poylchlorinated biphenyl compounds has caused a shift in thinking and a re-evaluation of the significance of the soluble release process. This process occurs when water flow conditions are unfavorable for any significant particle re-suspension. The objective of this paper is to demonstrate that a rapid soluble release process exists and to offer an algorithm for quantifying its flux from the bed. Data obtained from four major rivers show that the soluble fraction may vary from a few percent to nearly 100 percent of biphenyl release. A numerical ranking of the known and quantifiable individual soluble release processes places in-bed bioturbation first on the list. Coupled with the benthic boundary layer resistence, a simple theoretical algorithm is offered as the model for the overall mass-transfer coefficient Kf of the soluble release process. Although some laboratory and field data exist to support the algorithm, further studies will be needed in order to satisfy all members of the engineering science community.
Dechloromonas hortensis sp. nov. and strain ASK-1, two novel (per)chlorate-reducing bacteria, and taxonomic description of strain GR-1
Authors: Wolterink Arthur , Kim Sungyoun , Muusse Margje , Kim In S. , Roholl Paul J. M. , van Ginkel Cees G. , Stams Alfons J. M. , Kengen Servé W. M.
Published: September 2005

Recent studies on the occurrence of (per)chlorate-reducing bacteria have resulted in the characterization of strains capable of dissimilatory (per)chlorate reduction. Phylogenetic analysis has shown that these bacteria are members of theProteobacteria. Strains have been isolated from polluted and pristine sites, but only strains from polluted sites have been characterized in detail and deposited in culture collections. Herein we describe the isolation and characterization of perchlorate-reducing bacterium strain MA-1Tand chlorate-reducing bacterium strain ASK-1, respectively isolated from a pristine and a chlorate-polluted site. Both isolates are members of theProteobacteria. The 16S rRNA gene sequence similarity of MA-1TtoDechloromonas agitataDSM 13637Tis 97·6 %, but the relatedness in DNA–DNA reassociation is only 37 %. Therefore, we propose to classify strain MA-1T(=DSM 15637T=ATCC BAA-776T) as the type strain of a novel species,Dechloromonas hortensissp. nov. Strain ASK-1 and a previously described strain GR-1 show 100 and 99 % 16S rRNA gene sequence similarity toPseudomonas chloritidismutansDSM 13592TandDechlorosoma suillumDSM 13638T, respectively. DNA–DNA hybridization studies indicated that strains ASK-1 and GR-1 are related at the species level toP. chloritidismutansDSM 13592T(79 %) andDechlorosoma suillumDSM 13638T(85 %), respectively. As suggested previously,Dechlorosoma suillumappears to be a later heterotypic synonym ofAzospira oryzae. Although strain ASK-1 is identified asP. chloritidismutans, its morphology and growth requirements are different from those of the type strain.
Phyllobacterium trifolii sp. nov., nodulating Trifolium and Lupinus in Spanish soils
Authors: Valverde Angel , Velázquez Encarna , Fernández-Santos Félix , Vizcaíno Nieves , Rivas Raúl , Mateos Pedro F. , Martínez-Molina Eustoquio , Igual José Mariano , Willems Anne
Published: September 2005

Bacterial strain PETP02Twas isolated from nodules ofTrifolium pratensegrowing in a Spanish soil. Phylogenetic analysis of the 16S rRNA gene sequence showed that this strain represents a member of the genusPhyllobacterium. However, divergence found with the 16S rRNA gene sequence of the single recognized species of this genus,Phyllobacterium myrsinacearum, indicated that strain PETP02Tbelongs to a different species. The results of DNA–DNA hybridization, phenotypic tests and fatty acid analyses confirmed that this strain represents a novel species of the genusPhyllobacterium, for which the namePhyllobacterium trifoliisp. nov. is proposed. The type strain is PETP02T(=LMG 22712T=CECT 7015T). This strain was strictly aerobic and used several carbohydrates as carbon source. It was not able to reduce nitrate. Aesculin hydrolysis was negative. It did not produce urease, arginine dihydrolase, gelatinase orβ-galactosidase. The DNA G+C content was 56·4 mol%. ThenodDgene of this strain showed a sequence closely related to those of strains able to nodulateLupinus. Infectivity tests showed that this strain is able to produce nodules in bothTrifolium repensandLupinus albus.
Thalassobacillus devorans gen. nov., sp. nov., a moderately halophilic, phenol-degrading, Gram-positive bacterium
Authors: García María Teresa , Gallego Virginia , Ventosa Antonio , Mellado Encarnación
Published: September 2005

A novel moderately halophilic bacterium, strain G-19.1T, has been isolated from a phenol enrichment of samples collected in hypersaline habitats of southern Spain. This enrichment culture was a part of a screening programme to isolate halophilic bacteria able to degrade various aromatic compounds. Strain G-19.1Thas been characterized as a potential phenol-degrader over a wide range of saline conditions. Strain G-19.1Twas found to be an aerobic, Gram-positive, endospore-forming, non-pigmented, moderately halophilic rod that grew optimally in media containing 7·5–10 % NaCl at pH 7·0. The DNA G+C content was 42·4 mol%. Phylogenetic analysis based on comparison of 16S rRNA gene sequences indicated that the closest relatives wereHalobacillusspecies (96·2–97·0 %), although this novel isolate constitutes a separate line of descent within the radiation of Gram-positive rods. The cell-wall peptidoglycan containedmeso-diaminopimelic acid, indicating that this strain does not share the main characteristic that differentiates members of the genusHalobacillus(which contain Orn–d-Asp) from other related genera. The predominant cellular fatty acids were anteiso-C15 : 0, iso-C16 : 0and iso-C15 : 0. On the basis of phenotypic, genotypic and phylogenetic analyses, this isolate should be classified in a novel genus and species, for which the nameThalassobacillus devoransgen. nov., sp. nov. is proposed. The type strain is strain G-19.1T(=DSM 16966T=CECT 7046T=CCM 7282T).
Halomonas taeanensis sp. nov., a novel moderately halophilic bacterium isolated from a solar saltern in Korea
Authors: Lee Jae-Chan , Jeon Che Ok , Lim Jee-Min , Lee Sang-Mi , Lee Jung-Min , Song Sung-Min , Park Dong-Jin , Li Wen-Jun , Kim Chang-Jin
Published: September 2005

A moderately halophilic, Gram-negative bacterium, strain BH539T, which was isolated from a solar saltern at Taean in Korea, was considered to be a member of the genus Halomonas. Strain BH539T grew at salinities of 1–25 % (w/v) and at temperatures of 10–45 °C. Cells were short rods that were motile by means of several flagella. Their major fatty acids were C18 : 1
ω7c, C16 : 0 and C19 : 0 cyclo ω8c. The genomic DNA G+C content was about 65 mol% and the predominant ubiquinone was Q-9. Phylogenetic analyses based on 16S rRNA gene sequences indicated that the isolate formed a branch of the species Cobetia marina. However, 23S and 16S rRNA gene sequence similarities revealed that strain BH539T was related more closely to the type strains of the genus Halomonas. Phylogenetic analyses based on 23S rRNA gene sequences also indicated that the strain formed a phyletic line within the genus Halomonas. Therefore, it was concluded that strain BH539T should be classified within the genus Halomonas, rather than Cobetia. On the basis of physiological and molecular properties, strain BH539T represents a novel species of the genus Halomonas, for which the name Halomonas taeanensis sp. nov. is proposed. The type strain is BH539T (=KCTC 12284T=DSM 16463T).
Prevotella multisaccharivorax sp. nov., isolated from human subgingival plaque
Authors: Sakamoto Mitsuo , Umeda Makoto , Ishikawa Isao , Benno Yoshimi
Published: September 2005

Six bacterial strains isolated from the human oral cavity, PPPA16, PPPA20T, PPPA24, PPPA31, EPPA6 and EPPA7, were characterized by determining phenotypic and biochemical features, cellular fatty acid profiles, menaquinone profiles and phylogenetic position based on 16S rRNA gene sequence analysis. 16S rRNA gene sequence analysis showed that the isolates represented the same species of the genusPrevotella. The strains were related toPrevotella dentaliswith about 89 % similarity. In addition, the isolates were related toPrevotellasp. oral clone IDR-CEC-0032, which is a representative of the numerically dominant cluster VI in carious dentine lesions [Nadkarniet al. (2004).J Clin Microbiol42, 5238–5244], with about 99 % similarity. The strains were obligately anaerobic, non-pigmenting, non-spore-forming, non-motile, Gram-negative rods. The isolates could be differentiated from otherPrevotellaspecies byd-mannitol,d-melezitose,d-sorbitol andd-trehalose fermentation in API 20A tests. The cellular fatty acid composition of strains PPPA16, PPPA20T, PPPA24, PPPA31, EPPA6 and EPPA7 was significantly different from that of otherPrevotellaspecies. Compared with otherPrevotellaspecies, only these six strains contained dimethyl acetals. The major menaquinones of the clinical isolates were MK-12 and MK-13, whereas the major menaquinones of otherPrevotellaspecies were MK-10 and MK-11. On the basis of these data, a novelPrevotellaspecies,Prevotella multisaccharivoraxsp. nov., is proposed, with PPPA20T(=JCM 12954T=DSM 17128T) as the type strain.