bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete Deficiency of 5′-Nucleotidase Activity in Escherichia coli Leads to Loss of Growth on Purine Nucleotides but Not of Their Excretion
Authors: Kakehi Masahiro , Usuda Yoshihiro , Tabira Yukiko , Sugimoto Shinichi
Published: August 2007

Escherichia coli has many periplasmic phosphatase activities. To test whether it can take up and excrete purine nucleotides, we attempted to completely disrupt periplasmic 5′-nucleotidase activity. A 5′-nucleotidase activity was induced in ushA knockout mutant cells, which lack major 5′-nucleotidase activity, when they were grown with purine nucleotides as the sole carbon source. Using DNA macroarrays to compare global gene expression in wild-type and ushA knockout mutant cells cultured with IMP or GMP as the sole carbon source, we identified two genes that were induced in the ushA knockout mutant cells and encoded signal sequence needed for secretion. One of the genes, aphA, encoded a 5′-nucleotidase activity and was induced by IMP or inosine. An ushA aphA double knockout mutant was shown to be unable to grow on purine nucleotides as the sole carbon source. To investigate the excretion of purine nucleotides, we constructed an ushAaphA double knockout mutant of an inosine-producing strain and found that it accumulated IMP in the medium. In addition, when the guaBA operon was introduced into the ushAaphA double knockout IMP producer, GMP was released into the medium. These observations imply the existence of efflux activity for purine nucleotides in E. coli.
Growth Recovery on Glucose under Aerobic Conditions of an Escherichia coli Strain Carrying a Phosphoenolpyruvate:Carbohydrate Phosphotransferase System Deletion by Inactivating arcA and Overexpressing the Genes Coding for Glucokinase and Galactose Permease
Authors: Flores Noemí , Leal Lidia , Sigala Juan Carlos , de Anda Ramón , Escalante Adelfo , Martínez Alfredo , Ramírez Octavio T. , Gosset Guillermo , Bolivar Francisco
Published: August 2007

In Escherichia coli the phosphotransferase system (PTS) consumes one molecule of phosphoenolpyruvate (PEP) to phosphorylate each molecule of internalized glucose. PEP bioavailability into the aromatic pathway can be increased by inactivating the PTS. However, the lack of the PTS results in decreased glucose transport and growth rates. To overcome such drawbacks in a PTS– strain and reconstitute rapid growth on glucose phenotype (Glc+), the glk and galP genes were cloned into a plasmid and the arcA gene was inactivated. Simultaneous overexpression of glk and galP increased the growth rate and regenerated a Glc+ phenotype. However, the highest growth rate was obtained when glk and galP were overexpressed in the arcA– background. These results indicated that the arcA mutation enhanced glycolytic and respiratory capacities of the engineered strain.
The Phosphotransferase System-Dependent Sucrose Utilization Regulon in Enteropathogenic Escherichia coli Strains Is Located in a Variable Chromosomal Region Containing iap Sequences
Authors: Treviño-Quintanilla Luis Gerardo , Escalante Adelfo , Caro Alma Delia , Martínez Alfredo , González Ricardo , Puente José Luis , Bolívar Francisco , Gosset Guillermo
Published: August 2007

The capacity to utilize sucrose as a carbon and energy source (Scr+ phenotype) is a highly variable trait among Escherichia coli strains. In this study, seven enteropathogenic E. coli (EPEC) strains from different sources were studied for their capacity to grow using sucrose. Liquid media cultures showed that all analyzed strains have the Scr+ phenotype and two distinct groups were defined: one of five and another of two strains displaying doubling times of 67 and 125 min, respectively. The genes conferring the Scr+ phenotype in one of the fast-growing strains (T19) were cloned and sequenced. Comparative sequence analysis revealed that this strain possesses the scr regulon genes scrKYABR, encoding phosphoenolpyruvate:phosphotransferase system-dependent sucrose transport and utilization activities. Transcript level quantification revealed sucrose-dependent induction of scrK and scrR genes in fast-growing strains, whereas no transcripts were detected in slow-growing strains. Sequence comparison analysis revealed that the scr genes in strain T19 are almost identical to those present in the scr regulon of prototype EPEC E2348/69 and in both strains, the scr genes are inserted in the chromosomal intergenic region of hypothetical genes ygcE and ygcF. Comparison of the ygcE-ygcF intergenic region sequence of strains MG1655, enterohemorrhagic EDL933, uropathogenic ECFT073 and EPEC T19-E2348/69 revealed that the number of extragenic highly repeated iap sequences corresponded to nine, four, two and none, respectively. These results show that the iap sequence-containing chromosomal ygcE-ygcF intergenic region is highly variable in E. coli.
Bacterial Regulatory Networks Include Direct Contact of Response Regulator Proteins: Interaction of RegA and NtrX in Rhodobacter capsulatus
Authors: Gregor Jutta , Zeller Tanja , Balzer Angelika , Haberzettl Kerstin , Klug Gabriele
Published: August 2007

The formation of photosynthetic complexes in facultatively photosynthetic bacteria is controlled by the oxygen tension in the environment. In Rhodobacter capsulatus the two-component system RegB/RegA plays a major role in the redox control of photosynthesis genes but also controls other redox-dependent systems. The response regulator RegA is phosphorylated under low oxygen tension and activates the puf and puc operons, which encode pigment binding proteins, by binding to their promoter regions. Data from a yeast two-hybrid analysis as well as an in vitroanalysis indicate that RegA interacts with the NtrX protein, the response regulator of the NtrY/NtrX two-component system which is believed to be involved in regulation of nitrogen fixation genes. Our further analysis revealed that NtrX is indeed involved in the regulation of the puf and puc operons. Furthermore, we showed that an altered NtrX protein, which is predicted to adopt the conformation of phosphorylated NtrX protein, binds within the puf promoter region close to the RegA binding sites. We conclude that a direct interaction of two response regulators connects the regulatory systems for redox control and nitrogen control.
Relationships between Oxidative Stress Response and Virulence in Enterococcus faecalis
Authors: Riboulet Eliette , Verneuil Nicolas , La Carbona Stéphanie , Sauvageot Nicolas , Auffray Yanick , Hartke Axel , Giard Jean-Christophe
Published: August 2007

Enterococcus faecalis is a Gram-positive bacterium, member of the lactic acid bacteria group and is also one of the major causative agents of nosocomial infections. Moreover, the oxidative stress is one of the main challenges bacteria have to cope with during their process of infection. This review gives a description of this opportunist pathogen bacterium and an overview of the oxidative stress response and its regulation. We subsequently summarize results that suggest a relationship between this stress response and the virulence in E. faecalis.
Overproduction and Characterization of Two Distinct Aldehyde-Oxidizing Enzymes from Gluconobacter oxydans 621H
Authors: Schweiger Paul , Volland Sonja , Deppenmeier Uwe
Published: August 2007

The Gluconobacter oxydans 621H genome contains two genes (gox1122 and gox0499) that encode putative cytosolic NAD(P)-dependent aldehyde dehydrogenases. Each gene was expressed in Escherichia coli, and the recombinant enzymes were purified and characterized. The native protein Gox1122 exhibited an apparent molecular mass of 50.1 kDa, and the subunit mass was 50.5 kDa, indicating a monomeric structure of the native enzyme. The preferred substrates were acetaldehyde and NADP. The enzyme also oxidized other short-chained aliphatic and aromatic aldehydes at lower rates. Recombinant protein Gox0499 was composed of a single subunit and had an apparent molecular mass of 49.5 kDa. The substrate spectrum of Gox0499 was broad with a preference for long-chained aliphatic and aromatic aldehydes. Highest activities were obtained using dodecanal and NAD as substrates. RT real-time PCR showed that genes gox0499 and gox1122 were expressed at an elevated level (about 3-fold) when the cells were exposed to ethanol and dodecanal in comparison to control cells.
Analyses of the vrl Gene Cluster in Desulfococcus multivorans: Homologous to the Virulence-Associated Locus of the Ovine Footrot Pathogen Dichelobacter nodosus Strain A198
Authors: Knaust Florian , Kube Michael , Reinhardt Richard , Rabus Ralf
Published: August 2007

Major parts of the virulence-associated vrl locus known from the gammaproteobacterium Dichelobacter nodosus, the causative agent of ovine footrot, were analyzed in the genome of the sulfate-reducing deltaproteobacterium Desulfococcus multivorans. In the genome of D. multivorans 13 of the 19 vrl genes described for D. nodosus are present and highly conserved with respect to gene sequence and order. The vrl locus and its flanking regions suggest a bacteriophage-mediated transfer into the genome of D. multivorans. Comparative analysis of the deduced Vrl proteins reveals a wide distribution of parts of the virulence-associated vrl locus in distantly related bacteria. Horizontal transfer is suggested as driving mechanism for the circulation of the vrl genes in bacteria. Except for the vrlBMN genes D. multivorans and Desulfovibrio desulfuricans G20 together contain all vrl genes displaying a high degree of similarity. For D. multivorans it could be shown that guanine plus cytosine (GC) content, GC skew, di-, tri- or tetranucleotide distribution did not differ between the vrl locus and its flanking sequences. This could be a hint that the vrl locus originated from a related organism or at least a genome with similar characteristics. The conspicuous high degree of conservation of the analyzed vrl genes may result from a recent transfer event or reflect a function of the vrl genes, which is still unknown and not necessarily disease associated. The latter is supported by the evidence for expression of the vrl genes in D. multivorans, which has not been described as pathogen or to be associated to any disease pattern before.
Control of the Phosphorylation State of the HPr Protein of the Phosphotransferase System in Bacillus subtilis: Implication of the Protein Phosphatase PrpC
Authors: Singh Kalpana D. , Halbedel Sven , Görke Boris , Stülke Jörg
Published: August 2007

In the Gram-positive bacterium Bacillus subtilis as well as in other firmicutes, the HPr protein of the phosphotransferase system (PTS) has two distinct phosphorylation sites, His-15 and Ser-46. These sites are phosphorylated by the Enzyme I of the PTS and by the ATP-dependent HPr kinase/phosphorylase, respectively. As a result, the phosphorylation state of HPr reflects the nutrient supply of the cell and is in turn involved in several responses at the levels of transport activity and expression of catabolic genes. Most important, HPr(Ser-P) serves as a cofactor for the pleiotropic transcription regulator CcpA. In addition to the proteins that phosphorylate HPr, those that are involved in the dephosphorylation are important in controlling the overall HPr phosphorylation state and the resulting regulatory and physiological outputs. In this study, we found that in addition to the phosphorylase activity of the HPr kinase/phosphorylase, the serine/threonine protein phosphatase PrpC uses HPr(Ser-P) as a target.
Identification of a Hypothetical Protein of Plant Pathogenic Xanthomonas campestris as a Novel β-Galactosidase
Authors: Yang Tsuey-Ching , Hu Rouh-Mei , Weng Shu-Fen , Tseng Yi-Hsiung
Published: August 2007

Xc17L, a lactose-utilizing mutant of Xanthomonas campestris pv. campestris previously isolated by mutagenesis with nitrous acid, displays a level of β-galactosidase 3.5-fold higher than that in the parental Xc17. In this study, the gene encoding the enzyme displaying a higher specific activity in Xc17L was inactivated by mini-Tn5 transposition.Sequencing revealed that the product (579 aa, 63.5 kDa) of this gene, designated galD, was previously annotated to encode a hypothetical protein on the genome. Mutation of the gene by marker exchange, complementation test and Western blot analysis together confirmed that galD is indeed the gene involved in β-galactosidase elevation in Xc17L. With only the N-terminal region possessing similarity to the known β-galactosidases and partially conserved consensus motif, GalD is recognized as a member of the glycosyl hydrolase family 35. Insertion with GmΩ, which causes polar effects, into the upstream genes followed by Western blotting showed that galD is cotranscribed with the upstream genes and expressed constitutively. Mutation in galD causes no significant changes including pathogenicity in the bacterium.
The Road to Recovery from Depression – Don’t Drive Today with Yesterday’s Map
Authors: Fava Giovanni A. , Tomba Elena , Grandi Silvana
Published: August 2007

The issue of recovery is getting increasing attention in depression research, particularly after the publication of the STAR*D results. The paper analyzes some issues which may hinder effective treatment of major depressive disorders: the inadequacies of a cross-sectional DSM assessment without clinical differentiation of the extent, development and seriousness of the disturbances (staging); over-emphasis on and prolongation of drug treatment, without paying attention to problems related to tolerance; neglect of the active role of the patient in achieving recovery, with the integration of psychotherapeutic strategies in a sequential model. If we are able to remove the conceptual obstacles which obstruct our view of depression and silence the sound of propaganda, we may then become aware of a different scenario in mood disorders and be able to develop therapeutic strategies of enduring quality.
Antidepressant Dose Reduction and the Risk of Relapse in Major Depressive Disorder
Authors: Papakostas George I. , Perlis Roy H. , Seifert Cheryl , Fava Maurizio
Published: August 2007

Background: Whether the dose of antidepressants can be reduced following clinical improvement without subsequently increasing the likelihood of depressive relapse has not been established. Thus, the aim of this work was to compare relapse rates among patients with major depressive disorder (MDD) randomized to either continue receiving the full versus a reduced dose of antidepressants following partial or full improvement of symptoms. Methods: Five double-blind, randomized clinical trials involving 1,009 patients with MDD randomized to either continue receiving the full versus a reduced dose of antidepressants following partial or full improvement of symptoms were pooled using a random-effect meta-analysis model. Results: Patients randomized to continue treatment with lower doses of antidepressants were more likely to experience a depressive relapse than patients who continued treatment with the full dose (risk ratio 1.62, 95% confidence interval: 1.52–2.80, p = 0.001). Pooled relapse rates were 25.3 and 15.1% for the two treatment groups. Conclusions: Decreasing the antidepressant dose following partial or full symptom improvement is associated with an increased risk of relapse in MDD.
The Treatment of Psychotic Major Depression: Is There a Role for Adjunctive Psychotherapy?
Authors: Gaudiano Brandon A. , Miller Ivan W. , Herbert James D.
Published: August 2007

Background: Psychotic depression is a relatively prevalent mood disorder associated with greater symptom severity, a poorer course of illness and higher levels of functional impairment compared with nonpsychotic depression. Separate lines of investigation suggest that various forms of cognitive-behavioral therapy are efficacious for treating severe forms of nonpsychotic depression as well as primary psychotic disorders. However, there currently are no empirically supported psychotherapies specifically designed for treating psychotic depression. Method: We review the efficacy of current somatic treatments for the disorder and discuss the limited data to date on potentially useful psychotherapeutic approaches. In particular, we describe the clinical improvement observed in a subgroup of hospitalized patients with psychotic depression treated with Acceptance and Commitment Therapy as part of a larger clinical trial. Results: Pilot results demonstrated that Acceptance and Commitment Therapy was associated with clinically significant reductions in acute symptom severity and impairment compared with treatment as usual. Conclusion: The findings suggest that patients with psychotic depression can benefit from psychotherapy. Clinical and research recommendations in this area are presented.
Combination Treatment for Acute Depression Is Superior Only when Psychotherapy Is Added to Medication
Authors: Blom Marc B.J. , Jonker Kosse , Dusseldorp Elise , Spinhoven Philip , Hoencamp Erik , Haffmans Judith , van Dyck Richard
Published: August 2007

Background: Although several forms of effective therapy exist for outpatients suffering from major depressive disorder, many patients do not profit from treatment. Combining psychotherapy and medication may be an effective strategy. However, earlier studies have rarely found a clear advantage for the combination. Where an advantage was found, a possible placebo effect of adding 2 types of treatment could not be ruled out as cause for the superior effect of the combination. Methods: A total of 353 patients were screened, of whom 193 were randomized over 4 conditions: nefazodone plus clinical management, interpersonal psychotherapy (IPT), the combination of the two or the combination of IPT and pill-placebo. All patients suffered from major depressive disorder and had a score of at least 14 on the 17-item Hamilton Rating Scale (HAMD). The patients were treated for 12–16 weeks. At baseline, at 6 weeks and on completion of treatment, ratings were performed by independent raters. The primary outcome measure was the HAMD, and the Montgomery-Asberg Depression Rating Scale (MADRS) the secondary outcome measure. Results: Of the 193 patients included, 138 completed the trial. All treatments were effective. Using a random regression model, no differences between treatments were found on the HAMD. On the MADRS, however, the combination of medication with psychotherapy was more effective in reducing depressive symptoms compared to medication alone, but not to psychotherapy alone or IPT with pill-placebo. Conclusions: The results of this study yield support for the use of combining medication with psychotherapy instead of using medication only in the treatment of depressed outpatients. Combination treatment does not have an advantage over psychotherapy alone in the present study.
Psychiatrist Attitudes toward Self-Treatment of Their Own Depression
Authors: Balon Richard
Published: August 2007

Background: Self-treatment and treatments of friends or relatives is a controversial issue, tolerated by some and discouraged by others, including professionals. The author studied the attitudes toward self-treatment of depression among psychiatrists in Michigan. Method: A questionnaire asking whether the psychiatrist would or did self-treat for depression was mailed to 830 members of the Michigan Psychiatric Society. Results: The response rate was 68.3% (567 psychiatrists). Almost 43% of responders would consider self-medication or would self-medicate if afflicted with mild/moderate depression. Seven percent would self-medicate or consider self-medication for severe depression or if suicidal ideation became a component of one’s depression. In the past, 15.7% responders treated themselves for depression. Conclusion: These results suggest that a considerable number of psychiatrists would treat themselves for depression, possibly because of fear of stigma or fear of a permanent record, or other reasons.
Servo-Control of Water and Sodium Homeostasis during Renal Clearance Measurements in Conscious Rats
Authors: Thomsen Klaus , Shirley David G.
Published: August 2007

Servo-controlled fluid and sodium replacement during clearance studies is used in order to prevent loss of body fluid and sodium following diuretic/natriuretic procedures. However, even under control conditions, the use of this technique is sometimes associated with increases in proximal tubular fluid output (assessed by lithium clearance) and excretion rates. The present study examined the reason for these increases. The first series of experiments showed that one cause is volume overloading. This can occur if the servo system is activated from the start, i.e., during the establishment of a suitably high urine flow rate by constant infusion of hypotonic glucose solution. The second series of experiments showed that replacement of blood samples with donor blood can also lead to increases in fractional lithium excretion and accompanying increases in water and sodium excretion, a problem not seen when blood samples are replaced with the animal’s own red blood cells resuspended in isotonic saline. When these pitfalls are avoided, servo-controlled sodium and fluid replacement is a reliable technique that makes it possible to study the effects of natriuretic and/or diuretic stimuli without interference from unwanted changes in extracellular volume.
Role of GNRA Motif Mutations within Stem-Loop V of Internal Ribosome Entry Segment in Coxsackievirus B3 Molecular Attenuation
Authors: M’hadheb-Gharbi Manel Ben , El Hiar Raïda , Paulous Sylvie , Jaïdane Hela , Aouni Mahjoub , Kean Katherine M. , Gharbi Jawhar
Published: August 2007

The lengthy 5′ nontranslated region of coxsackievirus B3 (CVB3) forms a highly ordered secondary structure containing an internal ribosome entry segment (IRES), which plays an important role in controlling viral translation and pathogenesis. The stem-loop V (SL-V) of this IRES contains a large lateral bulge loop which encompasses two conserved GNRA motifs. In this study, we analyzed the effects of point mutations within the GNRA motifs of the CVB3 IRES. We characterized in vitro virus production and translation efficiency and we tested in vivo virulence of two CVB3 mutants produced by site-directed mutagenesis. The GNAA1 and GNAA2 RNAs displayed decreased translation initiation efficiency when translated in rabbit reticulocyte lysates. This translation defect was correlated with reduced yields of infectious virus particles in HeLa cells in comparison with the wild type.When inoculated orally into Swiss mice, both mutant viruses were avirulent and caused neither inflammation nor necrosis in hearts. These results highlight the important role of the GNRA motifs within the SL-V of the IRES of CVB3, in directing translation initiation.
Ethanol Catabolism in Corynebacterium glutamicum
Authors: Arndt Annette , Auchter Marc , Ishige Takeru , Wendisch Volker F. , Eikmanns Bernhard J.
Published: August 2007

Corynebacterium glutamicum grows on a variety of carbohydrates and organic acids as single or combined sources of carbon and energy. Here we show the ability of C. glutamicum to grow on ethanol with growth rates up to 0.24 h–1 and biomass yields up to 0.47 g dry weight (g ethanol)–1. Mutants of C. glutamicum deficient in phosphotransacetylase (PTA), isocitrate lyase (ICL) and malate synthase (MS) were unable to grow on ethanol, indicating that acetate activation and the glyoxylate cycle are essential for utilization of this substrate. In accordance, the expression profile of ethanol-grown C. glutamicum cells compared to that of glucose-grown cells revealed an increased expression of genes encoding acetate kinase (AK), PTA, ICL and MS. Furthermore, the specific activities of these four enzymes as well as those of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were found to be high in ethanol-grown and low in glucose-grown cells. Growth of C. glutamicum on a mixture of glucose and ethanol led to a biphasic growth behavior, which was due to the sequential utilization of glucose before ethanol. Accordingly, the specific activities of ADH, ALDH, AK, PTA, ICL and MS in cells grown in medium containing both substrates were as low as in glucose-grown cells in the first growth phase, but increased 5- to 100-fold during the second growth phase. The results indicate that ethanol catabolism in C. glutamicum is subject to carbon source-dependent regulation, i.e., to a carbon catabolite control.
Geography and Textual Allusions: Interpreting Isaiah xl-lv and Lamentations as Judahite Texts
Authors: Tiemeyer Lena-Sofia
Published: August 2007

This article proposes a new interpretation of the allusions to Lamentations as found in Isa. xl-lv. Scholars generally assume that the author of Isa. xl-lv transforms the Judahite material in Lamentations to fit his alleged exilic audience. Given the possible Judahite setting of Isa. xl-lv, however, there is need of reassessment. We shall here investigate the extent to which the bias toward an exilic setting of Isa. xl-lv has influenced the interpretation of the passages in which the allusions occur, and then explore how a Judahite setting of Isa. xl-lv alters this interpretation. As a result, we shall see that a Judahite setting of both texts not only facilitates but also enhances the interpretation of the same textual allusions.
Israelite, Moabite and Sabaean War-ḥērem Traditions and the Forging of National Identity: Reconsidering the Sabaean Text RES 3945 in Light of Biblical and Moabite Evidence
Authors: Monroe Lauren A.S.
Published: August 2007

In the biblical conquest accounts,hērem signifies ritual destruction and consecration to the deity of entire enemy populations and towns. The root hrm also appears in two extrabiblical conquest accounts: the Mesha Inscription and the Sabaean text, RES 3945. This article revisits the interpretation of the Sabaean text in light of recent scholarship in South Arabian Studies, and argues that RES 3945 should be placed on equal footing with the Mesha Inscription for its relevance for understanding the biblical hērem. Taken together, these sources situate the war-hērem in the context of early state formation, and suggest that the tripartite relationship between people, land and god, expressed in terms of b&ebrever&icaront, or “covenant,” in ancient Israel, may in fact have found expression more widely, in a tribal, inland Palestinian setting with cultural connections extending into the South Arabian Peninsula.
The Place of the Name in Deuteronomy
Authors: Richter Sandra L.
Published: August 2007

The location of Deuteronomy's central sanctuary is an old and important question. This article revisits the question via the lens of the oft' repeated deuteronomic phrase, lĕšakkēn šĕmô šām. Recent research indicates that this phrase is a loan-adaptation of Akkadian šuma šakānu, an idiom formulaic to the typology of the Mesopotamian royal monumental tradition, and associated with the inscription and installation of display monuments. Consequently, the frequent description of Deuteronomy's central sanctuary as hammāqôm ,ăšer yibḥar YHWH ,ĕlōhêkā lĕšakkēn šĕmo šām indicates that this place was associated in some manner with an inscribed monument. A survey of the theme of inscribed monuments throughout the Book of Deuteronomy confi rms this proposition, and points to the deuteronomic identity of “the place” as Mount Ebal. Although scholarship has tended to discount the significance of the Ebal tradition to the larger message of the Book of Deuteronomy, the literary, archaeological, epigraphic, and geographical data reviewed here confirm the probability of Ebal as Israel's first central sanctuary, and the installation of Yahweh's monument there as the climax of a critical theme within the book.
Notes on Metaphors, Notes as Metaphors
Authors: Lopez José Julián
Published: August 2007

This article is a contribution to the growing body of work that has emphasized the need to develop a theoretical framework capable of exploring metaphorical communication as a social rather than just as a cognitive process. The author draws attention to some of the social dynamics through which the inherent poly-valence of metaphors becomes stabilized, though never entirely neutralized. Specifically, he highlights the ways in which context, practices, and space serve to close down potential meanings. This is followed by an analysis of the deployment of a musical metaphor—nucleotide-bases-as-musical-notes that produce the “music of life”—in the context of a traveling science exhibition, The Geee! in Genome, whose stated goal is to educate and stimulate debate among the Canadian public. The author shows that although the musical metaphor lacks heuristic utility as a tool for explaining the “science” in the exhibition, it contributes to the staging of genomics and “life” itself as a spectacle; this makes it possible to frame contentious issues around genetic determinism, biotechnology-enabled health care, enhancement, commodification, and property rights in a more hospitable semantic terrain.
Slick PR? The Media Politics of the Prestige Oil Spill
Authors: Anderson Alison , Marhadour Agnès
Published: August 2007

This article examines the different ways in which Spanish, French, and U.K. newspapers framed the Prestige oil spill. In contrast to earlier large oil spills such as the Torrey Canyon, the Internet had a significant influence upon mainstream news coverage and the coordination of protest activities. The findings suggest that the local Spanish press provided the most sustained coverage, and geographic propinquity to the accident was a good predictor of the frequency and intensity of reporting. The regional Spanish press focused upon implications for the local economy rather than the effects on wildlife. In contrast, the sampled national newspapers in Spain, France, and the United Kingdom framed the oil spill in terms of its ecological impacts and the political controversy regarding who was to blame. The implications of these differences are discussed and considered in relation to the globalization of news and the changing politics of risk.
Training Failure as a Consequence of Organizational Culture
Authors: Bunch Kay J.
Published: August 2007

Organizations spend as much as US$200 billion annually on training and development; however, much of this investment appears squandered on ill-conceived or poorly implemented interventions. Scholars have pondered the causes of failed training for decades, focusing on issues such as methods, program design, and trainee characteristics. Recent interest in the role of organizational context rarely extends to organizational culture. The purpose of this article is to explore the relationship between training failure and the manifestations of various levels of culture.
Determining the Probability That an Employee Will Stay or Leave the Organization: A Mathematical and Theoretical Model for Organizations
Authors: Udechukwu Ikwukananne I. , Mujtaba Bahaudin G.
Published: August 2007

This article offers a simple mathematical and theoretical model for understanding voluntary turnover, as an interdisciplinary (social, psychological, and economic contexts) and multidimensional (employee, organization, and social affiliate) construct. The model provides a mathematical formula, received from assumptions, intended for use in determining the “probability that employees will stay or leave” an organization versus the traditional approach of determining the “intentions of staying” and/or the “intentions of leaving” the organization. Differences between existing concepts (intentions of quitting) and this model are discussed. The model hypothesizes that the “probability of staying or leaving” the organization (E — (P.i)) or (1 — (P.i)) should be positively related to the employee's “intentions of quitting” the organization. The model does not focus on the numerous individual determinants of employee turnover, as is the case with existing voluntary turnover models, but focuses on these determinants as internal (Employer [E]) and external (Social Affiliate [i]) factors relative to the Employee (P), who either stays with or leaves the organization. The article also suggests that leaving and staying behaviors are concepts on the same platform. They are not different thoughts or necessarily opposites.
Learning Environment at Work: Dilemmas Facing Professional Employees
Authors: Andersen Vibeke , Andersen Anders Siig
Published: August 2007

In an effort to increase efficiency and democracy, the modernization of the public sector has involved an increase in market and user control, an increased application of technology, a decentralization of responsibilities and competencies, and more management and personnel development initiatives. The concept of modernization signals a novel use of language and related concepts such as decentralization , self-management , self-government , de-bureaucratization , quality control , and user influence . These terms may sound positive on an intuitive level but constitute a source of uncertainty as to what is actually taking place. The article analyzes the learning environment in two governmental worksites in Denmark and shows how professional employees respond to the dilemmas posed by modernization at work.
Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome
Authors: Chase Andrew , Grand Francis H. , Cross Nicholas C. P.
Published: August 2007

The 8p11 myeloproliferative syndrome (EMS) is an aggressive, atypical stem cell myeloproliferative disorder associated with chromosome translocations that disrupt and constitutively activate FGFR1 by fusion to diverse partner genes. To explore the possibility of targeted therapy for EMS, we have investigated the use of TKI258, a multitargeted receptor tyrosine kinase inhibitor with activity against FGFR, VEGFR, PDGFR, FLT3, and KIT that is currently being assessed for the treatment of a variety of malignancies in phase 1 clinical studies. The viability of Ba/F3 cells transformed to IL3 independence by ZNF198-FGFR1 or BCR-FGFR1 was specifically inhibited by TKI258 with IC50 values of 150 nM and 90 nM, respectively. Inhibition was accompanied by dose-dependent inhibition of phosphorylation of each fusion gene, ERK, and STAT5. TKI258 also specifically inhibited proliferation and survival of the FGFR1OP2-FGFR1–positive KG1 and KG1A cell lines, resulting in increased levels of apoptosis. Primary cells from EMS patients showed significant, dose-dependent responses in liquid culture and in methylcellulose colony assays compared with controls. This work provides evidence that targeted therapy may be beneficial for patients with EMS.
Facile Derivatization of Pyridyloxazole-type Fluorophore via Click Chemistry
Authors: Shi Jing , Liu Lei , He Jing , Meng Xiangming , Guo Qingxiang
Published: August 2007

New derivatives of the pyridyloxazole-type fluorophore were synthesized in high efficiency through click chemistry. This method is potentially useful for the combinatory screening of fluorescent labels to target specific biological processes. Using this method, we successfully developed three new ratiometric dual-fluorescent pH sensors.
Phosphine-free Fabrication of CdSe Quantum Dots with Good Thermal Stability and Promising Application in Multiplexed Bioassay
Authors: Xing Bin , Li Wan-wan , Dou Hong-jing , Zhang Peng-fei , Sun Kang
Published: August 2007

High-quality cadmium selenide (CdSe) quantum dots (QDs) with good thermal stability were prepared by using liquid paraffin as a solvent and oleic acid as a ligand under relative low temperatures. Moreover, the as-prepared CdSe quantum dots were embedded into the porous polystyrene (PS) beads to fabricate optically encoded beads, which suggests their promising application in multiplexed bioassays.
A Novel One-pot Synthesis of Pyrroloquinoline and Pyrroloisoquinoline Derivatives in Ionic Liquid
Authors: Ma Chen , Ren Yan , Zhang Qun , Ding Kai , Zhao Jun , Zhang Dongju
Published: August 2007

A Sonogashira coupling–1,3-dipolar cycloaddition sequence of a (hetero)arenecarbonyl chloride 1, a terminal alkyne 2, and a suitable quinolinium bromide 3 or isoquinolinium bromide 4 was carried out in ionic liquid on the basis of a consecutive one-pot three-component process. Optimization of ionic liquid and recycling of the catalyst were discussed.
Comparing Estimates of Wind Turbine Fatigue Loads Using Time-Domain and Spectral Methods
Authors: Ragan Patrick , Manuel Lance
Published: August 2007

Fatigue analysis for wind turbines is typically carried out in the time domain, using cycle counting techniques such as ASTM's Rainflow Cycle-Counting Algorithm. As an alternative, earlier workers investigated the feasibility of estimating wind turbine fatigue loads using spectral techniques such as Dirlik's method to estimate stress range probability distributions that are based on spectral moments of the load in question. The present paper re-examines this approach with a particular view to assessing its limitations and advantages in the context of modern, large-scale wind turbines and design methods. These relative advantages are considered in terms of accuracy, statistical reliability, and efficiency of calculation. Field data on loads from a utility-scale 1.5 MW turbine near Lamar, Colorado in the Colorado Green Wind Farm are analyzed here as a representative example. The results show that valuable and reliable information about tower loads can be obtained very efficiently. By contrast, the limitations of the Dirlik method are highlighted by poor results for edgewise blade loads.
Wind Farm Site Assessment Using Measure—Correlate-Predict (MCP) Analysis
Authors: Sreevalsan E. , Das Siddarth Shankar , Sasikumar R. , Ramesh M.P.
Published: August 2007

This paper presents and discusses a Measure-Correlate-Predict (MCP) method using Fast-Fourier transforms (FFT), which is validated with measured data at the observed site.
Offshore Wind: The Potential to Contribute a Quarter of UK Electricity by 2024
Authors: Boyle Godfrey
Published: August 2007

The United Kingdom has very significant wind energy resources. In particular, the winds offshore could supply a major proportion of the nation's electricity requirements. Yet current offshore wind construction projects are progressing slowly. Over the next two decades, it is argued that Britain should adopt a much more ambitious programme to install many thousands of megawatts of offshore generating capacity by means of a public-private partnership, following the successful example of the offshore oil and gas industries of the 1970s and 1980s. By 2024, offshore wind could be contributing some 25% of UK electricity.
Bone Regeneration Is Regulated by Wnt Signaling
Authors: Kim Jae-Beom , Leucht Philipp , Lam Kentson , Luppen Cynthia , Ten Berge Derk , Nusse Roel , Helms Jill A
Published: August 2007

Tissue regeneration is increasingly viewed as reactivation of a developmental process that, when misappropriated, can lead to malignant growth. Therefore, understanding the molecular and cellular pathways that govern tissue regeneration provides a glimpse into normal development as well as insights into pathological conditions such as cancer. Herein, we studied the role of Wnt signaling in skeletal tissue regeneration.

Introduction: Some adult tissues have the ability to regenerate, and among these, bone is one of the most remarkable. Bone exhibits a persistent, lifelong capacity to reform after injury, and continual bone regeneration is a prerequisite to maintaining bone mass and density. Even slight perturbations in bone regeneration can have profound consequences, as exemplified by conditions such as osteoporosis and delayed skeletal repair. Here, our goal was to determine the role of Wnts in adult bone regeneration.

Materials and Methods: Using TOPgal reporter mice, we found that damage to the skeleton instigated Wnt reporter activity, specifically at the site of injury. We used a skeletal injury model to show that Wnt inhibition, achieved through adenoviral expression of Dkk1 in the adult skeleton, prevented the differentiation of osteoprogenitor cells.

Results: As a result, injury-induced bone regeneration was reduced by 84% compared with controls. Constitutive activation of the Wnt pathway resulting from a mutation in the Lrp5 Wnt co-receptor results in high bone mass, but our experiments showed that this same point mutation caused a delay in bone regeneration. In these transgenic mice, osteoprogenitor cells in the injury site were maintained in a proliferative state and differentiation into osteoblasts was delayed.

Conclusions: When considered together, these data provide a framework for understanding the roles of Wnt signaling in adult bone regeneration and suggest a feasible approach to treating clinical conditions where enhanced bone formation is desired.
Control of the SOST Bone Enhancer by PTH Using MEF2 Transcription Factors
Authors: Leupin Olivier , Kramer Ina , Collette Nicole M , Loots Gabriela G , Natt François , Kneissel Michaela , Keller Hansjoerg
Published: August 2007

Expression of the osteocyte-derived bone formation inhibitor sclerostin in adult bone requires a distant enhancer. We show that MEF2 transcription factors control this enhancer and mediate inhibition of sclerostin expression by PTH.

Introduction: Sclerostin encoded by the SOST gene is a key regulator of bone formation. Lack of SOST expression is the cause for the progressive bone overgrowth disorders sclerosteosis and Van Buchem disease. We have previously identified a distant enhancer within the 52-kb Van Buchem disease deletion downstream of the SOST gene that is essential for its expression in adult bone. Furthermore, we and others have reported that SOST expression is suppressed by PTH. The aim of this study was to identify transcription factors involved in SOST bone enhancer activity and mediating PTH responsiveness.

Materials and Methods: Regulation of the SOST enhancer and promoter was studied by luciferase reporter gene assays. Transcription factor binding sites were mapped by footprint analysis and functional mutation analyses using transient transfections of osteoblast-like UMR-106 cells that exhibit endogenous SOST expression. Specific transcription factor binding was predicted by sequence analysis and shown by gel retardation assays and antibody-induced supershifts. Expression of myocyte enhancer factors 2 (MEF2) was detected by in situ hybridization, quantitative RT-PCR (qPCR), and immunohistochemistry. The role of MEF2s in SOST expression was assessed by reporter gene assays and siRNA-mediated RNA knockdown.

Results: PTH completely suppressed the transcriptional activity of the SOST bone enhancer but did not affect the SOST promoter. A MEF2 response element was identified in the bone enhancer. It was essential for transcriptional activation, bound MEF2 transcription factors, and mediated PTH responsiveness. Expression of MEF2s in bone was shown by qPCR, in situ hybridization, and immunohistochemistry. MEF2s and sclerostin co-localized in osteocytes. Enhancer activity was stimulated by MEF2C overexpression and inhibited by co-expression of a dominant negative MEF2C mutant. Finally, siRNA-mediated knockdown of MEF2A, C, and D suppressed endogenous SOST expression in UMR-106 osteoblast-like cells.

Conclusions: These data strongly suggest that SOST expression in osteocytes of adult bone and its inhibition by PTH is mediated by MEF2A, C, and D transcription factors controlling the SOST bone enhancer. Hence, MEF2s are implicated in the regulation of adult bone mass.
Eine publizistische Debatte als Geburtsstunde des „Marburger Programms“
Authors: Schmidt-Recla Adrian , Steinberg Holger
Published: August 2007

I. Einleitung

Das „Marburger Programm“ von Liszts (1851–1919) markiert in der heutigen Wahrnehmung den Aufbruch in die kriminalpolitische Moderne. Zwar ist bekannt, dass relative, präventionistische Theorien in der Strafrechtswissenschaft auch schon vor von Liszt vertreten wurden. Die Untersuchungen, die zur Veröffentlichung des jungen von Liszt bislang angestellt worden sind, haben freilich den unmittelbaren Anlass und publizistischen Kontext des Aufsatzes noch nicht genügend ausgeleuchtet: Das Marburger Programm war keine singuläre Veröffentlichung, sondern eingebettet in eine zwischen Juristen, Strafvollzugsbeamten und Psychiatern in den Jahren 1879–1882 cum ira et studio geführte Debatte, deren genauere Überprüfung bislang unbeachtete Einsichten zu Tage fördert.
Wirtschaftsstrafrecht
Authors: Wohlers Wolfgang , Kudlich Hans
Published: August 2007

– Insbesondere Wirtschaftslenkung und Wettbewerb, Unternehmensstrafrecht und Straftaten aus Unternehmen heraus, Untreue sowie Schutz des geistigen Eigentums –
Täterschaft und Teilnahme im Statut des IStGH und Anpassungsbedarf der italienischen Regelung
Authors: Martino Alberto di
Published: August 2007

I. Anpassung der italienischen Vorschriften über Teilnahme an das „Römische Statut“

Im Zentrum dieses Beitrags steht die Frage, wie sich die Vorschriften über die Teilnahme mehrerer an einer Straftat im Römischen Statut des Internationalen Gerichtshofs (im Folgenden: „Statut“ und „IStGH“ abgekürzt) zu der wesentlich anders gefassten Regelung im italienischen Recht verhalten.
Der Europäische Haftbefehl und die polnische Verfassung – jüngste Entwicklungen
Authors: Weigend Ewa , Sakowicz Andrzej
Published: August 2007

1. Einführung

In Polen wurde die Verfassung geändert, um die Auslieferung eigener Staatsangehöriger aufgrund eines Europäischen Haftbefehls (EuHB) möglich zu machen. Diese Verfassungsänderung war nötig geworden, da der polnische Verfassungsgerichtshof im Jahr 2005 die Auslieferung polnischer Staatsangehöriger auf der Grundlage des Europäischen Haftbefehls für verfassungswidrig erklärt hatte. Bevor auf die Verfassungsänderung eingegangen wird (4.), sollen zunächst die Implementierung des EuHB in Polen sowie das Urteil des Verfassungsgerichtshofs (2.) und dessen Rechtsfolgen (3.) in Erinnerung gerufen werden.
Prophecy, Gender, and Culture: Ellen Gould Harmon [White] and the Roots of Seventh-day Adventism
Authors: Butler Jonathan M.
Published: August 2007

“… the weakest of the weak…”

Ellen G. White, nee Harmon (1827-1915), is among the least known of the prophet-founders of major American religious movements. The Seventh-day Adventist prophet has received neither the celebrity nor the notoriety of Mormonism’s Joseph Smith, Shakerism’s Ann Lee, or Christian Science’s Mary Baker Eddy. Yet she deserves at least the recognition of these other sect founders. Ill, introverted, and undereducated, White ultimately asserted the most forceful influence on Seventh-day Adventism and ensured it a place among the major American sects. Her long and resourceful career as the Adventist visionary inspired the transformation of a single-minded, other-worldly, Millerite off-shoot into a complex and established denomination with wide-ranging interests in sabbatarianism, eschatology, health reform, temperance, medicine, child nurture, education, and religious liberty. Her legacy includes an impressive global network of sanitariums and hospitals and a vast educational system unparalleled in contemporary Protestantism. Her writings number eighty printed volumes, circulated among an Adventist world membership of over five million.
Authoritarian or Authority-Minded? The Cognitive Commitments of Fundamentalists and the Christian Right
Authors: Owen Dennis E. , Wald Kenneth D. , Hill Samuel S.
Published: August 2007

One of the more consistent characterizations of both American Fundamentalism and other versions of conservative Evangelicalism is that these groups represent authoritarian religious and social systems. Such characterizations are not entirely without some basis in fact. Fundamentalism will almost always appear authoritarian, and so too will forms of Pentecostalism which, like Fundamentalism, place a heavy emphasis on correct thinking and combine a belief in the infallibility of scripture with a commitment to literal readings. Outsiders are sometimes disconcerted to find that “authoritarian” and related concepts are not assessed negatively in conservative Evangelical circles. Quite the contrary is the case: the Bible, infallible, inerrant, “God-breathed,” is the clear center of Evangelical authority. Many a Fundamentalist sermon has sought to clinch its case with the phrase, “on authority of the holy Word of God.”