bluuebunny/crossref_metadata_2025 huggingface dataset:
The coat protein of tobamovirus acts as elicitor of both L 2 and L 4 gene-mediated resistance in Capsicum
Authors: Gilardi P. , García-Luque I. , Serra M. T.
Published: June 2004

InCapsicum, the resistance conferred by theL2gene is effective against all of the pepper-infecting tobamoviruses exceptPepper mild mottle virus(PMMoV), whereas that conferred by theL4gene is effective against them all. These resistances are expressed by a hypersensitive response, manifested through the formation of necrotic local lesions (NLLs) at the primary site of infection. TheCapsicum L2gene confers resistance toPaprika mild mottle virus(PaMMV), while theL4gene is effective against both PaMMV and PMMoV. The PaMMV and PMMoV coat proteins (CPs) were expressed inCapsicum frutescens(L2L2) andCapsicum chacoense(L4L4) plants using the heterologousPotato virus X(PVX)-based expression system. InC. frutescens(L2L2) plants, the chimeric PVX virus containing the PaMMV CP was localized in the inoculated leaves and produced NLLs, whereas the chimeric PVX containing the PMMoV CP infected the plants systemically. Thus, the data indicated that the PaMMV CP is the only tobamovirus factor required for the induction of the host response mediated by theCapsicum L2resistance gene. InC. chacoense(L4L4) plants, both chimeric viruses were localized to the inoculated leaves and produced NLLs, indicating that either PaMMV or PMMoV CPs are required to elicit theL4gene-mediated host response. In addition, transient expression of PaMMV CP intoC. frutescens(L2L2) leaves and PMMoV CP intoC. chacoense(L4L4) leaves by biolistic co-bombardment with aβ-glucuronidase reporter gene led to the induction of cell death and the expression of host defence genes in both hosts. Thus, the tobamovirus CP is the elicitor of theCapsicum L2andL4gene-mediated hypersensitive response.
CD8+ T cells control corneal disease following ocular infection with herpes simplex virus type 1
Authors: Stuart Patrick M. , Summers Brett , Morris Jessica E. , Morrison Lynda A. , Leib David A.
Published: June 2004

The role that T cell subsets play in herpetic stromal keratitis (HSK) has been the subject of intense research efforts. While most studies implicate CD4+T cells as the principal cell type mediating primary corneal disease, recent reports using knockout mice have suggested that both CD4+and CD8+T cell subsets may play integral roles in modulating the disease. Furthermore, recent studies suggest that CD8+T cells are directly involved in maintaining virus latency in infected trigeminal ganglia. This work has addressed these discrepancies by infecting the corneas of mice lacking CD4+and CD8+T cells with herpes simplex virus type 1 (HSV-1) and monitoring both corneal disease and latent infection of trigeminal ganglia. Results indicated that mice lacking CD8+T cells had more severe corneal disease than either BALB/c or B6 parental strains. In contrast, mice lacking CD4+T cells had a milder disease than parental strains. When mice were evaluated for persistence of infectious virus, only transient differences were observed in periocular tissue and corneas. No significant differences were found in persistence of virus in trigeminal ganglia or virus reactivation from explanted ganglia. These data support the following conclusions. CD4+T cells are not required for resistance to infection with HSV-1 and probably mediate HSK. Mice lacking CD8+T cells do not display differences in viral loads or reactivation and thus CD8+T cells are not absolutely required to maintain latency. Finally, CD8+T cells probably play a protective role by regulating the immunopathological response that mediates HSK.
An approach to diversity training in Canada
Authors: Schmidt Patrick
Published: June 2004

The article begins by pointing out how Canada has undergone a huge demographic change in the last 30 years, forcing companies to rethink their training strategies. This means diversity training will assume an ever larger role. Different clichés about diversity training are discussed and demystified. The goal of all diversity training is to make participants aware of their perceptions and assumptions, so as to ensure correct understanding of different values. The characteristics of an effective diversity program are: it must be linked to a business objective, it cannot result in preferential treatment for some groups and it must have the 100 percent support from top management. The benefits will yield better communication with outsides as well as insiders, enlarge the customer base and will transpose one's mindset so that a person can engage successfully in any interracial or intercultural relationship.
Is diversity divisive? A positive training approach
Authors: Bagshaw Mike
Published: June 2004

In today's climate organisations increasingly need to recognise, harness and manage diversity. Equal opportunities legislation and policy, first developed in the 1970s, came about to redress past wrongs and to ensure equality of opportunity regardless of race, gender, disability, sexual orientation and faith. Managing diversity is founded on the premise that harnessing difference will create a productive environment in which everyone feels valued, where their talents are used and organisational goals are met. Diversity and ensuring equality of opportunity can be misunderstood. They are sometimes thought to be a politically correct requirement that does not really work. Equal opportunities policy focuses on being fair, but does not take the extra step of harnessing diversity to enhance business. Good diversity policy not only reduces the negatives, such as bullying, disputes, low morale, and sometimes litigation. It will also bring in extra talent, new perspectives, learning, and limitless opportunities for innovation. A case study with the London Fire Brigade shows a creative approach in diversity workshops.
How to increase diversity through your recruitment practices
Authors: Tipper Jeremy
Published: June 2004

Increasing the diversity of an organisation's workforce is a primary concern for many businesses with the realisation that it can bring significant competitive advantage. The challenge lies in how organisations can best do this. This article highlights a pragmatic guide as to how organisations can increase their diversity through their recruitment practices through activities such as: market research into your potential recruitment pool; building a business case to influence line managers and other stakeholders as to the need to recruit for diversity; using a variety of communication channels to reach your target candidates; and rewarding employees when they successfully increase diversity through recruitment.
A practical approach to diversity
Authors: Farrer Jane
Published: June 2004

There is an increasing interest in how organisations of all sizes and sectors can practically address and embrace “diversity issues” both internally within their workforce and externally in relation to their customer base. There are many differing definitions of diversity, however it is generally accepted that organisations who manage diversity effectively go beyond recognising and accommodating the uniqueness of each member of its team by celebrating, valuing and actively encouraging the diversity of the workforce, thus fully enabling each individual to maximise their contribution to achieving organisational goals. “The diversity driver” is a practical diversity performance management tool that has been developed by The Back to Work Company, BQC Performance Management Ltd and the Fair Play Partnership, with support from Yorkshire Forward. The driver is based upon the business excellence model and provides a structured self‐assessment tool that enables organisations to identify their current strengths in addressing diversity in addition to prioritising areas where further improvements could be made. This article provides an outline of why diversity is being taken seriously, how the diversity driver can be utilised within organisations of all sizes and the benefits of adopting this very practical approach to diversity.
Transnational spaces and everyday lives
Authors: Ley David
Published: June 2004

This paper discusses some of the limitations of the global city hypothesis, in particular its economistic tendencies, the suppression of political and cultural domains, and the underdevelopment of human agency and everyday life. It tries to establish more fully the identities of global subjects. Examining two sets of global actors, transnational businessmen and cosmopolitan professionals, it argues that the expansive reach and mastery imputed to global subjects, their flight from the particular and the partisan, their dominance and freedom from vulnerability, are far from complete. The separation of the global and the local and the ascription of mobility and universalism to the global and stasis and parochialism to the local is an oversimplification, for an optic of transnational global spaces should not conceal the intersecting reality of circumscribed everyday lives.
Local consumption cultures in a globalizing world
Authors: Jackson Peter
Published: June 2004

Focusing on the resilience of distinctive local consumption cultures, this paper challenges some of the more sweeping claims that have been advanced in the name of ‘globalization’. Thinking about a ‘globalizing’ rather than a fully ‘globalized’ world encourages us to examine the deeply contested nature of the concept and to explore the geographically uneven nature of recent economic, political and cultural transformations. This paper approaches globalization as a site of struggle rather than as an established fact, emphasizing the need for empirically grounded studies of the impact of ‘globalization’ on consumer cultures in different geographical contexts. The paper examines the way that producers have ‘customized’ their products for different markets (drawing on evidence from China and South Africa). It then reviews case study evidence from three contrasting consumption cultures: consumption and ‘public culture’ in India, ‘consumer nationalism’ in China, and ‘artful consumption’ in Russia. The paper concludes by identifying some current debates and outlining some directions for future research, including a re‐emphasis on consumption and material culture; an exploration of consumption as social practice; the delineation of commodity‐specific consumption cultures; and some reflections on the political, ethical and methodological issues that are being raised in contemporary consumption research.
Antinomies of community: some thoughts on geography, resources and empire
Authors: Watts Michael J
Published: June 2004

Community is a fundamental modality for the conduct of modern politics. This paper explores the antinomies of community in an oil nation: Nigeria. Oil states stand in relation to a particular sort of capitalism (what I call petro‐capitalism) in which a key resource (petroleum) and a logic of extraction figure centrally in the making and breaking of community. I pose the following questions: how are communities imagined (or not), territorialized (or not), identified (or not) and ruled (or not) at a multiplicity of scales and in relation to a particular natural resource, namely oil? Each community is imagined, so to say, through and with oil – the communities are ‘naturalized’ in relation to the effects, social, environmental, political, of oil exploration and production – but produces forms of rule and identity that are often fragmented, unruly and violent. The communities I address are, in a sense, all oil‐producing communities but of rather different qualities: namely, the chieftainship as a local form of customary community rule at the level of the village; the ethnic or indigenous community at the level of the region; and the nation, or more properly the nation‐state known as Nigeria. And standing at the heart of each community is a fundamental contradiction. Nigerian petro‐capitalism operates through a particular sort of ‘oil complex’ (a configuration of firm, state and community) that generates or refigures differing sorts of community, what I shall refer to as governable spaces, in which differing sorts of identities, forms of rule and territory come into play. These sorts of community emerge from oil extraction, but the dynamics of petro‐capitalism and the oil complex contribute to, and are constitutive of, a deep crisis of secular nationalist development. Imperial oil and its concessionary political economy can be read as a sort of enclosure or dispossession and it is out of this development crisis in Nigeria that particular senses of community are being constituted – with and through oil.
Regulating economic globalization
Authors: Amin Ash
Published: June 2004

It is widely accepted that the rising gap in recent years between the global rich and the global poor can be linked to globalization in one way or another, although the strength and causality of the link is debated. Against the backcloth of the havoc wreaked by neo‐liberalism and the Washington Consensus, new meta‐narratives of global order are emerging to suggest ways of reducing global poverty and inequality. This paper examines two ‘Olympian’ visions of re‐regulation along social democratic lines that propose new scalar arrangements. It evaluates these meta‐narratives against another spatial ontology of regulation thrown up by the economy of global flows and networks – an unfolding regime of heterarchical order that is topological, hybrid, decentred and coalitional in its workings. The paper argues that these new ‘micro‐worlds’ of regulation are as significant as, and equivalent to, so‐called macro‐orders of regulation in influencing global poverty and inequality, that they throw into doubt assumptions of control and reach held by the meta‐narratives, and that their rise amounts to a situation of global regulatory excess, rather than, as some have argued, a condition of regulatory deficit or global disorder.
Environmental science, sustainability and politics
Authors: O'Riordan Tim
Published: June 2004

Research evidence and pleas that humans are undermining their own survival on a robust and unforgiving planet seem to be falling on deaf ears. The drive for economic and military security remains more powerful than the evidence that both of these objectives are being undermined by environmental damage, social disruption, unjust treatment and forced migration. Yet the signs are growing that environmentally and socially sound futures may be vital prerequisites for economic and military stability. So, at the heart of multi‐nationalism, sustainable development is beginning to be recognized as a crucial element in reliable international agreements. The consequence of all this is that environmental science has become highly political, and geographers need to recognize and work within an expanding political process. Examples of new forms of governing via sustainability science for sustainable futures are offered in the latter part of the paper, especially at local government level. The antagonistic pressures of established power and economic hegemony are never far away. Indeed, the confirmation of these established patterns of power still pervades the politics of environmental science. But it is possible that these antagonistic political frameworks are beginning to be transcended by the more influential aspects of sustainability partnerships incorporating new arrangements between government, private capital and civil associations. These partnerships will not be easy to create, for they criss‐cross boundaries of familiarity and rules of operation. But geographers can play a critical role in helping to shape them and assess the best circumstances for ensuring their success.
High‐pressure cryoimmobilization of murine skin reveals novel structural features and prevents extraction artifacts
Authors: Reipert Siegfried , Fischer Irmgard , Wiche Gerhard
Published: June 2004

Abstract:  Cryoimmobilization by high‐pressure freezing (HPF) and subsequent freeze substitution has been proven as an effective method to preserve tissues. Here, we demonstrate for the first time that a comprehensive morphological and ultrastructural preservation of mouse skin throughout all its layers can be achieved in this way. Using conditions limiting tissue‐extraction during freeze substitution, we could prevent the massive interdigitation of cell membranes, the loss of tubular structures of the Golgi complex, the aggregation of keratin to electron‐dense bundles, the formation of round‐shaped keratohyalin aggregates, the dispersion of locally organized ribosomes, the excessive aggregation of material at hemidesmosomal plaques, the massive extraction of material from the basement membrane and the adjacent dermal region, and the dissociation of components of the dermal matrix. Taken together, HPF in combination with freeze substitution emerges as a highly sensitive tool for morphological and ultrastructural analysis.
Do Arctic waders use adaptive wind drift?
Authors: Green Martin , Alerstam Thomas , Gudmundsson Gudmundur A. , Hedenström Anders , Piersma Theunis
Published: June 2004

We analysed five data sets of flight directions of migrating arctic waders in relation to winds, recorded by tracking radar and optical range finder, in order to find out if these birds compensate for wind drift, or allow themselves to be drifted by winds. Our purpose was to investigate whether arctic waders use adaptive wind drift strategies or not. The data sets were collected in Siberia (two sets) and Canada during post‐breeding (autumn) migration, and in Mauritania and South Sweden during pre‐breeding (spring) migration. Both significant drift and compensation effects were found in three of the data sets, Canada, Mauritania and South Sweden. Almost no compensation was found in birds departing in easterly directions from the Siberian tundra (complete drift), while no drift effect was found in birds departing in westerly directions (complete compensation). There were indications that at least some populations of waders may use an adaptive drift strategy consisting of drift at high altitude and/or in high wind speed combined with compensation at low altitude and/or in lower wind speeds, but support for this idea was rather weak and not consistent. Our results were instead more in accordance with the adaptive drift theory that predicts initial drift during the migratory journey, followed by compensation during later stages as the birds are approaching their destinations. Such a strategy implies that arctic waders, at least adult birds, have the capacity of true navigation. A comparison with earlier studies of migrating arctic waders from different parts of the world show that all results so far may be interpreted in accordance with this general adaptive drift strategy. An element of non‐adaptive drift can, however, not be completely ruled out.
Brood rearing costs affect future reproduction in the precocial common goldeneye Bucephala clangula
Authors: Milonoff Markku , Pöysä Hannu , Runko Pentti , Ruusila Vesa
Published: June 2004

Life‐history theory assumes a trade‐off between current reproductive effort and future reproductive success. There are a large number of studies demonstrating reproductive trade‐offs in different animal taxa, particularly in birds. Most bird studies have focused on the costs of chick rearing in altricial species. These costs have been assumed to be low in precocial species, but this aspect has been little studied. We used long‐term individual reproductive data from the common goldeneye Bucephala clangula, an iteroparous precocial duck with uniparental female care, to examine whether brood rearing carries costs that affect future reproductive performance. All females were experienced breeders, and possible differences in female quality were ruled out. We compared within‐individual (between‐year) changes in clutch size, hatching date and body mass between females that had reared a brood in the previous year and females that had not. It turned out that brood rearing involved a cost in terms of clutch size and hatching date the next year, but not in terms of body mass: females that had reared a brood in the previous year laid relatively smaller clutches and laid relatively later than females that had not reared a brood. Our results show that normal brood rearing in a precocial species involves costs that affect future reproduction.
Can intraspecific brood parasitism be detected using egg morphology only?
Authors: Ådahl Emma , Lindström Jan , Ruxton Graeme D. , Arnold E. K. , Begg Tracey
Published: June 2004

Intraspecific brood parasites lay their eggs in the nests of conspecifics. There are a number of methods for detecting intraspecific brood parasitism (IBP) in birds based on egg morphology. Here we test Eadie's (1989) method, which calculates the Euclidean distances between eggs in a given clutch in a three‐dimensional space (weight, length and width). A parasitised clutch is predicted to contain an egg (or eggs) that is significantly different from the clutch's other eggs. Data from three species were analysed. Our captive zebra finch Taeniopygia guttata clutches did not include any instances of IBP, the wild jackdaw Corvus monedula data were unlikely to contain any, and for the goldeneye Bucephala clangula data set we had an observational estimate of IBP. We simulated IBP in the zebra finch, jackdaw and goldeneye data to test whether the method reliably detects an experimentally ‘parasitised’ clutch. We show that the distributions of the test statistics greatly overlap in ‘parasitised’ and unmodified clutches, and are dependent on the clutch size. We therefore conclude that the method can only be used with caution, after calibrating it for a given population.
Why do the females of many bird species sing in the tropics?
Authors: Slater Peter J. B. , Mann Nigel I.
Published: June 2004

In the tropics female birds sing much more frequently than in the temperate north, and sometimes even join their mates to form duets. Why might this be? We discuss how this phenomenon may relate to differences in life history that have been proposed between these regions, highlight likely hypotheses and point to areas of ignorance where studies are needed. The two reasons that appear at present most likely to explain the greater prevalence of female song in the tropics are: (1) the need for mutual stimulation to achieve breeding synchrony in a relatively aseasonal environment and, (2) sex role convergence arising from more long‐term relationships and greater fidelity than is usual among north temperate species.
Deleterious effects of minocycline in animal models of Parkinson's disease and Huntington's disease
Authors: Diguet Elsa , Fernagut Pierre‐Olivier , Wei Xing , Du Yansheng , Rouland Richard , Gross Christian , Bezard Erwan , Tison François
Published: June 2004

Minocycline has been shown to exert anti‐inflammatory effects underlying its putative neuroprotective properties in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of Parkinson's disease and in the R6/2 mouse model of Huntington's disease (HD). However, contradictory results have recently been reported. We report deleterious effects of minocycline in two phenotypic (toxic) models of Parkinson's disease and HD in monkey and mouse. Of seven MPTP‐intoxicated female cynomolgus monkeys (0.2 mg/kg, i.v. until day 15), three received minocycline (200 mg b.i.d.). While placebo‐MPTP‐treated animals displayed mild parkinsonism at day 15, the minocycline/MPTP‐treated animals tended to be more affected (P = 0.057) and showed a greater loss of putaminal dopaminergic nerve endings (P < 0.0001). In the 3‐nitropropionic acid (3‐NP) mouse model of HD, minocycline (45 mg/kg i.p.) was administered 30 min before each i.p. injection of 3‐NP (b.i.d., cumulated dose, 360 mg/kg in 5 days). Mice receiving minocycline exhibited a worsening of the mean motor score with a slower recovery slope, more impaired general activity and significantly deteriorated performances on the rotarod, pole test and beam‐traversing tasks. The histopathological outcome demonstrated that minocycline‐treated mice presented significantly more severe neuronal cell loss in the dorsal striatum. The effect of minocycline vs. 3‐NP was also investigated on hippocampal and cortical cell cultures. minocycline blocked 3‐NP‐induced neurotoxicity at certain doses (1 mm cortical neurons) but not at higher doses (10 mm). Thus, minocycline may have variable and even deleterious effects in different species and models according to the mode of administration and dose.
Activation of PKC induces rapid morphological plasticity in dendrites of hippocampal neurons via Rac and Rho‐dependent mechanisms
Authors: Pilpel Yair , Segal Menahem
Published: June 2004

Activation of protein kinase C (PKC) produced a novel and rapid formation of lamellae over large surfaces of dendrites in cultured hippocampal neurons. This action was dendrite‐specific, involved a postsynaptic locus of activation of PKC and required actin polymerization, but not activation of Erk. Over‐expression of active Rho‐A GTPase converted a mature, highly branched and spiny neuron into a primitive, non‐branching, aspiny neuron. Overexpression of active Rac1 caused massive lamellae formation in the transfected neurons. These morphologically aberrant neurons retained synaptic connectivity with adjacent, normal neurons, as well as the ability to form lamellae in response to PKC. On the other hand, transfection with a dominant negative Rac‐N17 or a toxin C3, Rho‐A‐inactivating plasmid blocked lamellae formation by PKC, but did not prevent PKC‐induced plasticity of synaptic currents. These data indicate that PKC activates two independent molecular pathways, one of which involves Rac1 and Rho‐A, to produce massive actin‐based structural plasticity in dendrites and spines.
Olfactory receptor cells on the cockroach antennae: responses to the direction and rate of change in food odour concentration
Authors: Hinterwirth Armin , Zeiner Reinhard , Tichy Harald
Published: June 2004

In insects, information about food odour is encoded by olfactory receptor cells with characteristic response spectra, located in several types of cuticular sensilla. Within short, hair‐like sensilla on the cockroach's antenna, antagonistic pairs of olfactory receptor cells shape information inflow to the CNS by providing excitatory responses for both increases and decreases in food odour concentration. The segregation of food odour information into parallel ON and OFF responses suggests that temporal concentration changes become enhanced in the sensory output. When food odour concentration changes slowly and continuously up and down with smooth transition from one direction to another, the ON and OFF olfactory cells not only signal a succession of odour concentrations but also the rate with which odour concentration happens to be changing. Access to the values of such cues is of great use to an insect orientating to an odour source. With them they may extract concentration gradients from odour plumes.
Direction tuning of human motion detection determined from a population model
Authors: Maurer J. Peter , Heinrich Thomas S. , Bach Michael
Published: June 2004

Mass responses that are obtained using electrophysiological or psychophysical techniques are inadequate to characterize motion detectors at the single‐unit level. Therefore, we have modelled a population of motion detectors and fitted their mass response to motion‐onset EEG data. By examining a single unit of the modelled population we could assess the range of directions and the level of adaptation an individual motion detector responded to. Stimuli were patterns of randomly distributed dots. After subjects had adapted to either a non‐moving pattern or to motion in one fixed direction, the pattern moved in one of seven possible test directions. The population model assumed elementary motion detectors with a Gaussian angle‐selectivity profile. The population response was calculated as the sum of all adaptation‐weighted individual responses to the test direction. In all subjects, we observed sizeable effects of adaptation on test directions close to the adapted direction and small amounts of direction‐independent adaptation for all test directions. The model fit explained 75% (Oz) and 94% (lateral derivation) of the total variance and revealed a motion detector bandwidth (full width at half maximum) of 72° (Oz) and 62° (lateral derivation). The maximal adaptation depth was estimated as 72% (Oz) and 66% (lateral derivation). Estimates inferred from the population model representing human motion detectors were found to be close to those obtained by single‐cell data from non‐human primates.
Organization of prefrontal outflow toward frontal motor‐related areas in macaque monkeys
Authors: Takada M. , Nambu A. , Hatanaka N. , Tachibana Y. , Miyachi S. , Taira M. , Inase M.
Published: June 2004

Linkage between the prefrontal cortex and the primary motor cortex is mediated by nonprimary motor‐related areas of the frontal lobe. In an attempt to analyse the organization of the prefrontal outflow from area 46 toward the frontal motor‐related areas, we investigated the pattern of projections involving the higher‐order motor‐related areas, such as the presupplementary motor area (pre‐SMA) and the rostral cingulate motor area (CMAr). Tracer injections were made into these motor‐related areas (their forelimb representation) on the medial wall that had been identified electrophysiologically. The following data were obtained from a series of tract‐tracing experiments in Japanese monkeys. (i) Only a few neurons in area 46 were retrogradely labelled from the pre‐SMA and CMAr; (ii) terminal labelling from area 46 occurred sparsely in the pre‐SMA and CMAr; (iii) a dual labelling technique revealed that the sites of overlap of anterograde labelling from area 46 and retrograde labelling from the pre‐SMA and CMAr were evident in the rostral parts of the dorsal and ventral premotor cortices (PMdr and PMvr); (iv) and tracer injections into the PMdr produced neuronal cell labelling in area 46 and terminal labelling in the pre‐SMA and CMAr. The present results indicate that a large portion of the prefrontal signals from area 46 is not directly conveyed to the pre‐SMA and CMAr, but rather indirectly by way of the PMdr and PMvr. This suggests that area 46 exerts its major influence on the cortical motor system via these premotor areas.
Spreading depression enhances the spontaneous epileptiform activity in human neocortical tissues
Authors: Gorji Ali , Speckmann Erwin‐Josef
Published: June 2004

Spreading depression (SD) is a well‐known phenomenon in animal models of experimental epilepsy. However, the interaction of SD with epileptiform activity in human neuronal tissues is not clear. The aim of the present study was to investigate the effect of SD on synchronous rhythmic sharp field potentials in human neocortical slices. Spreading depression was elicited in human neocortical slices that exhibited sharp potentials. Extracellular field potentials were recorded from the third and fifth layers. SD significantly enhanced the repetition rate and amplitude of spontaneous rhythmic potentials in all tested slices. The results indicate that SD may facilitate the synchronization of different foci of rhythmic sharp field potentials and increase the excitability in human brain tissue.
Minocycline protects basal forebrain cholinergic neurons from mu p75‐saporin immunotoxic lesioning
Authors: Hunter Christopher L. , Quintero E. Matthew , Gilstrap Lindsay , Bhat Narayan R. , Granholm Ann‐Charlotte
Published: June 2004

Two prominent characteristics of Alzheimer's disease are basal forebrain cholinergic degeneration and neuroinflammation characterized by glial activation and the release of pro‐inflammatory cytokines. Mu p75‐ saporin (SAP) is a novel immunotoxin that mimics the selective loss of basal forebrain cholinergic neurons and induces cognitive impairment in mice. We report that cholinergic cell loss in the medial septal nucleus and ventral diagonal band after i.c.v. injection of mu p75‐SAP is accompanied by simultaneous activation of microglia and astrocytes in the basal forebrain region as well as significant memory loss. Consistent with a role of glial cells in the pathology of Alzheimer's disease, minocycline, a second‐generation tetracycline with known anti‐inflammatory and neuroprotective properties, attenuated mu p75‐SAP‐induced cholinergic cell loss, glial activation and transcription of downstream pro‐inflammatory mediators. In addition to neuroprotection, minocycline treatment mitigated the cognitive impairment that appears to be a functional consequence of mu p75‐SAP lesioning. The current study demonstrates that glial‐related inflammation plays a significant role in the selective neurotoxicity of mu p75‐SAP, and suggests that minocycline may provide a viable therapeutic option for degenerating cholinergic systems.
Spinal NF‐kB activation induces COX‐2 upregulation and contributes to inflammatory pain hypersensitivity
Authors: Lee Kyung‐Min , Kang Bong‐Seok , Lee Hye‐Lim , Son Sun‐Joo , Hwang Sung‐Hun , Kim Dong‐Sun , Park Jae‐Sik , Cho Hee‐Jung
Published: June 2004

Cyclooxygenase‐2 (COX‐2) is a major contributor to the elevation of spinal prostaglandin E2, which augments the processing of nociceptive stimuli following peripheral inflammation, and dynorphin has been shown to have an important role in acute and chronic pain states. Moreover, the transcription factor, nuclear factor‐kappa B (NF‐kB), regulates the expressions of both COX‐2 and dynorphin. To elucidate the role of spinal NF‐kB in the induction of inflammatory pain hypersensitivity, we examined whether activated NF‐kB affects pain behavior and the expressions of the mRNAs of COX‐2 and prodynorphin following peripheral inflammation. Intrathecal pretreatment with different NF‐kB inhibitors, namely, NF‐kB decoy or pyrrolidine dithiocarbamate, significantly reduced mechanical allodynia and thermal hyperalgesia following unilateral hindpaw inflammation evoked by complete Freund's adjuvant (CFA). These NF‐kB inhibitors also suppressed the activation of spinal NF‐kB and the subsequent remarkable elevation of spinal COX‐2 mRNA, but not that of prodynorphin mRNA. In addition, the activation of spinal NF‐kB following CFA injection was inhibited by intrathecal pretreatments with interleukin‐1β receptor antagonist or caspase‐1 inhibitor. In view of the fact that interleukin‐1 beta (IL‐1β) is the major inducer of spinal COX‐2 upregulation following CFA injection, our results suggest that IL‐1β‐induced spinal COX‐2 upregulation and pain hypersensitivity following peripheral inflammation are mediated through the activation of the NF‐kB‐associated pathways.
Selective antagonism of medial prefrontal cortex D4 receptors decreases fear‐related behaviour in rats
Authors: Shah Akeel A. , Sjovold Travis , Treit Dallas
Published: June 2004

It is well known that the mesolimbocortical dopamine pathway is highly active during periods of stress and fear. However, very little research has directly examined how dopamine receptors in this pathway influence fear‐related behaviour. The present study examined the effects of selective antagonism of D4, D1 and D2 dopamine receptors of the medial prefrontal cortex (MPFC) on rats' fear behaviour in the elevated plus‐maze and the shock‐probe burying tests. The results demonstrated that bilateral intra‐MPFC infusions of the highly selective D4 antagonist, L‐745 870 (0.2, 1 or 10 nmol/0.5 µL), increased the percentage of open‐arm entries and open‐arm time in the elevated plus‐maze test (1 nmol/0.5 µL), and decreased the duration of burying in the shock‐probe test (0.2 or 1 nmol/0.5 µL). Furthermore, none of the doses of the D4 antagonist affected measures of general activity or pain sensitivity. Intra‐MPFC infusions of the D1 antagonist, SCH‐23390 (0.2 or 1 nmol/0.5 µL), or the D2 antagonist, remoxipride (0.2, 1 or 10 nmol/0.5 µL), had no significant behavioural effects in either test. Taken together, these findings suggest that MPFC D4 receptors may play an important role in the mediation of fear‐related behaviour.
Heparin‐mediated selective release of hepatocyte growth factor in humans
Authors: Salbach Peter Bernhard , Brückmann Martina , Turovets Oleg , Kreuzer Jörg , Kübler Wolfgang , Walter‐Sack Inge
Published: June 2004

Aims
The aim of this investigation was to compare the effects of standard (S) with low molecular weight (LMW) heparin on circulating levels of heparin‐binding growth factors (HBGF), known to have angiogenic properties in humans.

Methods
In two consecutive trials 18 healthy male voluteers were studied on three separate occasions, following a placebo‐controlled crossover design. Subjects were randomised to receive either S‐heparin or LMW heparin or placebo. Heparins were administered either by intravenous (i.v.) or subcutaneous (s.c.) injection and saline placebo by i.v. injection. Serum concentrations of hepatocyte growth factor (HGF), vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured before and up to 24 h after injection.

Results
Administration of i.v. S‐or LMW‐heparin (50 IU kg−1) resulted in rapid, highly significant (47 fold for S, 30.9 fold for LMW) increases in HGF serum values, reaching maxima of 10.51 ± 1.65 ng ml−1 (S) and 8.28 ± 1.04 ng ml−1 (LMW), respectively, 10 min after drug application. S.c. injection of S‐heparin or LMW heparin resulted in 4.1 and 5.4 fold increases in HGF serum values, respectively. Both agents showed no effects on circulating VEGF or bFGF levels, independent of the route of administration.

Conclusions
Circulating HGF levels were selectively increased in response to pharmacological doses of two, widely used heparin preparations. This may, in part, explain some of the biological effects of heparin separate from its anticoagulant properties. By this mechanism, the systemic administration of heparin may facilitate collateral vessel formation in various clinical settings of tissue ischaemia.
Escape of a plant virus from amplicon‐mediated RNA silencing is associated with biotic or abiotic stress
Authors: Taliansky Michael , Kim Sang Hyon , Mayo Mike A. , Kalinina Natalia O. , Fraser Gillian , McGeachy Kara D. , Barker Hugh
Published: June 2004

Strong RNA silencing was induced in plants transformed with an amplicon consisting of full‐length cDNA of potato leafroll virus (PLRV) expressing green fluorescent protein (GFP), as shown by low levels of PLRV‐GFP accumulation, lack of symptoms and accumulation of amplicon‐specific short interfering RNAs (siRNAs). Inoculation of these plants with various viruses known to encode silencing suppressor proteins induced a striking synergistic effect leading to the enhanced accumulation of PLRV‐GFP, suggesting that it had escaped from silencing. However, PLRV‐GFP escape also occurred following inoculation with viruses that do not encode known silencing suppressors and treatment of silenced plants with biotic or abiotic stress agents. We propose that viruses can evade host RNA‐silencing defences by a previously unrecognized mechanism that may be associated with a host response to some types of abiotic stress such as heat shock.
Cell wall invertase expression at the apical meristem alters floral, architectural, and reproductive traits in Arabidopsis thaliana
Authors: Heyer Arnd G. , Raap Maik , Schroeer Birgit , Marty Bruno , Willmitzer Lothar
Published: June 2004

Resource allocation is a major determinant of plant fitness and is influenced by external as well as internal stimuli. We have investigated the effect of cell wall invertase activity on the transition from vegetative to reproductive growth, inflorescence architecture, and reproductive output, i.e. seed production, in the model plant Arabidopsis thaliana by expressing a cell wall invertase under a meristem‐specific promoter. Increased cell wall invertase activity causes accelerated flowering and an increase in seed yield by nearly 30%. This increase is caused by an elevation of the number of siliques, which results from enhanced branching of the inflorescence. On the contrary, as cytosolic enzyme, the invertase causes delayed flowering, reduced seed yield, and branching. This demonstrates that invertases not only are important in determining sink strength of storage organs but also play a role in regulating developmental processes.
The risk for Chagas' disease in the Midwestern United States organ donor population is low
Authors: Bryan Christopher F , Tegtmeier Gary E , Rafik Nour , Markham Lori E , Murillo Daniel , Nelson Paul W , Shield Charles F , Warady Bradley A , Aeder Mark I
Published: June 2004

Abstract:  Purpose:  Several recent publications have increased awareness that transplanted organs can transmit infectious diseases. In light of the recent report describing the transmission of Trypanosoma cruzi infection by an organ donor in the United States (MMWR 2002: 51: 210), we have tested archived serum samples from our Organ Procurement Organization's (OPO's) deceased organ donors and live donors from 23 October 1995 through 1 March 2002.

Methods:  A total of 1117 serum samples from 558 locally recovered deceased donors, 178 imported deceased donors, and 212 live donors were tested (several duplicates were included). Samples were screened for antibodies to T. cruzi, the protozoan parasite that causes Chagas' disease, with a passive particle agglutination assay (Fujirebio, Inc., Tokyo, Japan). Indeterminate samples (those agglutinating both sensitized and control particles) were absorbed with control antigen and re‐tested. Inconclusive samples (those not yielding clearly negative or positive results) were re‐tested using the original test format, and if persistently inconclusive, were assayed by radio‐immune precipitation (RIPA).

Results:  Of the 770 local OPO donors (deceased and live donor) and the 178 imported donors tested, 52 (5.5%) were indeterminate, but following absorption, all were negative. Forty‐four samples (4.6%) were inconclusive and after re‐testing 34 were negative while 10 remained inconclusive. Those 10 samples were found to be negative by RIPA.

Conclusions:  The risk of transmission of Chagas' disease by organ transplantation in the Midwestern United States is low because during a 6.5 year period, none of our deceased or live donors tested positive for antibodies to T. cruzi. Although the passive particle agglutination test is simple to perform, easy to interpret and rapid enough to be used in screening organ donors, because of the rate of false positive results, it should only be utilized when the donor population is at high risk for previous exposure to T. cruzi.
Sensitivity of expanded‐criteria donor kidneys to cold ischaemia time
Authors: Johnston Thomas D , Thacker Leroy R , Jeon Hoonbae , Lucas Bruce A , Ranjan Dinesh
Published: June 2004

Abstract:  The United Network for Organ Sharing (UNOS), working in conjunction with organ procurement organizations and transplant programmes, has recently defined a class of cadaver kidney grafts for special allocation procedures to enhance utilization of those organs. The criteria defining these expanded‐criteria donor (ECD) kidneys are donor age ≥ 60 yr or donor age between 50 and 59 yr plus two of the following characteristics: donor history of cerebrovascular accident (CVA), donor history of hypertension (htn), and elevated creatinine (>1.5) at any time during donor management. Kidney grafts from ECD donors carry an increased relative risk of non‐function compared to other cadaver kidney grafts. The goal of the special allocation procedure is to reduce the time associated with placement by matching ECD grafts with patients previously designated as being willing to accept them. In assessing the potential impact of these allocation procedures, the sensitivity of ECD grafts to cold ischaemia time (CIT) became of great significance. Specifically, we questioned whether minimization of CIT might reduce the relative risk of poor graft function, justifying reduction of the geographical range of placement and thereby reducing the time the grafts would spend in‐transit.

Methods:  To assess this, we queried the SEOPF database for cadaveric kidney transplants between 1/1/1997 and 15/8/2002. There were 1312 transplants from ECD donors during this period and 8451 from non‐ECD donors. Between these groups, there were no significant differences in recipient gender, ethnicity, peak and most recent panel reactive antibody (PRA). Recipients of ECD kidneys were significantly older: 50.9 ± 13.0 yr vs. 44.9 ± 13.9 (mean age ± SD, P < 0.0001). There were statistically significant but very small differences in the degree of AB and DR mismatch between the groups.

Results:  Defining delayed graft function (DGF) as dialysis within the first week post‐transplant and primary non‐function (PNF) as dialysis within the first week and failure in the first year, we found an association with CIT as illustrated in Table 1. Overall, ECD kidneys had a significantly increased (P < 0.0001) incidence of PNF and DGF. Notably, PNF in ECD appeared to be uniformly distributed across CIT and while DGF was CIT‐dependent, the DGF differences between ECD and non‐ECD were fairly consistent across CIT.

Conclusion:  While CIT minimization is potentially beneficial, ECD kidneys do not appear to be more sensitive to it than non‐ECD kidneys.
The Living Organ Donor Network: a model registry for living kidney donors
Authors: McCune Thomas R , Armata Thomas , Mendez‐Picon Gerardo , Yium Jackson , Zabari Gazi B , Crandall Betty , Spicer Helen G , Blanton Jack , Thacker Leroy R
Published: June 2004

Abstract:  The South‐Eastern Organ Procurement Foundation presents the first report on a programme to track donors through questionnaires completed at the time of donation, 3 months, 6 months, and yearly thereafter. Donors at participating centres were eligible for an insurance policy with a total benefit of $250 000, covering accidental death related to donation, surgery, medical expenses of complications, and disability income. The four participating centres have registered 104 donors. Response rate to the questionnaires was 90.91%. The majority of the donors come from the immediate family (81.62%), either by blood or marriage. The majority of donors are employed full time, with income ranges similar to the national census. Donors rely on employer‐provided vacation time and sick leave to recuperate, but the average donor required 12 days of unpaid leave before returning to work. Donors also experienced costs of transportation, lodging, and childcare. Anti‐depressants were prescribed to 10.58% of donors, and 4.8% of donors reported they are treated for hypertension. Complications were reported by 37.5% of the donors, but only 7.6% of the complications were serious enough to require hospitalization or surgery. Donors reported higher complication rates than reported by the centres and experience financial burdens afterwards.