bluuebunny/crossref_metadata_2025 huggingface dataset:
574. LINUM DOERFLERI
Authors: Strange Kit , Rix Martyn
Published: May 2007

Summary Linum doerfleri Rech. fil. is illustrated and its relationship with L. arboreum and related species is discussed. Instructions for the successful cultivation of L. arboreum and L. doerfleri are given.
576. HELICHRYSUM ARWAE
Authors: Hind Nicholas , Strange Kit , Broome Jeremy
Published: May 2007

Summary Helichrysum arwae J.R.I.Wood, a narrow endemic from the Yemen Arab Republic, is described and illustrated, along with its cultivation requirements. Its position within Helichrysum is discussed, and comparisons made with H. sessile and H. sessilioides, two similar species from southern Africa.
578. IRIS NARYNENSIS
Authors: Hall Tony
Published: May 2007

Summary The rare juno Iris narynensis from Central Asia is illustrated. A full description of the species is provided, its taxonomy and possible relationships are discussed and cultivation requirements in the U.K. given, based on experience gained at Kew. The latest thinking regarding the evolutionary position of the junos within genus Iris L. is summarised – the results of molecular research carried out at Kew in recent years.
579. FRITILLARIA GUSSICHAE
Authors: Rix Martyn , Strange Kit
Published: May 2007

Summary Fritillaria gussichae (Degen & Dörfl.) Rix is described and illustrated and its relationship to other species in the F. graeca complex is discussed. Instructions for its cultivation are given.
582. PUSCHKINIA PESHMENII
Authors: Rix Martyn , Mathew Brian
Published: May 2007

Summary A new species of Puschkinia, P. peshmenii with green flowers is described and illustrated. The circumstances of its discovery and details of its habitat are given.
583. POLYGONATUM GRAMINIFOLIUM
Authors: Wilford Richard , Rix Martyn
Published: May 2007

Summary Polygonatum graminifolium Hook. is illustrated and a description is provided. Its relationship to P. hookeri Baker is discussed and conditions for its successful cultivation are described.
THE ALPINE HOUSES OF KEW
Authors: Wilford Richard
Published: May 2007

Summary There has been an alpine house at Kew since 1887. The first house was a traditional design that was in use for nearly a century. Subsequent alpine houses at Kew have been more radical in their design and helped raise the profile of Kew’s alpine collections. The latest, the innovative Davies Alpine House, opened in March 2006.
PAUL FURSE AND HIS PLANT COLLECTIONS AT KEW
Authors: Strange Kit
Published: May 2007

Summary Paul Furse was an accomplished botanical artist and amateur botanist who, after his retirement from the Navy, spent several years searching for bulbs, travelling to remote locations in the Near East. He went to Turkey, Iran, Iraq, Afghanistan, and collected many plants which are still in cultivation today. His pioneering expeditions and enthusiasm inspired a generation of botanists to explore these areas.
584. ISOTREMA MANSHURIENSE
Authors: Edwards Sara , Leon Christine
Published: May 2007

Summary The history, taxonomy, medicinal uses, pollination mechanism and interaction with insects, distribution and cultivation requirements of Isotrema manshuriense (Kom.) H. Huber (widely known in horticultural and medical circles as Aristolochia manshuriensis Kom.) are discussed; a full description, illustration and dissections are provided.
588. STENOMESSON PEARCEI
Authors: Weber Odile , Wilkin Paul
Published: May 2007

Summary The systematic relationships of Stenomesson Herb. and other Andean genera of Amaryllidaceae are discussed and one of its members, S. pearcei Baker, is compared to similar species, described and illustrated. The cultivation requirements, habitat, distribution and conservation status of S. pearcei are discussed. A lectotype is chosen.
The Basic Analytics of Access to Financial Services
Authors: Beck Thorsten , De La Torre Augusto
Published: May 2007

Access to financial services, or rather the lack thereof, is often indiscriminately decried as problem in many developing countries. This paper argues that the “problem of access” should rather be analyzed by identifying different demand and supply constraints. We use the concept of an access possibilities frontier, drawn for a given set of state variables, to distinguish between cases where a financial system settles below the constrained optimum, cases where this constrained optimum is too low, and—in credit services—cases where the observed outcome is excessively high. We distinguish between payment and savings services and fixed intermediation costs, on the one hand, and lending services and different sources of credit risk, on the other hand. We include both supply and demand side frictions that can lead to lower access. The analysis helps identify bankable and banked population, the binding constraint to close the gap between the two, and policies to prudently expand the bankable population. This new conceptual framework can inform the debate on adequate policies to expand access to financial services and can serve as basis for an informed measurement of access.
NBS1, the Nijmegen breakage syndrome gene product, regulates neuronal proliferation and differentiation
Authors: Lee Wang‐Tso , Chang Wen‐Hsin , Huang Chi‐Hung , Wu Kou‐Juey
Published: May 2007

Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder, characterized by progressive microcephaly, growth retardation, immunodeficiency, and pre‐disposition to tumor formation. To investigate the functions of the NBS gene product, NBS1, on neurons, PC12 cells overexpressing NBS1 and related mutants and primary cortical neuronal culture were used in the present study. Small interfering RNA (siRNA) was applied to repress the expression of endogenous Nbs1 in PC12 cells and primary cortical neurons. We demonstrated that overexpression of NBS1 increases cellular proliferation and decreases the apoptosis of PC12 cells in serum withdrawal and ionizing irradiation, through the activation of phosphatidylinositol 3‐kinase (PI 3‐kinase)/Akt pathway. Overexpression of NBS1 also decreases neurite elongation on PC12 cells under nerve growth factor stimulation. Transfection of NBS1‐overexpressing PC12 cells with a dominant negative Akt mutant attenuates the neuroprotection and cellular proliferation effects of NBS1 while having no effect on neurite elongation. PC12 cells overexpressing NBS657del5 and NBS653 mutants, in which the major NBS1 protein in cells are truncated proteins, have decreased cellular proliferation, increased cell death, and decreased neurite elongation compared with those of control PC12 cells. Repression of Nbs1 by siRNA decreases the PI 3‐kinase activity and Akt phosphorylation levels, and induces neurite elongation in PC12 cells even without nerve growth factor stimulation. Repression of Nbs1 by siRNA in primary cortical neurons also increased neurite elongation, but increased neuronal death. We conclude that NBS1 can regulate neuronal proliferation and neuroprotection via PI 3‐kinase/Akt pathway while regulating neuronal differentiation in a different pathway. Excessive accumulation of truncated protein secondary to 657del5 mutation may be detrimental to neurons, leading to defective neuronal proliferation and differentiation.
Neurochemical, morphological, and neurophysiological abnormalities in retinas of Sandhoff and GM1 gangliosidosis mice
Authors: Denny Christine A. , Alroy Joseph , Pawlyk Basil S. , Sandberg Michael A. , D’Azzo Alessandra , Seyfried Thomas N.
Published: May 2007

Retinal abnormalities are well documented in patients with ganglioside storage diseases. The total content and distribution of retinal glycosphingolipids was studied for the first time in control mice and in Sandhoff disease (SD) and GM1 gangliosidosis mice. Light and electron microscopy of the SD and the GM1 retinas revealed storage in ganglion cells. Similar to previous findings in rat retina, GD3 was the major ganglioside in mouse retina, while GM2 and GM1 were minor species. Total ganglioside content was 44% and 40% higher in the SD and the GM1 retinas, respectively, than in the control retinas. Furthermore, GM2 and GM1 content were 11‐fold and 51‐fold higher in the SD and the GM1 retinas than in the control retinas, respectively. High concentrations of asialo‐GM2 and asialo‐GM1 were found in the SD and the GM1 retinas, respectively, but were undetectable in the control retinas. The GSL abnormalities in the SD and the GM1 retinas reflect significant reductions in β‐hexosaminidase and β‐galactosidase enzyme activities, respectively. Although electroretinograms appeared normal in the SD and the GM1 mice, visual evoked potentials were subnormal in both mutants, indicating visual impairments. Our findings present a model system for assessing retinal pathobiology and therapies for the gangliosidoses.
Mitogen‐activated protein kinase phosphatase‐1 (MKP‐1) preferentially dephosphorylates p42/44MAPK but not p38MAPK in rat pinealocytes
Authors: Price Donald M. , Wloka Martin T. , Chik Constance L. , Ho Anthony K.
Published: May 2007

We recently reported a diurnal and norepinephrine (NE) ‐induced expression of mitogen‐activated protein kinase (MAPK) phosphatase‐1 (MKP‐1) in the rat pineal gland and postulated that this MKP‐1 expression might impact adrenergic‐regulated arylalkylamine‐N‐acetyltransferase (AA‐NAT) activity via modulation of MAPKs. In this study, we investigated the effect of depletion of MKP‐1 expression by using doxorubicin, a topoisomerase inhibitor that suppresses the expression of MKP‐1 in other cell types and small interfering RNA targeted against Mkp1 in NE‐stimulated pinealocytes. We found that both treatments were effective in inhibiting NE induction of MKP‐1 expression. Moreover, both treatments also resulted in a prolonged activation of p42/44MAPK and an increase in AA‐NAT induction by NE. In contrast, treatment of pinealocytes with PD98059, an inhibitor of MAPK kinase, reduced NE‐stimulated AA‐NAT activity. Interestingly, suppressing MKP‐1 expression had no effect on the time profile of NE‐stimulated p38MAPK activation. These results indicate that MKP‐1 modulates the profile of AA‐NAT activity by selectively shaping the activation profile of p42/44MAPK but not that of p38MAPK.
Nicotine induces tyrosine hydroxylase plasticity in the neurodegenerating striatum
Authors: Urbanavicius Jessika , Ferreira Margot , Costa Gustavo , Abin‐Carriquiry Juan Andrés , Wonnacott Susan , Dajas Federico
Published: May 2007

It has been shown that nicotine prevents the loss of dopamine (DA) in the corpus striatum (CS) after 6‐hydroxydopamine injection in the substantia nigra. To study the role of the enzyme tyrosine hydroxylase (TH; EC 1.14.16.2) in this experimental paradigm, we have examined its activity by assessing the accumulation of l‐3,4‐dihydroxyphenylalanine after inhibiting the subsequent enzyme in the DA synthetic pathway, aromatic l‐amino acid decarboxylase, with 3‐hydroxybenzylhydrazine. In addition the amount of TH protein was assessed by western blotting and its distribution in the CS was examined using immunohistochemical methods. 6‐hydroxydopamine injection produced a significant decrease in DA levels and l‐3,4‐dihydroxyphenylalanine accumulation, as well as decreases in TH protein and TH immunoreactive fibres in the CS. After nicotine treatment, the decrease in TH protein in the CS was significantly reduced, with a concomitant preservation of TH activity, but nicotine did not alter the number of TH immunoreactive fibres. The activity and amount of TH did not change in the contralateral (intact) CS. Thus, nicotine induces long lasting TH plasticity in the degenerating CS. A synergistic action of nicotine‐activated and lesion‐originated signals appears necessary for the expression of this neuronal molecular plasticity.
Atorvastatin partially prevents an inflammatory barrier breakdown of cultured human brain endothelial cells at a pharmacologically relevant concentration
Authors: Buttmann Mathias , Lorenz Alexander , Weishaupt Andreas , Rieckmann Peter
Published: May 2007

3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (i.e. statins) are currently under clinical investigation as a prophylactic immunomodulatory treatment for neurological diseases where an inflammatory disruption of the blood–brain barrier plays a pathogenic role. Here, we investigated whether atorvastatin pre‐treatment modulates inflammatory‐induced barrier dysfunction of cultured human brain microvascular endothelial cells (HBMEC). Pre‐treatment of immortalized HBMEC with atorvastatin (50 nmol/L to 1 μmol/L) dose‐dependently prevented an inflammatory up‐regulation of monocyte chemoattractant protein‐1/CCL2 but not of interleukin‐8/CXCL8 and intercellular adhesion molecule‐1 expression by tumor necrosis factor‐α or interleukin‐1β. It antagonized an inflammatory up‐regulation of claudin‐3 expression while zonula occludens‐1 and occludin protein levels remained unaltered. Like immortalized HBMEC, primary HBMEC also showed a reduction of claudin‐3 and of inducible CCL2 expression following atorvastatin pre‐treatment. On a functional level, atorvastatin pre‐treatment of HBMEC strongly and dose‐dependently reduced adhesion of activated T lymphocytes to pre‐activated primary endothelium. Atorvastatin effects could partially be abolished by parallel mevalonate treatment. These anti‐inflammatory effects of atorvastatin were observed already at a pharmacologically relevant concentration of 50 nmol/L. Our results obtained with human brain endothelial cells demonstrate how statins may partially prevent an inflammatory‐mediated blood–brain barrier breakdown in humans.
Delayed treatment with cannabidiol has a cerebroprotective action via a cannabinoid receptor‐independent myeloperoxidase‐inhibiting mechanism
Authors: Hayakawa Kazuhide , Mishima Kenichi , Nozako Masanori , Hazekawa Mai , Irie Keiichi , Fujioka Masayuki , Orito Kensuke , Abe Kohji , Hasebe Nobuyoshi , Egashira Nobuaki , Iwasaki Katsunori , Fujiwara Michihiro
Published: May 2007

We examined the neuroprotective mechanism of cannabidiol, non‐psychoactive component of marijuana, on the infarction in a 4 h mouse middle cerebral artery (MCA) occlusion model in comparison with Δ9‐tetrahydrocannabinol (Δ9‐THC). Release of glutamate in the cortex was measured at 2 h after MCA occlusion. Myeloperoxidase (MPO) and cerebral blood flow were measured at 1 h after reperfusion. In addition, infarct size and MPO were determined at 24 and 72 h after MCA occlusion. The neuroprotective effect of cannabidiol was not inhibited by either SR141716 or AM630. Both pre‐ and post‐ischemic treatment with cannabidiol resulted in potent and long‐lasting neuroprotection, whereas only pre‐ischemic treatment with Δ9‐THC reduced the infarction. Unlike Δ9‐THC, cannabidiol did not affect the excess release of glutamate in the cortex after occlusion. Cannabidiol suppressed the decrease in cerebral blood flow by the failure of cerebral microcirculation after reperfusion and inhibited MPO activity in neutrophils. Furthermore, the number of MPO‐immunopositive cells was reduced in the ipsilateral hemisphere in cannabidiol‐treated group. Cannbidiol provides potent and long‐lasting neuroprotection through an anti‐inflammatory CB1 receptor‐independent mechanism, suggesting that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders.
Genomic and proteomic microglial profiling: pathways for neuroprotective inflammatory responses following nerve fragment clearance and activation
Authors: Glanzer Jason G. , Enose Yoshimi , Wang Tong , Kadiu Irena , Gong Nan , Rozek Wojciech , Liu Jianuo , Schlautman Joshua D. , Ciborowski Pawel S. , Thomas Mark P. , Gendelman Howard E.
Published: May 2007

Microglia, a primary immune effector cell of the central nervous system (CNS) affects homeostatic, neuroprotective, regenerative and degenerative outcomes in health and disease. Despite these broad neuroimmune activities linked to specific environmental cues, a precise cellular genetic profile for microglia in the context of disease and repair has not been elucidated. To this end we used nucleic acid microarrays, proteomics, immunochemical and histochemical tests to profile microglia in neuroprotective immune responses. Optic and sciatic nerve (ON and SN) fragments were used to stimulate microglia in order to reflect immune consequences of nervous system injury. Lipopolysaccharide and latex beads‐induced microglial activation served as positive controls. Cytosolic and secreted proteins were profiled by surface enhanced laser desorption ionization‐time of flight (SELDI‐TOF) ProteinChip®, 1D and 2D difference gel electrophoresis. Proteins were identified by peptide sequencing with tandem mass spectrometry, ELISA and western blot tests. Temporal expression of pro‐inflammatory cytokines, antioxidants, neurotrophins, and lysosomal enzyme expression provided, for the first time, a unique profile of secreted microglia proteins with neuroregulatory functions. Most importantly, this molecular and biochemical signature supports a broad range of microglial functions for debris clearance and promotion of neural repair after injury.
Lysophosphatidylcholine potentiates Ca2+ influx, pore formation and p44/42 MAP kinase phosphorylation mediated by P2X7 receptor activation in mouse microglial cells
Authors: Takenouchi Takato , Sato Mitsuru , Kitani Hiroshi
Published: May 2007

The P2X7 receptor (P2X7R) is an ATP‐gated ion channel highly expressed in microglia. P2X7R plays important roles in inflammatory responses in the brain. However, little is known about the mechanisms regulating its functions in microglia. Lysophosphatidylcholine (LPC), an inflammatory phospholipid that promotes microglial activation, may have some relevance to P2X7R signaling in terms of microglial function. In this study, we examined its effects on P2X7R signaling in a mouse microglial cell line (MG6) and primary microglia. LPC facilitated the sustained increase in the intracellular Ca2+ concentration ([Ca2+]i) through P2X7R channels activated by ATP or BzATP. The potentiated increase in [Ca2+]i was actually inhibited by P2X7R antagonists, brilliant blue G and oxidized ATP. The potentiating effect of LPC was not observed with P2Y receptor systems, which are also expressed in MG6 cells. G2A, a receptor for LPC, was expressed in MG6 cells, but not involved in the facilitating effect of LPC on the P2X7R‐mediated change in [Ca2+]i. Furthermore, LPC enhanced the P2X7R‐associated formation of membrane pores and the activation of p44/42 mitogen‐activated protein kinase. These results suggest that LPC may regulate microglial functions in the brain by enhancing the sensitivity of P2X7R.
Presenilin dependence of phospholipase C and protein kinase C signaling
Authors: Dehvari Nodi , Cedazo‐Minguez Angel , Isacsson Ola , Nilsson Tatjana , Winblad Bengt , Karlström Helena , Benedikz Eirikur , Cowburn Richard F.
Published: May 2007

Presenilins (PSs) are involved in processing several proteins such as the amyloid precursor protein (APP), as well as in pathways for cell death and survival. We previously showed that some familial Alzheimer’s disease PS mutations cause increased basal and acetylcholine muscarinic receptor‐stimulated phospholipase C (PLC) activity which was γ‐secretase dependent. To further evaluate the dependence of PLC on PSs we measured PLC activity and the activation of variant protein kinase C (PKC) isoforms in mouse embryonic fibroblasts (MEFs) lacking either PS1, PS2, or both. PLC activity and PKCα and PKCγ activations were significantly lower in PS1 and PS2 double knockout MEFs after PLC stimulation. Protein levels of PKCα and PKCγ were lower in PS1 and PS2 double knockout MEFs. In contrast, PKCδ levels were significantly elevated in PS1 and PS2 double knockout as well as in PS1 knockout MEFs. Also, PKCδ levels were lowered after transfection of PS1 into PS1 knockout or PS double knockout MEFs. Using APP knockout MEFs we showed that the expression of PKCα, but not the other PKC isoforms is partially dependent on APP and can be regulated by APP intracellular domain (AICD). These results show that PLC and PKC activations are modulated by PS and also that PSs differentially regulate the expression of PKC isoforms by both APP/AICD‐dependent and independent mechanisms.
A Critical role for Bim in retinal ganglion cell death
Authors: McKernan Declan P. , Cotter T. G.
Published: May 2007

Optic nerve transection results in the death of retinal ganglion cells (RGCs) by apoptosis. Apoptosis is regulated by the Bcl‐2 family of proteins, of which the Bcl‐2 homology (BH3) ‐only proteins forms a subset. As BH3‐only proteins have been shown to play a significant role in regulating cell death in the central nervous system, we wished to investigate the role of Bcl‐2 interacting mediator of cell death (Bim), a prominent member of this protein family in the regulation of cell death in the RGC layer using in vitro retinal explants. In this study, we use an innovative retinal shaving procedure to isolate the cells of the ganglion cell layer to use for western blotting. Members of the BH3‐only protein family are down‐regulated during retinal development and are not normally expressed in the adult retina. Using this procedure, we demonstrate that Bim is re‐expressed and its expression is increased over time following axotomy. Expression of Bad and Bik decreases over the same time course, whereas there is no indication that Bid and Puma are re‐expressed. We show that explants from Bim knockout mice are resistant to axotomy‐induced death when compared with their wild‐type counterparts. Genetic deletion of Bim also prevents caspase 3 cleavage. The activity of Bim can be negatively regulated by phosphorylation. We show that the decrease of Bim phosphorylation correlates with a decrease in expression of survival kinases such as pAkt and pERK over the same time course. These results implicate Bim re‐expression as being essential for axotomy‐induced death of RGCs and that phosphorylation of Bim negatively regulates its activity in RGCs.
Syndapin I and endophilin I bind overlapping proline‐rich regions of dynamin I: role in synaptic vesicle endocytosis
Authors: Anggono Victor , Robinson Phillip J.
Published: May 2007

Dynamin I mediates vesicle fission during synaptic vesicle endocytosis (SVE). Its proline‐rich domain (PRD) binds the Src‐homology 3 (SH3) domain of a subset of proteins that can deform membranes. Syndapin I, amphiphysin I, and endophilin I are its major partners implicated in SVE. Syndapin binding is controlled by phosphorylation at Ser‐774 and Ser‐778 in the dynamin phospho‐box. We now define syndapin and endophilin‐binding sites by peptide competition and site‐directed mutagenesis. Both bound the same region of the dynamin PRD and both exhibited unusual bidirectional binding modes around core PxxP motifs, unlike amphiphysin which employed a class II binding mode. Endophilin binds to tandem PxxP motifs in the sequence 778SPTPQRRAPAVPPARPGSR796 in dynamin, with SPTPQ being an overhang sequence. In contrast, syndapin binding involves two components in the region 772RRSPTSSPTPQRRAPAVPPARPGSR796. It required a single PxxP core and a non‐PxxP N‐terminally anchored extension which bridges the phospho‐box and may contribute to binding specificity and affinity. Syndapin binding is exquisitely sensitive to the introduction of negative charges almost anywhere along this region, explaining why it is a highly tuned phospho‐sensor. Over‐expression of dynamin point mutants that fail to bind syndapin or endophilin inhibit SVE in cultured neurons. Due to overlapping binding sites the interactions between dynamin and syndapin or endophilin were mutually exclusive. Because syndapin acts as a phospho‐sensor, this supports its role in depolarization‐induced SVE at the synapse, which involves dynamin dephosphorylation. We propose syndapin and endophilin function either at different stages during SVE or in mechanistically distinct types of SVE.
Characterization of mature rat oligodendrocytes: a proteomic approach
Authors: Dumont Debora , Noben Jean‐Paul , Moreels Marjan , Vanderlocht Joris , Hellings Niels , Vandenabeele Frank , Lambrichts Ivo , Stinissen Piet , Robben Johan
Published: May 2007

Oligodendrocytes are glial cells responsible for the synthesis and maintenance of myelin in the central nervous system (CNS). Oligodendrocytes are vulnerable to damage occurring in a variety of neurological diseases. Understanding oligodendrocyte biology is crucial for the dissemination of de‐ and remyelination mechanisms. The goal of the present study is the construction of a protein database of mature rat oligodendrocytes. Post‐mitotic oligodendrocytes were isolated from mature Wistar rats and subjected to immunocytochemistry. Proteins were extracted and analyzed by means of two‐dimensional gel electrophoresis and two‐dimensional liquid chromatography, both coupled to mass spectrometry. The combination of the gel‐based and gel‐free approach resulted in confident identification of a total of 200 proteins. A minority of proteins were identified in both proteomic strategies. The identified proteins represent a variety of functional groups, including novel oligodendrocyte proteins. The results of this study emphasize the power of the applied proteomic strategy to study known or to reveal new proteins and to investigate their regulation in oligodendrocytes in different disease models.
The lack of CB1 receptors prevents neuroadapatations of both NMDA and GABAA receptors after chronic ethanol exposure
Authors: Warnault Vincent , Houchi Hakim , Barbier Estelle , Pierrefiche Olivier , Vilpoux Catherine , Ledent Catherine , Daoust Martine , Naassila Mickaël
Published: May 2007

As the contribution of cannabinoid (CB1) receptors in the neuroadaptations following chronic alcohol exposure is unknown, we investigated the neuroadaptations induced by chronic alcohol exposure on both NMDA and GABAA receptors in CB1−/− mice. Our results show that basal levels of hippocampal [3H]MK‐801 ((1)‐5‐methyl‐10,11‐dihydro‐5Hdibenzo[a,d]cyclohepten‐5,10‐imine) binding sites were decreased in CB1−/− mice and that these mice were also less sensitive to the locomotor effects of MK‐801. Basal level of both hippocampal and cerebellar [3H]muscimol binding was lower and sensitivity to the hypothermic effects of diazepam and pentobarbital was increased in CB1−/− mice. GABAAα1, β2, and γ2 and NMDA receptor (NR) 1 and 2B subunit mRNA levels were altered in striatum of CB1−/− mice. Our results also showed that [3H]MK‐801 binding sites were increased in cerebral cortex and hippocampus after chronic ethanol ingestion only in wild‐type mice. Chronic ethanol ingestion did not modify the sensitivity to the locomotor effects of MK‐801 in both genotypes. Similarly, chronic ethanol ingestion reduced the number of [3H]muscimol binding sites in cerebral cortex, but not in cerebellum, only in CB1+/+ mice. We conclude that lifelong deletion of CB1 receptors impairs neuroadaptations of both NMDA and GABAA receptors after chronic ethanol exposure and that the endocannabinoid/CB1 receptor system is involved in alcohol dependence.
Mechanisms of axon guidance: membrane dynamics and axonal transport in semaphorin signalling
Authors: Mann Fanny , Rougon Geneviève
Published: May 2007

The intricate geometry of neuronal networks poses many unique cell‐biological problems regarding the way a growing axon responds to its environment. Several groups of ligand–receptor pairs have been identified to regulate such processes. In this study, we take class 3 semaphorins as an example and review what is known about the intracellular movements of semaphorins throughout neuronal cells, transport support structures and location of release sites. We discuss how their receptor trafficking may contribute to regulate membrane dynamics underlying growth cone motility and the physiological contribution made by class 3 semaphorins‐induced acceleration of axoplasmic transport on neurite development.
An oligodendrocyte enhancer in a phylogenetically conserved intron region of the mammalian myelin gene Opalin
Authors: Aruga Jun , Yoshikawa Fumio , Nozaki Yayoi , Sakaki Yoshiyuki , Toyoda Atsushi , Furuichi Teiichi
Published: May 2007

Opalin is a transmembrane protein detected specifically in mammalian oligodendrocytes. Opalin homologs are found only in mammals and not in the genome sequences of other animal classes. We first determined the nucleotide sequences of Opalin orthologs and their flanking regions derived from four prosimians, a group of primitive primates. A global comparison revealed that an evolutionarily conserved region exists in the first intron of Opalin. When the conserved domain was assayed for its enhancer activity in transgenic mice, oligodendrocyte‐directed expression was observed. In an oligodendroglial cell line, Oli‐neu, the conserved domain showed oligodendrocyte‐directed expression. The conserved domain is composed of eight subdomains, some of which contain binding sites for Myt1 and cAMP‐response element binding protein (CREB). Deletion analysis and cotransfection experiments revealed that the subdomains have critical roles in Opalin gene expression. Over‐expression of Myt1, treatment of the cell with leukemia inhibitory factor (LIF), and cAMP analog (CREB activator) enhanced the expression of endogenous Opalin in Oli‐neu cells and activated the oligodendrocyte enhancer. These results suggest that LIF, cAMP signaling cascades and Myt1 play significant roles in the differentiation of oligodendrocytes through their action on the Opalin oligodendrocyte enhancer.
EAAT4 phosphorylation at the SGK1 consensus site is required for transport modulation by the kinase
Authors: Rajamanickam Jeyaganesh , Palmada Monica , Lang Florian , Boehmer Christoph
Published: May 2007

EAAT4 (SLC1A6) is a Purkinje‐Cell‐specific post‐synaptic excitatory amino acid transporter that plays a major role in clearing synaptic glutamate. EAAT4 abundance and function is known to be modulated by the serum and glucocorticoid inducible kinase (SGK) 1 but the precise mechanism of kinase action has not been defined yet. The present work aims to identify the molecular mechanism of EAAT4 modulation by the kinase. The EAAT4 sequence bears two putative SGK1 consensus sites (at Thr40 and Thr504) at the amino and carboxy terminus that are conserved among species. Expression studies in Xenopus oocytes demonstrated that EAAT4‐mediated [3H] glutamate uptake and cell surface abundance are enhanced by co‐expression of SGK1. Disruption of the SGK1 phosphorylation site at threonine 40 (T40AEAAT4) or of both phosphorylation sites (T40AT504AEAAT4) abrogated the effect of SGK1 on transporter function and expression. SGK1 modulates several transport proteins via inhibition of the ubiquitin ligase Nedd4‐2. Co‐expression of Nedd4‐2 inhibited wild‐type EAAT4 but not the T40AT504AEAAT4 mutant. Besides, RNA interference‐mediated reduction of endogenous Nedd4‐2 (xNedd4‐2) expression increased the activity of the transporter. In conclusion, maximal glutamate transport modulation by SGK1 is accomplished by direct EAAT4 stimulation and to a lesser extent by inhibition of intrinsic Nedd4‐2.
Induction of interleukin‐1β by interleukin‐4 in lipopolysaccharide‐treated mixed glial cultures: microglial‐dependent effects
Authors: Cao Ling , Fei Liang , Chang Tina Ting‐Lan , DeLeo Joyce A.
Published: May 2007

Glial‐secreted proinflammatory mediators are dynamically involved in central nervous system responses to exogenous stimuli such as infection, neurotoxins, and nerve injury. The therapeutic use of anti‐inflammatory agents may reduce certain central nervous system pathology induced by inflammatory responses. We investigated the role of interleukin (IL)‐4 in modulating the production of proinflammatory mediators from lipopolysaccharide‐stimulated mixed glia in vitro. Interestingly, IL‐4 significantly enhanced IL‐1β secretion and did not affect monocyte chemoattractant protein‐1 release, even though IL‐4 considerably inhibited IL‐6, tumor necrosis factor α, and nitric oxide production from rat neonatal mixed glia. Further, IL‐4 exhibited inhibitory effects on IL‐1β production in microglial‐enriched cultures, while significantly increasing IL‐1β production in microglial‐depleted glia. The enhancing effect of IL‐4 on IL‐1β production was found to be inversely correlated with the percentage of microglia present in the mixed glial population. In summary, IL‐4 did not act as a global anti‐inflammatory cytokine and in fact, under certain situations enhanced IL‐1β secretion. We conclude that IL‐4 exerts its anti‐inflammatory effects in a limited and target‐specific manner, which is delicately regulated by the cellular microenvironment. Therefore, precaution should be taken when clinically using IL‐4 to treat diseases manifested by overt inflammatory responses.
Species identification of birds through genetic analysis of naturally shed feathers
Authors: RUDNICK JAMIE A. , KATZNER TODD E. , BRAGIN EVGENY A. , DeWOODY J. ANDREW
Published: May 2007

Genetic analysis of noninvasively collected bird feathers is of growing importance to avian ecology; however, most genetic studies that utilize feathers make no mention of the need to verify their species of origin. While plumage patterns and collection location often are indicative of species identity, broad‐scale feather collections may require definitive species identification prior to analysis. Genetic species identification has been applied to noninvasively collected samples from a wide range of taxa but, to date, these techniques have not been widely used on bird feathers. Here, we develop and test a polymerase chain reaction (PCR)‐based technique for identifying eastern imperial eagle (Aquila heliaca) samples among a vast number of noninvasively collected feathers. Species identification is accomplished by amplifying a fragment of the mitochondrial cytochrome c oxidase I gene, then digesting that fragment with a restriction enzyme. The resulting species‐specific restriction fragment length polymorphisms (RFLPs) are easily visualized by gel electrophoresis. We tested this PCR‐RFLP assay on over 300 individuals that had been genetically identified from noninvasively collected feathers and demonstrated that the assay is both reliable and robust for DNA of low quality and quantity. The genetic methods of species identification used to develop this assay can readily be applied to other bird assemblages, making them particularly relevant to a broad range of future avian research.
Characterization of polymorphic microsatellites in the logrunner, Orthonyx temminckii (Aves: Orthonychidae)
Authors: NICHOLLS JAMES A. , AUSTIN JEREMY J. , PAVLACKY DAVID C. , GREEN DAVID J.
Published: May 2007

We isolated and characterized 10 polymorphic microsatellite loci in the logrunner (Orthonyx temminckii), a rainforest‐dwelling Australian bird. The number of alleles per locus observed within two populations ranged from three to 39, with observed heterozygosities of between 0.12 and 1.00. We demonstrate that these markers are useful for both population‐ and individual‐level analyses.
Melatonin counteracts the loss of agonist‐evoked contraction of aortic rings induced by incubation
Authors: Lartaud Isabelle , Faure Sébastien , Tabellion Aurore , Resende Angela C. , Nadaud Sophie , Bagrel Denyse , Capdeville‐Atkinson Christine , Atkinson Jeffrey
Published: May 2007

Incubation of aortic rings in a culture medium produces phenomena similar to those observed with aging, i.e. oxidative stress and inflammation leading to increased nitric oxide (NO)‐mediated dilation and decreased arterial sensitivity to vasoconstrictor agents. We evaluated whether melatonin protects aortic rings from such a decrease in vasoreactivity. Two concentrations of melatonin were used: 10−8 m, EC50 for vascular MT1–MT2 receptors, and 10−5 m, reported as anti‐oxidant. Anti‐oxidant capacity, inducible nitric oxide synthase (iNOS) expression and isometric contraction of thoracic aorta rings (Wistar rats) evoked by norepinephrine (NE) were assessed. Three days of incubation of aortic rings induced iNOS expression and a fall in NE‐evoked contraction. When melatonin was added to the organ bath, it (10−5 m) increased (+96%, P < 0.05), but did not restore (compared with freshly isolated rings) NE‐evoked contraction. Three days of treatment with melatonin increased (10−8 m, +99%) or restored (10−5 m, +216%) NE‐evoked contraction (compared with freshly isolated rings). The beneficial effects of 10−8 and 10−5 m melatonin on NE‐evoked contraction were abolished in the presence of luzindole (2 × 10−6 m, a melatonin receptor antagonist). The incubation‐induced increase in iNOS expression was reduced following 3 days of melatonin administration (10−8 and 10−5 m). Melatonin (10−5 m) increased catalase activity (6550 ± 256, P < 0.05 vs. nontreated fresh aortic rings 5554 ± 444 nmol min−1 mg protein−1). In conclusion, melatonin counteracts the incubation‐induced loss of agonist‐evoked contraction of aortic rings by a specific receptor‐mediated phenomenon involving iNOS expression; at higher melatonin concentrations, an anti‐oxidant effect is probably also involved.
Allopurinol Dosing in Renal Impairment: Walking the Tightrope Between Adequate Urate Lowering and Adverse Events
Authors: Dalbeth Nicola , Stamp Lisa
Published: May 2007

Allopurinol is the mainstay of urate‐lowering therapy for patients with gout and impaired renal function. Although rare, a life‐threatening hypersensitivity syndrome may occur with this drug. The risk of this allopurinol hypersensitivity syndrome (AHS) is increased in renal impairment. The recognition that AHS may be because of delayed‐type hypersensitivity to oxypurinol, the main metabolite of allopurinol, and that oxypurinol concentrations are frequently elevated in patients with renal impairment prescribed standard doses of allopurinol has led to the widespread adoption of allopurinol‐dosing guidelines. These guidelines advocate allopurinol dose reduction according to creatinine clearance in patients with renal impairment. However, recent studies have challenged the role of these guidelines, suggesting that AHS may occur even at low doses of allopurinol, and that these guidelines lead to under‐treatment of hyperuricemia, a key therapeutic target in gout. Based on current data, we advocate gradual introduction of allopurinol according to current treatment guidelines, with close monitoring of serum uric acid concentrations. In patients with severe disease and persistent hyperuricemia, allopurinol dose escalation above those recommended by the guidelines should be considered, with careful evaluation of the benefits and risks of therapy. Further work is needed to clarify the safety and efficacy of allopurinol dose escalation, particularly in patients with renal impairment.
Influence of bracket design on microbial and periodontal parameters in vivo
Authors: Van Gastel Jan , Quirynen Marc , Teughels Wim , Coucke Wim , Carels Carine
Published: May 2007

Aim: To compare undisturbed plaque formation on teeth bonded with different types of orthodontic brackets with non‐bonded control teeth, via a de novo plaque growth experiment over a 7‐day period.

Material and methods: A randomized controlled trial with split‐mouth design was set up enroling 16 dental students. Within each subject sites with Speed®(S) and GAC®(G), brackets and control sites were followed. Clinical periodontal parameters were recorded at baseline, on days 3 and 7. Microbiological samples were taken from the brackets and the teeth on days 3 and 7.

Results: Both anaerobe and aerobe colony‐forming units (CFU) were significantly higher in S‐sites than in G‐sites (p=0.0002, p=0.02). The shift from aerobic to anaerobic species was observed earlier in S‐sites than in G‐sites. The aerobe/anaerobe CFU ratio was significantly lower in S‐sites than in G‐sites (p=0.01). On day 3, the crevicular fluid flow was significantly higher in S‐sites than in control sites (p=0.01). On day 7, S‐sites and G‐sites showed a significantly higher crevicular flow than control sites (both p<0.0001). More hypertrophy was seen in S‐ than in G‐ and control sites (p=0.05). No significant differences for bleeding on probing were observed.

Conclusion: Bracket design can have a significant impact on bacterial load and on periodontal parameters.
MMP‐2, MMP‐9 and TIMP‐2 gene polymorphisms in Chinese patients with generalized aggressive periodontitis
Authors: Chen Dong , Wang Qi , Ma Zhi‐Wei , Chen Fa‐Ming , Chen Yue , Xie Guang‐Yuan , Wang Qin‐Tao , Wu Zhi‐Fen
Published: May 2007

Background: Aggressive periodontitis (AgP) has a genetic basis. It has been reported that the functional gene polymorphisms of matrix metalloproteinase (MMP)‐2, MMP‐9 and tissue inhibitor of metalloproteinase‐2 (TIMP‐2) alter their expressions in transcriptional level and they are involved in the tissue destruction of periodontitis. The study was carried out to analyse the association of functional polymorphisms in MMP‐2, MMP‐9 and TIMP‐2 with generalized AgP (G‐AgP) in a Chinese population.

Material and Methods: The study population consisted of 79 Chinese patients with G‐AgP and 128 healthy controls. DNA was obtained from oral mucosa swab samples. MMP‐2 genotypes were determined by PCR‐based denaturing high‐performance liquid chromatography analysis while MMP‐9 and TIMP‐2 genotypes were identified by a PCR‐based restriction fragment length polymorphism. χ2 test after Yates' correction was used to investigate the possible association of the genotypes with the G‐AgP.

Results: Although gene polymorphisms for MMP‐2 and MMP‐9 did not show any association with the G‐AgP, the analysis of the TIMP‐2 −418G to C gene polymorphism revealed significant differences between the patients and controls. Compared with controls, a significant increasing trend of TIMP‐2 −418C carrier in the G‐AgP patients occurred (p=0.013).

Conclusion: It is suggested that the TIMP2 −418G to C gene polymorphism is associated with G‐AgP in the Chinese subjects.
The association between embrasure morphology and central papilla recession
Authors: Chang Li‐Ching
Published: May 2007

Objective: To discover the association between embrasure morphology and central papilla recession.

Material and Methods: The central papilla was visually assessed in 330 adults using standardized periapical radiographs of the maxillary central incisors. The following vertical distances were measured: papilla recession [i.e., the distance from the papilla tip (PT) to the contact point (CP)], bone crest (BC) to contact point (BC–CP), proximal cementoenamel junction (pCEJ) to contact point (pCEJ–CP), and papilla height (PH). The horizontal distance measured was the inter‐dental width. Subjects were divided into four groups according to inter‐dental width and pCEJ‐CP distance, respectively: narrow‐long, narrow‐short, wide‐long, and wide‐short.

Results: A statistically positive relationship was evident between central papilla recession and age, and a statistically negative relationship was evident between age and PH in all study groups.

Conclusions: Central papilla recession as a result of ageing is most frequently associated with a wide inter‐dental width and long pCEJ–CP distance. However, other factors affect the likelihood of the presence of the inter‐dental papilla, and further study of the interaction among these factors is warranted.
Development of an open case‐based decision‐support system for diagnosis in oral pathology
Authors: Borra R. C. , Andrade P. M. , Corrêa L. , Novelli M. D.
Published: May 2007

Background:  Making diagnoses in oral pathology are often difficult and confusing in dental practice, especially for the less‐experienced dental student. One of the most promising areas in bioinformatics is computer‐aided diagnosis, where a computer system is capable of imitating human reasoning ability and provides diagnoses with an accuracy approaching that of expert professionals. This type of system could be an alternative tool for assisting dental students to overcome the difficulties of the oral pathology learning process. This could allow students to define variables and information, important to improving the decision‐making performance. However, no current open data management system has been integrated with an artificial intelligence system in a user‐friendly environment. Such a system could also be used as an education tool to help students perform diagnoses. The aim of the present study was to develop and test an open case‐based decision‐support system.

Methods:  An open decision‐support system based on Bayes’ theorem connected to a relational database was developed using the C++ programming language. The software was tested in the computerisation of a surgical pathology service and in simulating the diagnosis of 43 known cases of oral bone disease. The simulation was performed after the system was initially filled with data from 401 cases of oral bone disease.

Results:  The system allowed the authors to construct and to manage a pathology database, and to simulate diagnoses using the variables from the database.

Conclusion:  Combining a relational database and an open decision‐support system in the same user‐friendly environment proved effective in simulating diagnoses based on information from an updated database.
Pinealectomy reduces hepatic and muscular glycogen content and attenuates aerobic power adaptability in trained rats
Authors: Borges‐Silva Cristina das Neves , Takada Julie , Alonso‐Vale Maria Isabel Cardoso , Peres Sidney B. , Fonseca‐Alaniz Miriam H. , Andreotti Sandra , Cipolla‐Neto Jose , Pithon‐Curi Tania C. , Lima Fabio Bessa
Published: May 2007

Abstract:  The current study emphasizes the crucial role of the pineal gland on the effects of chronic training in different tissues focusing on carbohydrate metabolism. We investigated the maximal oxygen uptake (aerobic power), muscle and liver glycogen content, and also the enzymes involved in the carbohydrate metabolism of rat adipose tissue. Pinealectomized and sham‐operated adult male Wistar rats were distributed into four groups: pinealectomized (PINX) untrained, pinealectomized trained, control untrained and control trained. The maximal oxygen uptake capability was assayed before and after the training protocol by indirect open circuit calorimetry. The rats were killed after 8 wk of training. Blood samples were collected for glucose and insulin determinations. The glycogen content was assayed in the liver and muscle. Maximal activities of epididymal adipose tissue enzymes (hexokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase and malic enzyme) as well as adipocyte size were determined. The exercise training in control animals promoted an increase in the aerobic power and in liver glycogen content but caused a reduction in the malic enzyme activity in adipose tissue. However, PINX trained animals, in contrast to trained controls, showed a decrease in the aerobic power and in liver and muscle glycogen content, as well as an increase in the activity of the adipocyte enzymes involved in carbohydrate metabolism. In conclusion, these data show that the pineal gland integrity is necessary for the homeostatic control of energy metabolism among adipose, muscle and hepatic tissues. The pinealectomized animals showed alterations in adaptive responses of the maximal oxygen uptake to training. Therefore, the pineal gland must be considered an influential participant in the complex adaptation to exercise and is involved in the improvement of endurance capacity.
Dynamic Pipe Stresses During Water Hammer: A Finite Element Approach
Authors: Leishear Robert A.
Published: May 2007

Water hammer is defined as a sudden increase in pipe pressure, which results in pressure waves that travel along the pipe at sonic velocities. In the wake of the pressure wave, dynamic stresses are created in the pipe wall, which contribute to pipe failures. A finite element analysis computer program was used to determine the three-dimensional dynamic stresses that result from pipe wall vibration at a distance from the end of a pipe, during a water-hammer event. The analysis was used to model a moving shock wave in a pipe, using a step pressure wave. Both aluminum and steel were modeled for an 8 NPS pipe, using ABAQUS®. For either material, the maximum stress was seen to be equal when damping was neglected. At the time the maximum stress occurred, the hoop stress was equivalent to twice the stress that would be expected if an equivalent static stress was applied to the inner wall of the pipe. Also, the radial stress doubled the magnitude of the applied pressure.