Broad Complex Research Articles

Key roles of the Broad-Complex gene in insect embryogenesis

The Broad-Complex ( BR-C) is a primary response gene in the ecdysteroid signaling pathway which encodes a family of transcription factors that play a key role in metamorphic processes. With the aim of studying the possible functions of BR-C in the embryogenesis of a short germ band insect, we cloned BR-C cDNAs in the cockroach Blattella germanica (BgBR-C) and obtained the full coding region of six BR-C isoforms (Z1–Z6) of which, Z1–Z5 have homologous sequences in other insects, whereas Z6 is new. Temporal-expression patterns indicate that BgBR-C isoforms are present throughout the embryogenesis of B. germanica, although with weak fluctuations. Silencing all BgBR-C isoforms in the embryo through parental RNAi elicited a diversity of phenotypes. These phenotypes suggest roles for BgBR-C in different embryogenesis processes of B. germanica, mainly in the formation of the germ band, in the transition from 30% to 35% of total development, when the amnion and serosa rupture and the secondary dorsal organ is formed, and in the hatching process, which involves neural, endocrine and muscular coordination.

Abstract LB-271: The biological role of the transcription factor Kaiso in breast tumorigenesis

Abstract Introduction: The canonical Wnt signalling pathway regulates various cellular processes (e.g. proliferation, differentiation, apoptosis) and leads to tumorigenesis when aberrantly activated. -catenin, the key downstream effector in Wnt signalling, translocates to the nucleus upon Wnt pathway activation, and activates target genes involved in tumorigenesis. The transcription factor Kaiso is a novel BTB/POZ (Broad complex, Tramtrak, Bric à brac/Pox virus and zinc finger) zinc finger (POZ-ZF) protein that specifically interacts with the cell adhesion cofactor p120ctn. Recent studies from our lab and others have revealed that Kaiso negatively regulates the canonical Wnt pathway by repressing activation of Wnt/ -catenin target genes. Some studies implicate Kaiso as a tumor suppressor (decreased expression in breast, ovarian and colon tumors), and others implicate Kaiso in tumor initiation (Kaiso-deficient mice are resistant to intestinal cancer). The goal of this study is to elucidate the biological role of Kaiso in breast tumorigenesis using various cellular assays. Methods: To assess Kaiso's role in breast cancer, Kaiso was misexpressed in MCF7 (human breast adenocarcinoma) cell lines. Stable Kaiso overexpressing and depleted cell lines were generated and assessed for cell proliferation and cell migration using focus formation, wound healing and matrigel invasion assays. Western blot analysis was performed to assess the effects of Kaiso misexpression on p120 and E-cadherin as well as epithelial-mesenchymal transition markers such as N-cadherin, Snail, Twist and Vimentin. The subcellular localization of Kaiso and its putative target genes in vivo was examined using immunohistochemistry (IHC) analysis of matched pairs of human normal and tumor breast tissue. Results: Focus formation assays revealed increased transformation by cells over-expressing Kaiso, suggesting an oncogenic role for Kaiso in cell culture. Preliminary wound healing and matrigel assays show increased cell motility and migration respectively in Kaiso over-expressing cells compared to parental control cells, thereby suggesting a role for Kaiso in the epithelial-mesenchymal transition. IHC analysis revealed predominant nuclear Kaiso expression in lobular and ductal breast carcinomas in breast tissues. These data support Kaiso's potential role as an oncogene in human breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-271.

Cul8/Rtt101 Forms a Variety of Protein Complexes That Regulate DNA Damage Response and Transcriptional Silencing

The budding yeast, Saccharomyces cerevisiae, has three cullin proteins, which act as platforms for Cullin-based E3 ubiquitin ligases. Genetic evidence indicates that Cul8, together with Mms1, Mms22, and Esc4, is involved in the repair of DNA damage that can occur during DNA replication. Cul8 is thought to form a complex with these proteins, but the composition and the function of Cul8-based E3 ubiquitin ligases remain largely uncharacterized. Herein, we report a comprehensive biochemical analysis of Cul8 complexes. Cul8 was found to form a Cul8-Mms1-Mms22-Esc4 complex under physiological conditions, with Mms1 bridging Cul8 and Mms22 and Mms22 bridging Mms1 and Esc4. Domain analysis demonstrated that the N-terminal region of Mms1 and the C-terminal region of Mms22 are required for the Mms1-Mms22 interaction, whereas the N-terminal region of Mms22 is required for the Mms22-Esc4 interaction. We also found other Cul8-Mms1-binding proteins Ctf4, Esc2, and Orc5 using yeast two-hybrid screening. Esc4 and Ctf4 bound to Mms22 directly and bound to Cul8-Mms1 in the presence of Mms22, whereas Esc2 and Orc5 interacted with both Cul8 and Mms1, independently. We found that Cul8, Mms1, and Mms22 participated in the regulation of transcriptional silencing of yeast telomeres. These results suggest that Cul8-Mms1, as part of various protein complexes, is involved in the regulation of chromatin metabolism.

Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains

Keap1 is a substrate adaptor of a Cullin 3-based E3 ubiquitin ligase complex that recognizes Nrf2, and also acts as a cellular sensor for xenobiotics and oxidative stresses. Nrf2 is a transcriptional factor regulating the expression of cytoprotective enzyme genes in response to such stresses. Under unstressed conditions Keap1 binds Nrf2 and results in rapid degradation of Nrf2 through the proteasome pathway. In contrast, upon exposure to oxidative and electrophilic stress, reactive cysteine residues in intervening region (IVR) and Broad complex, Tramtrack, and Bric-à-Brac domains of Keap1 are modified by electrophiles. This modification prevents Nrf2 from rapid degradation and induces Nrf2 activity by repression of Keap1. Here we report the structure of mouse Keap1 homodimer by single particle electron microscopy. Three-dimensional reconstruction at 24-A resolution revealed two large spheres attached by short linker arms to the sides of a small forked-stem structure, resembling a cherry-bob. Each sphere has a tunnel corresponding to the central hole of the beta-propeller domain, as determined by x-ray crystallography. The IVR domain appears to surround the core of the beta-propeller domain. The unexpected proximity of IVR to the beta-propeller domain suggests that any distortions generated during modification of reactive cysteine residues in the IVR domain may send a derepression signal to the beta-propeller domain and thereby stabilize Nrf2. This study thus provides a structural basis for the two-site binding and hinge-latch model of stress sensing by the Nrf2-Keap1 system.

The Cul3–KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis

Cul3 (Cullin3)-based E3 ubiquitin ligases recently emerged as critical regulators of mitosis. In this study, we identify two mammalian BTB (Bric-a-brac-Tramtrack-Broad complex)-Kelch proteins, KLHL21 and KLHL22, that interact with Cul3 and are required for efficient chromosome alignment. Interestingly, KLHL21 but not KLHL22 is necessary for cytokinesis and regulates translocation of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase, similar to the previously described BTB-Kelch proteins KLHL9 and KLHL13. KLHL21 directly binds to aurora B and mediates ubiquitination of aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules in anaphase and recruits aurora B and Cul3 to this region. Together, our results suggest that different Cul3 adaptors nonredundantly regulate aurora B during mitosis, possibly by ubiquitinating different pools of aurora B at distinct subcellular localizations.

Arabidopsis thaliana BTB/ POZ‐MATH proteins interact with members of the ERF/AP2 transcription factor family

In Arabidopsis thaliana, the BTB/POZ-MATH (BPM) proteins comprise a small family of six members. They have been described previously to use their broad complex, tram track, bric-a-brac/POX virus and zinc finger (BTB/POZ) domain to assemble with CUL3a and CUL3b and potentially to serve as substrate adaptors to cullin-based E3-ligases in plants. In this article, we show that BPMs can also assemble with members of the ethylene response factor/Apetala2 transcription factor family, and that this is mediated by their meprin and TRAF (tumor necrosis factor receptor-associated factor) homology (MATH) domain. In addition, we provide a detailed description of BPM gene expression patterns in different tissues and on abiotic stress treatments, as well as their subcellular localization. This work connects, for the first time, BPM proteins with ethylene response factor/Apetala2 family members, which is likely to represent a novel regulatory mechanism of transcriptional control.

Current practice of cardiac resynchronization therapy (CRT) in the real world: insights from the European CRT survey

Large randomized controlled trials have demonstrated that cardiac resynchronization therapy (CRT) improves morbidity and mortality in patients with moderate to severe heart failure [New York Heart Association (NYHA) functional class III–IV], reduced left ventricular ejection fraction (LVEF ≤35%), and a broad QRS complex >120 ms on optimal medical therapy.1–3 As a result, the impressive survival benefit as well as the improvement in heart failure symptoms and quality of life observed in these trials have spurred interest in extending resynchronization therapy to a larger number of heart failure patients. Indeed, several lines of evidence indicate that currently employed guidelines (mainly based on the selection criteria used in the aforementioned pivotal trials) may not be perfect at identifying patients most likely to benefit from CRT, with a significant proportion of patients being ‘non-responders’ based on clinical outcomes or echocardiographic remodelling.4 Conversely, results from various small studies imply that certain patient populations may benefit from CRT despite the fact that they do not fulfil the criteria of current CRT guidelines.5–7 In the absence of randomized trials, data from large-scale ‘real world’ surveys provide a unique opportunity to study both the current practice regarding the employment of a novel type of therapy as well as its efficacy and safety, including ‘off-label’ indications. The European CRT Survey, a joint initiative by the Heart Failure Association (HFA) and the European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC), reports on the current European practice in the use of CRT.8 In order to provide this information, 2438 patients from 141 centres in 13 European countries who underwent successful implantation of a CRT device were followed from November 2008 until June 2009. In addition to providing a detailed description of …

Broad complex isoforms have unique distributions during central nervous system metamorphosis in Drosophila melanogaster

Broad Complex (BRC) is a highly conserved, ecdysone-pathway gene essential for metamorphosis in Drosophila melanogaster, and possibly all holometabolous insects. Alternative splicing among duplicated exons produces several BRC isoforms, each with one zinc-finger DNA-binding domain (Z1, Z2, Z3, or Z4), highly expressed at the onset of metamorphosis. BRC-Z1, BRC-Z2, and BRC-Z3 represent distinct genetic functions (BRC complementation groups rbp, br, and 2Bc, respectively) and are required at discrete stages spanning final-instar larva through very young pupa. We showed previously that morphogenetic movements necessary for adult CNS maturation require BRC-Z1, -Z2, and -Z3, but not at the same time: BRC-Z1 is required in the mid-prepupa, BRC-Z2 and -Z3 are required earlier, at the larval-prepupal transition. To explore how BRC isoforms controlling the same morphogenesis events do so at different times, we examined their central nervous system (CNS) expression patterns during the approximately 16 hours bracketing the hormone-regulated start of metamorphosis. Each isoform had a unique pattern, with BRC-Z3 being the most distinctive. There was some colocalization of isoform pairs, but no three-way overlap of BRC-Z1, -Z2, and -Z3. Instead, their most prominent expression was in glia (BRC-Z1), neuroblasts (BRC-Z2), or neurons (BRC-Z3). Despite sequence similarity to BRC-Z1, BRC-Z4 was expressed in a unique subset of neurons. These data suggest a switch in BRC isoform choice, from BRC-Z2 in proliferating cells to BRC-Z1, BRC-Z3, or BRC-Z4 in differentiating cells. Together with isoform-selective temporal requirements and phenotype considerations, this cell-type-selective expression suggests a model of BRC-dependent CNS morphogenesis resulting from intercellular interactions, culminating in BRC-Z1-controlled, glia-mediated CNS movements in late prepupa.

Overexpression of Nrp/ b (nuclear restrict protein in brain) suppresses the malignant phenotype in the C6/ST1 glioma cell line

Upon searching for glucocorticoid-regulated cDNA sequences associated with the transformed to normal phenotypic reversion of C6/ST1 rat glioma cells, we identified Nrp/ b (nuclear restrict protein in brain) as a novel rat gene. Here we report on the identification and functional characterization of the complete sequence encoding the rat NRP/B protein. The cloned cDNA presented a 1767 nucleotides open-reading frame encoding a 589 aminoacids residues sequence containing a BTB/POZ (broad complex Tramtrack bric-a-brac/Pox virus and zinc finger) domain in its N-terminal region and kelch motifs in its C-terminal region. Sequence analysis indicates that the rat Nrp/ b displays a high level of identity with the equivalent gene orthologs from other organisms. Among rat tissues, Nrp/ b expression is more pronounced in brain tissue. We show that overexpression of the Nrp/ b cDNA in C6/ST1 cells suppresses anchorage independence in vitro and tumorigenicity in vivo, altering their malignant nature towards a more benign phenotype. Therefore, Nrp/ b may be postulated as a novel tumor suppressor gene, with possible relevance for glioblastoma therapy.

Klhl31 is associated with skeletal myogenesis and its expression is regulated by myogenic signals and Myf-5

Klhl31 is an orthologue of Drosophila Kelch and belongs to a family of Kelch-like proteins in vertebrates. Members of this family contain multiple protein domains, including an amino-terminal broad complex/ tram-track/ bric-a-brac (BTB) or poxvirus and zinc finger (POZ) domain, carboxy-terminal Kelch repeats and a central linker region. We show that Klhl31 is highly expressed in the developing heart, the somite myotome and later in differentiated skeletal muscle and the myocardium. In developing somites expression of Klhl31 was initiated in the epaxial domain of the myotome, shortly after the skeletal muscle specific bHLH transcription factor, MyoD, was first expressed. Klhl31 remained expressed in skeletal muscle throughout embryonic and fetal development. Tissue ablations and rescue experiments that regulate myogenesis also govern expression of Klhl31 expression in somites. In particular, axial tissues, neural tube, floor plate and notochord, and surface ectoderm, provide combinatorial cues for myogenesis and the appropriate expression of Klhl31. We show that a combination of myogenic signals, Shh and either Wnt-1 or Wnt-6, are sufficient for Klhl31 expression in the dorsal somite. Furthermore, ectopic expression of Myf-5 led to expression of Klhl31 in the developing neural tube, indicating that Klhl31 is a novel and integral part of vertebrate myogenesis.

Laponite-derived porous clay heterostructures: II. FTIR study of the structure evolution

A comprehensive study in the middle infrared (MIR) and near infrared (NIR) regions aimed at characterizing materials obtained during the successive steps of Laponite-derived porous clay heterostructure (PCH) synthesis is presented. It is found that the exchange of hydrated Na + with hexadecyltrimethylammonium cations (HDTMA +) affects the vibrations of structural groups of Laponite with perpendicular orientation to the basal oxygens plane. The vibrating dipoles are more aligned with one another and related absorption bands become more narrow and intensive. Upon addition of co-surfactant (dodecylamine – DDA) and Si-source (tetraethylorthosilicate – TEOS) to HDTMA-Laponite a broad complex Si–O band at 1070 cm −1 appears, evidencing the hydrolysis of TEOS and development of silica network in the PCH-precursor. The NIR spectrum shows characteristic O–H and C–H bands of HDTMA-Laponite and the N–H overtones (6523 and 6478 cm −1) and combination (4935 cm −1) band of dodecylamine. Only this region permits identification of NH 2 groups because the N–H bands in the MIR region are overlapped with absorption bands of water molecules. No C–H or N–H vibrations relating to organic template could be recognized in the NIR spectrum after PCH-precursor calcination. Laponite component in the calcined PCH-precursor retains its layered structure, as evidenced by the presence of Mg 3OH and Si–O bands. The only thermal damage consists in the removal of OH groups bonded to both Mg and Li. The NIR spectrum of PCH after pyridine adsorption demonstrates that the Laponite-derived PCH contains SiOH groups of different local environment.

A broad complex tachycardia with conflicting information from pacing manoeuvres

A patient with a biventricular implantable cardioverter defibrillator for heart failure had a recurrent broad complex tachycardia and underwent electrophysiologic testing. The tachycardia was induced only with ventricular pacing. There was a 1:1 atrioventricular relationship with simultaneous atrial and ventricular activation. However, atrial pacing during tachycardia suggested atrial dissociation from the circuit. The findings, potential mechanisms, and treatment are discussed.

PLZF Outreach: A Finger in Interferon's Pie

In this issue of Immunity, Xu et al. (2009) find that the transcription factor PLZF activates interferon-stimulated genes and facilitates natural killer cell functions. Interferon-induced PLZF phosphorylation and histone deacetylase 1 recruitment probably mediates the repressor-to-activator conversion.

Wie nützlich sind die Algorithmen zur Differentialdiagnostik der monomorphen Tachykardien mit breitem QRS Komplex in kardiologischen Notfällen?

Diese Ubersicht stellt die drei alten und die zwei neuen EKG-Algorithmen zur Differentialdiagnose der monomorphen regularen Tachykardien mit breitem QRS-Komplex zusammenfassend dar. Mehrere Studien haben nachgewiesen, dass die Diagnose einer Kammertachykardie von den Notfallarzten oder Arzten in der Notaufnahme nur in 35–50% der Falle richtig gestellt wird. Ob ein Algorithmus im klinischen Alltag die Diagnostik wirklich verbessern kann und ob die Algorithmen fur die Arzte praktikabel sind, ist bisher noch nicht geklart worden. Die Algorithmen besitzen in den prospektiven Studien eine hohe Sensivitat von 88–95%, aber eine nur zufriedenstellende Spezifitat von 73–80%. Die Wertigkeit aller Algorithmen ist vergleichbar. In den Handen wenig erfahrener Arzte durfte die Inzidenz der korrekten Diagnosen deutlich geringer sein. Die Algorithmen haben erhebliche Limitationen, vor allem bei der Verwendung der „Morphologiekriterien“. Da die Nichterkennung einer Kammertachykardie fatale Folgen fur den Patienten haben kann, sollte in Notfallen jede Tachykardie mit breitem QRS-Komplex als Kammertachykardie behandelt werden. Eine diagnostische Gabe von Adenosin kann bei hamodynamisch stabilen Patienten sofort zur einen korrekten Diagnosestellung fuhren. Aufgrund der Studienlage wurde ein Schema zur Differentialdiagnostik anhand sehr einfacher, fur jeden Arzt erkennbarer EKG-Kriterien erstellt.

Wie nützlich sind die Algorithmen zur Differentialdiagnostik der monomorphen Tachykardien mit breitem QRS-Komplex in kardiologischen Notfällen?

This review gives an integrated summary of the three old and two new ECG algorithms for the differential diagnosis of monomorphic regular tachycardias with broad QRS complex. Several studies have provided evidence that a ventricular tachycardia was diagnosed correctly by doctors on call and emergency physicians only in 35-50% of cases. Whether an algorithm may really improve diagnosis in everyday clinical practice and whether the algorithms are feasible for physicians, has not yet been clarified.The algorithms possess a high sensitivity of 88-95%, but only a satisfactory specificity of 73-80%. The values of all algorithms are similar. In the hands of physicians with little experience, the incidence of correct diagnoses is likely to be markedly lower. The algorithms have considerable limitations, especially with regard to the application of the "morphology criteria". As the nondetection of a ventricular tachycardia can have fatal consequences for the patient, any tachycardia with broad QRS complex should be treated as ventricular tachycardia in emergencies. In hemodynamically stable patients, the administration of adenosine for diagnostic purposes should immediately lead to a correct diagnosis. Based on the study situation, a schematic representation for the differential diagnosis has been created which follows very simple ECG criteria identifiable by any physician.

Kardiale Resynchronisation – wie viel mechanische Dyssynchronie und wie viel Bildgebung ist im Vorfeld notwendig?

Cardiac resynchroinsation therapy (CRT) aims to correct the mechanical dyssynchrony in patients with heart failure and broad QRS complex. Until now, indication for CRT is based mainly on clinical and electrocardiographic criteria. Because QRS width is only weakly correlated to mechanical dyssynchrony, imaging techniques such as echocardiography and magnetic resonance tomography (MRT) seem suitable for analysis of dyssynchrony. Echocardiography has been studied in several studies for identification of suitable CRT candidates. Apart from conventional methods such as M mode-, 2 D-, and Doppler echocardiography other techniques which will be discussed in this article, including tissue Doppler echocardiography, have been used. Despite many positive results in individual studies no single echocardiographic parameter was able to predict positive CRT response in a prospective multicenter trial. Thus, QRS width remains the "gold standard" for CRT patient identification at present. In borderline cases, a combination of several echocardiographic measures of dyssynchrony may prove helpful. The results of studies with new techniques such as 2-dimensional strain analysis or 3D-echocardiography remain to be awaited. In the future, MRT may play a bigger role in this setting.

NAC-1, a potential stem cell pluripotency factor, contributes to paclitaxel resistance in ovarian cancer through inactivating Gadd45 pathway

Nucleus accumbens-1 (Nac1 or NAC-1) belongs to the BTB/POZ transcription factor family and is a novel protein that potentially participates in self-renewal and pluripotency in embryonic stem cells. In human cancer, NAC-1 is upregulated in several types of neoplasms, but particularly in recurrent chemoresistant ovarian carcinomas, suggesting a biological role for NAC-1 in the development of drug resistance in ovarian cancer. We have assessed this possibility and demonstrated a correlation between NAC-1 expression and ex vivo paclitaxel resistance in ovarian serous carcinoma tissues and cell lines. We found that expression of Gadd45gamma-interacting protein 1 (Gadd45gip1), a downstream target negatively regulated by NAC-1, was reduced in paclitaxel-resistant cells. Ectopic expression of NAC-1 or knockdown of Gadd45gip1 conferred paclitaxel resistance, while NAC-1 knockdown or ectopic expression of Gadd45gip1 increased paclitaxel sensitivity. Furthermore, silencing NAC-1 expression or disrupting NAC-1 homodimerization by a dominant negative NAC-1 protein that contained only the BTB/POZ domain induced expression of Gadd45gamma which interacted with Gadd45gip1. Reducing Gadd45gamma expression by shRNAs partially enhanced paclitaxel resistance. Thus, this study provides new evidence that NAC-1 upregulation and homodimerization contribute to tumor recurrence by equipping ovarian cancer cells with the paclitaxel-resistant phenotype through negative regulation of the Gadd45 pathway.

New visible spectra and mineralogical assessment of (21) Lutetia, a target of the Rosetta mission

The Rosetta spacecraft, launched on March 2nd 2004, in the course of its journey to the comet 67P/Churyumov-Gerasimenko (encounter foreseen in 2014), will fly past two asteroids: (2867) Steins and (21) Lutetia. On September 5th 2008 (2867) Steins was encountered. In this paper, we present two visible spectra of (21) Lutetia of different spectral resolutions covering the spectral ranges where possible absorption bands were previously revealed by Lazzarin and collaborators. We confirm detection of a broad complex feature between 0.45 and 0.55 microns and two narrower features around 0.47 and 0.52 microns. We discuss possible assignments of these bands and suggest that they might originate from electronic transitions in pyroxenes, although unambiguous identification is difficult and the published thermal infrared (TIR) spectrum of (21) Lutetia suggests that pyroxene cannot be the dominant silicate component at its surface. Furthermore, we discuss the published spectra of (21) Lutetia in the range from near-UV to thermal infrared. We conclude that carbonaceous meteorites (chondrites and achondrites) appear to be the closest meteorite analogues of (21) Lutetia, based on the observed spectral features. Among these meteorites, metal-rich carbonaceous chondrites seem to be the most plausible analogue materials.

Pentameric Assembly of Potassium Channel Tetramerization Domain-Containing Protein 5

We report the X-ray crystal structure of human potassium channel tetramerization domain-containing protein 5 (KCTD5), the first member of the family to be so characterized. Four findings were unexpected. First, the structure reveals assemblies of five subunits while tetramers were anticipated; pentameric stoichiometry is observed also in solution by scanning transmission electron microscopy mass analysis and analytical ultracentrifugation. Second, the same BTB ( bric-a-brac, tramtrack, broad complex) domain surface mediates the assembly of five KCTD5 and four voltage-gated K + (Kv) channel subunits; four amino acid differences appear crucial. Third, KCTD5 complexes have well-defined N- and C-terminal modules separated by a flexible linker that swivels by ∼ 30 o; the C-module shows a new fold and is required to bind Golgi reassembly stacking protein 55 with ∼ 1 μM affinity, as judged by surface plasmon resonance and ultracentrifugation. Fourth, despite the homology reflected in its name, KCTD5 does not impact the operation of Kv4.2, Kv3.4, Kv2.1, or Kv1.2 channels.

Polycyclic aromatic hydrocarbons and n-alkanes in sediments of the Upper Scheldt River Basin: contamination levels and source apportionment

The Scheldt River system is located in northern France, Belgium and the Netherlands and includes a dense network of rivers, which contributed to the urban and industrial development in this area. Three sediment cores, collected in the Upper Scheldt River (Helkijn) and two of its tributaries (the Lys River at Wervik and the Espierre Canal), were analysed for n-alkanes and polycyclic aromatic hydrocarbons (PAHs). Total n-alkane and PAH concentrations in all the sampled cores ranged from 2.8 to 29 mg kg(-1) and from 4.9 to 96 mg kg(-1), respectively. The contributions of biogenic, petrogenic and pyrolytic sources were investigated using n-alkane indexes and PAH diagnostic ratios. n-alkane chromatograms were characterized by the predominance of odd over even long chain n-alkanes (produced by terrestrial plants) and by the occurrence of a broad unresolved complex mixture (UCM) which evidenced biodegraded petroleum residues. For the three studied cores, correlations between the concentrations of UCM and n-alkanes (both expressed on an organic carbon basis) indicated a common origin or similar pathways of these allochtonous compounds to the aquatic environment. Wervik sediments were distinguished by higher n-alkane concentrations and by a major aquatic biogenic source for low molecular weight n-alkanes. The prevalence of combustion-derived PAHs was indicated by the high contribution of four, five and six rings compounds and was confirmed by isomer ratios. Higher levels of low molecular weight PAHs in Helkijn surface sediments suggested modest petrogenic inputs in this navigable canal. High PAH concentrations in Espierre sediments could be explained by a major historical contamination from urban and industrial emissions.