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Close Proximity (close + proximity)
Selected AbstractsGender and Ethnic Diversity Among UK Corporate BoardsCORPORATE GOVERNANCE, Issue 2 2007Stephen Brammer This paper investigates the ethnic and gender diversity of the corporate board of UK companies, placing particular emphasis on links to board size and industry characteristics. We employ a novel dataset that covers a large sample of UK PLCs and describes a director's gender, ethnicity and position held. We find both ethnic and gender diversity to be very limited, and that diversity is somewhat less pronounced among executive positions. We find significant cross-sector variation in gender diversity, with an above average prevalence of women in Retail, Utilities, Media and Banking, while such variation in ethnic diversity is considerably less pronounced. Our evidence suggests that a close proximity to final consumers plays a more significant role in shaping board diversity than does the female presence among the industry's workforce. We argue that this shows that board diversity is influenced by a firm's external business environment and particularly an imperative to reflect corresponding diversity among its customers. [source] Focal electroporation in ovoDEVELOPMENTAL DYNAMICS, Issue 12 2009J. E. Simkin Abstract Gene expression fields in embryogenesis are spatially precise and often small, so experimental gene expression often requires similar spatial definition. For in ovo electroporation, typically a gene construct is injected into a natural body cavity in the embryo prior to electroporation. Limited control of the size and location of the electroporated field can be obtained by varying electrode placement and geometry, and by altering the miscibility and viscosity of the construct vehicle but it is difficult to tightly constrain electroporation to small regions. Electroporation of different constructs in close proximity has not been possible. We show that loading the construct into an agarose bead, which is then microsurgically implanted, allows for focal electroporation. Different constructs can be electroporated in close proximity by emplacing several agarose beads. This technique is simple, cheap, rapid, and requires no more specialised equipment than that required for conventional in ovo electroporation. Developmental Dynamics 238:3152,3155, 2009. © 2009 Wiley-Liss, Inc. [source] Late Devonian tetrapod remains from Red Hill, Pennsylvania, USA: how much diversity?ACTA ZOOLOGICA, Issue 2009Edward B. Daeschler Abstract The remains of Late Devonian tetrapods from the Red Hill locality in Pennsylvania help to elucidate the early stages of tetrapod evolution. Red Hill is a particularly informative site that preserves a diverse fauna and flora within a depositional setting suggesting penecontemporaneous deposition of locally derived material. Here, for the first time, we report on the full suite of early tetrapod remains from Red Hill and consider the implications for tetrapod diversity within the Red Hill ecosystem. Previously described material is reviewed and considered in relation to newly reported specimens. New material described includes isolated skull elements (two jugals, a postorbital, a lacrimal and a coronoid) and postcranial elements (a femur and a gastral scale). The characteristics of many of the Red Hill tetrapod specimens conform to the morphological expectations of Late Devonian forms. Several elements, however, illustrate more derived characteristics and strongly suggest the presence of the oldest known whatcheeriid-like tetrapod. This study demonstrates the difficulty in making taxonomic associations with isolated remains, even when found in close proximity to one another. Exploration of the characteristics of each element, however, demonstrates the presence of at least three early tetrapod taxa at the Red Hill site. [source] The origins of kingship in early medieval KentEARLY MEDIEVAL EUROPE, Issue 1 2000Charlotte Behr In this article, it is argued that Bede's famous account of the origin and early development of the people and kings of Kent in Historia ecclesiastica (I.15) does not report historical events, but reflects eighth-century concepts of migration-period kingship with mythical links to the Jutes of Scandinavia. Bracteate evidence shows that the veneration of Woden existed in Kent by the sixth century. Support for a contemporary belief in the Scandinavian origin of Kentish kings is found in locally produced bracteates, which imitate Scandinavian styles, and where several recovered from Kentish cemeteries are found in close proximity to places with royal connections. These include the only known Kentish site linked to the veneration of Woden. Evidence suggests that Kentish genealogy reflects a mythical belief in ancestry from Woden, rather than historical descent from Scandinavian Jutes. Finally, it is argued that Kentish bracteates, usually found in exceptionally rich female graves, were worn by high status women. These women may have played a significant role in legitimizing new royal claims. [source] Plant,soil biota interactions and spatial distribution of black cherry in its native and invasive rangesECOLOGY LETTERS, Issue 12 2003Kurt O. Reinhart Abstract One explanation for the higher abundance of invasive species in their non-native than native ranges is the escape from natural enemies. But there are few experimental studies comparing the parallel impact of enemies (or competitors and mutualists) on a plant species in its native and invaded ranges, and release from soil pathogens has been rarely investigated. Here we present evidence showing that the invasion of black cherry (Prunus serotina) into north-western Europe is facilitated by the soil community. In the native range in the USA, the soil community that develops near black cherry inhibits the establishment of neighbouring conspecifics and reduces seedling performance in the greenhouse. In contrast, in the non-native range, black cherry readily establishes in close proximity to conspecifics, and the soil community enhances the growth of its seedlings. Understanding the effects of soil organisms on plant abundance will improve our ability to predict and counteract plant invasions. [source] Electrophoretic mapping of highly homologous keratins: A novel marker peptide approachELECTROPHORESIS, Issue 17 2010Santanu Deb-Choudhury Abstract Identification of the intermediate filament proteins (IFPs) in the wool proteome has formerly been hampered by limited sequence information, the high degree of IFP homology and their close proximity on 2-DE maps. This has been partially rectified by the recent acquisition of four new Type I and two Type II wool IFP sequences. Among closely migrating proteins, such as IFP clusters in a 2-DE map, proteins with higher sequence coverage will be assigned higher scores, but the identification of unique peptides in such tight clusters may distinguish these closely migrating proteins. Two approaches were adopted for the study of wool IFPs. In the first, searches were conducted for peptides known to be unique to each member of the family in each spot. In the second, MALDI imaging was employed to examine peptides bound to a PVDF membrane from a poorly resolved part of the Type I IFP region of the 2-DE map. As a result, a distinct picture has emerged of the distribution of the six Type I and four Type II IFPs across the 2-DE wool protein map. [source] Identifying the nonpoint source of perfluorinated compounds using a geographic information system based approachENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2009Yasuyuki Zushi Abstract Perfluorinated compounds (PFCs) have been detected in a wide range of places. They have also been reported to come from nonpoint sources, but the origin of these sources has not been identified. In the present study, we attempted to characterize the nonpoint source of PFCs in the Hayabuchi River, Japan, which runs through an urban area, using a geographic information system (GIS) and statistical analysis. We also estimated annual PFC loads from nonpoint sources in Japan as a whole, determining a magnitude comparable to that from sewage treatment plants (STPs); the range was a few tons per year for each PFC. Perfluorinated compound pollution in river water was found to increase when the river received drainage from an area with a high proportion of commercial and/or transportation land use. It was also found that more PFCs were discharged from the watersheds where train stations are located. This result could be interpreted as the use of land for commercial and transportation purposes is prevalent in close proximity to train stations, and that the effluents from those areas contain high concentrations of PFCs. These findings suggested that train stations could be indicators of nonpoint sources of PFCs. [source] Coexistence of Unverricht-Lundborg disease and congenital deafness: Molecular resolution of a complex comorbidityEPILEPSIA, Issue 6 2009Miljana Kecmanovi Summary Purpose:, We report on genetic analysis of a complex condition in a Serbian family of four siblings, wherein two had progressive myoclonic epilepsy (PME) and congenital deafness (CD), one had isolated congenital deafness (ICD), and one was healthy. Methods and Results:, Molecular diagnosis performed by Southern blotting confirmed Unverricht-Lundborg disease in the available sibling with PME/CD. In the sibling with ICD (heterozygote for expansion mutation in CSTB) we demonstrated recombination event between the D21S2040 marker and the CSTB gene and identified c.207delC (p.T70Xfs) mutation in the fourth exon of the transmembrane protease, serine-3 (TMPRSS3) gene (maps in close proximity to CSTB), responsible for nonsyndromic deafness in the sibling with PME/CD as well. Discussion:, To the best of our knowledge this is the first genetic confirmation of the coexistence of these two mutations. [source] Clinical anatomy of the equine sphenopalatine sinusEQUINE VETERINARY JOURNAL, Issue 6 2004J. L. McCANN Summary Reasons for performing study: Disorders of the equine sphenopalatine sinus, including empyema and neoplasia, have been reported to cause damage to cranial nerves II and V. However, the clinical anatomy of these sinuses is not well described in horses. Objective: To examine the anatomy of the sphenopalatine sinuses in a range of equidae and, in particular, to examine the relationship of these sinuses to adjacent major nerves and vessels. Methods: The anatomy of the sphenoidal and palatine paranasal sinuses was examined in 16 equidae, primarily using transverse skull sections. Relevant structures were documented and photographed. Results: There was much variation between individual horses in sphenopalatine sinus anatomy. The sphenoidal sinuses were small in young horses and appeared to become larger and more complex with age. Variation was present in the extent that the sphenopalatine sinus extended into the basisphenoid bone. The septum dividing left and right sphenoidal sinuses was frequently not midline, but was intact in all cases. The sphenoidal and palatine sinuses communicated in most horses. In such cases, what could accurately be termed the (combined) sphenopalatine sinuses usually drained directly into the caudal maxillary sinuses. Additionally, in 5 out of 16 cases, some compartments of the sphenoidal sinus also drained into the ethmoidal sinus. The dorsal and lateral walls of the sphenoidal sinus were very thin and directly adjacent to cranial nerves II, III, IV, V and VI and major blood vessels. Conclusions: The equine sphenoidal and palatine sinuses are very variable in their anatomy, but are always in close proximity to multiple cranial nerves and major blood vessels. Potential relevance: Many cranial nerves and blood vessels could be damaged with disorders involving the sphenopalatine sinus, potentially causing major and variable neurological syndromes, haemorrhage and extension of sepsis. [source] The effects of local anaesthetic solution in the navicular bursa of horses with lameness caused by distal interphalangeal joint painEQUINE VETERINARY JOURNAL, Issue 5 2003JOHN SCHUMACHER Summary Reasons for performing study: Analgesia of the palmar digital (PD) nerves has been demonstrated to cause analgesia of the distal interphalangeal (DIP) joint as well as the sole. Because the PD nerves lie in close proximity to the navicular bursa, we suspected that that analgesia of the navicular bursa would anaesthetise the PD nerves, which would result in analgesia of the DIP joint. Objectives: To determine the response of horses with pain in the DIP joint to instillation of local anaesthetic solution into the navicular bursa. Methods: Lameness was induced in 6 horses by creating painful synovitis in the DIP joint of one forefoot by administering endotoxin into the joint. Horses were videorecorded while trotting, before and after induction of lameness, at three 10 min intervals after instilling 3.5 ml local anaesthetic solution into the navicular bursa and, finally, after instilling 6 ml solution into the DIP joint. Lameness scores were assigned by grading the videorecorded gaits subjectively. Results: At the 10 and 20 min observations, median lameness scores were not significantly different from those before administration of local anaesthetic solution into the navicular bursa (P,0.05), although lameness scores of 3 of 6 horses improved during this period, and the 20 min observation scores tended toward significance (P = 0.07). At the 30 min observation, and after analgesia of the DIP joint, median lameness scores were significantly improved (P,0.05). Conclusions: These results indicate that pain arising from the DIP joint can probably be excluded as a cause of lameness, when lameness is attenuated within 10 mins by analgesia of the navicular bursa. Potential relevance: Pain arising from the DIP joint cannot be excluded as a cause of lameness when lameness is attenuated after 20 mins after analgesia of the navicular bursa. [source] Temporal Shifts in Conspicuousness: Mate Attraction Displays of the Texas Field Cricket, Gryllus texensisETHOLOGY, Issue 12 2004Susan M. Bertram Conspicuous mate attraction displays can simultaneously draw the attention of potential mates and predators, placing the signaller in peril of becoming prey. The balance between these countervailing forms of selection has the potential to shape mate attraction displays. Male Texas field crickets (Gryllus texensis; Orthoptera) signal acoustically to attract mates. Mating signals also attract acoustically orienting parasitoid flies (Ormia ochracea; Tachinidae). Both the abundance of female crickets and parasitoid flies fluctuates throughout the night. We show mate attraction displays exhibit diel shifts that correlate positively with expected female cricket presence and negatively with expected parasitoid fly activity. During early evening, when parasitoids are most common and mating is scarce, crickets signal less often and with reduced conspicuousness. During the second half of the evening, when sexually receptive females are abundant and parasitoids are scarce, crickets signal more often and with enhanced conspicuousness. These diel shifts in mate attraction displays do not appear to result from male crickets detecting parasitoid flies or female crickets and altering their behaviour accordingly. Males in close proximity to parasitoid flies or female crickets do not signal differently than lone males. Instead, diel pattern shifts in mate attraction displays appear to be a selective response to trade-offs between natural selection via parasitism and sexual selection via mate choice. [source] Correlates of Self-Directed Behaviour in Wild White-Faced CapuchinsETHOLOGY, Issue 4 2000Joseph H. Manson Elevated rates of self-directed behaviour (SDB) such as self-scratching and autogrooming have been widely used in recent years as an indicator of anxiety in catarrhine primates. This study presents the first examination of correlates of SDB rates in a platyrrhine primate. Subjects were 8 wild female white-faced capuchins at Lomas Barbudal, Costa Rica, who were observed for 119 h of focal individual follows. The subjects performed significantly more self-scratching and autogrooming while in close proximity to conspecifics than while alone, irrespective of whether the neighbour was dominant or subordinate to them. This result was attributable to elevated SDB rates during the 30 s preceding and following allogrooming bouts. Furthermore, subjects engaged in more SDB while in proximity to females (a) that were closer to them in dominance rank and (b) with whom they spent a larger proportion of their time in proximity. Self-directed behaviour rates after conflicts did not differ from non-postconflict rates. Nor were SDB rates above baseline levels during the 30 s before subjects descended to the ground. These results may provide support for the view that SDB rates index anxiety in this species, if grooming decisions signal individuals' current allegiances and are therefore a source of anxiety, even if being groomed is, itself, relaxing. Postconflict preparation for further aggression may mitigate against scratching and autogrooming in a fast-moving arboreal species. [source] Modulation of dendritic cell phenotype and functionin an in vitro model of the intestinal epitheliumEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2006Matt Butler Abstract A network of dendritic cells (DC) can be detected in close proximity to the epithelial cells overlying Peyer's patches in the gut. Intestinal DC show distinct phenotypes as compared to DC from the systemic lymph nodes (relatively low MHC and costimulatory molecules and high IL-10 and TGF,) and may play a role in maintaining tolerance to enteric antigens. We show that a similar phenotype is induced in the presence of a polarised epithelial cell monolayer in vitro. Monocyte-derived DC were co-cultured with Caco-2 intestinal epithelial monolayers for 24,h. Co-culture resulted in DC with reduced expression of MHC class,II, CD86, and CD80, and poor T,cell stimulatory capacity. Cytokine profiles showed reduced levels of inflammatory cytokine production, and co-cultured DC were less sensitive to stimulation via Toll-like receptors (TLR2, 4, and 6) as a result of increased levels of autocrine TGF, production. However, phenotypic changes in co-cultured DC could not be blocked by removal of apoptotic cells or addition of anti-TGF, antibodies, suggesting that other soluble factors are involved in DC modulation. Thus, polarised epithelial cell monolayers create a ,tolerogenic' environment which modulates the activity of DC. These results highlight the regulatory importance of the epithelial microenvironment at mucosal surfaces. [source] Managing the Unique Size-related Issues of Pediatric Resuscitation: Reducing Cognitive Load with Resuscitation AidsACADEMIC EMERGENCY MEDICINE, Issue 8 2002Robert Luten MD Abstract A resuscitation is a complicated event that requires for its optimal outcome the effective completion of a distinct series of actions, some simple, some complex, most occurring simultaneously or in close proximity. In children, these actions are determined not only by the clinical situation, but also by a series of age and size factors particular to each child. Different tasks require different levels of cognitive load, or mental effort. Cognitive load describes the mental burden experienced by the decision maker and will be higher when the task is less familiar or more demanding. In the setting of resuscitation, it refers to the cumulative demands of patient assessment, the ongoing decisions for each of the various steps, and decisions around procedural intervention (e.g., intubation). In children, the level of task complexity and, hence, cognitive load is increased by the unique component of variability of pediatric age and size, introducing logistical factors, many of which involve computations. The purpose of this paper is to examine the effects of age/size-related variables on the pediatric resuscitative process and to explore how these effects can be mitigated using resuscitation aids. The concept of cognitive load and its relation to performance in resuscitation is introduced and is used to demonstrate the effect of the various aids in the pediatric resuscitative process. [source] Do Metal,Metal Multiply-Bonded "Ligands" Have a trans Influence?EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 36 2008Magnetic Comparisons of Heterometallic CrCr···Co, MoMo···Co Interactions, Structural Abstract Reported here are two new compounds containing either a CrCr···Co [1, CrCrCo(dpa)4Cl2, dpa = 2,2,-dipyridylamide] or a MoMo···Co [2, MoMoCo(dpa)4Cl2] framework both having a multiply-bonded unit (CrCr in 1, MoMo in 2) in close proximity to the Co2+ ion and trans to a Co,Cl bond. Variable temperature magnetic susceptibility measurements reveal 1 to have a temperature-dependent spin equilibrium between a low-spin (S = 1/2) and high-spin (S = 3/2) state, whereas the Co2+ ion in 2 exists solely in its high-spin state. The crystal structures of 1 and 2 were determined. Variable temperature crystallographic data of 1 at 100 K and at room temperature reveal that the spin-transition affects not only the Co,ligand bond lengths but also the terminal Cr,ligand bond lengths. Whereas the Cr···Co distance becomes shorter by 0.13 Å in the low-spin form, the Co,Cldistance becomes longer by 0.2 Å. These observations,along with the crystal structure of 2, suggest that the multiply-bonded MM group has a trans influence on the Co2+ ion.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] A Polymer-Bound Oxidovanadium(IV) Complex Prepared from an L -Cysteine-Derived Ligand for the Oxidative Amination of StyreneEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 4 2008Mannar R. Maurya Abstract The ligand H2sal-cys (I) derived from salicylaldehyde and L -cysteine has been covalently bonded to chloromethylated polystyrene cross-linked with 5,% divinylbenzene. Upon treatment with [VO(acac)2] in dimethylformamide (DMF) the polystyrene-bound ligand PS-H2sal-cys (II) gave the oxidovanadium(IV) complex, PS-[VO(sal-cys)·DMF] (1). The corresponding neat complex, [VO(sal-eta)]2 (2), has also been prepared similarly in methanol. These complexes have been characterised by IR, electronic, EPR spectroscopic studies, magnetic susceptibility measurements and thermal as well as scanning electron micrographs studies. Complex [VO(sal-eta)]2 exhibits a medium intensity band at 980 cm,1 in the IR spectrum due to ,(V=O) stretch. Broad features of the EPR spectrum for the neat complex along with magnetic susceptibility studies suggest the presence of antiferromagnetic exchange interaction between two vanadium centers in close proximity. Both complexes catalyze the oxidative amination of styrene, in mild basic conditions, with secondary amines (diethylamine, imidazole, and benzimidazole) and gave a mixture of two aminated products in good yields. Amongst the two aminated products, the anti-Markovnikov product is favored over the Markovnikov one due to the steric hindrance posed by the secondary amines. The polymer-anchored heterogeneous catalyst is free from leaching during catalytic action and recyclable.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Pyrazole-Bridged NHC Ligands and Their Dimetallic (Allyl)palladium ComplexesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 3 2008Ulrich J. Scheele Abstract A set of compartmental pyrazole-based ligands with appended NHC donors has been synthesized and isolated as [H4L]Cl3 and [H3L](PF6)2 salts. Dinuclear (allyl)palladium complexes of these ligands are conveniently accessible via the in situ prepared silver species. Three complexes [(allyl)2Pd2L]PF6 and one derivative [(methallyl)2Pd2L]PF6 have been characterized crystallographically, which revealed that the metal ions are positioned in close proximity [d(Pd···Pd) = 3.97,4.05 Å], with two possible mutual orientations of the (meth)allyl ligands within the dimetallic pocket. NMR spectroscopy shows slow interconversion of these isomers (k = 0.05,0.4 s,1), where the (meth)allyl ligands are detached trans to the carbene during this ,3 -,1 -,3 dynamic process.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Heterobimetallic Systems Containing Organometallic and Classical Coordination Sites: Effects of Subtle Changes in the Werner-Type SiteEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 7 2005Tianlu Sheng Abstract Several highly unsymmetrical heterodinuclear Mn/Zn complexes are reported, in which an organometallic CpMn-(CO)2 fragment and a classical Werner-type zinc coordination unit are arranged in close proximity by means of a bridging pyrazolate. Ligand scaffolds differing in the chelate size of the tripodal tetradentate {N4} binding site, and different coligands for zinc are employed. Both the zinc-devoid precursor compounds and the bimetallic complexes with zinc(II) nested in the tris(pyridylalkyl)amine type {N4} compartment have been characterized by X-ray crystallography. Structural and spectroscopic features as well as the redox potentials of the MnI/MnII couple indicate slight effects of the redox-inactive Werner-type subunit on the properties of the organometallic site. Oxidation is highly localized at the organometallic manganese site, as is evidenced by IR and EPR spectroscopy and supported by DFT calculations. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Pyrazolate-Based Dinucleating Ligands in L2M2 Scaffolds: Effects of Bulky Substituents and Coligands on Structures and M···H,C InteractionsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 8 2004Jens C. Röder Abstract A series of nickel(II) and palladium(II) complexes [L2M2]2+ have been prepared and structurally characterized, where L is a pyrazolate ligand with bulky 2,6-dimethyl- or 2,6-di(isopropyl)anilinomethyl side arms. Coordinating counter anions such as chloride can bind to axial sites of the dinickel species in a solvent-dependent process, giving rise to five-coordinate high-spin metal ions. In the case of weakly coordinating anions, the metal ions are found in roughly square-planar environments, and the structures are governed by the tendency of the bulky aryl groups to avoid each other, which forces the methyl or isopropyl substituents in the aryl 2- and 6-positions to approach the metal ions from the axial directions. This leads to drastic low-field shifts of the respective 1H NMR signals, e.g. , = 7.86 ppm for the isopropyl ,CH which comes in close proximity to the low-spin nickel(II) center. The relevance of such low-field NMR resonances of protons close to the axial sites of d8 metal ions for possible three-center four-electron M···H,C hydrogen bonds involving the filled d orbital of the metal ion is discussed. In the present case, attractive M···H interactions are assumed to be of no major significance. This was corroborated by the structure of a further [L2Ni2]2+ type complex where the anilinomethyl side arms bear only a single 2-isopropyl group, which was found rotated away from the metal. Additional spectroscopic and electrochemical properties of the various complexes are reported. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2009M. L. F. Balthazar Background:, Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned. Methods:, We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls. Results:, Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices. Discussion:, We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD. [source] C1 neurons in the rat rostral ventrolateral medulla differentially express vesicular monoamine transporter 2 in soma and axonal compartmentsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2008C. P. Sevigny Abstract Vesicular monoamine transporter 2 (VMAT2) packages biogenic amines into large dense core and synaptic vesicles for either somatodendritic or synaptic release from neurons of the CNS. Whilst the distribution of VMAT2 has been well characterized in many catecholaminergic cell groups, its localization amongst C1 adrenergic neurons in the medulla has not been examined in detail. Within the rostral ventrolateral medulla (RVLM), C1 neurons are a group of barosensitive, adrenergic neurons. Rostral C1 cells project to the thoracic spinal cord and are considered sympathetic premotor neurons. The majority of caudal C1 cells project rostrally to regions such as the hypothalamus. The present study sought to quantitate the somatodendritic expression of VMAT2 in C1 neurons, and to assess the subcellular distribution of the transporter. Immunoreactivity for VMAT2 occurred in 31% of C1 soma, with a high proportion of these in the caudal part of the RVLM. Retrograde tracing studies revealed that only two of 43 bulbospinal C1 neurons contained faint VMAT2-immunoreactivity, whilst 88 ± 5% of rostrally projecting neurons were VMAT2-positive. A lentivirus, designed to express green fluorescent protein exclusively in noradrenergic and adrenergic neurons, was injected into the RVLM to label C1 neurons. Eighty-three percent of C1 efferents that occurred in close proximity to sympathetic preganglionic neurons within the T3 intermediolateral cell column contained VMAT2-immunoreactivity. These data demonstrate differential distribution of VMAT2 within different subpopulations of C1 neurons and suggest that this might reflect differences in somatodendritic vs. synaptic release of catecholamines. [source] The nitric oxide/cyclic guanosine monophosphate pathway modulates the inspiratory-related activity of hypoglossal motoneurons in the adult ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2008Fernando Montero Abstract Motoneurons integrate interneuronal activity into commands for skeletal muscle contraction and relaxation to perform motor actions. Hypoglossal motoneurons (HMNs) are involved in essential motor functions such as breathing, mastication, swallowing and phonation. We have investigated the role of the gaseous molecule nitric oxide (NO) in the regulation of the inspiratory-related activity of HMNs in order to further understand how neural activity is transformed into motor activity. In adult rats, we observed nitrergic fibers and bouton-like structures in close proximity to motoneurons, which normally lack the molecular machinery to synthesize NO. In addition, immunohistochemistry studies demonstrated that perfusion of animals with a NO donor resulted in an increase in the levels of cyclic guanosine monophosphate (cGMP) in motoneurons, which express the soluble guanylyl cyclase (sGC) in the hypoglossal nucleus. Modulators of the NO/cGMP pathway were micro-iontophoretically applied while performing single-unit extracellular recordings in the adult decerebrated rat. Application of a NO synthase inhibitor or a sGC inhibitor induced a statistically significant reduction in the inspiratory-related activity of HMNs. However, excitatory effects were observed by ejection of a NO donor or a cell-permeable analogue of cGMP. In slice preparations, application to the bath of a NO donor evoked membrane depolarization and a decrease in rheobase, which were prevented by co-addition to the bath of a sGC inhibitor. These effects were not prevented by reduction of the spontaneous synaptic activity. We conclude that NO from afferent fibers anterogradely modulates the inspiratory-related activity of HMNs by a cGMP-dependent mechanism in physiological conditions. [source] Somatodendritic localization of EFA6A, a guanine nucleotide exchange factor for ADP-ribosylation factor 6, and its possible interaction with ,-actinin in dendritic spinesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2007Hiroyuki Sakagami Abstract EFA6A is a member of the guanine nucleotide exchange factors that can specifically activate ADP ribosylation factor 6 (ARF6). In this study, we identified ,-actinin-1 as a possible interacting protein with EFA6A by the yeast two-hybrid screening with its C-terminal region as bait. The central region of ,-actinin-1 containing a part of spectrin repeat 1 and spectrin repeats 2,3 is responsible for this interaction. In the hippocampal formation, EFA6A immunoreactivity occurred at a high level as numerous fine puncta in the strata oriens, radiatum, lacunosum-moleculare of the hippocampal CA1,3 subfields and the dentate molecular layer, whereas the immunoreactivity was faint in the neuronal cell layers and the stratum lucidum, the mossy fiber-recipient layer of the CA3 subfield. Double-immunofluorescent analyses revealed a partial overlapping of EFA6A and ,-actinin at the dendritic spines of in vivo and cultured hippocampal neurons. Our present findings suggest that EFA6A may form a protein complex with ,-actinin and activate ARF6 in close proximity of the actin cytoskeleton and membrane proteins in the dendritic spines. [source] Characterization of the mouse adenylyl cyclase type VIII gene promoter: regulation by cAMP and CREBEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2002Jennifer R. Chao Abstract Adenylyl cyclase (AC) type VIII has been implicated in several forms of neural plasticity, including drug addiction and learning and memory. In the present study, we directly examined the role for the transcription factor CREB (cAMP response element binding protein) in regulating ACVIII expression by cloning a 5.2 kilobase region upstream of the translation start site of the mouse ACVIII gene. Analysis of this fragment revealed consensus elements for several transcription factors, including a canonical cAMP response element (CRE) in close proximity to the transcription initiation region. Next, ACVIII promoter activity was studied in two neural-derived cell lines and in primary cultures of rat striatal neurons. Activation of the cAMP pathway by forskolin treatment increased promoter activity, and a series of deletion and point mutants demonstrated that this activation is mediated specifically via the canonical CRE site. Gel shift assays confirmed that this site can bind CREB and several CREB family proteins. Further, activation of the ACVIII promoter by forskolin was potentiated by expression of a constitutively active form of CREB, CREB-VP16, whereas it was inhibited by expression of a dominant-negative form of CREB, A-CREB. Finally, over-expression of CREB in vivo, by viral-mediated gene transfer, induced ACVIII promoter activity in the brains of ACVIII-LacZ transgenic mice. These results suggest that the ACVIII gene is regulated by CREB in vitro and in vivo and that this regulation may contribute to CREB-dependent neural plasticity. [source] Close Proximity Dibenzo[a,c]phenazine,Fullerene Dyad: Synthesis and Photoinduced Singlet Energy TransferEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2010Rajeev K. Dubey Abstract A dibenzo[a,c]phenazine,fullerene (DBPZ-C60) dyad in which two chromophores are linked in close proximity to each other has been synthesized and studied in detail by optical spectroscopy to explore a new energy donor,acceptor system. The dyad was prepared by Prato reaction between 11-formyldibenzo[a,c]phenazine and fullerene. 3,5-Di- tert -butylbenzyl group was introduced onto the fulleropyrrolidine unit to achieve adequate solubility of the dyad. A thorough study of the photophysical properties of the dyad and relevant reference compounds, performed by means of steady state and time resolved spectroscopic measurements, has revealed the presence of highly efficient (ca. 98,%) and extremely fast (ken = 5,×,1011 s,1) intramolecular photoinduced singlet,singlet energy-transfer process from singlet excited state of the DBPZ moiety to fullerene. In both polar and nonpolar environment transduction of singlet excited state energy governs the excited state deactivation, but the efficiency and rate of energy transfer were found to be higher in nonpolar solvents in comparison to polar. The DBPZ singlet excited state decays within 2 and 4.7 ps in toluene andbenzonitrile, respectively, via singlet,singlet energy transfer to produce a fullerene singlet excited state which decays with a life time of 1.5 ns to give a very long-lived fullerene triplet state as final populated excited state. [source] The Langerhans' cell-like cell lines XS52 and XS106 express mRNA for ciliary neurotrophic factor and neurotrophic factor 4/5EXPERIMENTAL DERMATOLOGY, Issue 9 2004K. Seiffert Neurotrophins are responsible for the survival and outgrowth of nerves within the peripheral and central nervous systems. These factors include brain-derived neurotrophic factor (BDNF), CNTF, NT 3, and NT4/5. We have previously shown that LCs lie in close proximity to nerves and that several neuropeptides regulate LC function, implying that nerves send regulatory signals to LCs. To evaluate the possibility that LC signal nerves by release of neurotrophins, we examined LC expression of neurotrophins by RT-PCR. To eliminate the possibility of contaminating keratinocytes in highly enriched LC preparations, we utilized the LC-like cell lines XS52 (BALB/c derived) and XS106 (A/J derived) for initial experiments. The RNA obtained was digested with DNase to ensure complete absence of genomic DNA. Several independent RT-PCRs revealed expression of bands of the expected size for CTNF and NT4/5, but not for BDNF and NT3 in XS106 and XS52 cells. In contrast, the transformed keratinocyte cell line PAM212 expressed BDNF, as well as CTNF and NT4/5. Preliminary experiments with purified LC confirm the expression of CTNF and NT4/5 and also show the expression of BDNF. However, we cannot be sure that BDNF expression is not due to keratinocyte contamination. We conclude that LCs may regulate nerve cells by the release of neurotrophic factors. [source] The Vps4 C-terminal helix is a critical determinant for assembly and ATPase activity and has elements conserved in other members of the meiotic clade of AAA ATPasesFEBS JOURNAL, Issue 7 2008Parimala R. Vajjhala Sorting of membrane proteins into intralumenal endosomal vesicles, multivesicular body (MVB) sorting, is critical for receptor down regulation, antigen presentation and enveloped virus budding. Vps4 is an AAA ATPase that functions in MVB sorting. Although AAA ATPases are oligomeric, mechanisms that govern Vps4 oligomerization and activity remain elusive. Vps4 has an N-terminal microtubule interacting and trafficking domain required for endosome recruitment, an AAA domain containing the ATPase catalytic site and a , domain, and a C-terminal , helix positioned close to the catalytic site in the 3D structure. Previous attempts to identify the role of the C-terminal helix have been unsuccessful. Here, we show that the C-terminal helix is important for Vps4 assembly and ATPase activity in vitro and function in vivo, but not endosome recruitment or interactions with Vta1 or ESCRT-III. Unlike the , domain, which is also important for Vps4 assembly, the C-terminal helix is not required in vivo for Vps4 homotypic interaction or dominant-negative effects of Vps4,E233Q, carrying a mutation in the ATP hydrolysis site. Vta1 promotes assembly of hybrid complexes comprising Vps4,E233Q and Vps4 lacking an intact C-terminal helix in vitro. Formation of catalytically active hybrid complexes demonstrates an intersubunit catalytic mechanism for Vps4. One end of the C-terminal helix lies in close proximity to the second region of homology (SRH), which is important for assembly and intersubunit catalysis in AAA ATPases. We propose that Vps4 SRH function requires an intact C-terminal helix. Co-evolution of a distinct Vps4 SRH and C-terminal helix in meiotic clade AAA ATPases supports this possibility. [source] Crystal structures of CbiL, a methyltransferase involved in anaerobic vitamin B12 biosynthesis, and CbiL in complex with S -adenosylhomocysteine , implications for the reaction mechanismFEBS JOURNAL, Issue 2 2007Kei Wada During anaerobic cobalamin (vitamin B12) biosynthesis, CbiL catalyzes methylation at the C-20 position of a cyclic tetrapyrrole ring using S -adenosylmethionine as a methyl group source. This methylation is a key modification for the ring contraction process, by which a porphyrin-type tetrapyrrole ring is converted to a corrin ring through elimination of the modified C-20 and direct bonding of C-1 to C-19. We have determined the crystal structures of Chlorobium tepidum CbiL and CbiL in complex with S -adenosylhomocysteine (the S -demethyl form of S -adenosylmethionine). CbiL forms a dimer in the crystal, and each subunit consists of N-terminal and C-terminal domains. S -Adenosylhomocysteine binds to a cleft between the two domains, where it is specifically recognized by extensive hydrogen bonding and van der Waals interactions. The orientation of the cobalt-factor II substrate was modeled by simulation, and the predicted model suggests that the hydroxy group of Tyr226 is located in close proximity to the C-20 atom as well as the C-1 and C-19 atoms of the tetrapyrrole ring. These configurations allow us to propose a catalytic mechanism: the conserved Tyr226 residue in CbiL catalyzes the direct transfer of a methyl group from S -adenosylmethionine to the substrate through an SN2-like mechanism. Furthermore, the structural model of CbiL binding to its substrate suggests the axial residue coordinated to the central cobalt of cobalt-factor II. [source] The thioredoxin-independent isoform of chloroplastic glyceraldehyde-3-phosphate dehydrogenase is selectively regulated by glutathionylationFEBS JOURNAL, Issue 1 2007Mirko Zaffagnini In animal cells, many proteins have been shown to undergo glutathionylation under conditions of oxidative stress. By contrast, very little is known about this post-translational modification in plants. In the present work, we showed, using mass spectrometry, that the recombinant chloroplast A4 -glyceraldehyde-3-phosphate dehydrogenase (A4 -GAPDH) from Arabidopsis thaliana is glutathionylated with either oxidized glutathione or reduced glutathione and H2O2. The formation of a mixed disulfide between glutathione and A4 -GAPDH resulted in the inhibition of enzyme activity. A4 -GAPDH was also inhibited by oxidants such as H2O2. However, the effect of glutathionylation was reversed by reductants, whereas oxidation resulted in irreversible enzyme inactivation. On the other hand, the major isoform of photosynthetic GAPDH of higher plants (i.e. the AnBn -GAPDH isozyme in either A2B2 or A8B8 conformation) was sensitive to oxidants but did not seem to undergo glutathionylation significantly. GAPDH catalysis is based on Cys149 forming a covalent intermediate with the substrate 1,3-bisphosphoglycerate. In the presence of 1,3-bisphosphoglycerate, A4 -GAPDH was fully protected from either oxidation or glutathionylation. Site-directed mutagenesis of Cys153, the only cysteine located in close proximity to the GAPDH active-site Cys149, did not affect enzyme inhibition by glutathionylation or oxidation. Catalytic Cys149 is thus suggested to be the target of both glutathionylation and thiol oxidation. Glutathionylation could be an important mechanism of regulation and protection of chloroplast A4 -GAPDH from irreversible oxidation under stress. [source] A unique binding epitope for salvinorin A, a non-nitrogenous kappa opioid receptor agonistFEBS JOURNAL, Issue 9 2006Brian E. Kane Salvinorin A is a potent kappa opioid receptor (KOP) agonist with unique structural and pharmacological properties. This non-nitrogenous ligand lacks nearly all the structural features commonly associated with opioid ligand binding and selectivity. This study explores the structural basis to salvinorin A binding and selectivity using a combination of chimeric and single-point mutant opioid receptors. The experiments were designed based on previous models of salvinorin A that locate the ligand within a pocket formed by transmembrane (TM) II, VI, and VII. More traditional sites of opioid recognition were also explored, including the highly conserved aspartate in TM III (D138) and the KOP selectivity site E297, to determine the role, if any, that these residues play in binding and selectivity. The results indicate that salvinorin A recognizes a cluster of residues in TM II and VII, including Q115, Y119, Y312, Y313, and Y320. Based on the position of these residues within the receptor, and prior study on salvinorin A, a model is proposed that aligns the ligand vertically, between TM II and VII. In this orientation, the ligand spans residues that are spaced one to two turns down the face of the helices within the receptor cavity. The ligand is also in close proximity to EL-2 which, based on chimeric data, is proposed to play an indirect role in salvinorin A binding and selectivity. [source] | ||||||||||||||||||||||||||||||||||||||||||||||