bluuebunny/crossref_metadata_2025 huggingface dataset:
Receptor Activity Modifying Protein 2 Distribution in the Rat Central Nervous System and Regulation by Changes in Blood Pressure
Authors: Stachniak T. J. E. , Krukoff T. L.
Published: August 2003

The neuropeptide, adrenomedullin, acts in the central nervous system (CNS) to regulate blood pressure, at least partly through an adrenomedullin receptor which is composed of receptor activity modifying protein 2 (RAMP‐2) and calcitonin receptor‐like receptor (CRLR). We used in situ hybridization to localize RAMP‐2 mRNA throughout the brain, and we performed reverse transcription‐polymerase chain reaction to detect CRLR mRNA in the brain. We found that RAMP‐2 mRNA is expressed in numerous areas, including autonomic nuclei such as the paraventricular, supraoptic, arcuate and ventromedial nuclei, as well as the nucleus of the solitary tract (NTS), area postrema and dorsal motor nucleus of the vagus. Many regions expressing RAMP‐2 mRNA also express low levels of CRLR mRNA. We examined changes in the mRNA expression of RAMP‐2 and preproadrenomedullin in the brain in response to blood pressure manipulations. Rats received intravenous infusions of nitroprusside or phenylephrine to decrease or increase blood pressure, respectively. Decreased blood pressure elicited an increase in RAMP‐2 mRNA expression in the NTS and a decrease in preproadrenomedullin mRNA expression in the paraventricular nucleus (PVN). Increased blood pressure elicited a decrease in RAMP‐2 mRNA expression in the PVN and NTS. The CNS distribution and modulation of adrenomedullin signalling components by changes in blood pressure provide anatomical and physiological evidence for a homeostatic role for adrenomedullin in the brain.
Evidence That Gonadotropin‐Releasing Hormone II Is Not a Physiological Regulator of Gonadotropin Secretion in Mammals
Authors: Gault P. M. , Maudsley S. , Lincoln G. A.
Published: August 2003

Gonadotropin‐releasing hormone (GnRH)‐II stimulates luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) secretion when administered at high doses in mammals, and this effect has been assumed to be mediated through the GnRH‐II receptor expressed on gonadotropes. This study used two selective GnRH‐I receptor antagonists to test the alternative hypothesis that GnRH‐II acts through the GnRH‐I receptor to elicit gonadotropin secretion. The antagonist, antide, was used to characterize the receptor‐relay because it was a pure antagonist in vitro based on inositol phosphate responses in COS‐7 cells transfected with either mammalian GnRH‐I and GnRH‐II receptors and, in vivo, potently antagonized the gonadotropin‐releasing effect of a single injection of 250 ng GnRH‐I in our sexually inactive sheep model. In a series of studies in sheep, antide (i) blocked the acute LH response to a single injection of GnRH‐II (20 µg antide: 10 µg GnRH‐II); (ii) blocked both the acute, pulsatile LH response and the FSH priming response to 2‐hourly injections of GnRH‐II over 36 h (100 µg antide/8 h: 4 µg GnRH‐II/2 h); and (iii) chronically blocked both the pulsatile LH response and the marked FSH priming response to 4‐hourly injections of GnRH‐II over 10 days (75 µg antide/8 h: 4 µg GnRH‐II/4 h). In two final experiments, the GnRH‐I antagonist 135‐18, shown previously to agonize the mammalian GnRH‐II receptor, blocked the gonadotropin‐releasing effects of GnRH‐I (250 ng) but failed to elicit an LH response when given alone, and simultaneous administration of GnRH‐II (250 ng) failed to alter the LH‐releasing effect of GnRH‐I (50–500 ng). These data thus support our hypothesis. Based on additional literature, it is unlikely that the GnRH‐II decapeptide is a native regulator of the gonadotrope in mammals.
Palatable Solutions During Paradoxical Sleep Deprivation: Reduction of Hypothalamic‐Pituitary‐Adrenal Axis Activity and Lack of Effect on Energy Imbalance
Authors: Suchecki D. , Antunes J. , Tufik S.
Published: August 2003

Paradoxical sleep deprivation (PSD) induces increased energy expenditure in rats, insofar as rats eat more but loose weight throughout the deprivation period. In the present study, rats were offered water, saccharin or sucrose to drink during the deprivation period, since it has been proposed that carbohydrates reduce the hypothalamic‐pituitary‐adrenal (HPA) axis response to stress. Rats were submitted to the flower pot technique for 96 h. During the PSD period, they were weighed daily and food and fluid intake was assessed twice a day. At the end of the PSD period, rats were killed and plasma concentrations of glucose, adrenocorticotropic hormone (ACTH) and corticosterone were assayed. Compared to their control counterparts, all paradoxical sleep‐deprived rats consumed more food, but lost weight. Paradoxical sleep‐deprived rats given sucrose drank more than their control counterparts (especially in the light phase of the light/dark cycle). Paradoxical sleep‐deprived rats showed increased food intake during all periods throughout the experiment, with peak intake during the dark phase and nadir during the light phase of the light/dark cycle. All paradoxical sleep‐deprived rats showed lower glucose plasma levels than control rats and increased relative adrenal weight. However, when given saccharin or sucrose, paradoxical sleep‐deprived rats showed lower concentrations of ACTH and corticosterone than their water‐provided counterparts, indicating that palatable fluids were capable of lowering HPA axis activation produced by PSD. The fact that PSD induced energy imbalance regardless of the relative attenuation of the HPA axis activity produced by saccharin or sucrose suggests that the HPA axis may play only a secondary role in this phenomenon, and that other mechanisms may account for this effect. The data also suggest that supply of palatable fluids can be an additional modification to reduce the stress of the flower pot method.
Early Expression of Chicken Gonadotropin‐Releasing Hormone‐1 in the Developing Chick
Authors: Witkin J. W. , Dao D. , Livne I. , Dunn I. C. , Zhou X. L. , Pula K. , Silverman A. J.
Published: August 2003

Gonadotropin‐releasing hormone (GnRH), which is essential for reproductive function, is made by neurones that migrate from the nasal region into the brain during early embryonic development. This migration begins in chick when the olfactory pit is formed. This is approximately the time that GnRH neurones can be detected immunocytochemically. The present study investigated (i) how early in development the GnRH gene is expressed and (ii) the sites of its expression. Accordingly, reverse transcriptase‐polymerase chain reaction (PCR) and in situ hybridization were performed on chick embryos before gastrulation up until the stage by which GnRH neurones have begun to migrate into the central nervous system. Primers were made to the 5′‐ and 3′‐UTR region of the message for cGnRH‐I, the form of the peptide that is essential for reproductive function in the chicken. PCR product was found in all stages and the sequences of products from all stages were identical. Thus, the GnRH gene is expressed continuously throughout embryonic development. In situ hybridization with a digoxygenin labelled riboprobe revealed staining along the primitive streak immediately before gastrulation. In later stages, cGnRH‐I gene expression was seen in association with the anterior neural ridge. The expression was subsequently restricted to a narrow, clearly defined region, which is associated with the presumptive nasal cavity and olfactory placode. Later, GnRH neurones could be seen in their migratory routes by both in situ hybridization and immunocytochemistry. Expression of the GnRH gene has been described in preimplantation stages in mammals and there is evidence that the neuropeptide plays a role in formation and maintenance of the placenta. What role (if any) it may play in early avian development remains unknown. The demonstration of sites of GnRH expression during the early period of neurulation suggests that GnRH neurones arise before olfactory placode formation.
µ‐Opioid Receptor Modulates Peptide Release From Rat Neurohypophysial Terminals By Inhibiting Ca2+ Influx
Authors: Ortiz‐Miranda S. I. , Dayanithi G. , Coccia V. , Custer E. E. , Alphandery S. , Mazuc E. , Treistman S. , Lemos J. R.
Published: August 2003

The activation of opioid receptors in neurones of the central nervous system leads to a variety of effects including the modulation of diuresis and parturition, processes that are directly controlled by the hypothalamic–neurohypophysial system (HNS). The effects of µ‐opioid receptor activation on peptide release, voltage‐gated Ca2+ currents and intracellular calcium levels ([Ca2+]i) were studied in isolated nerve terminals of the HNS. The µ‐receptor agonist, DAMGO ([d‐Ala2,N‐Me‐Phe4,Gly5‐ol]‐enkephalin) inhibited high K+‐induced peptide release in a dose‐dependent manner, with oxytocin release being more sensitive to block than vasopressin release at all concentrations tested. The addition of the µ‐receptor antagonist CTOP (d‐Phe‐Cys‐Tyr‐d‐Trp‐Orn‐Thr‐Pen‐Thr amide) was able to overcome the inhibitory effects of DAMGO. By contrast to previous results, voltage‐gated Ca2+ currents were sensitive to blockage by DAMGO and this inhibition was also prevented by CTOP. Furthermore, [Ca2+]i measurements with Fura‐2 corroborated the inhibition by DAMGO of calcium entry and its reversal by the µ‐receptor antagonist in these nerve terminals. Thus, the decrease in neuropeptide release, particularly for oxytocin, induced by the activation of µ‐opioid receptors in neurohypophysial terminals is mediated, at least in part, by a corresponding decrease in Ca2+ entry due to the inhibition of voltage‐gated Ca2+ channels.
Epidermal (infundibular) and dermoid cysts in the dorsal midline of a three‐year‐old thoroughbred‐cross gelding
Authors: Hillyer Lynn L. , Jackson Anna P. , Quinn Greg C. , Day Michael J.
Published: August 2003

Abstract Epidermal (infundibular) and dermoid cysts are unusual in the horse in contrast with other species. The diagnosis and treatment of six lesions in the dorsal midline of a three‐year‐old Thoroughbred‐cross gelding is described. The lesions were believed to be congenital and presented asymptomatically but required attention because five of them were in the saddle region, thus preventing ridden exercise. Under general anaesthesia, the cysts were excised and subsequently examined histologically. The horse recovered uneventfully. This report is novel in that such midline cysts have not previously been described outside Australia and North America.
Tritium planigraphy comparative structural study of tobacco mosaic virus and its mutant with altered host specificity
Authors: Dobrov Eugenie N. , Badun Gennadii A. , Lukashina Elena V. , Fedorova Nataliya V. , Ksenofontov Alexander L. , Fedoseev Vladimir M. , Baratova Ludmila A.
Published: August 2003

Spatial organization of wild‐type (strain U1) tobacco mosaic virus (TMV) and of the temperature‐sensitive TMV ts21–66 mutant was compared by tritium planigraphy. The ts21–66 mutant contains two substitutions in the coat protein (Ile21→Thr and Asp66→Gly) and, in contrast with U1, induces a hypersensitive response (formation of necroses) on the leaves of plants bearing a host resistance gene N′ (for example Nicotiana sylvestris); TMV U1 induces systemic infection (mosaic) on the leaves of such plants. Tritium distribution along the coat protein (CP) polypeptide chain was determined after labelling of both isolated CP preparations and intact virions. In the case of the isolated low‐order (3–4S) CP aggregates no reliable differences in tritium distribution between U1 and ts21–66 were found. But in labelling of the intact virions a significant difference between the wild‐type and mutant CPs was observed: the N‐terminal region of ts21–66 CP incorporated half the amount of tritium than the corresponding region of U1 CP. This means that in U1 virions the CP N‐terminal segment is more exposed on the virion surface than in ts21–66 virions. The possibility of direct participation of the N‐terminal tail of U1 CP subunits in the process of the N′ hypersensitive response suppression is discussed.
Diversity, taxonomy and evolution of medium‐chain dehydrogenase/reductase superfamily
Authors: Riveros‐Rosas Héctor , Julián‐Sánchez Adriana , Villalobos‐Molina Rafael , Pardo Juan Pablo , Piña Enrique
Published: August 2003

A comprehensive, structural and functional, in silico analysis of the medium‐chain dehydrogenase/reductase (MDR) superfamily, including 583 proteins, was carried out by use of extensive database mining and the blastp program in an iterative manner to identify all known members of the superfamily. Based on phylogenetic, sequence, and functional similarities, the protein members of the MDR superfamily were classified into three different taxonomic categories: (a) subfamilies, consisting of a closed group containing a set of ideally orthologous proteins that perform the same function; (b) families, each comprising a cluster of monophyletic subfamilies that possess significant sequence identity among them and might share or not common substrates or mechanisms of reaction; and (c) macrofamilies, each comprising a cluster of monophyletic protein families with protein members from the three domains of life, which includes at least one subfamily member that displays activity related to a very ancient metabolic pathway. In this context, a superfamily is a group of homologous protein families (and/or macrofamilies) with monophyletic origin that shares at least a barely detectable sequence similarity, but showing the same 3D fold.

The MDR superfamily encloses three macrofamilies, with eight families and 49 subfamilies. These subfamilies exhibit great functional diversity including noncatalytic members with different subcellular, phylogenetic, and species distributions. This results from constant enzymogenesis and proteinogenesis within each kingdom, and highlights the huge plasticity that MDR superfamily members possess. Thus, through evolution a great number of taxa‐specific new functions were acquired by MDRs. The generation of new functions fulfilled by proteins, can be considered as the essence of protein evolution. The mechanisms of protein evolution inside MDR are not constrained to conserve substrate specificity and/or chemistry of catalysis. In consequence, MDR functional diversity is more complex than sequence diversity.

MDR is a very ancient protein superfamily that existed in the last universal common ancestor. It had at least two (and probably three) different ancestral activities related to formaldehyde metabolism and alcoholic fermentation. Eukaryotic members of this superfamily are more related to bacterial than to archaeal members; horizontal gene transfer among the domains of life appears to be a rare event in modern organisms.
Multiple enzymic activities of human milk lactoferrin
Authors: Kanyshkova Tat'yana G. , Babina Svetlana E. , Semenov Dmitry V. , Isaeva Natal'ya , Vlassov Alexander V. , Neustroev Kirill N. , Kul'minskaya Anna A. , Buneva Valentina N. , Nevinsky Georgy A.
Published: August 2003

Lactoferrin (LF) is a Fe3+‐binding glycoprotein, first recognized in milk and then in other human epithelial secretions and barrier fluids. Many different functions have been attributed to LF, including protection from iron‐induced lipid peroxidation, immunomodulation and cell growth regulation, DNA binding, and transcriptional activation. Its physiological role is still unclear, but it has been suggested to be responsible for primary defense against microbial and viral infection. We present evidence that different subfractions of purified human milk LF possess five different enzyme activities: DNase, RNase, ATPase, phosphatase, and malto‐oligosaccharide hydrolysis. LF is the predominant source of these activities in human milk. Some of its catalytically active subfractions are cytotoxic and induce apoptosis. The discovery that LF possesses these activities may help to elucidate its many physiological functions, including its protective role against microbial and viral infection.
Human intrinsic factor expressed in the plant Arabidopsis thaliana
Authors: Fedosov Sergey N. , Laursen Niels B. , Nexø Ebba , Moestrup Søren K. , Petersen Torben E. , Jensen Erik Ø. , Berglund Lars
Published: August 2003

Intrinsic factor (IF) is the gastric protein that promotes the intestinal uptake of vitamin B12. Gastric IF from animal sources is used in diagnostic tests and in vitamin pills. However, administration of animal IF to humans becomes disadvantageous because of possible pathogenic transmission and contamination by other B12 binders. We tested the use of recombinant plants for large‐scale production of pathogen‐free human recombinant IF. Human IF was successfully expressed in the recombinant plant Arabidopsis thaliana. Extract from fresh plants possessed high B12‐binding capacity corresponding to 70 mg IF per 1 kg wet weight. The dried plants still retained 60% of the IF activity. The purified IF preparation consisted of a 50‐kDa glycosylated protein with the N‐terminal sequence of mature IF. Approximately one‐third of the protein was cleaved at the internal site …PSNP↓GPGP. The key properties of the preparation obtained were identical to those of native IF: the binding curves of vitamin B12 to recombinant IF and gastric IF were the same, as were those for a B12 analogue cobinamide, which binds to IF with low affinity. The absorbance spectra of the vitamin bound to recombinant IF and gastric IF were alike, as was the interaction of recombinant and native IF with the specific receptor cubilin. The data presented show that recombinant plants have a great potential as a large‐scale source of human IF for analytical and therapeutic purposes.
Evidence for proteasome dysfunction in cytotoxicity mediated by anti‐Ras intracellular antibodies
Authors: Cardinale Alessio , Filesi Ilaria , Mattei Sonia , Biocca Silvia
Published: August 2003

Anti‐Ras intracellular antibodies inhibit cell proliferation in vivo by sequestering the antigen and diverting it from its physiological location [Lener, M., Horn, I. R., Cardinale, A., Messina, S., Nielsen, U.B., Rybak, S.M., Hoogenboom, H.R., Cattaneo, A., Biocca, S. (2000) Eur. J. Biochem.267, 1196–1205]. Here we demonstrate that strongly aggregating single‐chain antibody fragments (scFv), binding to Ras, induce apoptosis, and this effect is strictly related to the antibody‐mediated aggregation of p21Ras. Proteasomes are quickly recruited to the newly formed aggregates, and their activity is strongly inhibited. This leads to the formation of aggresome‐like structures, which become evident in the vast majority of apoptotic cells. A combination of anti‐Ras scFv fragments with a nontoxic concentration of the proteasome inhibitor, lactacystin, markedly increases proteasome dysfunction and apoptosis. The dominant‐negative H‐ras (N17‐H‐ras), which is mostly soluble and does not induce aggresome formation or inhibit proteasome activity, only affects cell viability slightly. Together, these observations suggest a mechanism linking antibody‐mediated Ras aggregation, impairment of the ubiquitin–proteasome system, and cytotoxicity.
Identification of sodium salicylate as an hsp inducer using a simple screening system for stress response modulators in mammalian cells
Authors: Ishihara Keiichi , Horiguchi Kenji , Yamagishi Nobuyuki , Hatayama Takumi
Published: August 2003

As heat shock proteins (Hsps) are involved in protecting cells and also in the pathophysiology of diseases such as inflammation, cancer and neurodegenerative disorders, modulators of Hsp expression in mammalian cells would seem to be useful for the treatment of various diseases. In this study, we isolated mammalian cell lines for screening of Hsp modulators; mouse C3H10T1/2 cells stably transfected with a plasmid containing the mouse Hsp105 or human Hsp70B promoter upstream of a luciferase or β‐galactosidase reporter gene, respectively. Using these cells, we examined the effect of sodium salicylate (SA), which may induce the transcription of hsp genes, on stress response in mammalian cells. When these cells were treated with SA for 1 h at 37 °C, both promoter activities were up‐regulated by SA at concentrations of more than 45 mm. The activation of heat shock factor and the subsequent accumulation of Hsp105α and Hsp70 were detected in cells treated with SA at concentrations of more than 20 and 45 mm, respectively. Furthermore, SA induced resistance against a subsequent lethal stress. These findings suggested that SA is a potent hsp inducer, and may be used to protect cells against deleterious stressors.
Cause of mortality in insects under severe stress
Authors: Matsumoto Hitoshi , Tanaka Kohjiro , Noguchi Hirofumi , Hayakawa Yoichi
Published: August 2003

Mortality in the host armyworm larvae Pseudaletia separata parasitized by the parasitic wasp Cotesia kariyai was dramatically increased when they were simultaneously infected by the entomopathogen Serratia marcescens. Previous studies have shown that this strong insecticidal effect is due to a metalloprotease‐like insecticide (MPLI) released from S. marcescens enterobacter. This study was conducted to elucidate the exact cause of the mortality resulting from MPLI. Injection of MPLI caused a sharp increase in hemolymph dopamine concentration followed by elevated levels of brain dopamine in armyworm larvae. [3H]Dopamine injected into the hemocoel, was incorporated into the brains of MPLI‐injected larvae to a level eight times greater than in BSA‐injected control larvae. Transmission electron microscopy showed an obvious decrease in thickness and density of the brain sheath in insects injected with MPLI. This was probably due to the MPLI‐induced elevation of hemocyte metalloprotease activities. Further, electron microscopic and TUNEL staining analyses showed a significant increase in apoptotic cells in the brain 12 h after the injection. Injection of 3‐iodotyrosine (a tyrosine hydroxylase inhibitor) before MPLI completely prevented the increase in hemolymph dopamine in test larvae and their following death. From these observations, we conclude that MPLI‐injected larvae may have suffered mortal damage through increased apoptosis of brain cells caused by an influx of dopamine from the hemolymph.
Coherently precessing spatially inhomogeneous structures of half magnetization in the B phase of superfluid He3
Authors: Mikeladze S. , Suramlishvili N.
Published: August 2003

Spatially inhomogeneous coherently precessing structures of half magnetization in superfluid He3-B are investigated in the presence of small nonuniformities of a high external magnetic field. It is shown that, depending on the degree of nonuniformity of the field, both two-domain and three-domain coherently precessing structures can exist.
Anisotropic magnetoresistive and magnetic properties of La0.5Sr0.5CoO3−δ film
Authors: Belevtsev B. I. , Krasovitsky V. B. , Panfilov A. S. , Chukanova I. N.
Published: August 2003

The magnetic and transport properties of a La0.5Sr0.5CoO3−δ film grown on a LaAlO3 substrate by pulsed-laser deposition are studied. The properties are found to be influenced by the magnetic anisotropy and inhomogeneity. Magnetoresistance anisotropy is determined by the shape anisotropy of the magnetization and the strain-induced magnetic anisotropy due to the film–substrate lattice interaction. Indications of the temperature-driven spin reorientation transition from an out-of-plane ordered state at low temperatures to an in-plane ordered state at high temperatures as a result of competition between the aforementioned sources of magnetic anisotropy are found.
Superradiance of J-aggregates: correspondence between an infinite disordered chain and a regular finite chain
Authors: Ratner M. A.
Published: August 2003

The radiative decay of excitons in a slightly disordered molecular chain is studied. The degree of disorder dictates the radius of the excitonic state which determines the enhancement of the decay rate Γ (superradiance). Γ is calculated as a function of the degree of disorder and the temperature and compared with that of a regular chain whose length N determines the excitonic radius. A value of N that gives essentially the same decay rate as a function of the temperature is found for every degree of disorder.
Combined atomic force microscope and electron-beam lithography used for the fabrication of variable-coupling quantum dots
Authors: Rogge M. C. , Fühner C. , Keyser U. F. , Haug R. J. , Bichler M. , Abstreiter G. , Wegscheider W.
Published: August 2003

We have combined direct nanofabrication by local anodic oxidation with conventional electron-beam lithography to produce a parallel double quantum dot based on a GaAs/AlGaAs heterostructure. The combination of both nanolithography methods allows fabrication of robust in-plane gates and Cr/Au top-gate electrodes on the same device for optimal controllability. This is illustrated by the tunability of the interdot coupling in our device. We describe our fabrication and alignment scheme in detail and demonstrate the tunability in low-temperature transport measurements.
The enhanced and optimal piezoelectric coefficients in single crystalline barium titanate with engineered domain configurations
Authors: Liu Dan , Li JiangYu
Published: August 2003

In this letter, we report a micromechanical analysis to explain the enhanced piezoelectric coefficients in ferroelectric single crystals poled along a nonpolar axis, where the coexistence of several variants leads to a complicated domain configuration. The engineered domain configuration in the crystal is constructed first using energy minimization approach, and the effective moduli of single crystal with engineered domain configuration is then determined using homogenization theory. Following this procedure, we calculate the effective electromechanical moduli of tetragonal barium titanate poled along [111] direction, where the piezoelectric coefficient d33 is found to be 70% higher than those poled along [001], consistent with experimental observation. Piezoelectric coefficient d32 is also found to be 114% higher. In addition, we notice that poling along [111] direction does not lead to the optimal domain configuration, since barium titanate poled along [110] direction has much higher d32 and d33. The analysis reveals that much higher electromechanical coupling can be obtained in ferroelectric crystals with engineered domain configurations, and offers insight on the design and optimization of ferroelectrics for enhanced functional properties.
Direct observation of microtubule dynamics at kinetochores in Xenopus extract spindles
Authors: Maddox Paul , Straight Aaron , Coughlin Peg , Mitchison Timothy J. , Salmon Edward D.
Published: August 2003

Microtubule plus ends dynamically attach to kinetochores on mitotic chromosomes. We directly imaged this dynamic interface using high resolution fluorescent speckle microscopy and direct labeling of kinetochores in Xenopus extract spindles. During metaphase, kinetochores were stationary and under tension while plus end polymerization and poleward microtubule flux (flux) occurred at velocities varying from 1.5–2.5 μm/min. Because kinetochore microtubules polymerize at metaphase kinetochores, the primary source of kinetochore tension must be the spindle forces that produce flux and not a kinetochore-based mechanism. We infer that the kinetochore resists translocation of kinetochore microtubules through their attachment sites, and that the polymerization state of the kinetochore acts a “slip-clutch” mechanism that prevents detachment at high tension. At anaphase onset, kinetochores switched to depolymerization of microtubule plus ends, resulting in chromosome-to-pole rates transiently greater than flux. Kinetochores switched from persistent depolymerization to persistent polymerization and back again during anaphase, bistability exhibited by kinetochores in vertebrate tissue cells. These results provide the most complete description of spindle microtubule poleward flux to date, with important implications for the microtubule–kinetochore interface and for how flux regulates kinetochore function.
Local ERM activation and dynamic growth cones at Schwann cell tips implicated in efficient formation of nodes of Ranvier
Authors: Gatto Cheryl L. , Walker Barbara J. , Lambert Stephen
Published: August 2003

Nodes of Ranvier are specialized, highly polarized axonal domains crucial to the propagation of saltatory action potentials. In the peripheral nervous system, axo–glial cell contacts have been implicated in Schwann cell (SC) differentiation and formation of the nodes of Ranvier. SC microvilli establish axonal contact at mature nodes, and their components have been observed to localize early to sites of developing nodes. However, a role for these contacts in node formation remains controversial.

Using a myelinating explant culture system, we have observed that SCs reorganize and polarize microvillar components, such as the ezrin-binding phosphoprotein 50 kD/regulatory cofactor of the sodium-hydrogen exchanger isoform 3 (NHERF-1), actin, and the activated ezrin, radixin, and moesin family proteins before myelination in response to inductive signals. These components are targeted to the SC distal tips where live cell imaging reveals novel, dynamic growth cone–like behavior. Furthermore, localized activation of the Rho signaling pathway at SC tips gives rise to these microvillar component–enriched “caps” and influences the efficiency of node formation.
After Hrs with HIV
Authors: Amara Ali , Littman Dan R.
Published: August 2003

To efficiently bud off from infected cells, HIV and other enveloped viruses hijack the host cellular machinery that is normally involved in vacuolar protein sorting and multivesicular body (MVB) biogenesis. The HIV Gag protein mimics hepatocyte growth factor–regulated tyrosine kinase substrate (Hrs), a modular adaptor protein that links membrane cargo recognition to its degradation after delivery to MVBs. In contrast to T cells, where HIV budding occurs at the plasma membrane, virus buds into vacuoles of macrophages, a process that may facilitate its spread within the infected host.
The Neurotrophins Nerve Growth Factor, Brain-derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4 Are Survival and Activation Factors for Eosinophils in Patients with Allergic Bronchial Asthma
Authors: Nassenstein Christina , Braun Armin , Erpenbeck Veit Johannes , Lommatzsch Marek , Schmidt Stephanie , Krug Norbert , Luttmann Werner , Renz Harald , Virchow Johann Christian
Published: August 2003

Neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and NT-4) have been observed in elevated concentrations in allergic diseases. Neurotrophin levels are up-regulated endobronchially after allergen challenge. This coincides with an influx of activated eosinophils into the bronchial lumen. These eosinophils have an increased viability and CD69 expression 18 h after segmental allergen provocation (SAP) which is not present in peripheral blood. To investigate whether these observations are related we studied the influence of neurotrophins on eosinophil function in allergic asthma.

Incubation with NGF, BDNF, NT-3, or NT-4 caused a significant increase in the viability and CD69 expression of isolated eosinophils from bronchoalveolar lavage fluid (BALF) but not from peripheral blood, suggesting a unique sensitivity of endobronchial eosinophils to neurotrophins. To elucidate the underlying mechanisms expression of the neurotrophin receptors p75NTR, trkA, trkB, and trkC on eosinophils was analyzed by RT-PCR and immunocytology. After SAP expression of all neurotrophin receptors was markedly elevated on eosinophils from BALF. Our findings suggest that neurotrophin-mediated activation of bronchial eosinophils might play a role in the regulation of eosinophilic inflammation in allergic asthma.
CSF-induced and HIV-1–mediated Distinct Regulation of Hck and C/EBPβ Represent a Heterogeneous Susceptibility of Monocyte-derived Macrophages to M-tropic HIV-1 Infection
Authors: Komuro Iwao , Yokota Yasuko , Yasuda Sachiko , Iwamoto Aikichi , Kagawa Kiyoko S.
Published: August 2003

Granulocyte/macrophage colony-stimulating factor (GM-CSF)–induced monocyte-derived macrophages (GM-MΦ) are permissive to M-tropic HIV-1 entry, but inhibit viral replication at posttranscriptional and translational levels, whereas M-CSF-induced macrophages (M-MΦ) produce a large amount of HIV-1. M-MΦ express a high level of Hck and a large isoform of C/EBPβ, and HIV-1 infection increases the expression of Hck but not of C/EBPβ. GM-MΦ express a high level of C/EBPβ and a low level of Hck, and HIV-1 infection drastically increases the expression of a short isoform of C/EBPβ but decreases that of Hck.

Treatment of M-MΦ with antisense oligonucleotide for Hck (AS-Hck) not only suppresses the expression of Hck, but also stimulates the induction of the short isoform of C/EBPβ and inhibits the viral replication. Treatment of GM-MΦ with a moderate amount of AS-C/EBPβ not only inhibits the expression of the small isoform of C/EBPβ preferentially, but also stimulates the induction of Hck and stimulates the virus production at a high rate. These results suggest that CSF-induced and HIV-1–mediated distinct regulation of Hck and small isoform of C/EBPβ represent the heterogeneous susceptibility of tissue MΦ to HIV-1 infection, and the regulation of Hck and C/EBPβ are closely related and these two molecules affect one another.
VEGF164-mediated Inflammation Is Required for Pathological, but Not Physiological, Ischemia-induced Retinal Neovascularization
Authors: Ishida Susumu , Usui Tomohiko , Yamashiro Kenji , Kaji Yuichi , Amano Shiro , Ogura Yuichiro , Hida Tetsuo , Oguchi Yoshihisa , Ambati Jayakrishna , Miller Joan W. , Gragoudas Evangelos S. , Ng Yin-Shan , D'Amore Patricia A. , Shima David T. , Adamis Anthony P.
Published: August 2003

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF164 increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF164-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF164-deficient (VEGF120/188) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF+/+) controls. In contrast, administration of a VEGFR-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte–mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF164 selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined.
Normal Thymocyte Negative Selection in TRAIL-deficient Mice
Authors: Cretney Erika , Uldrich Adam P. , Berzins Stuart P. , Strasser Andreas , Godfrey Dale I. , Smyth Mark J.
Published: August 2003

The molecular basis of thymocyte negative selection, which plays a critical role in establishing and maintaining immunological tolerance, is not yet resolved. In particular, the importance of the death receptor subgroup of the tumor necrosis factor (TNF)-family has been the subject of many investigations, with equivocal results. A recent report suggested that TRAIL was a critical factor in this process, a result that does not fit well with previous studies that excluded a role for the FADD-caspase 8 pathway, which is essential for TRAIL and Fas ligand (FasL) signaling, in negative selection. We have investigated intrathymic negative selection of TRAIL-deficient thymocytes, using four well-established models, including antibody-mediated TCR/CD3 ligation in vitro, stimulation with endogenous superantigen in vitro and in vivo, and treatment with exogenous superantigen in vitro. We were unable to demonstrate a role for TRAIL signaling in any of these models, suggesting that this pathway is not a critical factor for thymocyte negative selection.
The Chymase, Mouse Mast Cell Protease 4, Constitutes the Major Chymotrypsin-like Activity in Peritoneum and Ear Tissue. A Role for Mouse Mast Cell Protease 4 in Thrombin Regulation and Fibronectin Turnover
Authors: Tchougounova Elena , Pejler Gunnar , Åbrink Magnus
Published: August 2003

To gain insight into the biological role of mast cell chymase we have generated a mouse strain with a targeted deletion in the gene for mast cell protease 4 (mMCP-4), the mouse chymase that has the closest relationship to the human chymase in terms of tissue localization and functional properties. The inactivation of mMCP-4 did not affect the storage of other mast cell proteases and did not affect the number of mast cells or the mast cell morphology. However, mMCP-4 inactivation resulted in complete loss of chymotryptic activity in the peritoneum and in ear tissue, indicating that mMCP-4 is the main source of stored chymotrypsin-like protease activity at these sites. The mMCP-4 null cells showed markedly impaired ability to perform inactivating cleavages of thrombin, indicating a role for mMCP-4 in regulating the extravascular coagulation system. Further, a role for mMCP-4 in connective tissue remodeling was suggested by the inability of mMCP-4 null peritoneal cells to process endogenous fibronectin.
Doc.com: reviewing the literature on remote health information provision
Authors: Williams Peter , Nicholas David , Huntington Paul , Gunter Barrie
Published: August 2003

This paper attempts an overview of the literature on issues relating to the electronic provision of health information for the consumer, to provide a context for current work being undertaken by the Internet Studies Research Group (ISRG) examining the impact of various electronic platforms. Reasons why there has been an increase in interest and demand for health information and issues such as information need, take‐up and use, are elicited from the literature, and discussed with regard to previous research and the findings from the group’s own studies. Problems inherent in electronic provision, such as the dissemination of unregulated information, and barriers to information take‐up, are examined in depth. The review concludes with an outline of the implications of the issues for both the current and future work of the ISRG and the wider research community.
User privacy in the digital library environment: a matter of concern for information professionals
Authors: Sturges Paul , Teng Vincent , Iliffe Ursula
Published: August 2003

User privacy has taken on a fresh importance as digital resources and systems become increasingly important in libraries. Public and professional concern has been aroused by numerous instances of the privacy‐threatening effects of current technical and legal developments. Not only do loan and other transactions leave traces in library management systems, but Internet use at public terminals in libraries is also vulnerable to intrusion. Whilst the UK data protection legislation offers protection to personal data, new legislation such as the 2000 Regulation of Investigatory Powers Act suggest a different tendency. The Legal and Policy Research Group at Loughborough University’s Department of Information Science is working on a substantial investigation, funded by Re:source, of the issue of user privacy in the digital library environment. Guidelines on privacy matters for information professionals are being developed on the basis of the investigation.
Coping with an unstructured world
Authors: Davies Bruce
Published: August 2003

Discusses the merits of using soft actuation systems to create compliant robot mechanisms and the problems associated with controlling such robots.
Freedom of speech in a constitutional political economy perspective
Authors: Josselin Jean‐Michel G. , Marciano Alain
Published: August 2003

The article examines the issue of free speech in a law and economics perspective. The property rights approach is contrasted with the common law and constitutional standpoints. Consequentialist and market efficiency may not provide adequate criteria for judging limitations to freedom of speech. Constitutional instruments may then be required.
Inspired! Award‐winning library marketing
Authors: Brewerton Antony
Published: August 2003

Following restructuring at Oxford Brookes University Library, several functional groups – including a marketing group – were established. The marketing group’s successes include a highly effective outreach programme at Freshers’ Fair. Learning from its first stall in 2000, the group’s 2001 campaign focused on promoting the newly re‐launched Library Web site. The Inspiration Campaign used striking images of Newton’s apple, Rodin’s The Thinker, a penny dropping and a light bulb plus the message “inspiration … available now from the library” to promote the library’s Web address. This message was reinforced by library staff giving out apples and stickers at Freshers’ Fair. The campaign proved highly successful with the number of hits on the site tripling in a year. The Inspiration Campaign was entered in the Chartered Institute of Library and Information Professionals (CILIP)/Emerald Public Relations and Publicity Awards for a “promotional campaign with a budget under £500”. The Inspiration Campaign won.
Organisational learning, competencies, and firm performance: empirical observations
Authors: Murray Peter
Published: August 2003

Empirical research has already postulated the link between learning routines and the creation of competencies, but it is less clear how competencies influence organisational performance. This paper is an empirical investigation determining the relationship between the creation of competencies and the quality of learning. The purpose of the paper is to not only build on prior research that has validated the usefulness of linking levels of learning with the evidence of competencies, but also to illustrate how the creation of competencies is a socially constructed phenomenon. Thus, the paper has a strong theoretical disposition examining the existing literature as well as building on it. Socially constructed routines of themselves have little inimitable advantage to firms unless the routines are underpinned and harnessed by unique learning systems. The paper explores these concepts by showing how the creation of competencies depend on, and are predisposed to, the quality of learning interaction, the routines that are patterned from these, and the capacity of the organisation to turn the new socially constructed routines into superior performance. The paper is expected to make a major contribution to the strategic management literature by showing what types of competencies are more likely to lead to superior firm performance, and how competencies are linked to learning.
The power of world‐class performance management: use it!
Authors: de Waal André A.
Published: August 2003

“What you measure is what you get” is a favorite aphorism of many a management writer. As most practicing managers know, measures drive management behavior, especially if they are reinforced by reward systems. But few organizations have understood the importance of this connection and dealt with these issues in a holistic way. It means building new performance management systems in parallel with new management structures and redefining responsibility boundaries. This is not an easy message for a measurement industry that believes it has the complete solution. The article “The power of world‐class performance management: use it!” deals with the key measurement issues, tackles the organization problems concerned with aligning strategy and behaviors, and describes the way organizations can obtain a world‐class performance management process. The ideas described in the article are based on a benchmark study recently performed by the author at prominent, global companies, and during projects he performed, in the area of performance management, at various clients.
IT projects: evaluation, outcomes and impediments
Authors: Suwardy Themin , Ratnatunga Janek , Sohal Amrik S. , Speight Geoffrey
Published: August 2003

Aims to identify the motivational factors for investing in information technology (IT), the impediments to IT investments and the outcomes of the planning and implementation of IT projects by chartered accountants in Australia. The results indicate that firms are motivated to invest in IT primarily for five reasons. IT investments face a number of challenges, the most prominent being the need to keep up with technology, which is likely to worsen as the technology cycles continue to shorten. Identifies resource procurement, lack of appropriate development tools, lack of proper planning or project management and user resistance to change as the four main problems encountered in implementation of IT projects. Many IT projects were undertaken for the purpose of improving efficiency within the organisation and reducing costs, rather than more strategic usage such as providing a flexible IT infrastructure or aligning IT with corporate strategy. The results suggest that firms have largely only utilised IT in their internal operations, rather than for strategic reasons.
Evaluating application service providers
Authors: Ekanayaka Yamaya , Currie Wendy L. , Seltsikas Philip
Published: August 2003

Discusses the application service provider (ASP) model, which is emerging as a new form of application outsourcing. At present, the ASP marketplace is largely vendor driven with huge numbers of vendors offering a variety of applications to the customer. These offerings may belong to software applications such as enterprise resource planning, collaborative and vertical industry. Even though there are many benefits attributed to this model suggests that, in order to reap these benefits, customers should evaluate the offerings of the ASPs. Addressing this purpose develops a taxonomy to identify the various ASP offerings and a framework to evaluate the ASP offerings on categories such as security, pricing, integration, service level agreement, and reliability, availability and scalability. Even though this framework is in an early stage of development it intends to present existing customers with performance criteria for evaluating ASP offerings. Concludes that further empirical research needs to be carried out to refine this framework and also to find the relevance of traditional outsourcing literature to this new form of outsourcing.
Maximizing shareholder value: the risks to employees, customers and the community
Authors: Cassidy Denis
Published: August 2003

In this article the author traces the history of corporate governance in Britain over the past decade. He concludes that the movement has been “hijacked” by the city and large accountancy partnerships. This has led to an undue emphasis on achieving financial goals and compliance with codes of practice i.e. “box‐ticking”. In the drive to maximize shareholder value, the critical relationships with employees, customers, suppliers and the community have been sacrificed and long‐term shareholder value has been destroyed. In order to rebuild the trust of the individual shareholders, employees, pensioners and the public at large, city institutions must focus less on maximizing shareholder value in the short‐term and more on optimizing shareholder value through building strong relationships with all the stakeholders.