Study of the subcellular localization of cell cycle regulator Cks1 and its impact on cancer

La progression dans le cycle cellulaire est contrôlée par de vagues oscillantes de cyclines et des kinases cycline-dépendantes (Cdk). Ces kinases sont régulées positivement par l’association des sous-unités cyclines régulatrices et négativement en se liant aux inhibiteurs de Cdk. Parmi ces derniers, p27 inhibe tous les complexes cycline-Cdk quelle que soit la phase cellulaire et agit en tant que régulateur négatif principal de la prolifération cellulaire dans une variété de cellules et de tissus. Intrinsèquement, p27 phosphorylé est ubiquitiné et dégradé par le complexe SCFSkp2-Cks1. Des études génétiques de la souris, ainsi que des examens cliniques chez l’homme, ont montré que p27 est un important suppresseur de tumeur. Le gène est rarement muté. Cependant, p27 est fréquemment réprimé dans les cancers humains en raison d’une augmentation de l’expression de Skp2 et de Cks1 dans le noyau, ce qui est généralement associée à un mauvais pronostic. La localisation subcellulaire de Cks1 est donc d'une importance primordiale dans le contrôle de la prolifération cellulaire. Les résultats récents de notre laboratoire ont montré une interaction entre Cks1 et les protéines de transport nucléaire importine α1 et β3. Aussi, l’analyse de la séquence primaire de Cks1 a également révélé un signal de localisation nucléaire classique (NLS) à son extrémité C-terminale. Des mutations ont été effectuées sur le NLS suspect pour déterminer si oui ou non l'import nucléaire de Cks1 était contrôlé par cette séquence. Un inhibiteur synthétique de l’importine β a également été utilisé pour étudier l’import de Cks1 dans le noyau. Les résultats indiquent que l’extrémité C-terminale de Cks1 est en effet un NLS puisque les mutations de Cks1 et l'inhibition de l’importine β conduisent, tous deux, à l'accumulation de Cks1 dans le cytoplasme. Ces résultats ont été utiles pour mieux comprendre le mécanisme régulant la localisation de Cks1. Toutefois, des travaux futurs sont nécessaires pour mieux comprendre l'impact de la séquestration cytoplasmique de Cks1 sur le cancer et ainsi espérer aboutir à l'identification de nouvelles cibles pharmacologiques impliqués dans la prolifération cellulaire.

Misogyny in Health Professions? An Analysis of the Dalhousie Dentistry Scandal

Commentaire / Commentary

Elucidation of the biological roles of Wnt5a signaling in follicle development

La santé folliculaire est déterminée par un nombre de facteurs endocriniens, paracrines et autocrines. Les gonadotrophines hypophysaires sont les principaux moteurs du développement du follicule, mais leurs actions sont modulées localement par les hormones et des facteurs de croissance. Les glycoprotéines de la famille des WNTs représentent une grande famille de molécules impliquées dans différentes voies de signalisation. Ils sont sécrétés dans le but de moduler et coordonner la réponse des follicules aux gonadotrophines, et leurs activités sont indispensables à la fonction ovarienne et à la fertilité féminine. Les WNTs sont généralement classés en fonction de la (des) voie(s) qu’ils activent. Le rôle des membres de la voie canonique WNT et de ses composants tels que CTNNB1, WNT4, WNT2, FZD1 et FZD4 est bien établi au cours du développement du follicule chez les rongeurs. Un rôle similaire des WNTs dans les espèces mono-ovulatoires demeure essentiellement inconnu. De plus, le rôle des WNT non canoniques dans l'ovaire de rongeurs est méconnu. Les objectifs de cette thèse sont (1) d'élucider la régulation hormonale de l'expression de WNT5A et le rôle physiologique de WNT5A dans les cellules de la granulosa bovine in vitro et (2) d'identifier les rôles physiologiques de WNT5A dans l'ovaire de souris par inactivation génique conditionnelle. Chacun de ces objectifs a mené à la publication d’un article à partir des résultats obtenus au cours de cette thèse. Dans le premier article, le rôle de WNT5A dans les cellules de la granulosa bovine a été étudié in vitro. Nous avons constaté que WNT5A est un régulateur négatif de la stéroïdogenèse stimulée par la FSH issue des cellules de la granulosa, et qu'il agit en supprimant l'activité de signalisation des WNTs canoniques tout en induisant la voie de signalisation MAPK8/JUN. le deuxième article, afin d’examiner le rôle de deux WNTs non-canoniques, WNT5A et WNT11, à différents stades de développement folliculaire, nous avons généré des modèles de souris knock-out conditionnels ciblant les cellules de la granulosa pour chacun de ces WNTs. Les résultats obtenus ont permis de mettre en évidence que WNT5A est nécessaire pour assurer la fertilité normale chez la femelle, le développement folliculaire et la stéroïdogenèse ovarienne. Il est aussi un antagoniste de la réponse aux gonadotrophines, agissant par l’intermédiaire de la suppression de la signalisation canonique des WNTs. Chez les souris knock-out pour WNT11, nous ne constatons aucun défaut important dans la fertilité des femelles. L’ensemble de notre travail met en évidence que WNT5A est essentiel pour le développement normal du follicule et qu’il agit pour inhiber la différenciation des cellules de la granulosa. En résumé, nous avons fourni une étude novatrice et approfondie, utilisant plusieurs modèles et techniques pour déterminer les mécanismes par lesquels WNT5A régule le développement des follicules.

Characterization of the role of Drosophila JAK/STAT signalling in cellular proliferation

Der Janus Kinase / signal transducer and activator of transcription (JAK/STAT) Signal- transduktionsweg wird für viele Entwicklungsvorgänge benötigt und spielt eine zentrale Rolle bei der Hämatopoese und bei der Immunantwort. Obwohl der JAK/STAT-Signalweg in den vergangenen Jahren Gegenstand intensiver Forschung war, erschwert die Redundanz des Signalwegs bei Wirbeltieren genetische Untersuchungen zur Identifizierung derjenigen Mechanismen, die den JAK/STAT-Signalweg regulieren. Der JAK/STAT-Signaltransduktionsweg ist evolutionär konserviert und ebenfalls bei der Taufliege Drosophila melanogaster vorhanden. Im Gegensatz zu Wirbeltieren ist der Signaltransduktionsweg von Drosophila weniger redundant und beinhaltet folgende Hauptkomponenten: den Liganden Unpaired (Upd), den Transmembranrezeptor Domeless (Dome), die einzige JAK-Tyrosinkinase Hopscotch (hop), sowie den Transkriptionsfaktor STAT92E. In der vorliegenden Arbeit wird die Rolle des JAK/STAT-Signalwegs bei der zellulären Proliferation mithilfe der Modellsysteme der Flügel- und der Augen-Imaginalscheiben von Drosophila charakterisiert. "Loss-of-function"- und "Gain-of-function"-Experimente zur Verminderung beziehungs-weise Erhöhung der Signalaktivität zeigten, dass der JAK/STAT-Signalweg eine Rolle bei der zellulären Proliferation der Flügel-Imaginalscheiben spielte, ohne die Zellgröße oder Apoptose zu verändern. Bei der Flügelentwicklung während des zweiten und des frühen dritten Larvalstadiums war die Aktivität des JAK/STAT-Signalwegs sowohl notwendig für die zelluläre Proliferation als auch hinreichend, um Überproliferation anzutreiben. Allerdings änderte sich während der späten dritten Larvalstadien die JAK/STAT-Signalaktivität, sodass endogene STAT92E-Mengen einen anti-proliferativen Effekt im gleichen Gewebe aufwiesen. Weiterhin reichte die ektopische Aktivierung des JAK/STAT-Signalwegs zu diesem späten Entwicklungszeitpunkt aus, um die Mitose zu inhibieren und die Zellen in der Phase G2 des Zellzyklus zu arretieren. Diese Ergebnisse legen den Schluss nahe, dass der JAK/STAT-Signalweg sowohl pro-proliferativ in frühen Flügelscheiben als auch anti-proliferativ zu späten Stadien der Flügelscheiben-Entwicklung wirken kann. Dieser späte anti-proliferative Effekt wurde durch einen nicht-kanonischen Mechanismus der STAT92E-Aktivierung vermittelt, da späte hop defiziente Zellverbände im Vergleich zu Wildtyp-Zellen keine Veränderungen im Ausmaß der zellulären Proliferation aufwiesen. Ferner konnte gezeigt werden, dass eine während der Larvalstadien exprimierte dominant-negative und im N-Terminus deletierte Form von STAT92E (?NSTAT92E) nicht für den anti-proliferativen Effekt verantwortlich ist. Diese Tatsache ist ein weiteres Indiz dafür, dass das vollständige STAT92E den späten anti-proliferativen Effekt verursacht. Um Modulatoren für die von JAK/STAT vermittelte zelluläre Proliferation zu identifieren, wurde ein P-Element-basierter genetischer Interaktions-Screen in einem sensibilisierten genetischen Hintergrund durchgeführt. Insgesamt wurden dazu 2267 unabhängige P-Element-Insertionen auf ihre Wechselwirkung mit der JAK/STAT-Signalaktivität untersucht und 24 interagierende Loci identifiziert. Diese Kandidaten können in folgende Gruppen eingeordnet werden: Zellzyklusproteine, Transkriptionsfaktoren, DNA und RNA bindende Proteine, ein Mikro-RNA-Gen, Komponenten anderer Signaltransduktionswege und Zelladhäsionsproteine. In den meisten Fällen wurden mehrere Allele der interagierenden Kandidatengene getestet. 18 Kandidatengene mit übereinstimmend interagierenden Allelen wurden dann zur weiteren Analyse ausgewählt. Von diesen 18 Kandidaten-Loci wurden 7 mögliche JAK/STAT-Signalwegskomponenten und 6 neue Zielgene des Signalwegs gefunden. Zusammenfassend wurde das Verständnis um STAT92E verbessert. Dieses Protein hat die gleiche Funktion wie das STAT3-Protein der Wirbeltiere und treibt die zelluläre Proliferation voran. Analog zu STAT1 hat STAT92E aber auch einen anti-proliferativen Effekt. Ferner wurden 24 mögliche Modulatoren der JAK/STAT-Signalaktivität identifiziert. Die Charakterisierung dieser Wechselwirkungen eröffnet vielversprechende Wege zu dem Verständnis, wie JAK/STAT die zelluläre Proliferation reguliert und könnte bei der Entwicklung von neuartigen therapeutischen Targets zur Behandlung von Krebskrankheiten und Entwicklungsstörungen beitragen.

Unveiling the components of the signaling pathway between endosomes and the phagocytic uptake machinery in Dictyostelium discoideum

The soil amoebae Dictyostelium discoideum take up particles from their environment in order to obtain nutrition. The particle transits through the cell within a phagosome that fuses with organelles of different molecular compositions, undergoing a gradual degradation by different sets of hydrolytic enzymes. Griffiths’ concept of “phagosome individuality” predicts signaling from phagosomes into the cytoplasm, which might regulate many aspects of cell physiology. The finding that Dictyostelium cells depleted of the lysozyme AlyA or over-expressing the esterase Gp70 exhibit increased uptake of food particles, led to the postulation of a signaling cascade between endocytic compartments and the cytoskeletal uptake machinery at the plasma membrane. Assuming that Gp70 acts downstream of AlyA, gene-expression profiling of both mutants revealed different and overlapping sets of misregulated genes that might participate in this signaling cascade. Based on these results, we analyzed the effects of the artificial misregulation of six candidate genes by over-expression or negative genetic interference, in order to reconstruct at least part of the signaling pathway. SSB420 and SSL793 were chosen as candidates for the first signaling step, as they were up-regulated in AlyA-null cells and remained unaltered in the Gp70 over-expressing cells. The over-expression of SSB420 enhanced phagocytosis and raised the expression levels of Gp70, supporting its involvement in the signaling pathway between AlyA and Gp70 as a positive regulator of phagocytosis. However, this was not the case of cells over-expressing SSL793, as this mutation had no effects on phagocytosis. For the signaling downstream of Gp70, we studied four commonly misregulated genes in AlyA-depleted and Gp70 over-expressing cells. The expression levels of SLB350, SSB389 and TipD were lower in both mutants and therefore these were assumed as possible candidates for the negative regulation of phagocytosis. Cells depleted of SLB350 exhibited an increased phagocytic activity and no effect on Gp70 expression, proving its participation in the signaling pathway downstream of Gp70. Unlike SLB350, the disruption of the genes coding for SSB389 and TipD had no effects on particle uptake, excluding them from the pathway. The fourth candidate was Yipf1, the only gene that was commonly up-regulated in both mutants. Yet, the artificial over-expression of this protein had no effects on phagocytosis, so this candidate is also not included in the signaling pathway. Furthermore, localizing the products of the candidate genes within the cell helped unveiling several cellular organelles that receive signals from the phagosome and transduce them towards the uptake machinery.

Functional studies of the deubiquitinating enzymes USP19, USP4 and UCH-L1

El marcaje de proteínas con ubiquitina, conocido como ubiquitinación, cumple diferentes funciones que incluyen la regulación de varios procesos celulares, tales como: la degradación de proteínas por medio del proteosoma, la reparación del ADN, la señalización mediada por receptores de membrana, y la endocitosis, entre otras (1). Las moléculas de ubiquitina pueden ser removidas de sus sustratos gracias a la acción de un gran grupo de proteasas, llamadas enzimas deubiquitinizantes (DUBs) (2). Las DUBs son esenciales para la manutención de la homeostasis de la ubiquitina y para la regulación del estado de ubiquitinación de diferentes sustratos. El gran número y la diversidad de DUBs descritas refleja tanto su especificidad como su utilización para regular un amplio espectro de sustratos y vías celulares. Aunque muchas DUBs han sido estudiadas a profundidad, actualmente se desconocen los sustratos y las funciones biológicas de la mayoría de ellas. En este trabajo se investigaron las funciones de las DUBs: USP19, USP4 y UCH-L1. Utilizando varias técnicas de biología molecular y celular se encontró que: i) USP19 es regulada por las ubiquitin ligasas SIAH1 y SIAH2 ii) USP19 es importante para regular HIF-1α, un factor de transcripción clave en la respuesta celular a hipoxia, iii) USP4 interactúa con el proteosoma, iv) La quimera mCherry-UCH-L1 reproduce parcialmente los fenotipos que nuestro grupo ha descrito previamente al usar otros constructos de la misma enzima, y v) UCH-L1 promueve la internalización de la bacteria Yersinia pseudotuberculosis.

Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration

The AMPA receptor (AMPAR) subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine tumour necrosis factor alpha (TNF alpha) have both been implicated in motor neurone vulnerability in Amyotrophic Lateral Sclerosis/Motor Neurone Disease. TNF alpha has been reported to increase cell surface expression of AMPAR subunits to increase synaptic strength and enhance excitotoxicity, but whether this mechanism occurs in motor neurones is unknown. We used primary cultures of mouse motor neurones and cortical neurones to examine the interaction between TNF alpha receptor activation, GluR2 availability, AMPAR-mediated calcium entry and susceptibility to excitotoxicity. Short exposure to a physiologically relevant concentration of TNFalpha (10 ng/ml, 15 min) caused a marked redistribution of both GluR1 and GluR2 to the cell surface as determined by cell surface biotinylation and immunofluorescence. Using Fura-2 AM microfluorimetry we showed that exposure to TNFalpha caused a rapid reduction in the peak amplitude of AMPA-mediated calcium entry in a PI3-kinase and p38 kinase-dependent manner, consistent with increased insertion of GluR2-containing AMPAR into the plasma membrane. This resulted in a protection of motor neurones against kainate-induced cell death. Our data therefore, suggests that TNF alpha acts primarily as a physiological regulator of synaptic activity in motor neurones rather than a pathological drive in ALS

Probing the large-scale topology of the heliospheric magnetic field using Jovian electrons

Jupiter’s magnetosphere acts as a point source of near-relativistic electrons within the heliosphere. In this study, three solar cycles of Jovian electron data in near-Earth space are examined. Jovian electron intensity is found to peak for an ideal Parker spiral connection, but with considerable spread about this point. Assuming the peak in Jovian electron counts indicates the best magnetic connection to Jupiter, we find a clear trend for fast and slow solar wind to be over- and under-wound with respect to the ideal Parker spiral, respectively. This is shown to be well explained in terms of solar wind stream interactions. Thus, modulation of Jovian electrons by corotating interaction regions (CIRs) may primarily be the result of changing magnetic connection, rather than CIRs acting as barriers to cross-field diffusion. By using Jovian electrons to remote sensing magnetic connectivity with Jupiter’s magnetosphere, we suggest that they provide a means to validate solar wind models between 1 and 5 AU, even when suitable in situ solar wind observations are not available. Furthermore, using Jovian electron observations as probes of heliospheric magnetic topology could provide insight into heliospheric magnetic field braiding and turbulence, as well as any systematic under-winding of the heliospheric magnetic field relative to the Parker spiral from footpoint motion of the magnetic field.

The climatic effects of the direct injection of water vapour into the stratosphere by large volcanic eruptions

We describe a novel mechanism that can significantly lower the amplitude of the climatic response to certain large volcanic eruptions and examine its impact with a coupled ocean-atmosphere climate model. If sufficiently large amounts of water vapour enter the stratosphere, a climatically significant amount of water vapour can be left over in the lower stratosphere after the eruption, even after sulphate aerosol formation. This excess stratospheric humidity warms the tropospheric climate, and acts to balance the climatic cooling induced by the volcanic aerosol, especially because the humidity anomaly lasts for a period that is longer than the residence time of aerosol in the stratosphere. In particular, northern hemisphere high latitude cooling is reduced in magnitude. We discuss this mechanism in the context of the discrepancy between the observed and modelled cooling following the Krakatau eruption in 1883. We hypothesize that moist coignimbrite plumes caused by pyroclastic flows travelling over ocean rather than land, resulting from an eruption close enough to the ocean, might provide the additional source of stratospheric water vapour.

EfeO-cupredoxins: major new members of the cupredoxin superfamily with roles in bacterial iron transport

The EfeUOB system of Escherichia coli is a tripartite, low pH, ferrous iron transporter. It resembles the high-affinity iron transporter (Ftr1p-Fet3p) of yeast in that EfeU is homologous to Ftr1p, an integral-membrane iron-permease. However, EfeUOB lacks an equivalent of the Fet3p component—the multicopper oxidase with three cupredoxin-like domains. EfeO and EfeB are periplasmic but their precise roles are unclear. EfeO consists primarily of a C-terminal peptidase-M75 domain with a conserved ‘HxxE’ motif potentially involved in metal binding. The smaller N-terminal domain (EfeO-N) is predicted to be cupredoxin (Cup) like, suggesting a previously unrecognised similarity between EfeO and Fet3p. Our structural modelling of the E. coli EfeO Cup domain identifies two potential metal-binding sites. Site I is predicted to bind Cu2+ using three conserved residues (C41 and 103, and E66) and M101. Of these, only one (C103) is conserved in classical cupredoxins where it also acts as a Cu ligand. Site II most probably binds Fe3+ and consists of four well conserved surface Glu residues. Phylogenetic analysis indicates that the EfeO-Cup domains form a novel Cup family, designated the ‘EfeO-Cup’ family. Structural modelling of two other representative EfeO-Cup domains indicates that different subfamilies employ distinct ligand sets at their proposed metal-binding sites. The ~100 efeO homologues in the bacterial sequence databases are all associated with various iron-transport related genes indicating a common role for EfeO-Cup proteins in iron transport, supporting a new copper-iron connection in biology.

Ribonucleocapsid formation of severe acute respiratory syndrome coronavirus through molecular action of the N-terminal domain of N protein

Conserved among all coronaviruses are four structural proteins: the matrix (M), small envelope (E), and spike (S) proteins that are embedded in the viral membrane and the nucleocapsid phosphoprotein (N), which exists in a ribonucleoprotein complex in the lumen. The N-terminal domain of coronaviral N proteins (N-NTD) provides a scaffold for RNA binding, while the C-terminal domain (N-CTD) mainly acts as oligomerization modules during assembly. The C terminus of the N protein anchors it to the viral membrane by associating with M protein. We characterized the structures of N-NTD from severe acute respiratory syndrome coronavirus (SARS-CoV) in two crystal forms, at 1.17 A (monoclinic) and at 1.85 A (cubic), respectively, resolved by molecular replacement using the homologous avian infectious bronchitis virus (IBV) structure. Flexible loops in the solution structure of SARS-CoV N-NTD are now shown to be well ordered around the beta-sheet core. The functionally important positively charged beta-hairpin protrudes out of the core, is oriented similarly to that in the IBV N-NTD, and is involved in crystal packing in the monoclinic form. In the cubic form, the monomers form trimeric units that stack in a helical array. Comparison of crystal packing of SARS-CoV and IBV N-NTDs suggests a common mode of RNA recognition, but they probably associate differently in vivo during the formation of the ribonucleoprotein complex. Electrostatic potential distribution on the surface of homology models of related coronaviral N-NTDs suggests that they use different modes of both RNA recognition and oligomeric assembly, perhaps explaining why their nucleocapsids have different morphologies.

2,2-Dialkyl-2H-benzimidazoles, the high energy tautomers of the corresponding 1,2-dialkyl-1H-benzimidazoles. Syntheses and their complexes with Cu(I) and Ag(I)

Reaction of Cu(1,2-phenylenediamine)(2)(ClO4)(2) with neat RR'=O (R = methyl and/or ethyl) (lives Cu(2,2-dialkyl-2H-benzimidazole)ClO4. demetallation of which by the action of aqueous ammonia yields Pure 2,2-dialkyl-2H-benzimidazoles. These are characterised by NMR. hi the X-ray crystal Structure, Ag(2,2-methyl-2H-benzimi-dazolc)NO3 is Found to be a spiral 1D coordination polymer where the 2H-benzimidazole acts as an N,N bridge between two Ag(I) centus. Although 2H-benzimidazoles are very unstable in the free state, they are quite stable in their Cu(I)(1) and Ag(I) complexes. The 1,2-tautomerisation in imidazole and benzimidazole have been Studied by means of transition state calculations at B3LYP/6-3 11 +G(2d,p)* level.

Valuation accuracy: reconciling the timing of the valuation and sale

Carsberg (2002) suggested that the periodic valuation accuracy studies undertaken by, amongst others, IPD/Drivers Jonas (2003) should be undertaken every year and be sponsored by the RICS, which acts as the self-regulating body for valuations in the UK. This paper does not address the wider issues concerning the nature of properties which are sold and whether the sale prices are influenced by prior valuations, but considers solely the technical issues concerning the timing of the valuation and sales data. This study uses valuations and sales data from the Investment Property Databank UK Monthly Index to attempt to identify the date that sale data is divulged to valuers. This information will inform accuracy studies that use a cut-off date as to the closeness of valuations to sales completion date as a yardstick for excluding data from the analysis. It will also, assuming valuers are informed quickly of any agreed sales, help to determine the actual sale agreed date rather than the completion date, which includes a period of due diligence between when the sale is agreed and its completion. Valuations should be updated to this date, rather than the formal completion date, if a reliable measure of valuation accuracy is to be determined. An accuracy study is then undertaken using a variety of updating periods and the differences between the results are examined. The paper concludes that the sale only becomes known to valuers in the month prior to the sale taking place and that this assumes either that sales due diligence procedures are shortening or valuers are not told quickly of agreed sale prices. Studies that adopt a four-month cut-off date for any valuations compared to sales completion dates are over cautious, and this could be reduced to two months without compromising the data.

Induction of the ferritin gene (ftnA) of Escherichia coli by Fe2+–Fur is mediated by reversal of H-NS silencing and is RyhB independent

FtnA is the major iron-storage protein of Escherichia coli accounting for < or = 50% of total cellular iron. The FtnA gene (ftnA) is induced by iron in an Fe(2+)-Fur-dependent fashion. This effect is reportedly mediated by RyhB, the Fe(2+)-Fur-repressed, small, regulatory RNA. However, results presented here show that ftnA iron induction is independent of RyhB and instead involves direct interaction of Fe(2+)-Fur with an 'extended' Fur binding site (containing five tandem Fur boxes) located upstream (-83) of the ftnA promoter. In addition, H-NS acts as a direct repressor of ftnA transcription by binding at multiple sites (I-VI) within, and upstream of, the ftnA promoter. Fur directly competes with H-NS binding at upstream sites (II-IV) and consequently displaces H-NS from the ftnA promoter (sites V-VI) which in turn leads to derepression of ftnA transcription. It is proposed that H-NS binding within the ftnA promoter is facilitated by H-NS occupation of the upstream sites through H-NS oligomerization-induced DNA looping. Consequently, Fur displacement of H-NS from the upstream sites prevents cooperative H-NS binding at the downstream sites within the promoter, thus allowing access to RNA polymerase. This direct activation of ftnA transcription by Fe(2+)-Fur through H-NS antisilencing represents a new mechanism for iron-induced gene expression.

The basic ingredients of the North Atlantic Storm Track. Part II: Sea surface temperatures

The impact of North Atlantic SST patterns on the storm track is investigated using a hierarchy of GCM simulations using idealized (aquaplanet) and “semirealistic” boundary conditions in the atmospheric component (HadAM3) of the third climate configuration of the Met Office Unified Model (HadCM3). This framework enables the mechanisms determining the tropospheric response to North Atlantic SST patterns to be examined, both in isolation and in combination with continental-scale landmasses and orography. In isolation, a “Gulf Stream” SST pattern acts to strengthen the downstream storm track while a “North Atlantic Drift” SST pattern weakens it. These changes are consistent with changes in the extratropical SST gradient and near-surface baroclinicity, and each storm-track response is associated with a consistent change in the tropospheric jet structure. Locally enhanced near-surface horizontal wind convergence is found over the warm side of strengthened SST gradients associated with ascending air and increased precipitation, consistent with previous studies. When the combined SST pattern is introduced into the semirealistic framework (including the “North American” continent and the “Rocky Mountains”), the results suggest that the topographically generated southwest–northeast tilt in the North Atlantic storm track is enhanced. In particular, the Gulf Stream shifts the storm track south in the western Atlantic whereas the strong high-latitude SST gradient in the northeastern Atlantic enhances the storm track there.