bluuebunny/crossref_metadata_2025 huggingface dataset:
Mei4p coordinates the onset of meiosis I by regulating
cdc25
+
in fission yeast
Authors: Murakami-Tonami Yuko , Yamada-Namikawa Chisato , Tochigi Akiko , Hasegawa Norio , Kojima Hisae , Kunimatsu Mitoshi , Nakanishi Makoto , Murakami Hiroshi
Published: September 2007

The kinase Cdc2p is a central regulator of entry into and progression through nuclear division during mitosis and meiosis in eukaryotes. Cdc2p is activated at the onset of mitosis by dephosphorylation on tyrosine-15, the phosphorylation status of which is determined mainly by the kinase Wee1p and the phosphatase Cdc25p. In fission yeast, the forkhead-type transcription factor Mei4p is required for expression of many genes during meiosis, with
mei4
mutant cells arresting before meiosis I. The mechanism of cell cycle arrest in
mei4
cells has remained unknown, however. We now show that
cdc25
+
is an important target of Mei4p in control of entry into meiosis I. Forced dephosphorylation of Cdc2p on tyrosine-15 thus induced meiosis I in
mei4
mutant cells without a delay, although no spores were formed. We propose that Mei4p acts as a rate-limiting regulator of meiosis I by activating
cdc25
+
transcription in coordination with other meiotic events.
The missing piece of the type II fatty acid synthase system from
Mycobacterium tuberculosis
Authors: Sacco Emmanuelle , Covarrubias Adrian Suarez , O'Hare Helen M. , Carroll Paul , Eynard Nathalie , Jones T. Alwyn , Parish Tanya , Daffé Mamadou , Bäckbro Kristina , Quémard Annaïk
Published: September 2007

The
Mycobacterium tuberculosis
fatty acid synthase type II (FAS-II) system has the unique property of producing unusually long-chain fatty acids involved in the biosynthesis of mycolic acids, key molecules of the tubercle bacillus. The enzyme(s) responsible for dehydration of (3
R
)-hydroxyacyl-ACP during the elongation cycles of the mycobacterial FAS-II remained unknown. This step is classically catalyzed by FabZ- and FabA-type enzymes in bacteria, but no such proteins are present in mycobacteria. Bioinformatic analyses and an essentiality study allowed the identification of a candidate protein cluster, Rv0635-Rv0636-Rv0637. Its expression in recombinant
Escherichia coli
strains leads to the formation of two heterodimers, Rv0635-Rv0636 (HadAB) and Rv0636-Rv0637 (HadBC), which also occurs in
Mycobacterium smegmatis
, as shown by split-Trp assays. Both heterodimers exhibit the enzymatic properties expected for mycobacterial FAS-II dehydratases: a marked specificity for both long-chain (≥C
12
) and ACP-linked substrates. Furthermore, they function as 3-hydroxyacyl dehydratases when coupled with MabA and InhA enzymes from the
M. tuberculosis
FAS-II system. HadAB and HadBC are the long-sought (3
R
)-hydroxyacyl-ACP dehydratases. The correlation between the substrate specificities of these enzymes, the organization of the orthologous gene cluster in different
Corynebacterineae
, and the structure of their mycolic acids suggests distinct roles for both heterodimers during the elongation process. This work describes bacterial monofunctional (3
R
)-hydroxyacyl-ACP dehydratases belonging to the hydratase 2 family. Their original structure and the fact that they are essential for
M. tuberculosis
survival make these enzymes very good candidates for the development of antimycobacterial drugs.
Dual role of the RNA substrate in selectivity and catalysis by terminal uridylyl transferases
Authors: Stagno Jason , Aphasizheva Inna , Aphasizhev Ruslan , Luecke Hartmut
Published: September 2007

Terminal RNA uridylyltransferases (TUTases) catalyze template-independent UMP addition to the 3′ hydroxyl of RNA. TUTases belong to the DNA polymerase β superfamily of nucleotidyltransferases that share a conserved catalytic domain bearing three metal-binding carboxylate residues. We have previously determined crystal structures of the UTP-bound and apo forms of the minimal trypanosomal TUTase,
Tb
TUT4, which is composed solely of the N-terminal catalytic and C-terminal base-recognition domains. Here we report crystal structures of
Tb
TUT4 with bound CTP, GTP, and ATP, demonstrating nearly perfect superposition of the triphosphate moieties with that of the UTP substrate. Consequently, at physiological nucleoside 5′-triphosphate concentrations, the protein–uracil base interactions alone are not sufficient to confer UTP selectivity. To resolve this ambiguity, we determined the crystal structure of a prereaction ternary complex composed of UTP,
Tb
TUT4, and UMP, which mimics an RNA substrate, and the postreaction complex of
Tb
TUT4 with UpU dinucleotide. The UMP pyrimidine ring stacks against the uracil base of the bound UTP, which on its other face also stacks with an essential tyrosine. In contrast, the different orientation of the purine bases observed in cocrystals with ATP and GTP prevents this triple stacking, precluding productive binding of the RNA. The 3′ hydroxyl of the bound UMP is poised for in-line nucleophilic attack while contributing to the formation of a binding site for a second catalytic metal ion. We propose a dual role for RNA substrates in TUTase-catalyzed reactions: contribution to selective incorporation of the cognate nucleoside and shaping of the catalytic metal binding site.
A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist
Authors: Tolbert W. David , Daugherty Jennifer , Gao ChongFeng , Xie Qian , Miranti Cindy , Gherardi Ermanno , Vande Woude George , Xu H. Eric
Published: September 2007

Hepatocyte growth factor (HGF) activates the Met receptor tyrosine kinase by binding and promoting receptor dimerization. Here we describe a mechanistic basis for designing Met antagonists based on NK1, a natural variant of HGF containing the N-terminal and the first kringle domain. Through detailed biochemical and structural analyses, we demonstrate that both mouse and human NK1 induce Met dimerization via a conserved NK1 dimer interface. Mutations designed to alter the NK1 dimer interface abolish its ability to promote Met dimerization but retain full Met-binding activity. Importantly, these NK1 mutants act as Met antagonists by inhibiting HGF-mediated cell scattering, proliferation, branching, and invasion. The ability to separate the Met-binding activity of NK1 from its Met dimerization activity thus provides a rational basis for designing Met antagonists. This strategy of antagonist design may be applicable for other growth factor receptors by selectively abolishing the receptor activation ability but not the receptor binding of the growth factors.
SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase
Authors: Mattagajasingh Ilwola , Kim Cuk-Seong , Naqvi Asma , Yamamori Tohru , Hoffman Timothy A. , Jung Saet-Byel , DeRicco Jeremy , Kasuno Kenji , Irani Kaikobad
Published: September 2007

Reduced caloric intake decreases arterial blood pressure in healthy individuals and improves endothelium-dependent vasodilation in obese and overweight individuals. The SIRT1 protein deacetylase mediates many of the effects of calorie restriction (CR) on organismal lifespan and metabolic pathways. However, the role of SIRT1 in regulating endothelium-dependent vasomotor tone is not known. Here we show that SIRT1 promotes endothelium-dependent vasodilation by targeting endothelial nitric oxide synthase (eNOS) for deacetylation. SIRT1 and eNOS colocalize and coprecipitate in endothelial cells, and SIRT1 deacetylates eNOS, stimulating eNOS activity and increasing endothelial nitric oxide (NO). SIRT1-induced increase in endothelial NO is mediated through lysines 496 and 506 in the calmodulin-binding domain of eNOS. Inhibition of SIRT1 in the endothelium of arteries inhibits endothelium-dependent vasodilation and decreases bioavailable NO. Finally, CR of mice leads to deacetylation of eNOS. Our results demonstrate that SIRT1 plays a fundamental role in regulating endothelial NO and endothelium-dependent vascular tone by deacetylating eNOS. Furthermore, our results provide a possible molecular mechanism connecting the effects of CR on the endothelium and vascular tone to SIRT1-mediated deacetylation of eNOS.
Alternative
Neisseria
spp. type IV pilin glycosylation with a glyceramido acetamido trideoxyhexose residue
Authors: Chamot-Rooke Julia , Rousseau Benoit , Lanternier Fanny , Mikaty Guillain , Mairey Emilie , Malosse Christian , Bouchoux Guy , Pelicic Vladimir , Camoin Luc , Nassif Xavier , Duménil Guillaume
Published: September 2007

The importance of protein glycosylation in the interaction of pathogenic bacteria with their host is becoming increasingly clear.
Neisseria meningitidis
, the etiological agent of cerebrospinal meningitis, crosses cellular barriers after adhering to host cells through type IV pili. Pilin glycosylation genes (
pgl
) are responsible for the glycosylation of PilE, the major subunit of type IV pili, with the 2,4-diacetamido-2,4,6-trideoxyhexose residue. Nearly half of the clinical isolates, however, display an insertion in the
pglBCD
operon, which is anticipated to lead to a different, unidentified glycosylation. Here the structure of pilin glycosylation was determined in such a strain by “top-down” MS approaches. MALDI-TOF, nanoelectrospray ionization Fourier transform ion cyclotron resonance, and nanoelectrospray ionization quadrupole TOF MS analysis of purified pili preparations originating from
N. meningitidis
strains, either wild type or deficient for pilin glycosylation, revealed a glycan mass inconsistent with 2,4-diacetamido-2,4,6-trideoxyhexose or any sugar in the databases. This unusual modification was determined by in-source dissociation of the sugar from the protein followed by tandem MS analysis with collision-induced fragmentation to be a hexose modified with a glyceramido and an acetamido group. We further show genetically that the nature of the sugar present on the pilin is determined by the carboxyl-terminal region of the
pglB
gene modified by the insertion in the
pglBCD
locus. We thus report a previously undiscovered monosaccharide involved in posttranslational modification of type IV pilin subunits by a MS-based approach and determine the molecular basis of its biosynthesis.
Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci
Authors: Raelson John V. , Little Randall D. , Ruether Andreas , Fournier Hélène , Paquin Bruno , Van Eerdewegh Paul , Bradley W. E. C. , Croteau Pascal , Nguyen-Huu Quynh , Segal Jonathan , Debrus Sophie , Allard René , Rosenstiel Philip , Franke Andre , Jacobs Gunnar , Nikolaus Susanna , Vidal Jean-Michel , Szego Peter , Laplante Nathalie , Clark Hilary F. , Paulussen René J. , Hooper John W. , Keith Tim P. , Belouchi Abdelmajid , Schreiber Stefan
Published: September 2007

Genome-wide association (GWA) studies offer a powerful unbiased method for the identification of multiple susceptibility genes for complex diseases. Here we report the results of a GWA study for Crohn's disease (CD) using family trios from the Quebec Founder Population (QFP). Haplotype-based association analyses identified multiple regions associated with the disease that met the criteria for genome-wide significance, with many containing a gene whose function appears relevant to CD. A proportion of these were replicated in two independent German Caucasian samples, including the established CD lociNOD2andIBD5. The recently describedIL23Rlocus was also identified and replicated. For this region, multiple individuals with all major haplotypes in the QFP were sequenced and extensive fine mapping performed to identify risk and protective alleles. Several additional loci, including a region on 3p21 containing several plausible candidate genes, a region nearJAKMIP1on 4p16.1, and two larger regions on chromosome 17 were replicated. Together with previously published loci, the spectrum of CD genes identified to date involves biochemical networks that affect epithelial defense mechanisms, innate and adaptive immune response, and the repair or remodeling of tissue.
Review article:Greek syntax: A principles and parameters perspective
Authors:   Alexiadou,   Anagnostopoulou
Published: September 2007

The last decades have seen a particular growth of syntactic studies in Greek from different aspects within the principles and parameters framework. In this article we present an overview of the main areas of investigation. Reasons of space prevent us from an exhaustive presentation of all the issues examined in the literature. In what follows, we concentrate mainly on topics that have attracted a lot of attention in the more recent literature (see also the presentation in Theophanopoulou-Kontou 1994; Drachman et al. 1997; Alexiadou, Horrocks & Stavrou 1999).
Group adjectives
Authors: Markantonatou Stella , Ørsnes Bjarne
Published: September 2007

This paper attempts a comparative syntactic study of group adjectives in Danish, English and Modern Greek. The central problem with group adjectives is to account for the contrast between their seemingly argumental behaviour and their inability to introduce new referents into the discourse. We propose a novel analysis whereby group adjectives form a weakly lexical structure with their head noun and modify the first argument of the argument structure of the head noun while the argument itself remains unexpressed. If this analysis is right, it lends support to the representation of argument structure as a level which is simultaneously distinct from the representation of syntactic valency and participates in valency saturation phenomena. The framework is that of Head-Driven Phrase Structure Grammar (HPSG).
De l’adverbe au préfixe en passant par la préposition
Authors: Amiot Dany , De Mulder Walter
Published: September 2007

Summary
The aim of this article is to study the relationship between certain adverbs, prepositions, prefixes and conjunctions of subordination in French. A distinction is made between two classes of morphemes. The first one includes prefixes and ‘governed’ prepositions (which introduce arguments of the verb, such as the indirect object) : both types of expressions can be said to be ‘linked’, the first to the prefixed element, the second to the verb. The second one includes ‘not-governed’ prepositions (those which introduce adverbial phrases), certain adverbs and conjunctions of subordination ; these morphemes are not linked in the sense mentioned above and can thus said to be ‘free’. This distinction could suggest a grammaticalization channel leading from the free elements to the linked ones : from the adverbs via the related non governed and governed prepositions, in that order, to the prefixes. It is shown, however, that some Latin adverbs grammaticalize directly into preverbs, without an intervening prepositional stage, and that some prepositions directly inherit ‘governed’ as well as ‘not-governed’ uses from their Latin predecessors. Nevertheless, the hypothesis that there is a relation between the governed or non governed nature of some prepositions and the possibility to use them in order to create conjunctions of subordination, could explain why avant que and après que are still used as such conjunctions, whereas sur ce que / sour ce que has disappeared.
La possessivation dans les constructions à support
Authors: Buvet Pierre-André
Published: September 2007

Summary

The aim of this paper is to study possessive determiners in French when they are used with nouns that are predicates in support verb constructions. We distinguish two situations: the possessive refers either to the first or to the second argument of the predicate. We show that in these situations the possessives behave differently from possessives in other configurations, i.e. when the POSS N noun phrases are arguments. We show that the two interpretations of the possessive vary according to whether the support verb is standard or non standard. Some of those interpretations are connected to speech phenomena.
Biographical structuring
Authors: Fischer Wolfram , Goblirsch Martina
Published: September 2007

This article argues that the self is produced, maintained and modified in interaction and discourse. As a situated practice in ongoing social interaction, relying on biographical memory, cultural and situational impacts, the self is developed as a continuous structure allowing reliable expectations. We call this process biographical structuring and suggest a method of a reconstructive analysis. Distinguishing and triangulating the reconstructive perspectives of the lived life, the experienced life, and the presented life, we present a case analysis of an adolescent migrant, thus demonstrating how this kind of analysis can be applied in helping professions.
Narrative as construction and discursive resource
Authors: Taylor Stephanie
Published: September 2007

Discursive psychologists (Edley, 2001; Potter & Wetherell, 1987; Wetherell, 1998) have analysed identity work in talk, including the ways in which understandings which prevail in a wider social context are taken up or resisted as speakers position themselves and are positioned by others. In these terms, a narrative is generally understood in two ways. The first is as an established understanding of sequence or consequence, such as a potential life trajectory, which becomes a discursive resource for speakers to draw on (cf. Bruner’s ‘canonical narratives’, 1991). The second is of a narrative as a situated construction, such as the biography produced by a speaker within a particular interaction. In this article, I propose an expanded analytic focus which considers how the versions of a biographical narrative produced in previous tellings become resources for future talk, thus setting constraints on a reflexive speaker’s work to construct a coherent identity across separate interactions and contexts (Taylor & Littleton, forthcoming).
uPA deficiency exacerbates muscular dystrophy in MDX mice
Authors: Suelves Mònica , Vidal Berta , Serrano Antonio L. , Tjwa Marc , Roma Josep , López-Alemany Roser , Luttun Aernout , de Lagrán María Martínez , Díaz Maria Àngels , Jardí Mercè , Roig Manuel , Dierssen Mara , Dewerchin Mieke , Carmeliet Peter , Muñoz-Cánoves Pura
Published: September 2007

Duchenne muscular dystrophy (DMD) is a fatal and incurable muscle degenerative disorder. We identify a function of the protease urokinase plasminogen activator (uPA) in mdx mice, a mouse model of DMD. The expression of uPA is induced in mdx dystrophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular function. Bone marrow (BM) transplantation experiments revealed a critical function for BM-derived uPA in mdx muscle repair via three mechanisms: (1) by promoting the infiltration of BM-derived inflammatory cells; (2) by preventing the excessive deposition of fibrin; and (3) by promoting myoblast migration. Interestingly, genetic loss of the uPA receptor in mdx mice did not exacerbate muscular dystrophy in mdx mice, suggesting that uPA exerts its effects independently of its receptor. These findings underscore the importance of uPA in muscular dystrophy.
Selective Use of Intranasal Mupirocin and Chlorhexidine Bathing and the Incidence of Methicillin-ResistantStaphylococcus aureusColonization and Infection Among Intensive Care Unit Patients
Authors: Ridenour Glenn , Lampen Russell , Federspiel Jeff , Kritchevsky Steve , Wong Edward , Climo Michael
Published: September 2007

Objective.

To determine whether the use of chlorhexidine bathing and intranasal mupirocin therapy among patients colonized with methicillin-resistantStaphylococcus aureus(MRSA) would decrease the incidence of MRSA colonization and infection among intensive care unit (ICU) patients.

Methods.

After a 9-month baseline period (January 13, 2003, through October 12, 2003) during which all incident cases of MRSA colonization or infection were identified through the use of active-surveillance cultures in a combined medical-coronary ICU, all patients colonized with MRSA were treated with intranasal mupirocin and underwent daily chlorhexidine bathing.

Results.

After the intervention, incident cases of MRSA colonization or infection decreased 52% (incidence density, 8.45 vs 4.05 cases per 1,000 patient-days;P= .048). All MRSA isolates remained susceptible to chlorhexidine; the overall rate of mupirocin resistance was low (4.4%) among isolates identified by surveillance cultures and did not increase during the intervention period.

Conclusions.

We conclude that the selective use of intranasal mupirocin and daily chlorhexidine bathing for patients colonized with MRSA reduced the incidence of MRSA colonization and infection and contributed to reductions identified by active-surveillance cultures. This finding suggests that additional strategies to reduce the incidence of MRSA infection and colonization—beyond expanded surveillance—may be needed.
Risk Factors for and Impact of Infection or Colonization With Aztreonam-Resistant Pseudomonas aeruginosa
Authors: Gasink Leanne B. , Fishman Neil O. , Nachamkin Irving , Bilker Warren B. , Lautenbach Ebbing
Published: September 2007

Objective.

To identify risk factors for infection or colonization with aztreonam-resistant Pseudomonas aeruginosa and examine the impact of this organism on mortality.

Design.

A case-control study was performed to identify risk factors for infection or colonization with aztreonam-resistant P. aeruginosa. A cohort study was subsequently performed to examine the impact of aztreonam resistance on outcomes.

Setting.

A tertiary referral center in southeastern Pennsylvania.

Participants.

Inpatients with a clinical culture positive for P. aeruginosa between January 1, 1999, and December 31, 2000.

Results.

Of 720 P. aeruginosa, isolates, 183 (25.4%) were aztreonam-resistant and 537 (74.6%) were aztreonam susceptible. In a multivariable model, prior fluoroquinolone use (adjusted odds ratio [aOR], 1.81 [95% confidence interval {CI}, 1.17-2.80]), prior use of an antianaerobic agent (aOR, 1.56 [95% CI, 1.06-2.29]), and renal insufficiency (aOR, 1.59 [95% CI, 1.10-2.29]) were associated with infection or colonization with aztreonam-resistant P. aeruginosa, while older age (aOR, 0.98 [95% CI, 0.97-0.99] per year of age) was negatively associated with infection or colonization with this organism. In-hospital mortality was higher among subjects infected or colonized with aztreonam-resistant P. aeruginosa, compared with those who were infected or colonized with aztreonam-susceptible P. aeruginos (25.7% vs 16.8%;P = .009), but in multivariable analysis, no significant association was found between infection or colonization with aztreonam-resistant P. aeruginosa and mortality.

Conclusions.

Curbing the use of fluoroquinolones and antimicrobials with antianaerobic activity may be an effective strategy to limit the emergence of aztreonam-resistant P. aeruginosa.
Arrestins and Spinophilin Competitively Regulate Na+,K+-ATPase Trafficking through Association with a Large Cytoplasmic Loop of the Na+,K+-ATPase
Authors: Kimura Tohru , Allen Patrick B. , Nairn Angus C. , Caplan Michael J.
Published: September 2007

The activity and trafficking of the Na+,K+-ATPase are regulated by several hormones, including dopamine, vasopressin, and adrenergic hormones through the action of G-protein–coupled receptors (GPCRs). Arrestins, GPCR kinases (GRKs), 14-3-3 proteins, and spinophilin interact with GPCRs and modulate the duration and magnitude of receptor signaling. We have found that arrestin 2 and 3, GRK 2 and 3, 14-3-3 ε, and spinophilin directly associate with the Na+,K+-ATPase and that the associations with arrestins, GRKs, or 14-3-3 ε are blocked in the presence of spinophilin. In COS cells that overexpressed arrestin, the Na+,K+-ATPase was redistributed to intracellular compartments. This effect was not seen in mock-transfected cells or in cells expressing spinophilin. Furthermore, expression of spinophilin appeared to slow, whereas overexpression of β-arrestins accelerated internalization of the Na+,K+-ATPase endocytosis. We also find that GRKs phosphorylate the Na+,K+-ATPase in vitro on its large cytoplasmic loop. Taken together, it appears that association with arrestins, GRKs, 14-3-3 ε, and spinophilin may be important modulators of Na+,K+-ATPase trafficking.
ARL4D Recruits Cytohesin-2/ARNO to Modulate Actin Remodeling
Authors: Li Chun-Chun , Chiang Tsai-Chen , Wu Tsung-Sheng , Pacheco-Rodriguez Gustavo , Moss Joel , Lee Fang-Jen S.
Published: September 2007

ARL4D is a developmentally regulated member of the ADP-ribosylation factor/ARF-like protein (ARF/ARL) family of Ras-related GTPases. Although the primary structure of ARL4D is very similar to that of other ARF/ARL molecules, its function remains unclear. Cytohesin-2/ARF nucleotide-binding-site opener (ARNO) is a guanine nucleotide-exchange factor (GEF) for ARF, and, at the plasma membrane, it can activate ARF6 to regulate actin reorganization and membrane ruffling. We show here that ARL4D interacts with the C-terminal pleckstrin homology (PH) and polybasic c domains of cytohesin-2/ARNO in a GTP-dependent manner. Localization of ARL4D at the plasma membrane is GTP- and N-terminal myristoylation-dependent. ARL4D(Q80L), a putative active form of ARL4D, induced accumulation of cytohesin-2/ARNO at the plasma membrane. Consistent with a known action of cytohesin-2/ARNO, ARL4D(Q80L) increased GTP-bound ARF6 and induced disassembly of actin stress fibers. Expression of inactive cytohesin-2/ARNO(E156K) or small interfering RNA knockdown of cytohesin-2/ARNO blocked ARL4D-mediated disassembly of actin stress fibers. Similar to the results with cytohesin-2/ARNO or ARF6, reduction of ARL4D suppressed cell migration activity. Furthermore, ARL4D-induced translocation of cytohesin-2/ARNO did not require phosphoinositide 3-kinase activation. Together, these data demonstrate that ARL4D acts as a novel upstream regulator of cytohesin-2/ARNO to promote ARF6 activation and modulate actin remodeling.
Polyamines Regulate the Stability of Activating Transcription Factor-2 mRNA through RNA-binding Protein HuR in Intestinal Epithelial Cells
Authors: Xiao Lan , Rao Jaladanki N. , Zou Tongtong , Liu Lan , Marasa Bernard S. , Chen Jie , Turner Douglas J. , Zhou Huiping , Gorospe Myriam , Wang Jian-Ying
Published: September 2007

Maintenance of intestinal mucosal epithelial integrity requires polyamines that modulate the expression of various genes involved in cell proliferation and apoptosis. Recently, polyamines were shown to regulate the subcellular localization of the RNA-binding protein HuR, which stabilizes its target transcripts such as nucleophosmin and p53 mRNAs. The activating transcription factor-2 (ATF-2) mRNA encodes a member of the ATF/CRE-binding protein family of transcription factors and was computationally predicted to be a target of HuR. Here, we show that polyamines negatively regulate ATF-2 expression posttranscriptionally and that polyamine depletion stabilizes ATF-2 mRNA by enhancing the interaction of the 3′-untranslated region (UTR) of ATF-2 with cytoplasmic HuR. Decreasing cellular polyamines by inhibiting ornithine decarboxylase (ODC) with α-difluoromethylornithine increased the levels of ATF-2 mRNA and protein, whereas increasing polyamines by ectopic ODC overexpression repressed ATF-2 expression. Polyamine depletion did not alter transcription via the ATF-2 gene promoter but increased the stability of ATF-2 mRNA. Increased cytoplasmic HuR in polyamine-deficient cells formed ribonucleoprotein complexes with the endogenous ATF-2 mRNA and specifically bound to 3′-UTR of ATF-2 mRNA on multiple nonoverlapping 3′-UTR segments. Adenovirus-mediated HuR overexpression elevated ATF-2 mRNA and protein levels, whereas HuR silencing rendered the ATF-2 mRNA unstable and prevented increases in ATF-2 mRNA and protein. Furthermore, inhibition of ATF-2 expression prevented the increased resistance of polyamine-deficient cells to apoptosis induced by treatment with tumor necrosis factor-α and cycloheximide. These results indicate that polyamines modulate the stability of ATF-2 mRNA by altering cytoplasmic HuR levels and that polyamine-modulated ATF-2 expression plays a critical role in regulating epithelial apoptosis.
Vignettes of Communities in Action: an exploration of participatory methodologies in promoting community development in Nigeria
Authors: Abah Oga Steve
Published: September 2007

Three interconnected arguments are explored in this article. It begins by a reconsideration of community development, not from official and agency definitions but from what makes development real and satisfies not only physical needs, but also the spiritual as well as psychological. The second part looks at Theatre for Development (TFD) as a system of actualizing the participatory agenda so direly required, so often talked about and very consistently ignored in community development. I argue that TFD in its performative approach to discussing issues, forging alliances and community cohesion contributes to community development. In this instance, we witness TFD as a community art for instigating participation and change. I also talk about how in combination with other participatory methods, TFD can be empowering. This combination is what I call methodological conversation and the aesthetics that defines this conversation involves respect, dialogue, inclusion and flexibility. The case study section narrates the way in which this methodology has been applied in the turbulent environment of the Niger Delta in Nigeria. I argue that TFD, Participatory Learning and Action (PLA) and Questionnaire methods were the triumvirate of approaches that allowed us to understand issues and for communities to listen to us. The challenge remains how to define and develop an enduring relationship between researchers, community and government who may have the wherewithal for action.
Reed bunting females increase fitness through extra-pair mating with genetically dissimilar males
Authors: Suter Stefan M , Keiser Martin , Feignoux Raoul , Meyer Dietrich R
Published: September 2007

Females of many socially monogamous species accept or even actively seek copulations outside the social pair bond. As females cannot increase the number of offspring with promiscuous behaviour, the question arises why they engage in extra-pair mating. We used microsatellite data to determine paternity, heterozygosity and genetic relatedness in the reed bunting (
Emberiza schoeniclus
), a species with high levels of extra-pair paternity (EPP). We found that extra-pair young (EPY) were more heterozygous than within-pair young (WPY). The high heterozygosity of the EPY resulted from a low genetic similarity between females and their extra-pair mates. EPY were heavier and larger when compared with their maternal half-siblings shortly before they left the nest. Recapture data indicated a higher fledgling survival of EPY compared with WPY. Our data suggest that reed bunting females increase the viability of their offspring and thus fitness through extra-pair mating with genetically dissimilar males.
Mapping the C. elegans noncoding transcriptome with a whole-genome tiling microarray
Authors: He Housheng , Wang Jie , Liu Tao , Liu X. Shirley , Li Tiantian , Wang Yunfei , Qian Zuwei , Zheng Haixia , Zhu Xiaopeng , Wu Tao , Shi Baochen , Deng Wei , Zhou Wei , Skogerbø Geir , Chen Runsheng
Published: September 2007

The number of annotated protein coding genes in the genome of Caenorhabditis elegans is similar to that of other animals, but the extent of its non-protein-coding transcriptome remains unknown. Expression profiling on whole-genome tiling microarrays applied to a mixed-stage C. elegans population verified the expression of 71% of all annotated exons. Only a small fraction (11%) of the polyadenylated transcription is non-annotated and appears to consist of ∼3200 missed or alternative exons and 7800 small transcripts of unknown function (TUFs). Almost half (44%) of the detected transcriptional output is non-polyadenylated and probably not protein coding, and of this, 70% overlaps the boundaries of protein-coding genes in a complex manner. Specific analysis of small non-polyadenylated transcripts verified 97% of all annotated small ncRNAs and suggested that the transcriptome contains ∼1200 small (<500 nt) unannotated noncoding loci. After combining overlapping transcripts, we estimate that at least 70% of the total C. elegans genome is transcribed.
A Practical Use of Theory to Study Adherence
Authors: Granger Bradi B. , Moser Debra , Harrell Joanne , Sandelowski Margarete , Ekman Inger
Published: September 2007

Chronic heart failure (CHF) is a costly Medicare expenditure, with approximately 70% of the costs of heart failure care attributable to acute, symptom‐related hospitalizations. The most common preventable cause of rehospitalization is nonadherence to the CHF regimen. Theoretic models have been used to study adherence; however, these models are predominantly designed for health behavior interventions (ie, smoking cessation, diet modification, or exercise) and focus less on conceptualizing the work involved in carrying out complex self‐care regimens. The purpose of this paper was to present one approach for operationalizing the Trajectory Theory of Chronic Illness to study adherence in patients with heart failure. The trajectory model offers unique opportunities to study adherence, specifically because measurable patient attributes are clearer when evaluated in the context of the work required to adhere over time. Using trajectory theory may allow providers to better understand and facilitate patient adherence to the CHF regimen.
An electronic prompt in dispensing software to promote clinical interventions by community pharmacists: a randomized controlled trial
Authors: Reeve James F. , Tenni Peter C. , Peterson Gregory M.
Published: September 2007

What is already known about this subject

• Computerized prompts and reminders have been shown to be effective in changing the behaviour of health professionals in a variety of settings.

• There is little literature describing or evaluating electronic decision‐support for pharmacists.

What this study adds

• An electronic prompt in dispensing software for a targeted clinical intervention has a significant effect on pharmacists' behaviour. A markedly increased rate of recording and performing the targeted clinical intervention was found.

• The effect of the prompt reduces markedly once the prompt is deactivated.

Aim

To evaluate the effect of an electronic prompt in dispensing software on the frequency of clinical interventions recorded by community pharmacists.

Method

An electronic decision‐support prompt identifying patients for a targeted proactive clinical intervention was developed and implemented. Each time an oral antidiabetic agent was dispensed, a prompt was displayed reminding pharmacists to discuss the suitability of aspirin therapy in eligible patients with diabetes. The prompt was randomly assigned to 31 of 52 metropolitan pharmacies in Melbourne (Australia) for 6 weeks, with the remaining pharmacies as controls.

Results

One hundred and fifty pharmacists in 52 pharmacies recorded a total of 2396 clinical interventions at an intervention rate of 0.92 interventions per 100 patients [95% confidence interval (CI) 0.58, 1.23]. Pharmacists recorded a total of 201 target interventions related to aspirin therapy in diabetes at an intervention rate of 2.55 interventions per 100 diabetic patients (95% CI 0.85, 4.24). All of the targeted clinical interventions were recorded in the prompt arm; no targeted interventions were recorded in the control group. The effect of the prompt decreased over the study period and was not maintained after prompt deactivation.

Conclusion

An electronic prompt significantly increased pharmacists' recording of the targeted clinical intervention in diabetic patients. An electronic decision‐support prompt has significant potential to promote community pharmacists' contribution to the quality use of medicines.
Photorespiratory and respiratory decarboxylations in leaves of C3 plants under different CO2 concentrations and irradiances
Authors: PÄRNIK T. , IVANOVA H. , KEERBERG O.
Published: September 2007

We used an advanced radiogasometric method to study the effects of short‐term changes in CO2 concentration ([CO2]) on the rates and substrates of photorespiratory and respiratory decarboxylations under steady‐state photosynthesis and in the dark. Experiments were carried out on Plantago lanceolata, Poa trivialis, Secale cereale, Triticum aestivum, Helianthus annuus and Arabidopsis thaliana plants. Rates of photorespiration and respiration measured at a low [CO2] (40 µmol mol−1) were equal to those at normal [CO2] (360 µmol mol−1). Under low [CO2], the substrates of decarboxylation reactions were derived mainly from stored photosynthates, while under normal [CO2] primary photosynthates were preferentially consumed. An increase in [CO2] from 320 to 2300 µmol mol−1 brought about a fourfold decrease in the rate of photorespiration with a concomitant 50% increase in the rate of respiration in the light. Respiration in the dark did not depend on [CO2] up to 30 mmol mol−1. A positive correlation was found between the rate of respiration in the dark and the rate of photosynthesis during the preceding light period. The respiratory decarboxylation of stored photosynthates was suppressed by light. The extent of light inhibition decreased with increasing [CO2]; no inhibition was detected at 30 mmol mol−1 CO2.
TPK1, a Ca2+‐regulated Arabidopsis vacuole two‐pore K+ channel is activated by 14‐3‐3 proteins
Authors: Latz A. , Becker D. , Hekman M. , Müller T. , Beyhl D. , Marten I. , Eing C. , Fischer A. , Dunkel M. , Bertl A. , Rapp U. R. , Hedrich R.
Published: September 2007

The vacuole represents a pivotal plant organelle for management of ion homeostasis, storage of proteins and solutes, as well as deposition of cytotoxic compounds. Ion channels, pumps and carriers in the vacuolar membrane under control of cytosolic factors provide for ionic and metabolic homeostasis between this storage organelle and the cytoplasm. Here we show that AtTPK1 (KCO1), a vacuolar membrane localized K+ channel of the TPK family, interacts with 14‐3‐3 proteins (general regulating factors, GRFs). Following in planta expression TPK1 and GRF6 co‐localize at the vacuolar membrane. Co‐localization of wild‐type TPK1, but not the TPK1‐S42A mutant, indicates that phosphorylation of the 14‐3‐3 binding motif of TPK1 represents a prerequisite for interaction. Pull‐down assays and surface plasmon resonance measurements revealed GRF6 high‐affinity interaction with TPK1. Following expression of TPK1 in yeast and isolation of vacuoles, patch‐clamp studies identified TPK1 as a voltage‐independent and Ca2+‐activated K+ channel. Addition of 14‐3‐3 proteins strongly increased the TPK1 activity in a dose‐dependent manner. However, an inverse effect of GRF6 on the activity of the slow‐activating vacuolar (SV) channel was observed in mesophyll vacuoles from Arabidopsis thaliana. Thus, TPK1 seems to provide for a Ca2+‐ and 14‐3‐3‐sensitive mechanism capable of controlling cytoplasmic potassium homeostasis in plants.
Increased dental caries in people with neurofibromatosis 1
Authors: Tucker T , Birch P , Savoy DM , Friedman JM
Published: September 2007

Neurofibromatosis 1 (NF1) is an autosomal dominant disease that is associated with multiple café‐au‐lait spots and neurofibromas. Low bone mineral density is frequent in people with NF1, and focal boney abnormalities are characteristic but uncommon features. Dental abnormalities can occur in association with oral neurofibromas but have not otherwise been described in people with NF1. Questionnaires regarding dental caries were sent to families that included at least one individual with NF1. Siblings with NF1 reported significantly more dental caries (mean ± SD, 8.1 ± 6.6) than siblings without NF1 in these families (5.5 ± 5.8, p = 0.019). Our findings suggest that dental caries occur more frequently than expected among people with NF1 and that individuals with this condition may require a modified dental care program.
Assessment of Growth, Physiological and Biochemical Parameters and Activities of Antioxidative Enzymes in Salinity Tolerant and Sensitive Basmati Rice Varieties
Authors: Singh M. P. , Singh D. K. , Rai M.
Published: September 2007

This investigation was undertaken to compare the level of salinity tolerance of the newly bred CSR‐30 basmati rice variety with that of the salinity sensitive HBC‐19 and Pokkali rice varieties. Twenty‐one‐day‐old hydroponically raised seedlings at 6 and 12 dS m−1 were investigated for growth, photosynthetic rate, chlorophyll content, ribulose‐1,5‐bisphosphate carboxylase‐oxygenase (Rubisco) activity, relative water content (RWC), membrane stability index (MSI), lipid peroxidation, Na/K ratio and activities and gene expression of various isoforms of antioxidative enzymes. Salinity stress led to reduction in shoot length, leaf area, dry weight, RWC, MSI, rate of photosynthesis, chlorophyll content and Rubisco activity in all the three rice varieties. The levels of reduction in these parameters were maximal in HBC‐19 followed by those in CSR‐30 and Pokkali respectively. Cumulative superoxide dismutase (SOD) activity increased in Pokkali and CSR‐30 in consonance with increase in salinity stress while it decreased in HBC‐19. The Mn‐SOD activity however, was enhanced in all three varieties in the presence of salinity stress while the activities of Fe‐SOD, Cu/Zn‐SOD and ascorbate peroxidase were decreased in HBC‐19 when compared with CSR‐30 and Pokkali. The activity of catalase (CAT) was higher in HBC‐19 when compared with its activity in CSR‐30 and Pokkali. The levels of gene expressions of the three isoforms of SOD ascertained by reverse transcriptase polymerase chain reaction were not necessarily indicative of the activities of the corresponding enzymes. Thus, despite the maximal enhancement in gene expression of Fe‐SOD in HBC‐19 in response to salinity stress, the activity of this enzyme in HBC‐19 remained low. Similarly, despite a marginal increase in gene expression of Cu‐Zn SOD in the three varieties, its activity was significantly higher in Pokkali and CSR‐30 when compared with that in HBC‐19. A significant enhancement in the activity of CAT at 12 dS m−1 in HBC‐19 when compared with CSR‐30 and Pokkali might confer a degree of tolerance to H2O2 stress in this variety in the presence of higher levels of NaCl at the seedling stage.
Crossbred Bull Selection for Bigger Scrotum and Shorter Age at Puberty with Potentials for Better Quality Semen
Authors: Siddiqui MAR , Bhattacharjee J , Das ZC , Islam MM , Islam MA , Haque MA , Parrish JJ , Shamsuddin M
Published: September 2007

Contents

Shortening age at puberty of crossbred breeding bull is an important issue in the tropic. This study aimed at selecting crossbred bulls at earliest possible age with bigger scrotum and potential for donating quality semen. One hundred and 31 pre‐joining crossbred bulls of Central Artificial Insemination Laboratory, Saver, Dhaka were examined. The bulls being trained by seeing semen collection from mature bulls were allowed ejaculation into the artificial vagina at homosexual mount during a 20 min time at three occasions, every three month. Eighty one of 131 bulls produced at least one ejaculate during the study and their mean ± SD age and scrotal circumference (SC) were 20.3 ± 4.7 months and 28.2 ±2.7 cm, respectively. Bulls’ body weight, body condition score (BCS) and SC influenced the attainment of their puberty (p < 0.05). Bull's body weight had positive effects on scrotal circumference and ejaculate volume (p < 0.05). Scrotal circumference positively influenced the percentages of normal spermatozoa (p < 0.05). Scrotal skin‐fold thickness negatively influenced the proportion of spermatozoa with normal head (p < 0.05). Based on age at first ejaculate and SC, 29.6% bulls (n = 24) were selected by cluster analysis. Selected bulls had mean ± SD age 17.9 ± 2.2 months, body weight 287.3 ±48.6 kg, SC 30.5 ± 1.5 cm, ejaculate volume 3.4 ± 1.3 ml, sperm motility 50.8 ± 17.2%, total spermatozoa per ejaculate 2541.9 ± 1699.2 million and normal spermatozoa 81.5 ±14.5%. The selected pubertal bull group was different from the unselected pubertal bulls at manova (p < 0.0001). About 30% of pubertal crossbred bulls can be selected with shorter age and larger scrotum at puberty under conditions prevailed in Bangladesh.
PROFESSIONALISM: THE JAMES PRYOR MEMORIAL LECTURE*
Authors: Davies Geoffrey L.
Published: September 2007

James Pryor was born in country Victoria in 1928 and died there in 2002. He received his medical degree from Melbourne University in 1950 with honours in surgery. He went on to become a Fellow of the Royal College of Surgeons and of the Royal Australasian College of Surgeons.
CHEMICAL CLOSURE OF CHRONIC TYMPANIC MEMBRANE PERFORATIONS
Authors: Goldman Nelson C
Published: September 2007

Background:  The purposes of closing chronic dry perforations of the tympanic membrane are to improve hearing and prevent middle ear infections. Before the use of the operating microscope and improved instrumentation, tympanic membrane perforations were closed by application of chemicals or with a temporary patch. Today, although surgery is the treatment of choice, small dry perforations may be successfully closed by chemical means in an office setting.

Methods:  Twenty‐eight of the 69 patients with chronic dry tympanic membrane perforations on the surgical waiting list at Hawke’s Bay Regional Hospital, Hastings, New Zealand, underwent attempts at chemical myringoplasty. Two techniques were used: (i) cautery of the rim of the perforation with a silver nitrate bead on a metal probe and (ii) application of a urea ointment patch covering and overlapping the perforation.

Results:  Eighteen of the 28 patients (64%) treated by chemical means experienced closure of their tympanic membrane perforations. Successful closure was achieved in 26% of the patients on the waiting list during the 6‐month period.

Conclusion:  Chemical myringoplasty is not only of historical interest. It is an effective means of tympanic membrane closure in selected patients, thereby reducing the surgical waiting list and saving time and money for the patient, surgeon and hospital.
ENDORECTAL MAGNETIC RESONANCE IMAGING STAGING OF PROSTATE CANCER
Authors: Chandra Ronil V. , Heinze Stefan , Dowling Richard , Shadbolt Clair , Costello Anthony , Pedersen John
Published: September 2007

Background:  There are important treatment and prognostic implications in distinguishing between organ‐confined prostate cancer that has spread locally outside the capsule and that which has spread into the seminal vesicles. This study is the first Australian study to report local accuracy for the locoregional staging of prostate cancer with endorectal magnetic resonance imaging (MRI).

Methods:  From July 2002 to December 2005, 129 patients were referred for endorectal MRI for all indications. Inclusion criteria were biopsy‐proven prostate cancer, minimum 4 weeks from previous biopsy and radical retropubic prostatectomy within 12 months of MRI. This yielded 47 patients. Those with prior hormonal and neoadjuvant radiotherapy or significant postbiopsy haemorrhage were excluded. In addition, those patients examined with our alternate‐contrast‐enhanced protocol were also excluded. A total of 38 patients met all inclusion criteria. A General Electric 1.5‐T whole‐body MR imaging unit with an endorectal coil was used with interpretation by two genito‐urinary MR radiologists. Final histopathological report was used for correlation.

Results:  Median age was 60 years with a range 44–72 years. Median prostate‐specific antigen was 6.3 with a range of 2–82, and median Gleason score was 6 with a range of 5–8. Sensitivity, specificity and accuracy for extracapsular extension and seminal vesicle invasion were 69, 82 and 76% and 60, 100 and 95%, respectively. For extraprostatic extension, 71, 86 and 79%, respectively.

Conclusions:  Staging accuracy is similar to internationally published standards. Improvements in hardware and software and increased reader experience will add value to the local Australian prostate imaging programme.