bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for FGFR autoinhibition and activation
Authors: Lew Erin D. , Bae Jae Hyun , Rohmann Edyta , Wollnik Bernd , Schlessinger Joseph
Published: December 2007

Mutations in fibroblast growth factor receptor 2 (FGFR2) and its ligand, FGF10, are known to cause lacrimo-auriculo-dento-digital (LADD) syndrome. Multiple gain-of-function mutations in FGF receptors have been implicated in a variety of severe skeletal disorders and in many cancers. We aimed to elucidate the mechanism by which a missense mutation in the tyrosine kinase domain of FGFR2, described in the sporadic case of LADD syndrome, leads to reduced tyrosine kinase activity. In this report, we describe the crystal structure of a FGFR2 A628T LADD mutant in complex with a nucleotide analog. We demonstrate that the A628T LADD mutation alters the configuration of key residues in the catalytic pocket that are essential for substrate coordination, resulting in reduced tyrosine kinase activity. Further comparison of the structures of WT FGFR2 and WT FGFR1 kinases revealed that FGFR2 uses a less stringent mode of autoinhibition than FGFR1, which was also manifested in faster
in vitro
autophosphorylation kinetics. Moreover, the nearly identical conformation of WT FGFR2 kinase and the A628T LADD mutant to either the phosphorylated FGFR2 or FGFR2 harboring pathological activating mutations in the kinase hinge region suggests that FGFR autoinhibition and activation are better explained by changes in the conformational dynamics of the kinase rather than by static crystallographic snapshots of minor structural variations.
Chromosomal position of a VH gene segment determines its activation and inactivation as a substrate for V(D)J recombination
Authors: Bates Jamie Geier , Cado Dragana , Nolla Hector , Schlissel Mark S.
Published: December 2007

Complete IgHC gene rearrangement occurs only in B cells in a stage-specific and ordered manner. We used gene targeting to reposition a distal VH gene segment to a region just 5′ of the DH gene cluster and found its activation to be highly dependent on the chromosomal domain within which it resides. The targeted VH gene segment rearranged at a higher frequency than its endogenous counterpart, its rearrangement was no longer ordered, and its ability to be silenced by allelic exclusion was lost. Additionally, the targeted VH gene segment lost lineage specificity, as VDJH rearrangement was observed in thymocytes. These data suggest that locus contraction, mimicked by proximal targeting, can override any regulation imposed by DNA sequences immediately surrounding VH gene segments.
Inhibitory Potencies of Several Iridoids on Cyclooxygenase‐1, Cyclooxygnase‐2 Enzymes Activities, Tumor Necrosis Factor‐α and Nitric Oxide Production In Vitro
Authors: Park Kyoung Sik , Kim Bong Hyun , Chang Il-Moo
Published: December 2007

To verify the anti‐inflammatory potency of iridoids, seven iridoid glucosides (aucubin, catalpol, gentiopicroside, swertiamarin, geniposide, geniposidic acid and loganin) and an iridoid aglycone (genipin) were investigated with in vitro testing model systems based on inhibition of cyclooxygenase (COX)‐1/‐2 enzymes, the tumor necrosis factor‐α (TNF‐α) formation and nitric oxide (NO) production. The hydrolyzed‐iridoid products (H‐iridoid) with β‐gludosidase treatment only showed inhibitory activities, and revealed different potencies, depending on their chemical structures. Without the β‐gludosidase treatment, no single iridoid glycoside exhibited any activities. The aglycone form (genipin) also did not show inhibitory activities. To compare anti‐inflammatory potency, the inhibitory concentrations (IC50) in each testing system were measured. The hydrolyzed‐aucubin product (H‐aucubin) with β‐gludosidase treatment showed a moderate inhibition on COX‐2 with IC50 of 8.83 μM, but much less inhibition (IC50, 68.9 μM) on COX‐1 was noted. Of the other H‐iridoid products, the H‐loganin and the H‐geniposide exhibited higher inhibitory effects on COX‐1, revealing IC50 values of 3.55 and 5.37 μM, respectively. In the case of TNF‐α assay, four H‐iridoid products: H‐aucubin, H‐catalpol, H‐geniposide and H‐loganin suppressed the TNF‐α formation with IC50 values of 11.2, 33.3, 58.2 and 154.6 μM, respectively. But other H‐iridoid products manifested no significant activity. Additional experiments on NO production were conducted. We observed that only the H‐aucubin exhibited a significant suppression with IC50 value of 14.1 μM. Genipin, an agycone form, showed no inhibitory effects on all testing models, implying the hydrolysis of the glycosidic bond of iridoid glycoside is a pre‐requisite step to produce various biological activities.
Detecting the effects of environmental change above the species level with beetles in a fragmented tropical rainforest landscape
Authors: GRIMBACHER PETER S. , CATTERALL CARLA P. , KITCHING ROGER L.
Published: December 2007

Abstract 1. Invertebrate data identified to coarse groupings according to taxonomy or ecology are easier to obtain than species‐level data. However, it is unclear if such data are suitable for detecting environmental change.

2. We compared the performance of four types of data (species, family, trophic group, and body size) to quantify the responses of beetle assemblages with three types of environmental change on the Atherton Tableland in north‐eastern Queensland, Australia. Clearing of rainforest creates two levels of environmental change: first the extreme, forest loss, and second, the more subtle change associated with forest fragmentation. A strong rainfall gradient across the study landscape also influences the biota, imposing a third type of environmental change, independent of rainforest modification.

3. Almost 20 000 beetles were sampled from six replicate sites in each of pasture, small rainforest remnants, and both the edges and interiors of large rainforest remnants.

4. All four types of data showed significant multivariate differences in assemblage composition between pasture and rainforest sites. Species‐level data in multivariate analyses showed an effect of fragmentation on small remnants and also showed variation which corresponded with the spatial aridity gradient across sites. Both of these patterns were only weakly evident or were non‐existent at the level of family, trophic group, or body size class. No level of taxonomic resolution gave consistently stronger results when univariate tests were applied to individual component taxa.

5. We conclude that data above the species level may not have the sensitivity required to detect more subtle forms of environmental change.
Mineral trioxide aggregate in the treatment of external invasive resorption: a case report
Authors: Pace R. , Giuliani V. , Pagavino G.
Published: December 2007

Aim  To describe the management of external invasive resorption using mineral trioxide aggregate (MTA).

Summary  External invasive root resorption may occur as a consequence of trauma, orthodontic treatment, intracoronal bleaching and surgical procedures, and may lead to the progressive and destructive loss of tooth structure. Depending on the extent of the resorptive process, different treatment regimens have been proposed. A 19‐year‐old male patient presented with tooth 11 (FDI) showing signs and symptoms of irreversible pulpitis, external invasive resorption and periodontal pocket on the disto‐palatal. After root canal treatment, the defect was accessed coronally. The resorption area was chemo‐mechanically debrided using ultrasonic tips and irrigant solution. MTA was used to fill the resorptive defect, and the coronal access was temporarily sealed. The definitive coronal restoration was performed after 3 days. Radiographs at 1, 2 and 4 years showed adequate repair of the resorption and endodontic success. Clinically, the tooth was asymptomatic, and no periodontal pocket was found.

Key learning points 

Mineral trioxide aggregate was successfully used to restore a small area of external invasive resorption.

A coronal approach can sometimes be successfully used in order to avoid surgery and periodontal complications.
Effect of storage conditions on potassium iodide stability in iodised table salt and collagen preparations
Authors: Waszkowiak Katarzyna , Szymandera‐Buszka Krystyna
Published: December 2007

To determine the influence of storage conditions on potassium iodide (KI) stability, its traditional carrier – iodised table salt and alternative collagen carriers (i.e. iodinated collagen fibre and collagen hydrolysate) were stored at high (90%) and medium (60%) relative humidity of air. At medium humidity, these carriers were additionally stored at limited and unlimited access of air. The stability of KI was estimated by determining iodine retention during storage. The obtained results showed that the storage of iodised table salt resulted in iodine content decrease. The iodine losses in the salt tended to increase at high humidity or unlimited access of air. However, application of collagen preparations as carriers increased the KI stability, reducing iodine losses during storage and making them independent on the storage conditions.
Peroxisome proliferator‐activated receptors – from active regulators of macrophage biology to pharmacological targets in the treatment of cardiovascular disease
Authors: Bouhlel M. A. , Staels B. , Chinetti‐Gbaguidi G.
Published: December 2007

Altered macrophage functions contribute to the pathogenesis of many infectious, immunological and inflammatory disease processes. Pharmacological modulation of macrophage activities therefore represents an important strategy for the prevention and treatment of inflammation‐related diseases, such as atherosclerosis. This review focuses on recent advances on the role of the peroxisome proliferator‐activated receptor transcription factor family in the modulation of lipid homeostasis and the inflammatory response in macrophages and the potential participation of these actions in the modulation of metabolic and cardiovascular disease.
Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector
Authors: COMBS CHRISTIAN A. , SMIRNOV ALEKSANDR V. , RILEY JASON D. , GANDJBAKHCHE AMIR H. , KNUTSON JAY R. , BALABAN ROBERT S.
Published: December 2007

We have constructed a device that maximizes the probability of collecting all of the scattered and ballistic light isotropically generated at the focal spot of multiphoton excited emissions (MPE) to optimize the signal‐to‐noise ratio (SNR) for micro‐imaging. This was accomplished by optically coupling a parabolic reflector (that surrounds the sample and top of the objective) to a pair of collimating lenses (above the sample) that redirects emitted light to a separate detector. These additional optics, combined with the objective, allow the total emission detection (TED) condition to be approached. Numerical simulations suggest an approximately 10‐fold improvement in SNR with TED. Comparisons between the objective detection and TED reveal an enhancement of 8.9 in SNR (77% of predicted) for GFP‐labelled brain slices and similar results for fluorescent beads. This increase in SNR can be used to improve time resolution, reduce laser power requirements/photodynamic damage, and, in certain cases, detection depth, for MPE imaging techniques.
The morphology of the inner ear from the domestic pig (Sus scrofa)
Authors: LOVELL J. M. , HARPER G. M.
Published: December 2007

The morphology of the hair cells of the inner ear end organs from the domestic pig (Sus scrofa) have been studied using a combination of Scanning and Transmission Electron Microscopy (SEM and TEM), revealing hair cells from the cochlea and vestibule using a novel surgical and technical approach. This is the first time that the inner ear hair cells from S. scrofa have been studied, thus providing useful anatomical information on the morphology of the hair cells from the cochlea, saccule and utricle from a large mammal. Anatomical information in relation to the morphology of the inner ear is of considerable importance, both in the pathological diagnosis of trauma and in the development of cochlea implants and other biotechnological systems associated with the enhancement of hearing. Standard fixation protocols using cardiac perfusion was not employed in this study as this method cannot always be applied, such as the pathological examination of the human ear, or the study of animals protected by endangered species legislation. With the exception of a very few countries, cetaceans cannot be killed for research purposes, yet physiological information on the inner ear from these species is urgently required for ecological assessment reasons. Supporting the use of S. scrofa as a model for cetacean hearing research is that this animal is a member of the order Artiodactyla, which includes both the hippopotamus and cetaceans. Being of a similar size, the pig is an ideal subject for developing protocols and surgical techniques required to investigate both the human and small cetacean auditory systems.
Near‐field photothermal microspectroscopy for adult stem‐cell identification and characterization
Authors: GRUDE OLAUG , HAMMICHE AZZEDINE , POLLOCK HUBERT , BENTLEY ADAM J. , WALSH MICHAEL J. , MARTIN FRANCIS L. , FULLWOOD NIGEL J.
Published: December 2007

The identification of stem cells in adult tissue is a challenging problem in biomedicine. Currently, stem cells are identified by individual epitopes, which are generally tissue specific. The discovery of a stem‐cell marker common to other adult tissue types could open avenues in the development of therapeutic stem‐cell strategies.

We report the use of the novel technique of Fourier transform infrared near‐field photothermal microspectroscopy (FTIR–PTMS) for the characterization of stem cells, transit amplifying (TA) cells and terminally differentiated (TD) cells in the corneal epithelium. Principal component analysis (PCA) data demonstrate excellent discrimination of cell type by spectra. PCA in combination with linear discriminant analysis (PCA–LDA) shows that FTIR–PTMS very effectively discriminates between the three cell populations. Statistically significant differences above the 99% confidence level between IR spectra from stem cells and TA cells suggest that nucleic acid conformational changes are an important component of the differences between spectral data from the two cell types.

FTIR–PTMS is a new addition to existing spectroscopy methods based on the concept of interfacing a conventional FTIR spectrometer with an atomic force microscope equipped with a near‐field thermal sensing probe. FTIR‐PTMS spectroscopy currently has spatial resolution that is similar to that of diffraction‐limited optical detection FTIR spectroscopy techniques, but as a near‐field probing technique has considerable potential for further improvement. Our work also suggests that FTIR–PTMS is potentially more sensitive than synchrotron radiation FTIR spectroscopy for some applications.

Microspectroscopy techniques like FTIR–PTMS provide information about the entire molecular composition of cells, in contrast to epitope recognition that only considers the presence or absence of individual molecules. Our results with FTIR–PTMS on corneal stem cells are promising for the potential development of an IR spectral fingerprint for stem cells.
Evaluating performance in three‐dimensional fluorescence microscopy
Authors: MURRAY JOHN M. , APPLETON PAUL L. , SWEDLOW JASON R. , WATERS JENNIFER C.
Published: December 2007

In biological fluorescence microscopy, image contrast is often degraded by a high background arising from out of focus regions of the specimen. This background can be greatly reduced or eliminated by several modes of thick specimen microscopy, including techniques such as 3‐D deconvolution and confocal. There has been a great deal of interest and some confusion about which of these methods is ‘better’, in principle or in practice. The motivation for the experiments reported here is to establish some rough guidelines for choosing the most appropriate method of microscopy for a given biological specimen. The approach is to compare the efficiency of photon collection, the image contrast and the signal‐to‐noise ratio achieved by the different methods at equivalent illumination, using a specimen in which the amount of out of focus background is adjustable over the range encountered with biological samples. We compared spot scanning confocal, spinning disk confocal and wide‐field/deconvolution (WFD) microscopes and find that the ratio of out of focus background to in‐focus signal can be used to predict which method of microscopy will provide the most useful image. We also find that the precision of measurements of net fluorescence yield is very much lower than expected for all modes of microscopy. Our analysis enabled a clear, quantitative delineation of the appropriate use of different imaging modes relative to the ratio of out‐of‐focus background to in‐focus signal, and defines an upper limit to the useful range of the three most common modes of imaging.
The host–parasite neuroimmunoendocrine network in schistosomiasis: consequences to the host and the parasite
Authors: MORALES‐MONTOR J. , HALL C. A.
Published: December 2007

The physiological interactions during the course of any immune response are complex. Infection induces antigen‐specific recognition by the immune system, which is consequently charged with the responsibility of marshalling the appropriate effector responses necessary to destroy the pathogen, or at the very least inhibit its progression. Obviously, the immune system should accomplish this while minimizing collateral damage to the host or it risks, winning a Pyrrhic victory. As our understanding of the neuroendocrine system grows, it has become increasingly clear that this complex network of neurotransmitters, hormones and cytokines plays an important role in mediating immunity. Schistosomes present an especially complex relationship between pathogen and these physiological systems, with hormonally dependent host factors such as sex and age correlated with parasite success. In this report, we review the current literature on sex and age associations between infection and progression of disease. We then follow with a discussion on interactions between the host neuroendocrine and immune systems. We also speculate on strategies to apply this knowledge to novel treatment strategies. Results argue for a complex network comprising the immune, endocrinological and nervous systems of both host and schistosome in the regulation of the plural outcomes of infection.
Contributions to the study of Trichinella spiralis TSL‐1 antigens in host immunity
Authors: YÉPEZ‐MULIA L. , HERNÁNDEZ‐BELLO R. , ARIZMENDI‐PUGA N. , FONSECA‐LIÑÁN R. , ORTEGA‐PIERRES G.
Published: December 2007

The observation on different hosts infected with Trichinella spiralis that recognized similar muscle larvae (ML) antigens and the fact that different monoclonal antibodies (mAb) had a similar reactivity to ML components prompted a proposal to define a useful classification system for these antigens. For this purpose, an international workshop provided a platform for the classification of T. spiralis antigens. ML antigens were classified in eight groups –Trichinella spiralis larvae groups, TSL‐1 to TSL‐8. TSL‐1 antigens are highly immunogenic and a number of important studies have been performed to analyse the role of these antigens in the host–parasite interplay.

In this context, we have focused on the analysis of the role of TSL‐1 antigens in the induction of innate immune responses with particular emphasis on the activation of mast cells (MC) by an IgE‐independent pathway. These studies provided evidence on the role of mediator release from TSL‐1‐activated MC in the development of Type 2 immune responses. The protective role of TSL‐1 in T. spiralis‐infected mice has been described. In addition, it has been demonstrated that the use of TSL‐1 antigens allows for a more sensitive and specific diagnosis of human and animal trichinellosis.
Mexican immunoparasitology: what is done and has to be done
Authors: MORALES‐MONTOR J.
Published: December 2007

In this special issue of Parasite Immunology, the reader will find reviewed some of the hottest topics in immunoparasitology, with emphasis on the most studied parasite species in México. For instance, the immunological conditions that appear favorable for the survival or destruction of the parasite in the intermediate and definitive hosts in cysticercosis, as well as the use of immunodiagnostic tests in epidemiological/intervention studies are discussed in two different articles. The role that alternatively activated macrophages plays in modulating host immunity is also discussed, while in the field of Leishmaniasis, the reader will find reviewed the role that CD8+ T cells play in the host defense during the human infection. The role that antibodies may play as biomarkers of protective or pathological cellular immune events in Toxoplasma gondii infections, as well as the new insights about the regulation of the inflammatory immune response by the cytokine/chemokine network in amebiasis, are topics reviewed. The use that TSL‐1 antigens may have in the development of more sensitive and specific diagnosis of human and animal trichinellosis as well as the role that the neuroimmunoendocrine network plays during schistosomiasis are also presented. We hope that our readers will find fascinating and enticing, the first ever Special Issue devoted to Mexican Immunoparasitology.
CD8 cytotoxic T cells in cutaneous leishmaniasis
Authors: RUIZ J. H. , BECKER I.
Published: December 2007

CD8 T cells are essential in the defence against viruses, yet little is known of their participation in the host defence against parasites, such as Leishmania, which can cause a variety of clinical diseases, such as localized cutaneous, diffuse cutaneous, mucocutaneous and visceral leishmaniasis. Murine models of leishmaniasis suggest that CD8 T cells participate through IFN‐γ production, yet their cytotoxic capacity also plays an important role, as has been found in patients infected with various Leishmania strains, where CD8 T cell cytotoxicity and apoptosis of autologous Leishmania‐infected macrophages correlate with cure. Yet the mechanisms underlying the CD8 T activation in patients with leishmaniasis remain an enigma. It is possible that dendritic cells activate CD8 T cells through mechanisms that include antigen cross‐presentation. Here we summarize the recent findings of CD8 T cells in cutaneous leishmaniasis and discuss their significance in the control of the disease. Further knowledge in this field will undoubtedly improve the design of therapeutic and vaccine strategies.
How minerals may influence the development and expression of immunity to endoparasites in livestock
Authors: McCLURE S. J.
Published: December 2007

This review attempts to explain how dietary mineral intake may affect the immune system, with particular reference to gastrointestinal nematode infestations of livestock, and considers its significance for other gut infections as well as for other species. Of the 56 minerals found in mammalian tissues, 16 are currently considered to be essential, and a further 13 probably essential, for cell and tissue function. To date, eight of these have been shown to affect the function of the mammalian immune system directly. Nine others have roles in physiological pathways such as neurological or endocrine function, or protein or carbohydrate metabolism, which in turn regulate the immune system. The remainder may in the future be shown to have immunologically specific roles. The pathogenesis of mineral effects on immunity involves a number of pathways and molecular mechanisms. Major areas requiring further investigation are the relationship between deficiency of minerals and in vivo immune‐mediated protection against disease, in particular diseases of the mucosa, and the mechanisms by which the minerals or their deficiency exert their effect on immunity. Research is also required into the possibility that animals in the process of acquiring gut immunity have higher requirements for minerals.
Vitamin E is essential for the tolerance of Arabidopsis thaliana to metal‐induced oxidative stress
Authors: COLLIN VALÉRIE C. , EYMERY FRANÇOISE , GENTY BERNARD , REY PASCAL , HAVAUX MICHEL
Published: December 2007

Arabidopsis (Arabidopsis thaliana) plants were grown in a hydroponic culture system for 7 to 14 d in the absence or presence of 75 µM Cd or 75 µM Cu. The Cu treatment resulted in visual leaf symptoms, together with anthocyanin accumulation and loss of turgor. Pronounced lipid peroxidation, which was detected by autoluminescence imaging and malondialdehyde titration, was observed in Cu‐treated leaves. The Cd treatment also resulted in loss of leaf pigments but lipid peroxidation and oxidative stress were less pronounced than in the leaves exposed to Cu. Analysis of low‐molecular‐weight chloroplast and cytosolic antioxidants (ascorbate, glutathione, tocopherols, carotenoids) and antioxidant enzymes (thiol‐based reductases and peroxidases) revealed relatively few responses to metal exposure. However, there was a marked increase in vitamin E (α‐tocopherol) in response to Cd and Cu treatments. Ascorbate increased significantly in Cu‐exposed leaves. Other antioxidants either remained stable or decreased in response to metal stress. Transcripts encoding enzymes of the vitamin E biosynthetic pathway were increased in response to metal exposure. In particular, VTE2 mRNA was enhanced in Cu‐ and Cd‐treated plants, while VTE5 and hydroxylpyruvate dioxygenase (HPPD) mRNAs were only up‐regulated in Cd‐treated plants. Consistent increases in HPPD transcripts and protein were observed. The vitamin E‐deficient (vte1) mutant exhibited an enhanced sensitivity towards both metals relative to the wild‐type (WT) control. Unlike the vte1 mutants, which showed enhanced lipid peroxidation and oxidative stress in the presence of Cu or Cd, the ascorbate‐deficient (vtc2) mutant showed WT responses to metal exposure. Taken together, these results demonstrate that vitamin E plays a crucial role in the tolerance of Arabidopsis to oxidative stress induced by heavy metals such as Cu and Cd.
A nodular granulomatous posthitis caused byHalicephalobussp. in a horse
Authors: Muller Stéphanie , Grzybowski Marco , Sager Heinz , Bornand Valérie , Brehm Walter
Published: December 2007

This report describes a case of nodular posthitis caused byHalicephalobus gingivalisin a 24‐year‐old warmblood horse. Macroscopic examination revealed a multinodular, partially ulcerated mass on the external lamina of the prepuce. Nematode migration from unfixed biopsy material in phosphate‐buffered saline revealed adult nematodes with the typical morphological features ofH. gingivalis:distinctive rhabditiform oesophagus with corpus, isthmus and bulb and the dorsoflexed ovary. The main histopathological features consisted of submucosal confluent granulomatous foci containing cross‐ and tangential sections of larval and adult nematodes surrounded by cellular debris, epitheloid macrophages, multinucleated giant cells, lymphocytes and plasma cells. Therapy including oral administration of moxidectin and local application of an ointment containing prednisolone and moxidectin was initiated but clinical response was poor. Five months later, the nodular mass was still present and histologically, the same lesions with numerous intact nematodes were identified. In the present case, a localized infection with granuloma formation in the area of the prepuce was observed. Clinically, it cannot be distinguished from other nematode infections or even from a squamous cell carcinoma. An accurate clinical examination followed by histopathological and parasitological examinations was necessary to establish the final diagnosis. This case is unusual in that the lesions were locally very extensive (10 cm), but they remained confined to the preputium and the nematodes did not spread haematogenously to other internal organs.
Molecular Characterization of Phytoplasma Associated with Rose Witches’‐Broom in China
Authors: Gao R. , Zhang G.‐M. , Lan Y.‐F. , Zhu T.‐S. , Yu X.‐Q. , Zhu X.‐P. , Li X.‐D.
Published: December 2007

In 2005, rose plants (Rosa rugosa cv. ‘Plena’) exhibiting typical phytoplasma disease symptoms of stunting, yellowing, witches’‐broom and dieback were observed in Pingyin, Shandong Province, China. The disease, rose witches’‐broom (RoWB), is progressively destructive and can be graft‐transmitted. Polymerase chain reaction (PCR), sequencing of PCR products and electron microscopy were used to investigate the possible association of phytoplasma with RoWB. All results indicated that presence of phytoplasma in the symptomatic rose plants. Sequence alignment of 16S rRNA gene, tuf gene and rp gene confirmed that the phytoplasma associated with RoWB is the causal agent of Paulownia witches’‐broom disease, which might be transmitted from the paulownia tree that is several meters away. To our knowledge, this is the first report of the molecular characterization of phytoplasma infecting rose in China.
Identification of Barley mild mosaic virus Isolates in Germany Breaking rym5 Resistance*
Authors: Habekuss A. , Kühne T. , Krämer I. , Rabenstein F. , Ehrig F. , Ruge‐Wehling B. , Huth W. , Ordon F.
Published: December 2007

In winter and early spring 2004 unequivocal mosaic symptoms were detected for the first time in Germany on six plants of the barley cv. ‘Tokyo’ carrying the resistance gene rym5. By serological and electron microscopic investigations Barley mild mosaic virus (BaMMV) was identified in all plants and could be re‐transmitted to cv. ‘Tokyo’ as well as to additional cultivars carrying rym5. In contrast to this, genotypes carrying the resistance genes rym1 + rym5, Rym2, rym4, rym7, rym9, rym11, rym12, rym13, Rym14Hb, rym15 or Rym16Hb turned out to be resistant. Furthermore, the BaMMV isolates were not transmissible to different dicotyledonous species. Sequence analyses in the VPg coding region of RNA1 revealed differences to the known sequence of the original BaMMV isolate (BaMMV‐ASL1, AJ 242725) and also of a French pathotype (BaMMV‐Sil, AJ 544267, AJ 544268) which is also able to overcome the resistance mediated by rym5. At least in one location a spread of the area infested by this new strain was observed in 2004/2005 and 2005/2006.
Utilization of Caffeic Acid Phenethyl Ester to Control Alternaria alternata Rot in Tomato (Lycopersicon esculentum Mill.) Fruit
Authors: Ojeda‐Contreras A.‐J. , Hernández‐Martínez J. , Domínguez Z. , Mercado‐Ruiz J.‐N. , Troncoso‐Rojas R. , Sánchez‐Estrada A. , Tiznado‐Hernández M.‐E.
Published: December 2007

Chemical fungicides that are related with resistant strains develop negative effects on human health and environment. Propolis is a resinous substance collected by bees with positive effects on human health and inhibitory activity against Alternaria alternata. Caffeic acid phenethyl ester (CAPE) is a component of the propolis. The objective of this experiment was to test the effect of CAPE on fungi infecting tomato fruit using as a model the pathosystem A. alternata‐tomato. CAPE was chemically synthesized in our laboratory and analysed with nuclear magnetic resonance spectroscopy. Different concentrations (0, 16, 32, 48, 64, 80, 90 and 100 μm) of CAPE were tested on A. alternata growing in vitro. For the in vivo experiment, red ripe tomato fruit was inoculated with A. alternata and untreated or treated with 1, 50 and 100 μm of CAPE. After that, the fruit was stored at 25°C for up to 20 days. Colony size (CS) was recorded in vitro. In tomato fruits, the severity of infection (SI), respiration rate (RR), ethylene production (EP), pH, total soluble solids (TSS), weight loss (WL) and titratable acidity (TA) were evaluated during the storage time. CAPE melting point and spectral data probed to be the right molecule. In vitro, 64 and 100 μm of CAPE reduced CS by 30%. In vivo, 50 and 100 μm of CAPE reduced SI higher than the fungicide Captan® with no effects on RR, EP, WL, pH, TSS and TA. It was concluded that CAPE controls A. alternata infection better than a commercial fungicide without negative effects on tomato fruit ripening and fruit quality.
Kinematic Gait Analysis of the Hind Limb after Tibial Plateau Levelling Osteotomy and Cranial Tibial Wedge Osteotomy in Ten Dogs
Authors: Lee J. Y. , Kim G. , Kim J. ‐H. , Choi S. H.
Published: December 2007

This study identifies and compares the kinematic gait changes occurring in tibial plateau levelling osteotomy (TPLO) and cranial tibial wedge osteotomy (CTWO) limbs after transection of the cranial cruciate ligament (CrCL). Ten, healthy, adult beagle dogs were assigned to TPLO (five dogs) and CTWO (five dogs) groups. Hind limb kinematics were assessed, while dogs were trotted at speeds ranging from 2.0 to 2.3 m/s. The animals were evaluated preoperatively (prior to TPLO and CTWO surgery) and at both 8 and 12 weeks after surgery. Two‐dimensional evaluation was synchronized to obtain the three‐dimensional coordinates using the APAS motion analysis software. Gait patterns were assessed by measuring stifle, tibiotarsal joint angles and stifle joints angular velocity. Stifle and tibiotarsal joint functions were not affected by TPLO surgery, but stifle and tibiotarsal joint angles were changed, following CTWO surgery, compared with their preoperative values. The angular velocity patterns of CTWO were characterized by increased stifle joint extension velocity from the middle to end swing phase and decrease in the peak velocities (flexion) during swing phase. None of these changes was observed in the stance phase after the CTWO surgery. These kinematic results showed that dogs that underwent a CTWO procedure were more likely to have significantly hyperextended gait patterns of the swing phase postoperatively than the dogs that had a TPLO procedure for repair of a ruptured CrCL.
The impact of glycaemic control on outcomes in patients with end‐stage renal disease and type 2 diabetes (Review Article)
Authors: ZOUNGAS SOPHIA , KERR PETER G , LUI MICHELLE , TEEDE HELENA J
Published: December 2007

SUMMARY:  In Australia and New Zealand the prevalence and incidence of end‐stage renal disease (ESRD) has increased. In Australia alone the financial burden is estimated to reach $500 million by 2007 (data from the National Chronic Kidney Disease Strategy Workshop Report 2005). The leading cause of ESRD in Australia and New Zealand, and throughout the developed world, is type 2 diabetes, having overtaken glomerulonephritis in 2004.1 To date, management of patients with diabetes and ESRD has been, according to guidelines, given for patients without ESRD. This commentary raises three important emerging concerns in the clinical care of these patients: (i) the lack of reliable tools to measure glycaemic control; (ii) limitations of the current data set supporting a relationship between outcome and glycaemic control in ESRD; and (iii) lack of studies examining the effect of intensive diabetes care and glucose control in patients with ESRD.
Cytochemical characterization of the endomembranous system during oocyte secondary growth in Serrasalmus spilopleura (Teleostei, Characiformes, Characidae)
Authors: Guimarães A. C. D. , Quagio‐Grassiotto I.
Published: December 2007

The endomembranous system of Serrasalmus spilopleura oocyte secondary growth was analysed using structural and ultrastructural cytochemical techniques. In vitellogenic oocytes, the endoplasmic reticulum components, the nuclear envelope intermembranous space, some Golgi dictiossomes, lysosomes, yolk granules, regions of the egg envelope and sites of the follicle cells react to acid phosphatase detection (AcPase). The cortical alveoli, some heterogeneous cytoplasmic structures, regions of the egg envelope, and sites of the follicle cells are strongly contrasted by osmium tetroxide and zinc iodide impregnation (ZIO). The endoplasmic reticulum components, some vesicles, and sites of the follicle cells also react to osmium tetroxide and potassium iodide impregnation (KI). The biosynthetic pathway of lysosomal proteins, such as acid phosphatase, required for vitellogenesis, involves the endoplasmic reticulum, Golgi complex, vesicles with inactive hydrolytic enzymes, and, finally, lysosomes. In S. spilopleura oocytes at secondary growth, the endomembranous system takes part in the production of the enzymes needed for vitellogenesis, and in the metabolism of yolk exogenous components (AcPase detection). The endomembranous system compartments also show reduction capacity (KI reaction) and are involved in the metabolism of proteins rich in SH‐groups (ZIO reaction).
Invertebrate and protozoan epibionts on the velvet swimming crab Liocarcinus puber (Linnaeus, 1767) from Scotland
Authors: Fernandez‐Leborans Gregorio , Gabilondo Regina
Published: December 2007

Invertebrate and ciliate protozoan epibionts of velvet swimming crabs collected near Millport (Scotland) were analysed. The ecdysis peak for male crabs was at the time of collection while that for female crabs was 2 months later. The epibionts were: the polychaetes Pomatoceros triqueter and Hydroides norvegica, the cirriped Balanus crenatus, the entoproct Barentsia matsushimana, the hydroids Leuckartiara sp. and Clytia sp., and the ciliate protozoans Ephelota plana, Ephelota gemmipara, Chilodochona quennerstedti and Cothurnia longipes. The polychaetes, cirripeds, entoprocts and hydroids, all of them with comparatively larger size, were distributed on the carapace, ventral surface of the cephalothorax and the pereiopods; meanwhile the protozoans, with smaller size, were attached also on pleopods, antennae, eyes and buccal appendages. Chilodochona quennerstedti was the epibiont most abundant on the crab, followed by Ephelota plana. Cothurnia longipes was, in contrast, the least abundant epibiont, followed by Barentsia matsushimana. The anatomical unit most colonized was the left third maxilliped, followed by the left first maxilliped and the ventral surface. The less colonized anatomical units were the left antenna and the ocular orbits. Epibionts on this crab have not been described before. Statistical analyses of the epibiont distribution on the crab were carried out. There were significant correlations between right and left appendages in 66.67% of the cases. Males and females differed significantly with respect to the distribution of epibionts on their anatomical units. The comparison analysis indicated a significant differential distribution of each epibiont species on the anatomical units of the crab. Principal component analysis grouped the epibiont species according to their colonization pattern in three clusters: (1) Ephelota plana, Ephelota gemmipara and Chilodochona quennerstedti; (2) Leuckartiara sp., Clytia sp., Barentsia matsushimana and Cothurnia longipes; and (3) Pomatoceros triqueter, Balanus crenatus and Hydroides norvegica. The hierarchical cluster analysis grouped the anatomical units of the crab in relation to their colonization in five clusters.
A randomized cross‐over trial to identify the optimal use of insulin glargine in prepubertal children using a three‐times daily insulin regimen
Authors: Fröhlich‐Reiterer E. E. , Ong K. K. , Regan F. , Salzano G. , Acerini C. L. , Dunger D. B.
Published: December 2007

Aims  The long‐acting insulin analogue glargine reduces nocturnal hypoglycaemia and stabilizes morning blood glucose levels in patients with Type 1 diabetes (T1DM) on multiple injection therapy. However, young children may not tolerate such intensive insulin regimens. We investigated the effects of glargine in various three‐injections‐daily insulin combinations on 24‐h glucose control in prepubertal children.

Methods  Seventeen T1DM prepubertal children (10 boys), median age 10.2 years (range 6.0–12.4), glycated haemoglobin (HbA1c) 8.8% (6.8–11.5) were recruited to a randomized, open‐label, cross‐over study. After a 2‐week run‐in period (with NPH pre‐bed), every child underwent three different 3‐week treatment blocks in random order. All treatment blocks included glargine pre‐bed, but used different morning insulins: block 1, soluble only; block 2, soluble + NPH; block 3, aspart + NPH. Continuous glucose monitoring was performed for 3 days at the end of the run‐in and each treatment block.

Results  Compared with the run‐in period on NPH, the three glargine treatment blocks were associated with lower (P < 0.0001) and less variable (P < 0.05) pre‐breakfast glucose levels, and with an 8–15% reduction in total daily insulin dose (P < 0.0001). Risk of nocturnal hypoglycaemia detected by continuous glucose monitoring varied significantly between the three glargine treatment blocks, and was lowest when children were given aspart + NPH in the morning (block 3).

Conclusion  Insulin glargine pre‐bed can be used in three‐injections‐daily regimens in prepubertal children to lower and stabilize pre‐breakfast glucose levels. However, to avoid the risk of nocturnal hypoglycaemia, the pre‐bed glargine dose should be lowered by giving a further long‐acting insulin, such as NPH, in the morning.
Constant dopaminergic stimulation by transdermal delivery of dopaminergic drugs: a new treatment paradigm in Parkinson's disease
Authors: Steiger M.
Published: December 2007

Current dopaminergic therapies for the treatment of Parkinson's disease are associated with the development of long‐term motor complications. Abnormal pulsatile stimulation of dopamine receptors is thought to underlie the development of motor complications. There is thus a need for therapies that mimic the normal physiological state more closely by resulting in constant dopaminergic stimulation (CDS). Several studies support the hypothesis that CDS can reverse levodopa‐induced motor complications. Other potential benefits of CDS include alleviating nocturnal disturbances, minimizing daytime sleepiness, avoiding priming for motor fluctuations and dyskinesia, preventing the development of gastrointestinal dysfunction and reducing the risk of developing psychosis or behavioural disturbances. Continuous infusion of dopaminergic therapies is impractical for the routine treatment of large numbers of patients. Although catechol‐O‐methyltransferase inhibitors or sustained‐release preparations of levodopa may be beneficial, they do not entirely eliminate pulsatile stimulation of dopamine receptors. A new dopamine agonist (rotigotine), delivered over 24 h by a once‐daily transdermal patch, has been investigated in several clinical trials. Continuous delivery of rotigotine has been shown to provide ‘true’ CDS in animal models. The potential of true CDS therapy to prevent or reduce long‐term motor and non‐motor complications requires investigation in appropriately designed clinical trials.
A potential catastrophic trap: an unusually presenting sellar lesion
Authors: Locatelli M. , Spagnoli D. , Caroli M. , Isalberti M. , Branca V. , Gaini S. M. , Lania A.
Published: December 2007

A 63‐year‐old man was admitted to our emergency unit complaining headache, vomit and vertigo. A MR of the brain showed an expanding lesion within the sellar region. A subsequent angio‐MR excluded any intracranial vascular malformations. Surprisingly, a cerebral angiography performed later on the basis of worsening of neurological signs and symptoms, demonstrated an aneurysm of the internal carotid artery. At the best of our knowledge, this is the first case of a thrombosis of an intracavernous carotid aneurysm mimicking a pituitary apoplexy documented by MR and angio‐MR. The treatment of a milder syndrome of pituitary apoplexy is still controversial. This case would favour conservative treatment opposed to surgery at least when an intracavernous extension or invasion of the adenoma would limit the opportunity of a complete tumour removal.
Brainstem in Machado–Joseph disease: atrophy or small size?
Authors: Horimoto Y. , Matsumoto M. , Yuasa H. , Kojima A. , Nokura K. , Katada E. , Yamamoto T. , Yamamoto H. , Mitake S.
Published: December 2007

Machado–Joseph disease (MJD), one of the most common types of hereditary spinocerebellar degeneration caused by abnormal expansion of the CAG repeat in the MJD1 gene, presents atrophy of the infratentorial structures neuropathologically and neuroradiologically. Although a significant positive correlation has been reported between infratentorial atrophy and the number of expanded CAG repeat units, the exact changing course of brainstem size in the individual case remains to be resolved. We investigated seven cases of genetically confirmed MJD longitudinally by magnetic resonance imaging with observation periods of 4.5–10.6 years. Measurement of the midsagittal areas of infratentorial structures disclosed progressive atrophy of the pontine base and cerebellum, which correlated significantly with age, whilst midbrain and pontine tegmentum showed atrophy with no significant progression, suggesting it was better identified as ‘small size’ and might have mostly been completed before the initial symptoms. Such differences between regions in atrophy progression must be caused by a difference in the neuropathological course.
Individual Characteristics and Service Expenditure on Challenging Behaviour for Adults with Intellectual Disabilities
Authors: Hassiotis Angela , Parkes Charles , Jones Lee , Fitzgerald Brian , Romeo Renee
Published: December 2007

Background  English policy argues that people with intellectual disabilities should be supported in their local communities. There is considerable evidence that this aspiration is not being achieved. This paper seeks to look at the subsection of people with intellectual disabilities who have expensive care needs because of challenging behaviour, to identify the decision‐making processes that have led to current service provision and expenditure and to suggest improvements.

Materials and Methods  We carried out a survey within five North London boroughs to investigate the characteristics of a cohort of people with intellectual disabilities and challenging behaviour in high‐cost accommodation (over £70 000/annum). Postal questionnaires and face‐to‐face interviews were conducted with stakeholders with intellectual disabilities and patterns of current costs were estimated from existing data provided by the commissioning authorities in the five boroughs.

Results  Two hundred and five individuals with intellectual disabilities and challenging behaviour were identified. They were accommodated in placements provided by 97 separate providers, both in and out‐of‐area. Those more likely to be placed out‐of‐area were younger, had multiple health problems, significant challenging behaviour and mental health problems including autistic spectrum disorders. The local community intellectual disabilities teams identified a number of difficulties in meeting the needs of those service users.

Conclusions  Expenditure on all placements for service users with intellectual disabilities is significant. There is a notable lack of investment in local service development. A coherent approach is required, often across service boundaries. The authors suggest a model for targeted investment aimed at supporting effective local services, and reducing the need for and expense of out‐of‐area placements.