Electron microscopy at the Marine Biological Association: 1961-2006. Occasional Publication of the Marine Biological Association 23

This memoir recalls the instruments in the Electron Microscope Unit and the staff, students and visitors who used them. Accessory equipment is also described because much of it was innovative and built in the laboratory, also, much of the science would not have been possible without it. This publication includes 33 figures, 4 plates and 7 appendices. The appendices record that 54 MBA staff and 196 students and visitors have used the microscopes and that 413 titles have been published (to the end of 2006).

23. Revisión nomenclatural de la alianza Cistion laurifolii Rivas Goday 1956 y de sus sintaxones subordinados

La alianza Cistion laurifolii (Lavanduletalia stoechadis Br.-Bl. 1940 em. Rivas-Martínez 1968, Cisto-Lavanduletea Br.-Bl. 1940) reúne los jarales dominados por diversas especies de Cistus —principalmente Cistus laurifolius— y Lavandula pedunculata —cantueso endémico del interior de la península Ibérica—, a los que acompañan en algunas asociaciones gayubas (Arctostaphylos uva-ursi var. crassifolia) y ciertos brezos (Erica scoparia, Calluna vulgaris); como rasgo diferencial frente a otras alianzas de la clase destaca la ausencia de diversos caméfitos termófilos.

IMPACT OF RNA VIRUSES ON THE REGULATION OF IL-23 IN MOUSE AND HUMAN MODELS OF INFECTION.

Interluekin-23 (IL-23) is a pro-inflammatory cytokine critical to the regulation of innate and adaptive immune responses. The main role for this cytokine is in the proliferation and differentiation of the IL-17 producing CD4 T helper cell, Th17. Virus infection deregulates IL-23 expression and function, but little is known about the mechanism behind this phenomena. Here, I demonstrate a reduction of Toll like receptor (TLR) ligand-induced IL-23 expression in lymphocytic choriomeningitis virus (LCMV)-infected bone marrow-derived dendritic cells (BMDCs), indicating that a function of these cells is disrupted during virus infection. I propose a mechanism of TLR ligand-induced IL-23 expression inhibition upon LCMV infection via the deactivation of p38, AP-1, and NF-κB. Further analysis revealed a direct relationship between LCMV infection with the IL-10 and SOCS3 expression. To understand IL-23 function, I characterized IL-23-induced JAK/STAT signalling pathway and IL-23 receptor expression on human CD4 T cells. My results demonstrate that IL-23 induces activation of p-JAK2, p-Tyk2, p-STAT1, p-STAT3, and p-STAT4 in CD4 T cells. For the first time I show that IL-23 alone induces the expression of its own receptor components, IL-12Rβ1 and IL-23Rα, in CD4 T cells. Blocking JAK2, STAT1, and STAT3 activation with specific inhibitors detrimentally effected expression of IL-23 receptor demonstrating that activation of JAK/STAT signalling is important for IL-23 receptor expression. I also addressed the effect of viral infection on IL-23 function and receptor expression in CD4 T cells using cells isolated from HIV positive individuals. These studies were based on earlier reports that the expression of IL-23 and the IL-23 receptor are impaired during HIV infection. I demonstrate that the phosphorylation of JAK2, STAT1, and STAT3 induced by IL-23, as well as IL-23 receptor expression are deregulated in CD4 T cells isolated from HIV positive individuals. This study has furthered the understanding of how the expression and function of IL-23 is regulated during viral infections.

The SuperWASP wide-field exoplanetary transit survey: candidates from fields 23 h <RA <03 h

Photometric transit surveys promise to complement the currently known sample of extra-solar planets (ESPs) by providing additional information on the planets and especially their radii. Here, we present ESP candidates from one such survey called, the Wide Angle Search for Planets (WASP) obtained with the SuperWASP wide-field imaging system. Observations were taken with SuperWASP North located in La Palma during the 2004 April to October observing season. The data cover fields between 23 and 03 h in RA at declinations above +12. This amounts to over ~400000 stars with V magnitudes 8-13.5. For the stars brighter than 12.5, we achieve better than 1 per cent photometric precision. Here, we present 41 sources with low-amplitude variability between ~1 and 10 mmag, from which we select 12 with periods between 1.2 and 4.4 d as the most promising ESP candidates. We discuss the properties of these ESP candidates, the expected fraction of transits recovered for our sample and implications for the frequency and detection of hot-Jupiters.

Optical observations of 23 distant Jupiter Family Comets, including 36P/Whipple at multiple phase angles

We present photometry on 23 Jupiter Family Comets (JFCs) observed at large heliocentric distance, primarily using the 2.5-m Isaac Newton Telescope (INT). Snapshot images were taken of 17 comets, of which five were not detected, three were active and nine were unresolved and apparently inactive. These include 103P/Hartley 2, the target of the NASA Deep Impact extended mission, EPOXI. For six comets we obtained time-series photometry and use this to constrain the shape and rotation period of these nuclei. The data are not of sufficient quantity or quality to measure precise rotation periods, but the time-series do allow us to measure accurate effective radii and surface colours. Of the comets observed over an extended period, 40P/Väisälä 1, 47P/Ashbrook-Jackson and P/2004 H2 (Larsen) showed faint activity which limited the study of the nucleus. Light curves for 94P/Russell 4 and 121P/Shoemaker-Holt 2 reveal rotation periods of around 33 and 10h, respectively, although in both cases these are not unique solutions. 94P was observed to have a large range in magnitudes implying that it is one of the most elongated nuclei known, with an axial ratio a/b >= 3. 36P/Whipple was observed at five different epochs, with the INT and ESO's 3.6-m NTT, primarily in an attempt to confirm the preliminary short rotation period apparent in the first data set. The combined data set shows that the rotation period is actually longer than 24h. A measurement of the phase function of 36P's nucleus gives a relatively steep ß = 0.060 +/- 0.019. Finally, we discuss the distribution of surface colours observed in JFC nuclei, and show that it is possible to trace the evolution of colours from the Kuiper Belt Object (KBO) population to the JFC population by applying a `dereddening' function to the KBO colour distribution.

A Paradoxical Effect of Systemic IL-23 in EAE – Limitation of Autoimmune Inflammatory Demyelination

The heterodimeric cytokine IL-23 plays a non-redundant function in the development of cell-mediated, organspecific autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE). To further characterize the mechanisms of action of IL-23 in autoimmune inflammation, we administered IL-23 systemically at different time points during both relapsing and chronic EAE. Surprisingly, we found suppression of disease in all treatment protocols. We observed a reduction in the number of activated macrophages and microglia in the CNS, while T cell infiltration was not significantly affected. Disease suppression correlated with reduced expansion of myelin-reactive T cells, loss of T-bet expression, loss of lymphoid structures, and increased production of IL-6 and IL-4. Here we describe an unexpected function of exogenous IL-23 in limiting the scope and extent of organ-specific autoimmunity.

Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes

Background and Purpose-Disease of the cardiovascular system is the main cause of long-term complications and mortality in patients with type I (insulin-dependent) and type 11 (non-insulin-dependent) diabetes. Cerebrovascular mortality rates have been shown to be raised in patients with type 11 diabetes but have not previously been reported by age and sex in patients with type I diabetes.

Inhibition of Secretion of Interleukin (IL)-12/IL-23 Family Cytokines by 4-Trifluoromethyl-celecoxib Is Coupled to Degradation via the Endoplasmic Reticulum Stress Protein HERP

Interleukin-12 (IL-12), p80, and IL-23 are structurally related cytokines sharing a p40 subunit. We have recently demonstrated that celecoxib and its COX-2-independent analogue 4-trifluoromethyl-celecoxib (TFM-C) inhibit secretion but not transcription of IL-12 (p35/p40) and p80 (p40/p40). This is associated with a mechanism involving altered cytokine-chaperone interaction in the endoplasmic reticulum (ER). In the present study, we found that celecoxib and TFM-C also block secretion of IL-23 (p40/p19 heterodimers). Given the putative ER-centric mode of these compounds, we performed a comprehensive RTPCR analysis of 23 ER-resident chaperones/foldases and associated co-factors. This revealed that TFM-C induced 1.5-3-fold transcriptional up-regulation of calreticulin, GRP78, GRP94, GRP170, ERp72, ERp57, ERdj4, and ERp29. However, more significantly, a 7-fold up-regulation of homocysteine-inducible ER protein (HERP) was observed. HERP is part of a high molecular mass protein complex involved in ER-associated protein degradation (ERAD). Using co-immunoprecipitation assays, we show that TFM-C induces protein interaction of p80 and IL-23 with HERP. Both HERP siRNA knockdown and HERP overexpression coupled to cycloheximide chase assays revealed that HERP is necessary for degradation of intracellularly retained p80 by TFM-C. Thus, our data suggest that targeting cytokine folding in the ER by small molecule drugs could be therapeutically exploited to alleviate in appropriate inflammation in autoimmune conditions.

Metabolic and structural properties of human obestatin {1-23} and two fragment peptides

Obestatin is a peptide produced in the oxyntic mucosa of the stomach and co-localizes with ghrelin on the periphery of pancreatic islets. Several studies demonstrate that obestatin reduces food and water intake, decreases body weight gain, inhibits gastrointestinal motility, and modulates glucose-induced insulin secretion. In this study we evaluated the acute metabolic effects of human obestatin {1-23} and fragment peptides {1-10} or {11-23} in high-fat fed mice, and then investigated their solution structure by NMR spectroscopy and molecular modelling. Obestatins {1-23} and {11-23} significantly reduced food intake (86% and 90% respectively) and lowered glucose responses to feeding, whilst leaving insulin responses unchanged. No metabolic changes could be detected following the administration of obestatin (1-10). In aqueous solution none of the obestatin peptides possessed secondary structural features. However, in a 2,2,2-trifluoroethanol (TFE-d(3))-H2O solvent mixture, the structure of obestatin {1-23} was characterized by an a-helix followed by a single turn helix conformation between residues Pro(4) and Gln(15) and His(19) and Ala(22) respectively. Obestatin {1-10} showed no structural components whereas {11-23} contained an a-helix between residues Val(14) and Ser(20) in a mixed solvent. These studies are the first to elucidate the structure of human obestatin and provide clear evidence that the observed a-helical structures are critical for in vivo activity. Future structure/function studies may facilitate the design of novel therapeutic agents based on the obestatin peptide structure. (C) 2010 Elsevier Inc. All rights reserved.

Optical source model for the 23.2-23.6 nm radiation from the multielement germanium soft X-ray laser

Distributions of source intensity in two dimensions (designated the source model), averaged over a single laser pulse, based on experimental measurements of spatial coherence, are considered for radiation from the unresolved 23.2/23.6 nm spectral lines from the germanium collisional X-ray laser. The model derives from measurements of the visibility of Young slit interference fringes determined by a method based on the Wiener-Khinchin theorem. Output from amplifiers comprising three and four target elements have similar coherence properties in directions within the horizontal plane corresponding to strong plasma refraction effects and fitting the coherence data shows source dimensions (FWHM) are similar to 26 mu m (horizontal), significantly smaller than expected by direct imaging, and similar to 125 mu m (vertical: equivalent to the height of the driver excitation). (C) 1999 Elsevier Science B.V. All rights reserved.