bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and biological evaluation of constrained analogues of the opioid peptide H‐Tyr‐d‐Ala‐Phe‐Gly‐NH2 using the 4‐amino‐2‐benzazepin‐3‐one scaffold
Authors: Ballet S. , Frycia A. , Piron J. , Chung N.N. , Schiller P.W. , Kosson P. , Lipkowski A.W. , Tourwé D.
Published: September 2005

Abstract:  The synthesis of conformationally restricted dipeptidic moieties 4‐amino‐1,2,4,5‐tetrahydro‐2‐benzazepin‐3‐one (Aba)‐Gly ([(4S)‐amino‐3‐oxo‐1,2,4,5‐tetrahydro‐1H‐2‐benzazepin‐2‐yl]‐acetic acid) and 8‐hydroxy‐4‐amino‐1,2,4,5‐tetrahydro‐2‐benzazepin‐3‐one (Hba)‐d‐Ala ([(4S)‐amino‐8‐hydroxy‐3‐oxo‐1,2,4,5‐tetrahydro‐benzo[c]azepin‐2‐yl]‐propionic acid) was based on a synthetic strategy that uses an oxazolidinone as an N‐acyliminium precursor. Introducing these Aba scaffolds into the N‐terminal tetrapeptide of dermorphin (H‐Tyr‐d‐Ala‐Phe‐Gly‐Tyr‐Pro‐Ser‐NH2)‐induced remarkable shifts in affinity and selectivity towards the opioid μ‐ and δ‐receptors. This paper provides the synthesis and biological in vitro and in vivo evaluation of constricted analogues of the N‐terminal tetrapeptide H‐Tyr‐d‐Ala‐Phe‐Gly‐NH2, which is the minimal subunit of dermorphin needed for dermorphin‐like opiate activity.
A novel route to synthesize Freidinger lactams by micowave irradiation*
Authors: Lama T. , Campiglia P. , Carotenuto A. , Auriemma L. , Gomez‐Monterrey I. , Novellino E. , Grieco P.
Published: September 2005

Abstract:  The incorporation of a Freidinger‐like lactam structure into the backbone of peptides has been proven to be an useful strategy in the design of a variety of conformationally restricted targets. Several different strategies have been developed toward Freidinger lactams but no one resulted to be completely facile. Here, we report an efficient strategy that involves the iodo‐derivatives in side chain of an appropriate amino acid used as electrophilic agent, and the standard solid phase peptide synthesis assisted by microwave irradiation. The methodology developed could be useful to perform Freidinger‐like lactams with defined stereochemistry for routine use in solid phase peptide chemistry.
Contrasting genetic structures across two hybrid zones of a tropical reef fish, Acanthochromis polyacanthus (Bleeker 1855)
Authors: Van Herwerden L. , Doherty P. J.
Published: September 2005

Hybrid zones are natural laboratories offering insights into speciation processes. Narrow hybrid zones are less common in the sea than on land consistent with higher dispersal among marine populations. Acanthochromis polyacanthus is an unusual bony marine fish with philopatric dispersal that exists as allopatric stocks of white, bicoloured and black fish on the Great Barrier Reef (GBR). At two latitudes, different morphs coexist and hybridize at narrow contact zones. Sequence data from mitochondrial Hypervariable Region 1 revealed contrasting patterns of introgression across these zones. At the northern hybrid zone, a single clade of mitochondrial haplotypes was found in all white fish, hybrids and tens of kilometres into pure bicoloured stock. At the southern hybrid zone, there was no introgression of mitochondrial genes into black fish and hybrids shared the bicoloured haplotypes. Based on this asymmetry, we postulate that black fish from the southern GBR have experienced a selective sweep of their mitochondrial genome, which has resulted in almost total reproductive isolation.
Stable genetic polymorphism in heterogeneous environments: balance between asymmetrical dispersal and selection in the acorn barnacle
Authors: Véliz D. , Duchesne P. , Bourget E. , Bernatchez L.
Published: September 2005

Elucidating the processes responsible for maintaining polymorphism at ecologically relevant genes is intimately related to understanding the interplay between selection imposed by habitat heterogeneity and a species’ capacity for dispersal in the face of environmental constraints. In this paper, we used a model-based approach to solve equilibria of balanced polymorphism, given values of fitness and larval dispersal among different habitats in the acorn barnacle Semibalanus balanoides from the Gulf of St Lawrence. Our results showed that allele frequencies observed at both MPI* and GPI* loci represented stable equilibria, given empirical estimates of fitness values, and that considerably more larvae dispersed from one region (north) to the other (south) than vice versa. Dispersal conditions were predicted to be similar for the maintenance of polymorphism at both loci. Moreover, the values of asymmetrical dispersal required by the model to reach stable equilibria were compatible with empirical estimates of larval dispersal and oceanic circulation documented in this system. Overall, this study illustrated the usefulness of a modified and computable version of Bulmer's model (1972) in order to test hypotheses of balanced polymorphism resulting from interactions between spatial selection and asymmetrical dispersal.
Correlations between heterozygosity and measures of genetic similarity: implications for understanding mate choice
Authors: Roberts S. C. , Hale M. L. , Petrie M.
Published: September 2005

There is currently considerable interest in testing the effects of genetic compatibility and heterozygosity on animal mate preferences. Evidence for either effect is rapidly accumulating, although results are not always clear-cut. However, correlations between mating preferences and either genetic similarity or heterozygosity are usually tested independently, and the possibility that similarity and heterozygosity may be confounded has rarely been taken into account. Here we show that measures of genetic similarity (allele sharing, relatedness) may be correlated with heterozygosity, using data from 441 human individuals genotyped at major loci in the major histocompatibility complex, and 281 peafowl (Pavo cristatus) individuals genotyped at 13 microsatellite loci. We show that average levels of allele sharing and relatedness are each significantly associated with heterozygosity in both humans and peafowl, that these relationships are influenced by the level of polymorphism, and that these similarity measures may correlate with heterozygosity in qualitatively different ways. We discuss the implications of these inter-relationships for interpretation of mate choice studies. It has recently become apparent that mating preferences for ‘good genes’ and ‘compatible genes’ may introduce discordant choice amongst individuals, since the optimal mate for one trait may not be optimal for the other, and our results are consistent with this idea. The inter-relationship between these measures of genetic quality also carries implications for the way in which mate choice studies are designed and interpreted, and generates predictions that can be tested in future research.
An experimental test of the causes of small-scale phenotypic differentiation in a population of great tits
Authors: Shapiro B. J. , Garant D. , Wilkin T. A. , Sheldon B. C.
Published: September 2005

Phenotypic differentiation between populations is thought to occur mainly at spatial scales where gene-flow is restricted and selection regimes differ. However, if gene flow is nonrandom, dispersal may reinforce, rather than counteract, evolutionary differentiation, meaning that differences occurring over small scales might have a genetic basis. The purpose of this study was to determine the cause of differences in mean phenotype between two parts of a population of great tits Parus major, separated by <3 km. We conducted a partial cross-fostering experiment between two contrasting parts of this population to separate genetic and environmental sources of variation, and to test for gene–environment interaction. We found strong environmental effects on nestling size, mass and condition index, with nestlings reared in a low density part of the population being larger, heavier and in better condition, than those in a high density part, irrespective of their origin. In addition, we found smaller, but significant, differences in nestling condition and shape associated with the areas that birds originated from, suggesting the presence of genetic differences between parts of this population. There was no evidence of gene–environment interaction for any character. This experiment is thus consistent with previous analyses suggesting that differences between parts of this population had evolved recently, apparently due to phenotype-dependent dispersal, and indicates that population differentiation can be maintained over small spatial scales despite extensive dispersal.
Does selection by resistant hosts trigger local adaptation in plant–pathogen systems?
Authors: Montarry J. , Corbiere R. , Lesueur S. , Glais I. , Andrivon D.
Published: September 2005

Understanding the consequences of selection by host resistance on pathogen population structure provides useful insights into the dynamics of host–parasite co-evolution processes and is crucial for effective disease management through resistant cultivars. We tested general vs. local population adaptation to host cultivars, by characterizing a French collection of Phytophthora infestans (the causal organism of potato late blight) sampled during two consecutive years on cultivars exhibiting various levels of resistance. Local populations were structured by the host for virulence (qualitative pathogenicity) but also for aggressiveness (quantitative pathogenicity). All populations had a low genotypic diversity for amplified fragment length polymorphisms (AFLPs), and presumably consisted of a few closely related clonal lineages. No correlation was detected between pathogenicity traits and AFLP genotypes. The data support the hypothesis of general adaptation for aggressiveness, to which directional selection for virulence is superimposed when race-specific resistance is introduced.
Prograde eclogites from the Tonaru epidote amphibolite mass in the Sambagawa Metamorphic Belt, central Shikoku, southwest Japan
Authors: Miyagi Yasuo , Takasu Akira
Published: September 2005

Abstract  Prograde eclogites occur in the Tonaru epidote amphibolite mass in the Sambagawa Metamorphic Belt of central Shikoku. The Tonaru mass is considered to be a metamorphosed layered gabbro, and occurs as a large tectonic block (approximately 6.5 km × 1 km) in a high‐grade portion of the Sambagawa schists. The Tonaru mass experienced high‐P/low‐T prograde metamorphism from the epidote‐blueschist facies to the eclogite facies prior to its emplacement into the Sambagawa schists. The estimated P–T conditions are T = 300–450°C and P = 0.7–1.1 GPa for the epidote‐blueschist facies, and the peak P–T conditions for the eclogite facies are T = 700–730°C and P ≥ 1.5 GPa. Following the eclogite facies metamorphism, the Tonaru mass was retrograded to the epidote amphibolite facies. It subsequently underwent additional prograde Sambagawa metamorphism, together with the surrounding Sambagawa schists, until the conditions of the oligoclase–biotite zone were reached. The high‐P/low‐T prograde metamorphism of the eclogite facies in the Tonaru mass and other tectonic blocks show similar steep dP/dT geothermal gradients despite their diverse peak P–T conditions, suggesting that these tectonic blocks reached different depths in the subduction zone. The individual rocks in each metamorphic zone of the Sambagawa schists also recorded steep dP/dT geothermal gradients during the early stages of the Sambagawa prograde metamorphism, and these gradients are similar to those of the eclogite‐bearing tectonic blocks. Therefore, the eclogite‐bearing tectonic blocks reached greater depths in the subduction zone than the Sambagawa schists. All the tectonic blocks were ultimately emplaced into the hanging wall side of the later‐subducted Sambagawa high‐grade schists during their exhumation.
Late Oligocene post‐obduction granitoids of New Caledonia: A case for reactivated subduction and slab break‐off
Authors: Cluzel Dominique , Bosch Delphine , Paquette Jean‐Louis , Lemennicier Yves , Montjoie Philippe , Ménot René‐Pierre
Published: September 2005

Abstract  In southern New Caledonia, Late Oligocene granodiorite and adamellite are intruded into an ultramafic allochthon emplaced in the Late Eocene period. Previous studies of these granitoids proposed an origin associated with the melting of the underlying continental crust, but our new data show that these high‐K to medium‐K calc‐alkaline granitoids display the geochemical and isotopic features of volcanic arc magmas uncontaminated by crust‐derived melts. These magmas were probably generated in a post‐Eocene and pre‐Miocene subduction, the geophysical traces of which have been detected along the western coast of New Caledonia. Sr, Nd and Pb isotopic ratios indicate derivation from an almost isotopically homogeneous mantle wedge, but in contrast, some variation in trace element ratios uncorrelated to differentiation is indicative of source heterogeneity. Prominent heavy rare earth element (HREE) depletion of some of the younger granitoids may be the result of an equilibrium achieved with garnet‐bearing subcrustal material (granulite) found as xenoliths, while a relative Nb, Ta and Hf enrichment, irrespective of crystal fractionation, may be related to either a modest contamination by previously underplated mafic material, heterogeneous hydration of the mantle wedge, or mixing with uplifted Nb‐rich mantle. Post‐obduction slab break‐off can be proposed to have played a role in sublithospheric mantle mixing and the subsequent heterogeneity. The Late Oligocene subduction described here may be tentatively extended southward into northern New Zealand allochthons.
Complete mantle section of a slow‐spreading ridge‐derived ophiolite: An example from the Isabela ophiolite in the Philippines
Authors: Andal Eric S. , Arai Shoji , Yumul Graciano P.
Published: September 2005

Abstract  The Isabela ophiolite shows a complete ophiolite sequence exposed along the eastern coast of northern Luzon, the Philippines. It forms the Cretaceous basement complex for the northeastern Luzon block. This ophiolite is located at the northern end of a trail of ophiolites and ophiolitic bodies along the eastern margin of the Philippine Mobile Belt. This paper presents new findings regarding the nature and characteristics of the Isabela ophiolite. Peridotites from the Isabela ophiolite are relatively fresh and are composed of spinel lherzolites, clinopyroxene‐rich harzburgites, depleted harzburgites and dunites. The modal composition, especially the pyroxene content, defines a northward depletion trend from fertile lherzolite to clinopyroxene‐rich harzburgites and more refractory harzburgites. Variation in modal composition is accompanied by petrographic textural variations. The chromium number of spinel, an indicator of the degree of partial melting, concurs with petrographic observations. Furthermore, the Isabela ophiolite peridotites are similar in spinel and olivine major‐element geochemistry and clinopyroxene rare earth‐element composition to abyssal peridotites from modern mid‐oceanic ridges. Petrological and mineral compositions suggest that the Isabela ophiolite is a transitional ophiolite subtype, with the fertile lherzolites representing lower sections of the mantle column that are usually absent in most ophiolitic massifs. The occurrence of the fertile peridotite presents a rare opportunity to document the lower sections of the ophiolitic mantle. The variability in composition of the peridotites in one continuous mantle section may also represent a good analogy of the melting column in the present‐day mid‐oceanic ridges.
Role of chondroitin sulphate in the uptake of β‐VLDL by brain cells
Authors: Rapp Alfred , Hüttinger Manfred
Published: September 2005

Proteoglycans (PGs) have been suggested to work as receptors in lipoprotein uptake mechanisms. An interaction between apolipoprotein E (apoE) and glucosaminoglycans (GAG), polysaccharides linked to proteoglycans, has been proposed in this pathway. At the same time, proteoglycans, apoE as well as lipoprotein receptors have been reported to be constituents of amyloid plaques, one hallmark of Alzheimer's disease. With this study, we are the first to investigate the interaction between beta very low density lipoprotein (β‐VLDL) and a neuronal highly abundant GAG, chondroitin sulphate (CS), comparing hippocampal neurons, expressing high levels of low density lipoprotein receptor related protein (LRP) and U373 astrocytoma cells, highly positive for the low density lipoprotein receptor (LDLR). We were able demonstrate that degradation of chondroitin sulphate proteoglycans (CSPGs) with chondroitinase ABC resulted in reduced 125I‐β‐VLDL uptake. We showed that externally added CSs compete with internalization of β‐VLDL. The effect was found to be dose‐dependent, but was influenced neither by cell type, nor receptor type. The position of sulphation of added CSs showed only a slight influence. The data generated suggested an interaction between apolipoproteins and soluble CSs; therefore, 3H‐cholesterol linked to apoE was coadministered with CSs to the cells. The results revealed that apoE bound, but no unbound cholesterol, was reduced in cellular internalization, suggesting that CSPGs may be involved in lipoprotein uptake in the intact brain, mediated, at least in part, by apoE.
Hemispheric asymmetry for spectral and temporal processing in the human antero‐lateral auditory belt cortex
Authors: Schönwiesner Marc , Rübsamen Rudolf , Von Cramon D. Yves
Published: September 2005

The present study investigates the acoustic basis of the hemispheric asymmetry for the processing of speech and music. Experiments on this question ideally involve stimuli that are perceptually unrelated to speech and music, but contain acoustic characteristics of both. Stimuli in previous studies were derived from speech samples or tonal sequences. Here we introduce a new class of noise‐like sound stimuli with no resemblance of speech or music that permit independent parametric variation of spectral and temporal acoustic complexity. Using these stimuli in a functional MRI experiment, we test the hypothesis of a hemispheric asymmetry for the processing of spectral and temporal sound structure by seeking cortical areas in which the blood oxygen level dependent (BOLD) signal covaries with the number of simultaneous spectral components (spectral complexity) or the temporal modulation rate (temporal complexity) of the stimuli. BOLD‐responses from the left and right Heschl's gyrus (HG) and part of the right superior temporal gyrus covaried with the spectral parameter, whereas covariation analysis for the temporal parameter highlighted an area on the left superior temporal gyrus. The portion of superior temporal gyrus in which asymmetrical responses are apparent corresponds to the antero‐lateral auditory belt cortex, which has been implicated with spectral integration in animal studies. Our results support a similar function of the anterior auditory belt in humans. The findings indicate that asymmetrical processing of complex sounds in the cerebral hemispheres does not depend on semantic, but rather on acoustic stimulus characteristics.
Loss of Gli3 enhances the viability of embryonic telencephalic cells in vitro
Authors: Zaki Paulette A. , Martynoga Ben , Delafield‐Butt Jonathan T. , Fotaki Vassiliki , Yu Tian , Price David J.
Published: September 2005

The transcription factor Gli3 is important for brain and limb development. Mice homozygous for a mutation in Gli3 (Gli3Xt/Xt) have severe abnormalities of telencephalic development and previous studies have suggested that aberrant cell death may contribute to the Gli3Xt/Xt phenotype. We demonstrate that telencephalic cells from embryonic Gli3Xt/Xt embryos survive better and are more resistant to death induced by cytosine arabinoside, a nucleoside analogue that induces death in neuronal progenitors and neurons, than are control counterparts in vitro. Culture medium conditioned by Gli3Xt/Xt cells is more effective at enhancing the viability of control telencephalic cells than medium conditioned by control cells, indicating that Gli3Xt/Xt cells release a factor or factors which enhance telencephalic cell viability. Gli3Xt/Xt cells are also more sensitive to released factors present in conditioned media. These data suggest that Gli3 plays both cell‐autonomous and cell‐nonautonomous roles in mediating telencephalic cell viability.
Anatomical evidence for an anticonvulsant relay in the rat ventromedial medulla
Authors: Shehab Safa , McGonigle David , Hughes David I. , Todd Andrew J. , Redgrave Peter
Published: September 2005

Pharmacological manipulation of the ventrolateral pontine reticular formation (vlPRF) of rats has an anticonvulsant effect in the maximal electroshock model of epilepsy. This study presents three anatomical experiments that determine the efferent projections from this region likely to mediate this anticonvulsant effect. In the first, the anterograde tracer biotinylated dextran amine (BDA) was injected into the vlPRF. A strong projection to the ventromedial medullary reticular formation (vmMRF) was revealed which continued only weakly to the spinal cord. In the second experiment, double‐label procedures were used to indicate whether the BDA‐labelled terminals from the vlPRF make contacts with neurons in vmMRF, retrogradely labelled with cholera‐toxin B subunit from the lumbar spinal cord. Sections of the vmMRF were examined by: (i) light microscopy which showed significant overlap between terminals from vlPRF and retrogradely‐labelled reticulospinal cells; (ii) confocal microscopy which showed labelled terminals in close association with reticulospinal cell bodies; and (iii) electron microscopy which showed vlPRF terminals making synaptic contact with reticulospinal neurons. Finally, immunohistochemical procedures in combination with anterograde tracing revealed that significant numbers of terminals labelled from vlPRF were also positive for markers of glutamatergic or GABAergic neurotransmission. This suggests that the projection from the vlPRF to the vmMRF is likely to include several different functional components. These connections could represent a final critical link of an anticonvulsant circuit that originates in the dorsal midbrain and projects via relays in the vlPRF and the vmMRF to interact with the low‐level motor circuitry in the spinal cord.
Differential expression of the homeobox gene Pitx3 in midbrain dopaminergic neurons
Authors: Korotkova Tatiana M. , Ponomarenko Alexei A. , Haas Helmut L. , Sergeeva Olga A.
Published: September 2005

The transcription factor Pitx3 is expressed selectively in the midbrain and regulates the differentiation and survival of dopaminergic neurons. Lack of this factor results in a degeneration similar to that seen in Parkinson's disease. We have studied the pattern and the level of expression of Pitx3 in dopaminergic neurons of 3‐ to 4‐week‐old Wistar rats. We report Pitx3 expression in almost all dopaminergic substantia nigra (SN) and ventral tegmental area (VTA) neurons. It is coexpressed with the neuroprotective marker calbindin (CB) in a larger population of VTA (43%) than SN (16%) dopaminergic neurons. The level of Pitx3 mRNA, determined by semiquantitative RT‐PCR, is ≈ 6× higher in VTA than in SN single neurons. In the VTA but not in SN the level of Pitx3 is associated with the presence of CB: in CB‐positive neurons the expression of Pitx3 mRNA is 3.6× higher than in CB‐negative cells. CB is expressed in a larger population of VTA than SN neurons and the relative level of CB expression is 4× higher in VTA than in SN. A higher Pitx3 expression level and higher coexpression of Pitx3 and CB in VTA than in SN neurons may contribute to the different vulnerability of these dopaminergic nuclei to neurodegeneration.
Laminar differences in field potential morphology and long‐term potentiation in motor cortex coronal slices from both unstimulated and previously potentiated rats
Authors: Ji Zhanxin , Boyd Tiffany E. , Froc David J. , Racine Ronald J.
Published: September 2005

We have reported that long‐term potentiation (LTP) can be reliably induced in motor cortex of adult, freely moving rats by the application of spaced and repeated high frequency stimulating trains to the white matter. In the present study, we monitored field potentials (FPs) and LTP in both layer II/III and V in coronal slices of motor cortex taken from implanted control and previously potentiated Long–Evans rats. The baseline FP amplitudes were decreased in layer II/III, and the amplitude of small spikes was significantly increased in layer V in slices from previously potentiated rats compared to unpotentiated control rats. In response to high frequency stimulation applied to the slice itself, both implanted control and previously potentiated rats showed similar levels of LTP in layer II/III. LTP could not be induced in layer V. These results show that layer II/III and V respond differently to high frequency stimulation in vitro. In addition, layer II/III responds very differently in slice compared to chronic preparations.
Specific expression of olfactory binding protein in the aerial olfactory cavity of adult and developing Xenopus
Authors: Millery Julie , Briand Loïc , Bézirard Valérie , Blon Florence , Fenech Claire , Richard‐Parpaillon Laurent , Quennedey Brigitte , Pernollet Jean‐Claude , Gascuel Jean
Published: September 2005

Olfactory binding proteins (OBP), commonly associated with aerial olfaction, are found in the olfactory mucus of mammals but have never been identified in fish. It is still not clear whether the presence of OBP in aerial olfactory systems is due to phylogenetic or to functional differences linked to the adaptation of the olfactory system to an aerial environment. To test this alternative, the olfactory system of Xenopus offers a unique opportunity because it includes two olfactory cavities, one of which is thought to be devoted to aquatic olfaction and the other to aerial olfaction. We therefore purified and cloned OBPs in two Xenopus species. Xenopus laevis OBP (XlaeOBP) and Xenopus tropicalis OBP (XtroOBP) exhibit 158 and 160 amino acids, respectively, sharing 89 residues. cRNA probes allowed us to demonstrate that XlaeOBP and XtroOBP are expressed at the level of Bowman's gland specifically in the aerial olfactory cavity, as confirmed using anti‐XlaeOBP antiserum. OBP mRNA transcription occurs early during metamorphosis, as early as stage 57. This is the first study to demonstrate that OBPs are exclusively present in the aerial chamber and are only expressed as the tadpole becomes an adult in species which possess both aquatic and aerial olfactory organs.
Size‐mediated ageing reduces vigour in trees
Authors: Mencuccini M. , Martínez‐Vilalta J. , Vanderklein D. , Hamid H. A. , Korakaki E. , Lee S. , Michiels B.
Published: September 2005

There is increasing interest in understanding the costs and benefits of increased size and prolonged lifespan for plants. Some species of trees can grow more than 100 m in height and can live for several millennia, however whether these achievements are obtained at the cost of some other physiological functions is currently unclear. As increases in size are usually associated with ageing, it is also unclear whether observed reductions in growth rates and increased mortality rates are a function of size or of age per se. One theory proposes that reduced growth after the start of the reproductive phase is caused by cellular senescence. A second set of theories has focussed instead on plant size and the increased respiratory burdens or excessive height. We report on experimental manipulations to separate the effects of extrinsic factors such as size from those of intrinsic factors such as age for four tree species of contrasting phylogeny and life history. For each species, we measured growth, gas exchange and leaf biochemical properties for trees of different ages and sizes in the field and on propagated material obtained from the same genetic individuals but now all of small similar size in our common gardens. For all species, evidence indicated that size, not cellular senescence, accounted for the observed age‐related declines in relative growth rates and net assimilation rates. Two species exhibited evidence of genetic control on leaf characters such as specific leaf area, although size also exerted an independent, and stronger, effect. We found partial support for the theory of hydraulic limitations to tree growth. The lack of a marked separation of soma and germline, an unlimited proliferation potential of meristem cells and the exponential increase in reproductive effort with size all help explain the lack of a senescence‐induced decline in trees. It is possible that trees much older than the ones we sampled exhibit senescence symptoms.
Novel genes for nitrite reductase and Amo‐related proteins indicate a role of uncultivated mesophilic crenarchaeota in nitrogen cycling
Authors: Treusch Alexander H. , Leininger Sven , Kletzin Arnulf , Schuster Stephan C. , Klenk Hans‐Peter , Schleper Christa
Published: September 2005

Mesophilic crenarchaeota are frequently found in terrestrial and marine habitats worldwide, but despite their considerable abundance the physiology of these as yet uncultivated archaea has remained unknown. From a 1.2 Gb large‐insert environmental fosmid library of a calcareous grassland soil, a 43 kb genomic fragment was isolated with a ribosomal RNA that shows its affiliation to group 1.1b of crenarchaeota repeatedly found in soils. The insert encoded a homologue of a copper‐containing nitrite reductase with an unusual C‐terminus that encoded a potential amicyanin‐like  electron  transfer  domain  as  well  as  two proteins related to subunits of ammonia monooxygenases or particulate methane monooxygenases (AmoAB/PmoAB) respectively. Expression of nirK and the amoA‐like gene was shown by reverse transcription polymerase chain reaction (PCR) analyses in soil samples, the latter being found at higher levels when the soil was incubated with ammonia (measured by quantitative PCR). Further variants of both genes were amplified from soil samples and were found in the environmental database from the Sargasso Sea plankton. Taken together, our findings suggest that mesophilic terrestrial and marine crenarchaeota might be capable of ammonia oxidation under aerobic and potentially also under anaerobic conditions.
Lateral gene transfer and phylogenetic assignment of environmental fosmid clones
Authors: Nesbø Camilla L. , Boucher Yan , Dlutek Marlena , Doolittle W. Ford
Published: September 2005

Metagenomic data, especially sequence data from large insert clones, are most useful when reasonable inferences about phylogenetic origins of inserts can be made. Often, clones that bear phylotypic markers (usually ribosomal RNA genes) are sought, but sometimes phylogenetic assignments have been based on the preponderance of blast hits obtained with predicted protein coding sequences (CDSs). Here we use a cloning method which greatly enriches for ribosomal RNA‐bearing fosmid clones to ask two questions: (i) how reliably can we judge the phylogenetic origin of a clone (that is, its RNA phylotype) from the sequences of its CDSs? and (ii) how much lateral gene transfer (LGT) do we see, as assessed by CDSs of different phylogenetic origins on the same fosmid? We sequenced 12 rRNA containing fosmid clones, obtained from libraries constructed using DNA isolated from Baltimore harbour sediments. Three of the clones are from bacterial candidate divisions for which no cultured representatives are available, and thus represent the first protein coding sequences from these major bacterial lineages. The amount of LGT was assessed by making phylogenetic trees of all the CDSs in the fosmid clones and comparing the phylogenetic position of the CDS to the rRNA phylotype. We find that the majority of CDSs in each fosmid, 57–96%, agree with their respective rRNA genes. However, we also find that a significant fraction of the CDSs in each fosmid, 7–44%, has been acquired by LGT. In several cases, we can infer co‐transfer of functionally related genes, and generate hypotheses about mechanism and ecological significance of transfer.
Patient‐centred and professional‐directed implementation strategies for diabetes guidelines: a cluster‐randomized trial‐based cost‐effectiveness analysis
Authors: Dijkstra R. F. , Niessen L. W. , Braspenning J. C. C. , Adang E. , Grol R. T. P. M.
Published: September 2005

Aims  Economic evaluations of diabetes interventions do not usually include analyses on effects and cost of implementation strategies. This leads to optimistic cost‐effectiveness estimates. This study reports empirical findings on the cost‐effectiveness of two implementation strategies compared with usual hospital outpatient care. It includes both patient‐related and intervention‐related cost.

Patients and methods  In a clustered‐randomized controlled trial design, 13 Dutch general hospitals were randomly assigned to a control group, a professional‐directed or a patient‐centred implementation programme. Professionals received feedback on baseline data, education and reminders. Patients in the patient‐centred group received education and diabetes passports. A validated probabilistic Dutch diabetes model and the UKPDS risk engine are used to compute lifetime disease outcomes and cost in the three groups, including uncertainties.

Results  Glycated haemoglobin (HbA1c) at 1 year (the measure used to predict diabetes outcome changes over a lifetime) decreased by 0.2% in the professional‐change group and by 0.3% in the patient‐centred group, while it increased by 0.2% in the control group. Costs of primary implementation were < 5 Euro per head in both groups, but average lifetime costs of improved care and longer life expectancy rose by 9389 Euro and 9620 Euro, respectively. Life expectancy improved by 0.34 and 0.63 years, and quality‐adjusted life years (QALY) by 0.29 and 0.59. Accordingly, the incremental cost per QALY was 32 218 Euro for professional‐change care and 16 353 for patient‐centred care compared with control, and 881 Euro for patient‐centred vs. professional‐change care. Uncertainties are presented in acceptability curves: above 65 Euro per annum the patient‐directed strategy is most likely the optimum choice.

Conclusion  Both guideline implementation strategies in secondary care are cost‐effective compared with current care, by Dutch standards, for these patients. Additional annual costs per patient using patient passports are low. This analysis supports patient involvement in diabetes in the Netherlands, and probably also in other Western European settings.
The Lem2 gene promoter of barley directs cell‐ and development‐specific expression of gfp in transgenic plants
Authors: Abebe Tilahun , Skadsen Ron , Patel Minesh , Kaeppler Heidi
Published: September 2005

Transgenic approaches to combating fungal pathogens, such as Fusarium graminearum, require the targeting of antifungal gene expression in tissues of developing seed spikes of cereal grains, especially lemmas and epicarps. The Lem2 gene of barley encodes a lectin‐like protein that is strongly up‐regulated by salicylic acid and is preferentially expressed in lemmas, paleas (lemma/palea) and coleoptiles. Transient expression studies have indicated that the proximal −75/+70 region (relative to the transcription start site) determines organ specificity. In the present study, Golden Promise barley stably transformed with Morex Lem2 promoter/gfp reporter constructs displayed cell‐ and development‐specific expression of gfp (green fluorescent protein gene). This expression corresponded to the expression seen in Northern blots of Morex organs. Under the full‐length promoter, strong GFP fluorescence was observed in the lemma/palea, glumes, coleoptile, auricle and ligule. Weak GFP fluorescence was also observed in the rachis, tips of primary leaves and the leaf sheath. Unexpectedly, strong expression occurred in the epicarp, even though Lem2 is not expressed in this organ in Morex. Studies showed that the Lem2 promoter is more highly methylated in the epicarp than in the lemma of Morex. In the lemma/palea, gfp underwent a temporal shift in expression from the mesophyll to specialized epidermal cork cells. Similar to the lemma/palea, expression in the leaf sheath was localized in the cork cells. Progressive 5′ deletions of the promoter to nucleotide −75 gradually reduced the level of gfp expression, but tissue‐ and cell‐specific expression was retained.
Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine in the treatment of episodic tension‐type headache: a double‐blind, randomized, nimesulide‐controlled, parallel group, multicentre trial
Authors: Cerbo R. , Centonze V. , Grazioli I. , Tavolato B. , Trenti T. , Uslenghi C. , Sternieri E.
Published: September 2005

In this double‐blind, randomized, parallel group, multicentre study the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) and nimesulide were compared over an 8‐h period in the treatment of two consecutive episodes of tension‐type headache (TTH). Both drugs were administered orally. Of 54 randomized patients, 40 were compliant to the protocol. More patients on IndoProCaf than on nimesulide were pain‐free at 2 h post‐dose (45% vs. 10%; P < 0.05), reached a pain reduction of at least 50% at 2 (75% vs. 30%; P < 0.05) and 4 h post‐dose (90% vs. 58%; P < 0.05), and had a statistically significant lower mean time to a 50 and 100% pain reduction in the second TTH episode. A higher percentage of patients reached a 50 or 100% pain reduction at 2 h post‐dose with IndoProCaf compared with nimesulide, in two of two treated TTH episodes. A clinically and statistically significant change within each treatment group over time was found for the severity of pain, the headache intensity difference (HID), the sum of headache intensity difference (SHID), the maximum headache intensity difference (MAXHID), the headache relief (HER), the sum of total headache relief (TOTHER) and the maximum headache relief (MAXHER). In conclusion, IndoProCaf showed to be superior, but globally not statistically different from nimesulide in the treatment of episodic TTH. Both drugs were very effective and well tolerated.
Clinical and radiological features of symptomatic central nervous system tuberculomas
Authors: Unal A. , Sutlas P. N.
Published: September 2005

Tuberculomas may present with meningitis, may lead to meningitis, or may develop during the treatment of TBM. In this study, we report a series of 22 adult cases of symptomatic central nervous system tuberculomas, in eight of them tuberculomas were coexisting with TBM on admission and in 14 of them symptomatic tuberculomas developed during anti‐tuberculosis therapy. We also aimed to compare the clinical, laboratory and outcome data of the 14 TBM patients that developed symptomatic tuberculomas, with the data of 41 TBM that did not, under the same treatment regimen. Most of the patients developed symptomatic tuberculomas in the first 6 weeks of treatment. Five patients developed late tuberculomas. The characteristics of tuberculomas and the role of corticosteroids in TBM patients are discussed. In conclusion, although steroids may diminish neurologic symptoms and improve outcome, tuberculomas may appear during the course of anti‐tuberculosis and steroid treatment. Because of the possibility of late development of tuberculomas after initial successful treatment, all TBM patients need to be followed‐up carefully for a long period.
Raising the dead: war, memory and American national identity*
Authors: Grant Susan‐Mary
Published: September 2005

Abstract.The dead, particularly the war dead, play a central role in the development of nationalism, nowhere more so than in America. America's mid‐nineteenth century Civil War produced a recognisable and influential ‘cult of the dead’, comparable in its construction with similar developments in Europe following World War I. Focused on the figure of the fallen soldier, especially the volunteer soldier, this cult found physical expression in the development of national cemeteries devoted not just to the burial of those who fell in the war but to the idea of America as a nation, in the development of monuments to the dead that, again, reinforced the new national symbolism of the war era, and in the beginnings of Memorial Day, an American sacred ceremony with clear parallels with the later Armistice Day ceremonies in Europe. In all these developments, America preceded the European nations by several decades, making America a valuable case study for the role that the cult of the fallen soldier plays in national development more generally.
A novel alternative splicing form of excitatory amino acid transporter 1 is a negative regulator of glutamate uptake
Authors: Vallejo‐Illarramendi Ainara , Domercq María , Matute Carlos
Published: September 2005

EAAT1 is a major glutamate transporter in the CNS and is required for normal neurotransmission and neuroprotection from excitotoxicity. In the present study, we have identified a novel form of the human EAAT1, named here as EAAT1ex9skip, which lacks the entire exon 9. Quantitative PCR analysis indicates that this variant is expressed throughout the CNS, both in grey matter and axonal tracts, at levels ranging between 10% and 20% of the full‐length EAAT1 form. When expressed in HEK293 cells, EAAT1ex9skip mRNA is translated into a truncated protein localized in the endoplasmic reticulum. EAAT1ex9skip has no functional glutamate uptake activity but instead, exerts a dominant negative effect over full‐length EAAT1 function. In turn, co‐expression of full‐length EAAT1 and EAAT1ex9skip variants reduces the insertion of the former into the plasma membrane. Together, these results indicate that the EAAT1ex9skip splice variant is a negative regulator of full‐length EAAT1 function in the human brain.
Characterization of glial cell line‐derived neurotrophic factor family receptor α‐1 in peripheral nerve Schwann cells
Authors: Hase Asako , Saito Fumiaki , Yamada Hiroki , Arai Ken , Shimizu Teruo , Matsumura Kiichiro
Published: September 2005

Glial cell line‐derived neurotrophic factor (GDNF) family receptor α‐1 (GFRα‐1) is a receptor component of GDNF that associates with and activates the tyrosine kinase receptor Ret. To further understand GDNF and its receptor system in the PNS, we first characterized the expression of GFRα‐1 in bovine peripheral nerve in vivo. GFRα‐1 immunoreactivity was localized adjacent to the outermost layer of myelin sheath, as well as in the endoneurium and axoplasm. In a fractionation study, GFRα‐1 was recovered mostly in the soluble fraction, although a small amount was recovered in the membrane fraction. A substantial amount of GFRα‐1 in the membrane fraction was extractable by detergent and alkaline conditions. To further clarify the expression of GFRα‐1 in Schwann cells, we examined cultured rat Schwann cells and the Schwannoma cell line RT4. Schwann cells expressed GFRα‐1 in both the soluble/cytosolic and membrane fractions, and the membrane form of GFRα‐1 was expressed at the outer surface of the Schwann cell plasma membrane. We also confirmed the secretion of the soluble form of GFRα‐1 from Schwannoma cells in a metabolic labeling experiment. These data contribute to our knowledge of the production, expression and functions of GFRα‐1 in the PNS.
Regulation of hippocampal cholesterol metabolism by apoE and environmental stimulation
Authors: Levi Ofir , Lütjohann Dieter , Devir Aliza , Von Bergmann Klaus , Hartmann Tobias , Michaelson Daniel M.
Published: September 2005

Alzheimer's disease is associated with genetic risk factors, of which the allele E4 of apolipoprotein E (apoE4) is the most prevalent, and it is also affected by environmental factors such as early life education. We have recently shown, utilizing apoE‐deficient and apoE transgenic mice, that synaptogenesis in the hippocampus following environmental stimulation is affected by apoE. In view of the pivotal role of cholesterol in synaptic plasticity, and of its suggested role in synaptogenesis, we presently examined the effects of apoE and environmental stimulation on brain cholesterol homeostasis. The hippocampal levels of cholesterol and its precursors and metabolites in control mice were not affected by exposure to environmental stimulation. In contrast, the hippocampal levels of cholesterol and its precursors lathosterol and desmosterol and metabolite 24S‐hydroxycholesterol were lower in apoE‐deficient mice that were maintained in a regular environmental than those of corresponding control mice, whereas they were markedly elevated following environmental stimulation. Histological and immunohistochemical experiments revealed that the combined stimulatory effects of apoE deficiency and environmental stimulation on cholesterol metabolism were associated with marked activation of hippocampal astrocytes and with the abnormal accumulation of cholesterol in neurons and astrocytes. These effects were rescued similarly in apoE3 and apoE4 transgenic mice. These findings suggest that apoE plays an important role in the translocation of cholesterol from astrocytes to neurons in vivo and in the regulation and homeostasis of this process.
A nonlethal method of identification of Ambystoma laterale, A. jeffersonianum and sympatric unisexuals
Authors: RAMSDEN C. , BÉRIAULT K. , BOGART J. P.
Published: September 2005

Unisexual salamanders in the genus Ambystoma live in obligate sympatry with the sexual species Ambystoma laterale or Ambystoma jeffersonianum, from which they are not easily distinguished. Because the sexual species are protected in many parts of their range, accurate identification of sexual and unisexual individuals is required for conservation purposes. Unisexual individuals are currently identified using isozyme electrophoresis, which requires sacrificing the animal. Here we present a nonlethal method of identification for members of the A. laterale–jeffersonianum part of the Ambystoma complex utilizing genome‐specific microsatellites with or without the addition of flow cytometry.
Constraining the P–T path of a MORB‐type eclogite using pseudosections, garnet zoning and garnet‐clinopyroxene thermometry: an example from the Bohemian Massif
Authors: ŠTÍPSKÁ P. , POWELL R.
Published: September 2005

A mid‐ocean ridge basalt (MORB)‐type eclogite from the Moldanubian domain in the Bohemian Massif retains evidence of its prograde path in the form of inclusions of hornblende, plagioclase, clinopyroxene, titanite, ilmenite and rutile preserved in zoned garnet. Prograde zoning involves a flat grossular core followed by a grossular spike and decrease at the rim, whereas Fe/(Fe + Mg) is also flat in the core and then decreases at the rim. In a pseudosection for H2O‐saturated conditions, garnet with such a zoning grows along an isothermal burial path at c. 750 °C from 10 kbar in the assemblage plagioclase‐hornblende‐diopsidic clinopyroxene‐quartz, then in hornblende‐diopsidic clinopyroxene‐quartz, and ends its growth at 17–18 kbar. From this point, there is no pseudosection‐based information on further increase in pressure or temperature. Then, with garnet‐clinopyroxene thermometry, the focus is on the dependence on, and the uncertainties stemming from the unknown Fe3+ content in clinopyroxene. Assuming no Fe3+ in the clinopyroxene gives a serious and unwarranted upward bias to calculated temperatures. A Fe3+‐contributed uncertainty of ±40 °C combined with a calibration and other uncertainties gives a peak temperature of 760 ± 90 °C at 18 kbar, consistent with no further heating following burial to eclogite facies conditions. Further pseudosection modelling suggests that decompression to c. 12 kbar occurred essentially isothermally from the metamorphic peak under H2O‐undersaturated conditions (c. 1.3 mol.% H2O) that allowed the preservation of the majority of garnet with symplectitic as well as relict clinopyroxene. The modelling also shows that a MORB‐type eclogite decompressed to c. 8 kbar ends as an amphibolite if it is H2O saturated, but if it is H2O‐undersaturated it contains assemblages with orthopyroxene. Increasing H2O undersaturation causes an earlier transition to SiO2 undersaturation on decompression, leading to the appearance of spinel‐bearing assemblages. Granulite facies‐looking overprints of eclogites may develop at amphibolite facies conditions.