bluuebunny/crossref_metadata_2025 huggingface dataset:
Taxonomy and fossils: a critical appraisal
Authors: Forey Peter L. , Fortey Richard A. , Kenrick Paul , Smith Andrew B.
Published: April 2004

Many compendia at the species, genus and family levels document the fossil record, but these are not standardized, nor usually critical in content, and few are available on the World Wide Web. The sampling of the available record is good for organisms with fossilizable parts, but preservational constraints on the entire morphology, life history and geographical distribution lead to difficulties in recognizing and naming species. We recommend abandoning some of the palaeontological species concepts such as chronospecies and stratospecies, and we advocate species recognition based on unique combinations of characters. The compilation of species lists is extremely time consuming, and given the inherent problems we suggest that compilation of generic lists is a more achievable goal because genera are recognized by definitive morphological characters. In calculating taxon duration, care must be taken to distinguish between mono–, para– and polyphyletic groups, the first being the only reliable unit for use in calculating diversity curves. We support the inclusion of fossils into classifications based on Recent organisms, but we recognize some of the problems this may pose for standard Linnaean classifications. Web–based taxonomy is the way forward, having the advantages of speed and currency of information dissemination, universal access with links to primary literature and increasingly sophisticated imagery. These advantages over conventional outlets will only be realized with careful Web design and a commitment to maintenance.
The role of taxonomy in species conservation
Authors: Mace Georgina M.
Published: April 2004

Taxonomy and species conservation are often assumed to be completely interdependent activities. However, a shortage of taxonomic information and skills, and confusion over where the limits to ‘species’ should be set, both cause problems for conservationists. There is no simple solution because species lists used for conservation planning (e.g. threatened species, species richness estimates, species covered by legislation) are often also used to determine which units should be the focus of conservation actions; this despite the fact that the two processes have such different goals and information needs. Species conservation needs two kinds of taxonomic solution: (i) a set of practical rules to standardize the species units included on lists; and (ii) an approach to the units chosen for conservation recovery planning which recognizes the dynamic nature of natural systems and the differences from the units in listing processes that result. These solutions are well within our grasp but require a new kind of collaboration among conservation biologists, taxonomists and legislators, as well as an increased resource of taxonomists with relevant and high–quality skills.
Introduction
Authors: Godfray H. C. J. , Knapp S.
Published: April 2004

As we enter the twenty–first century, the demand for taxonomy is greater than ever before. The global imperative for the conservation of biodiversity has brought into sharp focus both the need for and the needs of taxonomic research. Although commentators today frequently, and rightly, stress how comparatively little we know about the diversity of organisms with which we share our planet, we should not lose sight of the enormous progress that has been made in cataloguing, describing and understanding the Earth's plants, animals and microbes. This research programme was probably born among our hunter–gatherer ancestors, baptized by the Greeks, and then reached maturity in post–Enlightenment Europe with the Linnaean revolution. Its success has been due to the legion of naturalists and taxonomists who have explored every nook and cranny of the living world, and to a series of rules and protocols that have allowed this massive corpus of knowledge to be organized and arranged in an age of paper and post. Any student of biology in the nineteenth century, and for perhaps the first three–quarters of the twentieth century, would have spent a large fraction of his or her time learning systematic biology, and the tools and techniques needed to identify and describe various elements of the flora and fauna. Systematic biology and taxonomy was the fertile soil in which emerging sciences such as physiology, genetics, ecology and evolutionary biology had their roots and drew nourishment.
Prokaryote diversity and taxonomy: current status and future challenges
Authors: Oren Aharon
Published: April 2004

The prokaryotes are by far the most abundant organisms inhabiting planet Earth. They are also by far the most diverse, both metabolically and phylogenetically; they encompass the Bacteria and the Archaea, two out of the three major divisions of living organisms. The current prokaryote species classification is based on a combination of genomic and phenotypic properties. The recommended cut–off value of 70% DNA–DNA similarity to delineate species signifies an extremely broad species definition for the prokaryotes compared with the higher eukaryotes. The number of validly named species of prokaryotes is currently slightly more than 6200. However, on the basis of small–subunit rDNA characterization of whole communities and other approaches, the more exact number of species present can be inferred to be at least two orders of magnitude larger. Classic culturing methods based on colony formation on agar are generally unsatisfactory for the recovery of bacteria from the environment. Many of the most abundant prokaryotes in nature have not yet been brought into culture. Some of these may thrive by means of as yet unknown modes of energy generation. Several novel methods have recently enabled the isolation of some interesting organisms of environmental significance. A better coverage of the prokaryote diversity on Earth depends on such innovative approaches, combined with appropriate funding.
Taxonomy and environmental policy
Authors: Samper Cristián
Published: April 2004

In 1992, with the United Nations Conference on Environment and Development in Rio de Janeiro and the subsequent Convention on Biological Diversity (CBD), the world changed for the science of taxonomy. Many taxonomists appear not to have noticed this change, but it has significantly altered the political climate in which taxonomic research is undertaken. By the late 1990s it was clear that effective implementation of the CBD needed the participation of and funding for the taxonomic community. In this paper, I chart the rise of the Global Taxonomy Initiative (GTI), review some of its goals and explore how it interacts with the CBD. The interactions of the GTI with the Global Environment Facility, a potential funding body, are explored, as are the possible synergies between the GTI and the many other global initiatives linking to taxonomy. Finally, I explore some of the challenges ahead as taxonomy begins to take a front seat in the implementation of environmental policy on the world stage.
Consequences of pastoral abandonment for the structure and diversity of the alpine avifauna
Authors: Laiolo Paola , Dondero Francesca , Ciliento Enza , Rolando Antonio
Published: April 2004

There is a long‐term trend of depopulation of rural areas and pasture abandonment throughout the Alps. This trend peaked after the Second World War and is now omnipresent. Its ecological consequences are evident mostly below the timberline, where grassland gradually turns into shrub and, ultimately, to forest. This study addresses the consequences of land abandonment and the decline of pastoral practices on the diversity and structure of the bird communities of the Italian Alps.

The breeding birds of Gran Paradiso Natural Park in north‐western Italy were surveyed, and bird diversity, abundance of grassland, ecotone, woodland and shrub species were analysed using regression in relation to a set of explanatory variables including elevation, local habitat variables, landscape variables and grazing intensity.

Avian diversity increased in abandoned pastures as higher numbers of shrub species followed tree and shrub encroachment. Conversely, open habitat species that benefited from grazing were mostly confined to pure grasslands and high altitudes.

The effects of grazing were more evident in the montane belt. Grazing maintained open habitats by limiting tree and scrub encroachment, thereby favouring grassland bird species. At higher altitudes, however, grazing had little effect on typical open habitat alpine species (choughsPyrrhocoraxspp., water pipitAnthus spinoletta, alpine accentorPrunella collaris, wheatearOenanthe oenanthe, snow finchMontifringilla nivalis, rock thrushMonticola saxatilis) and only skylarkAlauda arvensisand linnetCarduelis cannabinapreferred grazed meadows.

Synthesis and applications. This study shows that the abandonment of grazing in the Alps has significant effects on bird species diversity and abundance, especially below the timberline where pastoral decline leads to significant changes in vegetation structure. However, grazing importance differs markedly depending on whether the focus is avian α‐diversity or grassland bird abundance. Pastoral abandonment leads to an overall increase in avian diversity, but most species invading abandoned pastures are already common, whereas several grassland bird species that are dependent upon grazed pastures have an unfavourable conservation status. Overall, in terms of bird conservation objectives, large‐scale abandonment of long‐established pastoral habitats and their complete replacement with scrub, or even forest, is likely to be detrimental.
Platelet storage solution effects on the accuracy of laboratory tests for platelet function: a multi‐laboratory study
Authors: VandenBroeke T. , Dumont L. J. , Hunter S. , Nixon J. , Murphy S. , Roger J. , Herschel L. , AuBuchon J. P. , Gulliksson H. , Dengler T. , Hornsey V. , Prowse Chris ,   for the Biomedical Excellence for Safer Transfusion Working Party of the International Society of Blood Transfusion
Published: April 2004

Background and Objectives  Extent of shape change (ESC) and hypotonic shock response (HSR) have been widely used to characterize the in vitro function of platelets and have been shown to correlate with in vivo viability. These assays have been routinely performed using platelet‐poor plasma (PPP) as the test sample diluent. Because of the increasing popularity of storing platelets in synthetic media, it is important to understand the effects of using these synthetic media as test diluents for ESC and HSR measurements. The objective of this study was to determine the effect of using platelet storage solutions vs. plasma for the in vitro testing of ESC and HSR.

Materials and Methods  Six laboratories participated in this study. Platelets were prepared by apheresis, the platelet‐rich plasma (PRP) method, or derived from buffy‐coats. Each platelet preparation was divided, half being stored in plasma and the other half in storage solution. ESC and HSR testing were performed in duplicate on days 1 and 5, using each of three diluents: autologous plasma; fresh‐frozen plasma; or storage solution.

Results  For both ESC and HSR, dilutions made in each of the three diluents yielded significantly different results. Dilutions made in storage solutions were more than 30% lower for ESC and HSR than those made in autologous plasma (P < 0·0001). Dilutions made in thawed fresh‐frozen plasma were more than 16% lower for ESC and HSR than those made in liquid autologous plasma (P < 0·0005).

Conclusions  ESC and HSR test results are significantly affected by the test diluent. Platelets should be diluted in plasma (preferably autologous) for the in vitro testing of ESC and HSR, regardless of the media in which they are stored.
Population status and structure of mountain nyala in the Bale Mountains National Park, Ethiopia
Authors: Refera Befekadu , Bekele Afework
Published: April 2004

The study on the population status and structure of mountain nyala (Tragelaphus buxtoni) was carried out in the Bale Mountains National Park, Ethiopia during the wet and dry seasons of 2000/2001. Total counts were carried out in an area of 13.1 km2. The count ranged between 682 and 732 individuals. Females comprised 62.9% while males 27.4%. The calf ratio was 9.7%. The group structure of the animals varied with season. Large herds were frequently observed during the wet season and smaller groups during the dry season. Group size changed seasonally. In both seasons, 7–12 individuals were the frequent group size formation. The maximum group (62) was observed during the wet season. The population trend of the animal from 1975 to 1990 indicated a recovery and increase. But between 1990 and 1995 the population showed a continuous and steep decline. However, between 1995 and 2000 the population trend showed a better condition when compared with the previous years.
Spatial dynamics of lions and their prey along an environmental gradient
Authors: Ogutu J. O. , Dublin H. T.
Published: April 2004

Establishing the ecological determinants of the spatial dynamics of large African savanna mammals is necessary for understanding the cumulative impacts on the suitability and resilience of their natural habitats, of progressive habitat fragmentation and temporal shifts in climate, fire regimes and elephant browsing. Systematic directional gradients and small‐scale spatial dependence were evident in rainfall, herbivore biomass and lion density in the Masai Mara National Reserve during September 1990 to July 1992. Lion density, the biomass of resident and all herbivore species were autocorrelated within 4.3, 4.1 and 3.3 km, respectively, and peaked in areas of relatively low rainfall but higher microtopographic and vegetation heterogeneity and complexity and more diverse drainage systems. Rainfall influenced herbivore biomass and hence lion density non‐linearly and that influence was apparently modified by forage mineral nutrients, structural habitat complexity, degree of drainage and distance to waterpoints. Lion density was related to the biomass of resident herbivores, even after controlling for rainfall and spatial trends. Persistence of the recent decline in Mara woodlands and increasing human population along the reserve–ranch boundary would likely reduce the reserve's lion population because most lions spent the daytime within the vegetation mosaic fringing drainage lines, away from humans and domestic livestock.
Human impact on wildlife populations within a protected Central African forest
Authors: Blom Allard , Van Zalinge Robert , Mbea Eugene , Heitkönig Ignas M. A. , Prins Herbert H. T.
Published: April 2004

This paper addresses the effect of human activities on the density of large mammals in the Dzanga‐Ndoki National Park and the adjacent Dzanga‐Sangha Reserve in the Central African Republic.

Between six and eight 20 km long permanent transects were walked on a monthly basis from January 1997 to August 1999 to assess large mammal populations as well as human intrusion. There were no obvious seasonal or monthly trends in elephant, gorilla or non‐human primate densities.

Overall, it appears that human activities negatively influence the distribution of most of the large forest animals in Dzanga‐Sangha. Elephants in particular were significantly less common in areas used by humans, but also other species such as non‐human primates showed lower densities closer to the main road and the town of Bayanga. This study confirms the findings of previous studies that roads have a negative impact on wildlife populations.

Results of this study stress the need for conservation of large uninterrupted forest blocks to maintain wildlife populations at normal levels. Simply creating roads, even within a protected Central African forest, is likely to have negative impacts on wildlife populations.
Crop raiding around Lake Mburo National Park, Uganda
Authors: Kagoro‐Rugunda Grace
Published: April 2004

In areas around Lake Mburo National Park, large wild animals wander in close proximity to human settlements. This poses serious conflict in terms of crop damage. The integration of conservation with other land uses is difficult where densely settled agricultural land surrounds a protected area potentially containing problem animals, as is the case for several parks in Africa and Asia. The intensity of crop raiding was quantified through the use of random crop quadrants/plots and area estimation techniques in a portion of raided fields. The animal species concerned were documented from observations, footprints and any other marks left behind. Three variables were tested as predictors of damage: human population density, distance from the park boundary and season. In this study, data is presented regarding crop loss in the different seasons of the year, analysis of crop damage variation and animal species involved in crop loss. A diverse assemblage of animals foraged on subsistence crops and analysis of crop damage revealed significant crop depreciation by wildlife.
The food and feeding habits of blackspot snapper, Lutjanus fulviflamma (Pisces: Lutjanidae) in shallow waters of Mafia Island, Tanzania
Authors: Kamukuru A. T. , Mgaya Y. D.
Published: April 2004

Natural diet and feeding habits of blackspot snapper, Lutjanus fulviflamma (Forsskål 1775) were investigated in Mafia Island Marine Park (MIMP) and intensively fished areas (IFA) between May 1999 and April 2001. An index of relative importance (IRI) was used to assess the food preference for L. fulviflamma. Feeding habits were studied with respect to sex and size of the predator, seasons and feeding periodicity. Of 4642 L. fulviflamma specimens sampled, 46% had empty stomachs. Brachyurans were the main prey of L. fulviflamma accounting for 48% IRI. Benthic invertebrates dominated by other crustaceans, gastropods, bivalves, cephalopods and polychaetes and demersal teleosts made up the remainder of the diet. Female and male L. fulviflamma were not effectively segregated by trophic dimension in the study areas. Specimens in the 90–120 mm total length (TL) fed exclusively on crustaceans, with shrimps accounting for 40% IRI. Lutjanus fulviflamma in the 270–300 mm TL preferred fish prey accounting for 50% IRI. The diet of fish species showed clear spatial differences, which were dependent on size distributions. Lutjanus fulviflamma fed mostly but not exclusively at night peaking at dusk and dawn. The results clearly demonstrate that L. fulviflamma is an opportunistic forager, which exhibits both diel and ontogenetic feeding habits.
Paraneoplastic immunobullous disease with an epidermolysis bullosa acquisita phenotype: Two cases demonstrating remission with treatment of gynaecological malignancy
Authors: Chamberlain Alexander J , Cooper Susan M , Allen Jill , Dean Diane , Baxter Kay F , Goodfield Mark JD , Wojnarowska Fenella
Published: April 2004

Two cases of paraneoplastic immunobullous disease occurring in women with gynaecological malignancies are reported. Both cases demonstrated mechanobullous mucocutaneous blistering as is typically seen in epidermolysis bullosa acquisita. Their immunopathology, however, favoured a dermal‐binding mucous membrane pemphigoid (MMP) (or possibly bullous pemphigoid) for patient 1 and laminin‐5 MMP for patient 2. Both patients showed resolution of blistering within 1 year of treatment of their malignancies; uterine and ovarian carcinoma, respectively. These cases are of interest because of their paraneoplastic nature; as well as overlapping clinicoimmunopathological features. In addition, patient 2 is, as far as we are aware, the first report of ovarian‐carcinoma‐associated laminin‐5 MMP.
Intralesional 5‐fluorouracil in the treatment of keloid scars
Authors: Apikian Martine , Goodman Greg
Published: April 2004

Two patients with keloid scars are described. The first patient presented with extensive keloid scarring on both cheeks secondary to acne. The second patient developed a keloid scar on her chest following excision of a mole. Both patients' scars were diagnosed clinically and treated with fortnightly injections of a mixture of 5‐fluorouracil and betamethasone acetate and betamethasone sodium phosphate. At each injection session up to 1.6 mL of 5‐fluorouracil at a concentration of 500 mg/10 mL and 0.4 mL of betamethasone acetate and betamethasone sodium phosphate (as betamethasone acetate 3 mg in suspension and betamethasone sodium phosphate 3.9 mg in solution) were used. Multiple treatments were required to obtain resolution of the keloid scars. Improvement was maintained in both patients at 1 year post treatment.
Mouse photoreceptor synaptic ribbons lose and regain material in response to illumination changes
Authors: Spiwoks‐Becker Isabella , Glas Martin , Lasarzik Irina , Vollrath Lutz
Published: April 2004

Chemical synapses equipped with ribbons are tonically active, high‐output synapses. The ribbons may play a role in the trafficking of synaptic vesicles. Recent findings in retinal rod cells of BALB/c mice indicate that ribbons are large and smooth in the dark phase, and, due to the formation and release of protrusions, small during the light phase. As a consequence of these changes, ribbons may traffick fewer vesicles in the light than in the dark phases. The aim of the present study was to find out whether the above ribbon changes in this mouse strain are strictly illumination‐dependent and which signalling processes may be involved. Here, we show that ribbons form protrusions and release them into the cytoplasm within 30–60 min after lights on, the reverse occurring within 30 min after lights off. Under constant light or constant dark, no circadian rhythm of synaptic ribbon changes is observed. The illumination‐dependence of ribbon structure is supported by in vitro experiments showing that in dark‐adapted retinas, light induces the same morphological changes as in vivo. In vitro, the effect of light on the ribbons can be counteracted by cyclic guanosine monophosphate and melatonin. In dark‐adapted retinas, light effects can be produced by decreasing the calcium ion concentrations in the incubation media. These results suggest that in retinal rod cells, the well known phototransduction signalling mechanisms may be responsible for the ribbon changes presently and previously reported.
Mutational scanning of the human serotonin transporter reveals fast translocating serotonin transporter mutants
Authors: Kristensen Anders S. , Larsen Mads B. , Johnsen Laust B. , Wiborg Ove
Published: April 2004

The serotonin transporter (SERT) belongs to a family of sodium–chloride‐dependent transporters responsible for uptake of amino acids and biogenic amines from the extracellular space. SERT represents a major pharmacological target in the treatment of several clinical conditions, including depression and anxiety. In the present study we have undertaken a mutational scanning of human SERT in order to identify residues that are responsible for individual differences among related monoamine transporters. One mutant, G100A, was inactive in transport. However, ligand binding affinity was similar to wild‐type, suggesting that G100A amongst different possible SERT conformations is restrained to a binding conformation. We suggest that the main role of glycine‐100 is to confer structural flexibility during substrate translocation. For the two single mutants, T178A and F263C, uptake rates and Km values were both several‐fold higher than wild‐type while binding affinities and inhibitory potencies decreased considerably for several drugs. Ion dependency increased and only at hyperosmotic concentrations were Km values partly restored. For the double mutant, T178A/F263C, shifts in uptake kinetics and ligand affinities, as well as ion dependencies, were drastic. Effects were synergistic compared to the corresponding single mutants. In conclusion, we suggest that mutating threonine‐178 to an alanine and phenylalanine‐263 to a cysteine mainly alter the overall uptake kinetics of SERT by affecting the conformational equilibrium of different transporter conformations.
PACAP inhibits delayed rectifier potassium current via a cAMP/PKA transduction pathway: evidence for the involvement of IK in the anti‐apoptotic action of PACAP
Authors: Mei Y. A. , Vaudry D. , Basille M. , Castel H. , Fournier A. , Vaudry H. , Gonzalez B. J.
Published: April 2004

Activation of potassium (K+) currents plays a critical role in the control of programmed cell death. Because pituitary adenylate cyclase‐activating polypeptide (PACAP) has been shown to inhibit the apoptotic cascade in the cerebellar cortex during development, we have investigated the effect of PACAP on K+ currents in cultured cerebellar granule cells using the patch‐clamp technique in the whole‐cell configuration. Two types of outward K+ currents, a transient K+ current (IA) and a delayed rectifier K+ current (IK) were characterized using two different voltage protocols and specific inhibitors of K+ channels. Application of PACAP induced a reversible reduction of the IK amplitude, but did not affect IA, while the PACAP‐related peptide vasoactive intestinal polypeptide had no effect on either types of K+ currents. Repeated applications of PACAP induced gradual attenuation of the electrophysiological response. In the presence of guanosine 5′‐[γthio]triphosphate (GTPγS), PACAP provoked a marked and irreversible IK depression, whereas cell dialysis with guanosine 5′‐[βthio]diphosphate GDPβS totally abolished the effect of PACAP. Pre‐treatment of the cells with pertussis toxin did not modify the effect of PACAP on IK. In contrast, cholera toxin suppressed the PACAP‐induced inhibition of IK. Exposure of granule cells to dibutyryl cyclic adenosine monophosphate (dbcAMP) mimicked the inhibitory effect of PACAP on IK. Addition of the specific protein kinase A inhibitor H89 in the patch pipette solution prevented the reduction of IK induced by both PACAP and dbcAMP. PACAP provoked a sustained increase of the resting membrane potential in cerebellar granule cells cultured either in high or low KCl‐containing medium, and this long‐term depolarizing effect of PACAP was mimicked by the IK specific blocker tetraethylammonium chloride (TEA). In addition, pre‐incubation of granule cells with TEA suppressed the effect of PACAP on resting membrane potential. TEA mimicked the neuroprotective effect of PACAP against ethanol‐induced apoptotic cell death, and the increase of caspase‐3 activity observed after exposure of granule cells to ethanol was also significantly inhibited by TEA. Taken together, the present results demonstrate that, in rat cerebellar granule cells, PACAP reduces the delayed outward rectifier K+ current by activating a type 1 PACAP (PAC1) receptor coupled to the adenylyl cyclase/protein kinase A pathway through a cholera toxin‐sensitive Gs protein. Our data also show that PACAP and TEA induce long‐term depolarization of the resting membrane potential, promote cell survival and inhibit caspase‐3 activity, suggesting that PACAP‐evoked inhibition of IK contributes to the anti‐apoptotic effect of the peptide on cerebellar granule cells.
BDNF and NT‐3 promote thalamocortical axon growth with distinct substrate and temporal dependency
Authors: Hanamura Kenji , Harada Akiko , Katoh‐Semba Ritsuko , Murakami Fujio , Yamamoto Nobuhiko
Published: April 2004

The role of neurotrophins in thalamic axon growth was studied by culturing embryonic rat thalamus on collagen‐coated substrate or fixed cortical slices in the presence of either brain‐derived neurotrophic factor (BDNF) or neurotrophin‐3 (NT‐3). Both BDNF and NT‐3 promoted axonal growth, but the axonal growth‐promoting activity depended on culture substrates. Axonal growth on collagen‐coated membrane was accelerated by BDNF, but not by NT‐3. In contrast, axonal outgrowth on fixed cortex was significantly enhanced by NT‐3, but not by BDNF. Semi‐quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) analysis of cultured thalamic cells demonstrated that culture substrates did not alter the expression of their receptors, trkB and trkC. Terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling (TUNEL) staining further demonstrated that axonal growth promoted by neurotrophins was not due to reduction of cell death. Measurement of the developmental changes in BDNF and NT‐3 levels revealed that, in contrast to the rapid elevation of BDNF after the arrival of thalamocortical axons to their target layer, the regulation of NT‐3 protein accompanies the phase of their outgrowth in neocortex. These findings suggest that BDNF and NT‐3 promote thalamic axon growth in different manners in terms of substrate dependency and developmental stage.
Repeated acetyl‐l‐carnitine administration increases phospho‐Thr34 DARPP‐32 levels and antagonizes cocaine‐induced increase in Cdk5 and phospho‐Thr75 DARPP‐32 levels in rat striatum
Authors: Scheggi Simona , Rauggi Riccardo , Nanni Giulio , Tagliamonte Alessandro , Gambarana Carla
Published: April 2004

Acute cocaine administration increases phosphorylation of dopamine and cAMP‐regulated phosphoprotein (Mr 32 kDa) (DARPP‐32) at threonine (Thr)‐34, whereas repeated cocaine administration increases DARPP‐32 phosphorylation at Thr‐75 in Sprague–Dawley rat striatum. Repeated acetyl‐l‐carnitine (ALCAR) administration persistently increases dopamine outflow in the nucleus accumbens. The present study examined the effect of repeated ALCAR administration on the DARPP‐32 phosphorylation pattern in the nucleus accumbens and caudate‐putamen. ALCAR increased phosphoThr‐34 DARPP‐32 levels and decreased phosphoThr‐75 DARPP‐32 levels, after 1 and 10 days of washout. We compared the effects of repeated cocaine and repeated ALCAR administrations on the behavioural response to cocaine challenge and on the DARPP‐32 phosphorylation pattern and cyclin‐dependent kinase 5 (Cdk5) levels in the striatum. We also studied whether ALCAR administered daily during or after cocaine sensitization procedure would interfere with the effects of cocaine. When the response to the cocaine challenge was assessed, cocaine‐ and ALCAR‐treated rats showed a similar sensitized behavioural response, and rats receiving combined cocaine and ALCAR treatments, irrespective of treatment order, also showed a sensitized response. A week after the cocaine challenge, the two drugs had induced opposite modifications in DARPP‐32 phosphorylation, as cocaine increased phosphorylation at Thr‐75, while ALCAR increased phosphorylation at Thr‐34. In cocaine plus ALCAR treated rats, irrespective of treatment order, ALCAR administration antagonized cocaine effects on DARPP‐32 phosphorylation. Moreover, cocaine, but not ALCAR, increased ΔFosB and Cdk5 expression, and the increase in Cdk5 was antagonized by ALCAR administration in rats receiving combined treatments. These effects were relatively persistent, as they were still present 7 days after the last treatment.
Heterozygous PAX6 mutation, adult brain structure and fronto‐striato‐thalamic function in a human family
Authors: Ellison‐Wright Zoë , Heyman Isobel , Frampton Ian , Rubia Katya , Chitnis Xavier , Ellison‐Wright Ian , Williams Steve C. R. , Suckling John , Simmons Andrew , Bullmore Edward
Published: April 2004

Recent progress in developmental neurobiology and neuroimaging can be drawn together to provide new insight into the links between genetically specified processes of embryonic brain development and adult human brain structure and function. We used magnetic resonance imaging (MRI) to show that individuals with aniridia and deficits in executive and social cognition, due to heterozygous mutation of the neurodevelopmental control gene PAX6, have structural abnormalities of grey matter in anterior cingulate cortex, cerebellum and medial temporal lobe, as well as white matter deficits in corpus callosum. Functional MRI demonstrated reduced activation of fronto‐striato‐thalamic systems during performance of overt verbal fluency and nonsense sentence completion; the most consistent abnormality of verbal executive activation was located in the thalamus. These results provide the first evidence for brain functional differences in humans with PAX6 mutation that are compatible both with anatomical abnormalities in the same subjects and, more circumstantially, with the known roles of murine Pax6 in regional differentiation, axonal guidance and other aspects of early forebrain development. Highly conserved homeobox genes may be critical for normal ontogenesis of large‐scale neurocognitive networks supporting phylogenetically advanced mental functions.
NGF and GDNF ameliorate the increase in ATF3 expression which occurs in dorsal root ganglion cells in response to peripheral nerve injury
Authors: Averill Sharon , Michael Gregory J. , Shortland Peter J. , Leavesley Rachel C. , King Von R. , Bradbury Elizabeth J. , McMahon Stephen B. , Priestley John V.
Published: April 2004

Activating transcription factor‐3 (ATF3) is a member of the ATF/CREB transcription factor superfamily and is induced in dorsal root ganglion (DRG) cells after nerve injury. In order to study the regulation of ATF3, we have examined the effect of nerve growth factor (NGF) and glial cell line‐derived neurotrophic factor (GDNF) on ATF3 expression. In untreated rats, sciatic nerve transection induced ATF3 immunoreactivity in 82% of L4 DRG cells at 14 days after axotomy. Intrathecal delivery of NGF or GDNF for 2 weeks commencing immediately after injury reduced the ATF3 expression to 35 and 23% of DRG cells, respectively. Cell size analysis indicated that NGF had protected a population of mainly small‐ to medium‐sized cells, but that the GDNF had protected a population of both small and large cells. This effect was confirmed by double labelling for P2X3, CGRP and 200 kDa neurofilament, markers for small peptide‐poor cells, peptide‐rich cells and large cells, respectively. Thus GDNF reduced the percentage of ATF3‐immunoreactive P2X3 cells from 70 to 4%, and the percentage of ATF3‐immunoreactive neurofilament cells from 63 to 24%. NGF was less effective than GDNF in reducing ATF3 expression in these cell types, but reduced the percentage of ATF3‐immunoreactive CGRP cells from 10% to < 1%. These results show that ATF3 expression in specific populations of DRG cells can be modulated by exogenous supplementation of specific trophic factors, and suggest that ATF3 expression may normally be induced by the loss of target‐derived NGF and GDNF.
Enhanced mismatch negativity brain response after binaural word presentation
Authors: Endrass Tanja , Mohr Bettina , Pulvermüller Friedemann
Published: April 2004

An oddball paradigm was used to investigate brain processes elicited by spoken words and pseudowords played monaurally, to the left or right ear, or simultaneously to both ears of human subjects instructed to ignore acoustic stimuli but watch a silent video film. The mismatch negativity (MMN), a neurophysiological index of the automatic activation of cortical memory traces, was calculated as the difference between the event‐related potential elicited by an infrequent deviant stimulus and the event‐related potential to the same item presented as a frequent standard stimulus. Consistent with earlier reports, the MMN to words was larger than that to pseudowords, possibly reflecting the existence of memory traces for spoken words. Bilateral redundant stimulus presentation led to a further increase of the MMN to words relative to both unilateral stimulation modes. This bilateral redundancy gain was absent for pseudowords. We interpret the neurophysiological manifestation of a word‐specific bilateral redundancy gain as evidence for interhemispheric cooperation in the automatic access to memory traces for spoken words. Accordingly, word‐related cortical networks distributed over both hemispheres allow summation of neural activity between and within hemispheres, thereby potentiating the word‐related MMN.
Effects of brain‐derived neurotrophic factor on cell survival, differentiation and patterning of neuronal connections and Müller glia cells in the developing retina
Authors: Pinzón‐Duarte Germán , Arango‐González Blanca , Guenther Elke , Kohler Konrad
Published: April 2004

The aim of the present study was to determine the influence of brain‐derived neurotrophic factor (BDNF) on survival, phenotype differentiation and network formation of retinal neurons and glia cells. To achieve a defined concentration and constant level of BDNF over several days, experiments were performed in an organotypic culture of the developing rat retina. After 6 days in vitro, apoptosis in the different cell layers was determined by TUNEL staining and cell‐type‐specific antibodies were used to identify distinct neuronal cell types and Müller cells. Cultured retinas treated with BDNF (100 ng BDNF/mL medium) were compared with untreated as well as with age‐matched in vivo retinas. Quantitative morphometry was carried out using confocal microscopy. BDNF promoted the in vitro development and differentiation of the retina in general, i.e. the number of cells in the nuclear layers and the thickness of the plexiform layers were increased. For all neurons, the number of cells and the complexity of arborizations in the synaptic layers were clearly up‐regulated by BDNF. In control cultures, the synaptic stratification of cone bipolar cells within the On‐ and Off‐layer of the inner plexiform layer was disturbed and a strong reactivity of Müller cell glia was observed. These effects were not present in BDNF‐treated cultures. Our data show that BDNF promotes the survival of retinal interneurons and plays an important role in establishing the phenotypes and the synaptic connections of a large number of neuronal types in the developing retina. Moreover, we show an effect of BDNF on Müller glia cells.
Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson's disease
Authors: Yasuhara Takao , Shingo Tetsuro , Kobayashi Kazuki , Takeuchi Akira , Yano Akimasa , Muraoka Kenichiro , Matsui Toshihiro , Miyoshi Yasuyuki , Hamada Hirofumi , Date Isao
Published: April 2004

Vascular endothelial growth factor (VEGF) has previously been shown to display neuroprotective effects following ischemia, suggesting that VEGF may potentially be applied as a neuroprotective agent for the treatment of other neurological diseases. In this study, we investigated the neuroprotective capacity of VEGF in a model of Parkinson's disease. VEGF was found to be neuroprotective against cell death of primary E14 murine ventral mesencephalic neurons induced by 6‐hydroxydopamine (6‐OHDA) treatment in vitro. Further, rats receiving a continuous infusion of VEGF into the striatum via encapsulated hVEGF‐secreting cells (baby hamster kidney‐VEGF) displayed a significant decrease in amphetamine‐induced rotational behavior and a significant preservation of tyrosine hydroxylase‐positive neurons and fibers compared with control animals. VEGF likely functions via direct mechanisms by signaling through the neuropilin receptor expressed upon dopaminergic neurons in response to 6‐OHDA treatment. Further, VEGF is likely to promote neuroprotection indirectly by activating the proliferation of glia and by promoting angiogenesis. Our results support a potential neuroprotective role for VEGF in the treatment of Parkinson's disease.
Glutamate release increases during mossy‐CA3 LTP but not during Schaffer‐CA1 LTP
Authors: Kawamura Yoshinobu , Manita Satoshi , Nakamura Takeshi , Inoue Masashi , Kudo Yoshihisa , Miyakawa Hiroyoshi
Published: April 2004

It is still a matter of dispute whether the expression of hippocampal long‐term potentiation (LTP) is due to enhanced transmitter release or enhanced postsynaptic sensitivity. Recently we developed a novel method to monitor synaptically released glutamate. In this method, brain slice preparations are stained with a voltage‐sensitive dye RH155 which preferentially stains glial cells, and synaptically induced glial depolarization (SIGD) are optically detected in the presence of the blockers for ionotropic glutamate receptors. We have previously shown that SIGD is due to uptake of synaptically released glutamate by glial glutamate transporters. Here we applied this method to examine change in glutamate release during hippocampal LTP. To examine mossy‐CA3 LTP, stimulating electrodes were placed in dentate gyrus and tetanic stimulation was delivered in the presence of 50 µm APV. The amplitude of SIGD after inducing LTP was significantly greater than that in control experiments in which tetanus was not delivered. The amplitude of SIGD after inducing LTP by a brief (3–5 min) application of 50 µm forskolin was also significantly greater than that in control experiments. At the Schaffer‐CA1 synapse, the change in the amplitude of SIGD during LTP induced either by 100 Hz tetanus LTP or 200 Hz tetanus was not significantly greater than that of control experiments. These results provide evidence for increased glutamate release from the presynaptic terminals as the expression mechanism for both tetanus‐induced and forskolin‐induced LTP at mossy‐CA3 synapses, and evidence supporting a postsynaptic expression mechanism at Schaffer‐CA1 synapses.
Neurogenic and intact or apoptotic non‐neurogenic areas of adult brain release diffusible molecules that differentially modulate the development of subventricular zone cell cultures
Authors: Agasse Fabienne , Roger Michel , Coronas Valérie
Published: April 2004

In the adult mammalian brain, neurogenic activity is maintained in the subventricular zone (SVZ). Damage to non‐neurogenic areas can stimulate SVZ cell proliferation and trigger addition of new neurons in the affected areas. We therefore examined the possible control exerted by specific microenvironment cues on SVZ neurogenic activity. To this end, neonatal SVZ neurospheres were maintained in the presence of diffusible signals derived from the adult neurogenic SVZ or from the non‐neurogenic cerebral cortex either previously treated (apoptotic cortex) or not (untreated cortex) with staurosporine, a known apoptosis inducer. To restrict interactions to soluble signals, the explants were separated from the SVZ neurospheres by a microporous membrane. The results indicated that molecules released by the SVZ itself promoted the expansion of SVZ cell population through increased proliferation and reduced apoptosis. In contrast, untreated cortex factors reduced the expansion of SVZ cell population by decreasing proliferation. In addition, SVZ or untreated cortex factors, respectively, promoted or inhibited neuronal differentiation. Following apoptotic damage, cortex factors no longer inhibited and instead promoted the expansion of the SVZ cell population by increasing proliferation. These effects on cell numbers were replicated following use of culture media conditioned with the different explants but were no longer present following heat inactivation, which indicates that proteins were involved. These findings indicate that the neurogenic SVZ delivers autocrine/paracrine signals that promote neurogenesis whereas the non‐neurogenic cerebral cortex releases signals that inhibit proliferation and neuronal differentiation. Interestingly, this constitutive growth inhibitory effect of the cerebral cortex is inverted following apoptotic lesion.
CD81‐induced behavioural changes during chronic cocaine administration: in vivo gene delivery with regulatable lentivirus
Authors: Bahi Amine , Boyer Frederic , Kafri Tal , Dreyer Jean‐Luc
Published: April 2004

CD81, a tetraspanin transmembrane protein involved in cell adhesion, is up‐regulated in the mesolimbic dopaminergic pathway 24 h following acute administration of high doses of cocaine [Brenz‐Verca et al., (2001) Mol. Cell. Neurosci., 17, 303–316]. Further evidence consecutive with this observation and based on microarray analysis are presented here. In addition, a regulatable lentivirus was developed bearing the rat CD81 gene under the control of a tetracycline inducible system. This lentivirus vector was stereotaxically injected into the ventral tegmental area (VTA) of two groups of animals, one fed water (expressing CD81) and the other Doxycycline solution (which down‐regulates CD81 expression) and locomotor activity after chronic cocaine administration (10 mg/kg daily) was monitored. After 2 weeks, the groups were inverted, animals receiving water were placed on Doxycycline and the second group was placed on water. In all cases highly a significant increase (3.2‐fold) in locomotor activity was observed in animals expressing CD81 in the VTA vs. animals placed on Doxycycline. Similar studies where CD81 was delivered into the nucleus accumbens (NAcc) resulted in significantly higher effects (30%), in accordance with microarray data and our previous reports, yielding a 4.2‐fold increase in locomotor activity. No change was observed under similar conditions in control animals, which were injected a regulatable lentivirus expressing GFP. These findings suggest that CD81 expression in the mesolimbic dopaminergic pathway contributes to behavioural changes associated with cocaine sensitization. This study provides a powerful approach for evaluating a gene function in vivo in a single animal under various paradigms, even on gene candidates, which display small changes of expression.
Inactivation of the olfactory amygdala prevents the endocrine response to male odour in anoestrus ewes
Authors: Gelez H. , Archer E. , Chesneau D. , Magallon T. , Fabre‐Nys C.
Published: April 2004

Our aim was to study the role of the olfactory amygdala (medial and cortical nuclei) and the ventromedial nucleus of the hypothalamus (VMN) in the ability of the male odour or live males to induce a release of luteinizing hormone in anoestrus ewes. To achieve this, we temporarily blocked the activity of these structures by localized retrodialysis administration of the anaesthetic lidocaine. The effect of ram odour on the secretion of luteinizing hormone was completely blocked by inactivation of the cortical nucleus of the amygdala. In contrast, inactivation of part of the accessory olfactory system (the medial nucleus of the amygdala or the VMN) had no effect. In the presence of the male, lidocaine never impaired the endocrine response of the ewes. These results show that modulation of reproduction by the sexual partner even through pheromonal cues does not occur via the direct circuit of the accessory system. On the contrary, the cortical nucleus of the amygdala is absolutely necessary for the treatment of and/or the response to the male olfactory signal but this structure can be bypassed when other sensory cues are available.
Unusual cone and rod properties in subterranean African mole‐rats (Rodentia, Bathyergidae)
Authors: Peichl Leo , Němec Pavel , Burda Hynek
Published: April 2004

We have determined the presence of spectral cone types, and the population densities of cones and rods, in subterranean mole‐rats of the rodent family Bathyergidae, for which light and vision seems of little importance. Most mammals have two spectral cone types, a majority of middle‐ to long‐wave‐sensitive (L‐) cones, and a minority of short‐wave‐sensitive (S‐)cones. We were interested to see whether the subterranean bathyergids show the same pattern. In three species, Ansell's mole‐ratCryptomys anselli, the giant mole‐ratCryptomys mechowiand the naked mole‐ratHeterocephalus glaber, spectral cone types and rods were assessed immunocytochemically with opsin‐specific antibodies. All three species had rod‐dominated retinae but possessed significant cone populations. A quantitative assessment inC. anselliandC. mechowirevealed surprisingly low photoreceptor densities of 100 000–150 000/mm2, and high cone proportions, ≈ 10% (8000–15 000/mm2). In all three species, the vast majority of the cones were strongly S‐opsin‐immunoreactive; L‐opsin immunoreactivity was much fainter. InC. anselli, ≈ 20% of the cones showed exclusive S‐opsin label, ≈ 10% exclusive L‐opsin label and ≈ 70% strong S‐opsin and faint L‐opsin double label (potential dual‐pigment cones). This is the first observation in any mammal of an S‐opsin dominance and low levels of L‐opsin across the entire retina. It contrasts starkly with the situation in the muroid blind mole‐ratSpalax ehrenbergi,which has been reported to possess L‐opsin but no S‐opsin. Evidently, within rodents an adaptation to subterranean life is compatible with very different spectral cone properties.