Comparison of thermogenic activity induced by the new sympathomimetic Ro 16-8714 between normal and obese subjects.

In a previous study, we demonstrated that the new beta-adrenoceptor agonist Ro 16-8714 possesses thermogenic property in normal male volunteers. The aim of the present study was to compare the metabolic response of lean vs obese individuals to a similar dose of this compound. Following an overnight fast, Ro 16-8714 (0.17 mg/kg fat free mass) or a placebo was given per os to six normal-weight subjects and to six moderately obese subjects. The rate of energy expenditure (EE) and the substrate utilization were determined by indirect calorimetry (hood system) before and for 6 h following the drug administration. Heart rate and blood pressure as well as plasma glucose, insulin and free fatty acid (FFA) concentrations were also measured at regular intervals throughout the study. The increment relative to base-line (mean +/- s.e.m.) in EE was similar in the two groups and averaged 4.0 +/- 1.4 per cent and 12.2 +/- 1.4 per cent with placebo and with Ro 16-8714 respectively in lean subjects, whereas the values reached 3.5 +/- 1.2 per cent and 14.4 +/- 2.0 per cent in obese subjects. Heart rate, systolic blood pressure, insulin and FFA were increased without any significant difference between the two groups. This study shows that Ro 16-8714 is a potent thermogenic agent both in normal and obese subjects.

Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission.

Synaptic transmission depends critically on the Sec1p/Munc18 protein Munc18-1, but it is unclear whether Munc18-1 primarily operates as a integral part of the fusion machinery or has a more upstream role in fusion complex assembly. Here, we show that point mutations in Munc18-1 that interfere with binding to the free Syntaxin1a N-terminus and strongly impair binding to assembled SNARE complexes all support normal docking, priming and fusion of synaptic vesicles, and normal synaptic plasticity in munc18-1 null mutant neurons. These data support a prevailing role of Munc18-1 before/during SNARE-complex assembly, while its continued association to assembled SNARE complexes is dispensable for synaptic transmission.

Intervention of carbonate components in petrogenesis of the pyroxene nephelinites from the Jbel Saghro (Anti-Atlas, Morocco)

The Jbel Saghro alkaline complex was emplaced close to the eastern edge of the Moroccan Anti-Atlas. Within the northern part, two types of nephelinite were recognized [Ibhi and Nachit, 1999 and lbhi, 2000]. The first type (olivine-rich nephelinite) constitutes the main volcanic mass south of the Bou Gafer granit (fig. 1), where the volcanism had been active at least during 2 Ma, between 9.6 and 7.5 +/- 0.1 Ma [Berrahma et al., 1993]. The second group outcrops in the north (Foum El Kouss). It consists of pyroxene nephelinites which are younger (2.9 +/- 0.1 Ma) [Berrahma et al., 1993], and bears carbonatitic xenoliths, melteigitic pyroxenites and metasomatised peridotite xenoliths. Geochemically, the pyroxene nephelinite is highly enriched in LILE compared with the first one. The mineralogical and geochemical characteristics may be explained by the incorporation of carbonatitic and melteigitic pyroxenite segregates of carbonatitic affinity.

Integration of Bridge Damage Detection Concepts and Components (3 volumes), TR-636, 2013

This work is divided into three volumes: Volume I: Strain-Based Damage Detection; Volume II: Acceleration-Based Damage Detection; Volume III: Wireless Bridge Monitoring Hardware. Volume I: In this work, a previously-developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. The statistical damage-detection tool, control-chart-based damage-detection methodologies, were further investigated and advanced. For the validation of the damage-detection approaches, strain data were obtained from a sacrificial specimen attached to the previously-utilized US 30 Bridge over the South Skunk River (in Ames, Iowa), which had simulated damage,. To provide for an enhanced ability to detect changes in the behavior of the structural system, various control chart rules were evaluated. False indications and true indications were studied to compare the damage detection ability in regard to each methodology and each control chart rule. An autonomous software program called Bridge Engineering Center Assessment Software (BECAS) was developed to control all aspects of the damage detection processes. BECAS requires no user intervention after initial configuration and training. Volume II: In this work, a previously developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. The objective of this part of the project was to validate/integrate a vibration-based damage-detection algorithm with the strain-based methodology formulated by the Iowa State University Bridge Engineering Center. This report volume (Volume II) presents the use of vibration-based damage-detection approaches as local methods to quantify damage at critical areas in structures. Acceleration data were collected and analyzed to evaluate the relationships between sensors and with changes in environmental conditions. A sacrificial specimen was investigated to verify the damage-detection capabilities and this volume presents a transmissibility concept and damage-detection algorithm that show potential to sense local changes in the dynamic stiffness between points across a joint of a real structure. The validation and integration of the vibration-based and strain-based damage-detection methodologies will add significant value to Iowa’s current and future bridge maintenance, planning, and management Volume III: In this work, a previously developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. This report volume (Volume III) summarizes the energy harvesting techniques and prototype development for a bridge monitoring system that uses wireless sensors. The wireless sensor nodes are used to collect strain measurements at critical locations on a bridge. The bridge monitoring hardware system consists of a base station and multiple self-powered wireless sensor nodes. The base station is responsible for the synchronization of data sampling on all nodes and data aggregation. Each wireless sensor node include a sensing element, a processing and wireless communication module, and an energy harvesting module. The hardware prototype for a wireless bridge monitoring system was developed and tested on the US 30 Bridge over the South Skunk River in Ames, Iowa. The functions and performance of the developed system, including strain data, energy harvesting capacity, and wireless transmission quality, were studied and are covered in this volume.

Components del procés interactiu que afavoreixen la formació de l'alumnat a l'educació secundària obligatòria

L'educació secundària obligatòria sembla que estigui permanentment en crisi: situacions conflictives entre els diferents agents, fracàs escolar, bullying o reiterades modificacions curriculars són alguns dels múltiples exemples que envaeixen els medis educatius i el debat social i accentuen les crítiques i les experiències negatives que es donen en aquesta etapa educativa. Certament, la secundària obligatòria té com a repte fonamental la comprensivitat, que comporta l'atenció a la diversitat de tots els adolescents en una etapa vital complicada; aquest repte educatiu i social, sens dubte, ha de tenir ombres, però també té llums en forma d'experiències reeixides que convergeixen en un millor i major aprenentatge de l¿alumnat. La recerca que es presenta en aquest article es proposa fer emergir i difondre les característiques que reuneixen les pràctiques exitoses que es donen a les aules de la secundària obligatòria. La metodologia usada per assolir aquesta finalitat essencial ha estat el recull i l'anàlisi de relats de persones de diferents trams d'edat sobre les seves millors experiències en la secundària obligatòria com a alumnes.Els diversos objectius que es pretenen amb el recull i l'estructuració d'aquestes veus es poden sintetitzar en dos: identificar les característiques essencials o components de les «bones pràctiques» i contribuir a la reflexió i el debat en la formació inicial i permanent del professorat. A partir de les aportacions recollides es pot concloure que: - A l'ESO, en el nostre context, es registren nombroses experiències reeixides per a l'aprenent. Les experiències tenen incomptables formes de concretar-se en la pràctica (en forma de projectes, plans estratègics, programes concrets de determinades matèries, etc.). - Malgrat la diversitat de pràctiques concretes, hi ha un nombre reduït de components que determinen i caracteritzen aquestes pràctiques reeixides. El nostre treball identifica aquests components i els agrupa en cinc categories que es refereixen a aspectes de metodologia, continguts, relació educativa, relació entre iguals i projecte de centre.

Qualitative and quantitative analysis of thalamo-cortical axons in the somatosensory cortex of normal and barrelless mice

Résumé Les rongeurs utilisent leurs moustaches (vibrisses) pour explorer le milieu environnant. Chaque moustache est mue par un système des muscles. Les récepteurs situés à sa base transmettent les informations au système nerveux central. La transmission vers l'écorce se fait via trois neurones de relais qui se trouvent au niveau du ganglion trigéminé, du tronc cérébral et du thalamus. La représentation corticale d'une vibrisse est une concentration des axones thalamo-corticaux (ATC) autour desquelles s'organisent leurs cibles, les cellules de la couche IV. La structure peut être identifiée histologiquement en coupes tangentielles et porte le nom de « barrel » (« tonneau »). Cette correspondance vibrisse - barrel fait de ce système un model idéal pour étudier l'influence de l'activité périphérique sur l'établissement et le maintien des cartes somatotopiques. Notre laboratoire dispose d'une souche de souris qui a subi une mutation spontanée pour le gène codant l'adenylyl cyclase I (ACI). Cette enzyme membranaire catalyse la formation de l'AMPc et joue un rôle important dans le guidage axonal, la libération des neurotransmetteurs et l'intégration des signaux postsynaptiques. Nous avons démontré dans un premier temps que cette souris adulte ne développe pas de barrels. Cela est dû à un manque d'organisation des ATC et aussi des cellules de la couche IV. De plus, les résultats électrophysiologiques montrent que les informations venant des vibrisses adjacentes ne sont pas intégrées d'une manière normale. Dans ce travail de thèse, j'ai analysé la morphologie des ATC révélés individuellement avec de la biocytine. L'analyse quantitative des ATC a mis en évidence les points suivants: 1. Les axones de la souris normale (NOR) quittent le thalamus, traversent la capsule interne et la substance blanche sous-corticale et pénètrent dans le cortex somato-sensoriel primaire. A l'intérieur de l'écorce ils traversent au maximum 3 colonnes corticales adjacentes dont une contient le barrel cible. En passant à travers les couches VI et V, ces axones arborisent et convergent progressivement vers le barrel dans lequel ils forment une riche arborisation. Un petit nombre des branches « errantes », pleines de boutons synaptiques, pénètrent dans les barrels voisins. Deux axones NOR provenant de corps cellulaires très proches dans le thalamus peuvent avoir un cheminement très divergent lors de la traversée de la capsule interne et de la substance blanche sous-corticale mais, à leur entrée dans le cortex, ils sont distants d'au maximum 2 colonnes corticales de la colonne qui contient le barrel cible et ils convergent progressivement vers ce barrel. 2. Les axones de la souris mutante (BRL) ont le même trajet sous-cortical que les axones NOR, mais leur entrée dans le cortex somato-sensoriel primaire est aléatoire. A l'interface entre la substance blanche sous-corticale et le cortex, l'axone principal se divise rapidement en troncs axonaux qui traversent les couches VI et V d'une manière divergente pour arriver dans la couche IV. Cela contraste beaucoup avec la trajectoire des NOR qui convergent graduellement vers leur barrel cible. Le nombre de branches radiales que les axones BRL utilisent pour entrer dans le cortex et dans la couche IV est double par rapport aux axones NOR. Parmi ces branches, seules quelques-unes donnent des arborisations, les autres ne sont pas développées et leur morphologie est semblable à celle des branches formées par les axones de la souris normale lors du développement. Deux axones BRL issus de corps cellulaires proches dans le thalamus peuvent avoir une trajectoire très divergente jusqu'à leur entrée dans la couche IV, mais à ce niveau ils sont réorientés pour se retrouver et faire un nombre maximal de branches et boutons synaptiques dans la même région corticale. Dans un cas extrême, un des axones observés est entré dans le cortex à la limite entre l'aire somatosensorielle primaire et secondaire et a parcouru une distance de 2 mm pour retrouver son partenaire thalamique et donner avec celui-ci un nombre maximal de branches dans la même région de la couche IV. 3. Les mesures quantitatives ont montré que les arborisations corticales des axones NOR ont une longueur moyenne de 18mm et sont formées par 200 segments qui portent 1200 boutons synaptiques. Par rapport à la souris NOR, les axones BRL ont en moyenne la même longueur, le même nombre de segments et boutons synaptiques, mais donnent deux fois plus de branches radiales. La surface tangentielle occupée par les arborisations BRL dans la couche IV est 2 fois plus grande que celle des NOR. Cela signifie que les 1000 boutons synaptiques qui caractérisent les arborisations NOR et BRL dans la couche IV sont disséminés sur une surface tangentielle double chez les derniers, et donc que la densité des boutons par unité de surface corticale est en moyenne plus faible. En effet, l'augmentation de la surface corticale tangentielle des BRL est due aux surfaces de faible et moyenne densité synaptique (0 - 8 boutons / 400pn2) qui augmentent 2 fois tandis que les surfaces de haute densité synaptiques (8 - 64 boutons / 4001.tm2) sont les mêmes. Nous émettons l'hypothèse selon laquelle, durant le développement, les ATC de la souris BRL divergent et forment un nombre exubérant de branches. Grâce à cette divergence et aux branches supranuméraires, ils trouvent l'endroit de l'écorce où se trouvent leurs voisins thalamiques et arborisent abondamment dans cette région. Cependant, le déficit en AGI ne leurs permet pas par la suite, sous influence de l'activité périphérique, de retirer les branches qui se trouvent dans les endroits inappropriés de l'écorce, avec de possibles conséquences sur la discrimination tactile.

" Arabidopsis Thaliana " response to insect feeding : new components controlling defense gene expression and plant resistance

Abstract: Plants cannot run away to escape attacking herbivores, but they defend themselves by producing anti-digestive proteins and toxic compounds (for example glucosinolates). The first goal of this thesis was to study changes in gene expression after insect attack using microarrays. The responses of Arabidopsis thaliana to feeding by the specialist Pieris rapae and the generalist Spodoptera liffora is were compared. We found that the transcript profiles after feeding by the two chewing insects were remarkably similar, although the generalist induced a slightly stronger response. The second goal was to evaluate the implication of the four signals jasmonic acid (JA), salicylic acid (SA), ethylene (ET), and abscisic acid (ABA) in the control of insect-regulated gene expression. Using signaling mutants, we observed that JA was the predominant signal and that ABA modulated defense gene expression. In contrast, SA and ET appeared to control slightly gene expression, but only after feeding by S. litforalis. The third goal was to establish whether plant responses are really effective against insects. In accordance with the transcript profile, both insects were affected by the JA-dependent defenses, as they performed better on the JA-insensitive mutant. S. littoralis also performed better on ABA-deficient mutants, providing evidence for the role of ABA in defense against insects. When testing indole or aliphatic glucosinolate deficient mutants, we found that they were also more susceptible to insect feeding, providing some of the first genetic evidence for the defensive role of glucosinolates in planta. Finally, a glutathione-deficient mutant, pad2-1, was also more susceptible to insect feeding and we could attribute this phenotype to a lowered accumulation of the major indole glucosinolate. In this thesis, we provide a comprehensive list of insect-regulated genes, including many transcription factors that constitute interesting candidate genes for the further study of insect-induced expression changes. Understanding how the plant responses to insects are regulated will provide tools for a better management of insect pest in the field. Résumé: Les plantes ne peuvent s'échapper pour fuir les insectes qui les attaquent, mais elles se défendent en produisant des protéines anti-digestives et des composés toxiques (par exemple des glucosinolates). Le premier but de cette thèse était d'étudier les changements de l'expression génétique lors d'attaque par des insectes en utilisant des puces à ADN. Nous avons comparé la réponse d'Arabidopsis thaliana à deux espèces d'insectes avec des habitudes alimentaires différentes : le spécialiste Pieris rapae et le généraliste Spodoptera littoralis. Nous avons trouvé que les profils de transcription après l'attaque par les deux insectes sont remarquablement similaires, bien que le généraliste induise une réponse légèrement plus forte. Le deuxième but était de déterminer l'implication de quatre signaux dans le contrôle de la réponse :l'acide jasmonique (JA), l'acide salicylique (SA), l'éthylène (ET), et l'acide abscissique (ABA). En utilisant de mutants de signalisation, nous avons montré que l'acide jasmonique était le signal prédominant et que l'acide abscissique modulait l'expression génétique. D'autre part, l'acide salicylique et l'éthylène contrôlent à un degré moindre l'expression génétique, mais seulement après l'attaque par S. littoralís. Le troisième but était d'établir si les réponses des plantes sont efficaces contre les insectes. En accord avec le profil de transcription, les deux espèces d'insectes se sont mieux développées sur un mutant insensible au JA, indiquant que les défenses contrôlées par ce signal sont cruciales pour la plante. De plus, les larves de S. littorales se sont mieux développées sur des mutants déficients en ABA, ce qui fournit une preuve du rôle de l'acide abscissique dans la défense contre les insectes. En testant des mutants déficients en glucosinolates de type indole ou aliphatique, nous avons trouvé qu'ils étaient plus sensibles aux insectes, démontrant ainsi le rôle défensif des glucosinolates in planta. Finalement, le mutant déficient en glutathion pad2-1 était aussi plus sensible à l'attaque des insectes, et nous avons pu attribuer ce phénotype à une plus faible augmentation d'un indole glucosinolate dans ce mutant. Dans cette thèse, nous avons mis en évidence un nombre important de gènes contrôlés par les insectes, comprenant de nombreux facteurs de transcription qui constituent des candidats intéressants pour`étudier plus en détail les changements d'expression génétique induits par les insectes. Une meilleure compréhension de la réponse des plantes contre l'attaque des insectes devrait nous permettre de développer de nouvelles stratégies pour mieux gérer les ravageurs des cultures.

Macular and retinal dysfunction of unknown origin in adults with normal fundi: evidence for an autoimmune pathophysiology.

Here we report the discovery of and phenotypic characterization of a retinal disorder of unknown origin in adults using clinical, electrophysiological and psychophysical techniques, and to seek the presence of circulating retinal autoantibodies in the sera of these patients. Sixteen patients were identified with progressive bilateral visual loss over a period of months. Ten of the patients were male, and the average age was 55.3 years (range from 43 to 76 years). Known causes such as carcinoma-associated retinopathy, acute zonal occult outer retinopathy and hereditary cone dystrophy appeared unlikely. Investigations included electrophysiology, fundus autofluorescence imaging and psychophysical tests. The sera of these patients were analyzed with indirect immunocytochemistry and Western immunoblot analysis on murine (BALB/c) retinal tissue for the presence of retinal autoantibodies. Bilateral visual loss and photophobia progressed over a period of months to years (average 28.7 months, range 3-67) and subsequently stabilized. No abnormality was observed by biomicroscopy, angiography or autofluorescence imaging. Electrophysiology indicated predominant cone-system dysfunction, either macular or generalized, and post-phototransduction involvement in 9 patients (56%). Photopic and scotopic visual fields and dark adaptation kinetics showed both cone and rod system involvement in all cases. Heterogeneous immunohistochemical staining patterns were seen with the sera of these patients as compared with controls. A majority of the affected patients (9/15) stained with an antinuclear pattern. The retinal autoantibodies from the sera of most patients reacted with the retinal proteins of molecular weight between 34 and 40 kDa. The aetiology of this distinctive retinal disorder therefore appears to be mediated through an autoimmune mechanism.

Volcanic stratigraphy of Hannah Point, Livingston Island, South Shetland Islands, Antarctica

The Upper Cretaceous volcanic succession of Hannah Point is the best exposure of the Antarctic Peninsula Volcanic Group on L ivingston Island. The aim of the present paper is to contribute to the characterisation of the stratigr a p hy and petrogr a p hy of this little studied succession, and briefly discuss some aspects of the eru p t ive style of its volcanism. The succession is about 470 m thick and is here subdivided into five lithostratigraphic units (A to E from base to top). Unit A, approximately 120 m thick, is mainly composed of polymict clast-supported volcaniclastic breccias and also includes a dacitic lava laye r. Interstratified in the breccias of this unit, there is a thin laminated devitrified layer which shows some degree of welding. Unit B, approx imately 70 m thick, is almost entirely composed of volcaniclastic breccias, and includes a volcaniclastic conglomerate laye r. Breccias in this unit can be subdivided into two distinct types; polymict clast-supported breccias, and monomict matrix-supported breccias rich in juvenile components and displaying incipient welding. Unit C, about 65 m thick, is mainly composed of basaltic lavas, which are interlayered with minor vo lcaniclastic breccias. Unit D, approximately 65 m thick, is lithologically similar to unit B, composed of an alternation of polymict clasts upported breccias and matrix-supported breccias, and includes a volcaniclastic conglomerate laye r. Unit E, about 150 m thick, is mainly formed of thick andesitic lava layers. Minor basaltic dykes and a few normal faults cut the succession, and the contact betwe e n units A and B can be interpreted both as an unconformity or a fault. The matrix-supported breccias included in the succession of Hannah Point have high contents of juvenile components and incipient welding, which suggest that part of the succession is the result of pyroclastic fragmentation and emplacement from pyroclastic flows. In contrast, the polymict clast-supported breccias suggest reworking of previous deposits and deposition from cool mass flows. The lavas indicate eff u s ive volcanic eruptions, and the absence of features indicative of subaqueous volcanism suggests that at least these portions of the succession were emplaced in a subaerial environment .

Prevalence of normal weight obesity in Switzerland: effect of various definitions

BACKGROUND: Normal weight obesity (NWO) is defined as an excessive body fat associated with a normal body mass index (BMI < 25 kg/m(2)), but its prevalence in the general population is unknown. AIM OF THE STUDY: To assess the prevalence of NWO in Switzerland according to different cut points used to define excess body fat. METHODS: Cross-sectional study including 3,213 women and 2,912 men aged 35-75 years. Body fat was assessed by bioelectrical impedance analysis and prevalence of NWO was assessed using four previously published definitions for excess body fat. RESULTS: Percent body fat increased with age: in men, the values (mean +/- SD) were 20.2 +/- 5.4, 23.0 +/- 5.4, 26.3 +/- 5.2 and 28.2 +/- 4.6 for age groups 35-44, 45-54, 55-64 and 65-75 years, respectively; the corresponding values for women were 29.9 +/- 7.8, 33.1 +/- 7.4, 36.7 +/- 7.5 and 39.6 +/- 6.9. In men, prevalence of NWO was <1% irrespective of the definition used. Conversely, in women, a 1- to 20-fold difference (from 1.4 to 27.8%) in NWO prevalence was found. The prevalence of NWO increased with age when age-independent cut points were used in women, but not in men. CONCLUSIONS: Prevalence of NWO is low in the general population and higher in women than in men. The prevalence is highly dependent on the criteria used to define excess body fat, namely in women. The use of gender- and age-specific cut points to define excess body fat is better than fixed or gender-specific only cut points.

Normal pathogen-specific immune responses mounted by CTLA-4-deficient T cells: a paradigm reconsidered.

CTLA-4 is a critical negative regulator of T cell responses and CTLA-4-deficient (CTLA-4(-/-)) mice die of a lymphproliferative disease. Nevertheless, RAG-2-deficient mice reconstituted with a mixture of CTLA-4(-/-) and normal (CTLA-4(+/+)) bone marrow survive in the absence of any signs of disease, although 50% of their T cells do not express CTLA-4. Using such mixed chimeras, we analyzed the role of CTLA-4 in specific T cell responses to lymphocytic choriomeningitis virus, Leishmania major and mouse mammary tumor virus, which cause acute, chronic and persistent infections, respectively. The populations of antigen-specific CTLA-4(-/-)CD4(+) and CTLA-4(-/-)CD8(+) T cells became activated, expanded and contracted indistinguishably from CTLA-4(+/+)CD4(+) and CTLA-4(+/+)CD8(+) T cells after infection with all three pathogens. Thus, CTLA-4 is not involved in the down-regulation of specific T cell responses and peripheral deletion in a T cell-autonomous fashion.

Increased titers of anti-Saccharomyces cerevisiae antibodies in Crohn's disease patients with reduced H-ficolin levels but normal MASP-2 activity.

BACKGROUND AND AIMS: Mannan-binding lectin (MBL) and ficolins are microbial pattern recognition molecules that activate the lectin pathway of complement. We previously reported the association of MBL deficiency with anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with Crohn's disease (CD). However, ASCA are also frequently found in MBL-proficient CD patients. Here we addressed expression/function of ficolins and MBL-associated serine protease-2 (MASP-2) regarding potential association with ASCA. METHODS: ASCA titers and MBL, ficolin and MASP-2 concentrations were determined by ELISA in the serum of patients with CD, ulcerative colitis (UC), and in healthy controls. MASP-2 activity was determined by measuring complement C4b-fixation. Anti-MBL autoantibodies were detected by ELISA. RESULTS: In CD and UC patients, L-ficolin concentrations were significantly higher compared to healthy controls (p<0.001 and p=0.029). In contrast, H-ficolin concentrations were slightly reduced in CD and UC compared to healthy controls (p=0.037 for UC vs. hc). CD patients with high ASCA titers had significantly lower H-ficolin concentrations compared to ASCA-low/negative CD patients (p=0.009). However, MASP-2 activity was not different in ASCA-negative and ASCA-positive CD patients upon both, ficolin- or MBL-mediated MASP-2 activation. Finally, anti-MBL autoantibodies were not over-represented in MBL-proficient ASCA-positive CD patients. CONCLUSIONS: Our results suggest that low expression of H-ficolin may promote elevated ASCA titers in the ASCA-positive subgroup of CD patients. However, unlike MBL deficiency, we found no evidence for low expression of serum ficolins or reduced MASP-2 activity that may predispose to ASCA development.

P16 Mediated Suppression Of Telomerase In Normal And Malignant Human Breast Cells.

Summary The cyclin-dependent kinase inhibitor p16(INK4a) (CDKN2A) is an important tumor-suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal.