bluuebunny/crossref_metadata_2025 huggingface dataset:
The genetic structure of Australasian green turtles (Chelonia mydas): exploring the geographical scale of genetic exchange
Authors: DETHMERS KIKI E. M. , BRODERICK DAMIEN , MORITZ CRAIG , FITZSIMMONS NANCY N. , LIMPUS COLIN J. , LAVERY SHANE , WHITING SCOTT , GUINEA MICK , PRINCE ROBERT I. T. , KENNETT ROD
Published: August 2006

Ecological and genetic studies of marine turtles generally support the hypothesis of natal homing, but leave open the question of the geographical scale of genetic exchange and the capacity of turtles to shift breeding sites. Here we combine analyses of mitochondrial DNA (mtDNA) variation and recapture data to assess the geographical scale of individual breeding populations and the distribution of such populations through Australasia. We conducted multiscale assessments of mtDNA variation among 714 samples from 27 green turtle rookeries and of adult female dispersal among nesting sites in eastern Australia. Many of these rookeries are on shelves that were flooded by rising sea levels less than 10 000 years (c. 450 generations) ago. Analyses of sequence variation among the mtDNA control region revealed 25 haplotypes, and their frequency distributions indicated 17 genetically distinct breeding stocks (Management Units) consisting either of individual rookeries or groups of rookeries in general that are separated by more than 500 km. The population structure inferred from mtDNA was consistent with the scale of movements observed in long‐term mark–recapture studies of east Australian rookeries. Phylogenetic analysis of the haplotypes revealed five clades with significant partitioning of sequence diversity (Φ = 68.4) between Pacific Ocean and Southeast Asian/Indian Ocean rookeries. Isolation by distance was indicated for rookeries separated by up to 2000 km but explained only 12% of the genetic structure. The emerging general picture is one of dynamic population structure influenced by the capacity of females to relocate among proximal breeding sites, although this may be conditional on large population sizes as existed historically across this region.
The Arabidopsis thaliana/Myzus persicae model system demonstrates that a single gene can influence the interaction between a plant and a sap‐feeding insect
Authors: HUNT E. J. , PRITCHARD J. , BENNETT M. J. , ZHU X. , BARRETT D. A. , ALLEN T. , BALE JS , NEWBURY H. J.
Published: August 2006

We have developed an Arabidopsis thaliana/Myzus persicae model system to allow the dissection of plant/insect interactions at a molecular genetic level. This allows the examination of the role of single plant genes in the interaction between the plant and an aphid. Our initial studies have exploited an Arabidopsis genotype in which the function of the amino acid transporter ANT1 has been abolished. This mutation results in a change in the proportions of several amino acids within the phloem sieve elements (SEs) resulting in an increase in the proportion of essential amino acids. This has been measured using aphid stylectomy to collect SE samples, followed by a novel micellar electrokinetic chromatography method for amino acid analysis. The SE content represents the aphid's diet, and use of electrical penetration graph technology and honeydew clocks have demonstrated that this altered diet results in a change in the feeding rate of the aphid. Balance sheets can be produced to show the amount (nmoles/24 h) of each of 18 amino acids taken up and excreted by aphids feeding on wild type and ant1 mutant plants. The data show that aphids feeding on the ant1 mutant take up larger amounts of amino acids. However, we could not detect any effect on the reproductive rate of the aphids. The results show that, under experimental conditions, this model system can be used to identify plant genes that control the behaviour and fecundity of an insect pest.
Inbreeding depression and multiple regions showing heterozygote advantage in Drosophila melanogaster exposed to stress
Authors: FERREIRA ÁLVARO G. A. , AMOS WILLIAM
Published: August 2006

Recent studies that reveal a correlation between heterozygosity and fitness in natural populations have rekindled interest in whether balancing selection is widespread or an evolutionary oddity. We therefore quantified heterozygote advantage at 12 microsatellite markers in both inbred and outbred crosses of Drosophila grown under different forms of environmental stress. As expected, inbreeding depression reduces fitness relative to the outbred controls. In addition, many loci exhibit heterozygote advantage over and above any effect due to inbreeding, with ∼30% of markers showing an effect in any given culture condition and ∼75% of markers showing an effect in at least one of the four culture conditions. To explore the extent of linkage disequilibrium surrounding these loci we further typed four new markers close to each of the three strongest hits. We find a pattern where the extent of heterozygote excess tends to decline to nonsignificance within around 1.5 megabases (Mb) either side of the original hit. Crude extrapolation suggests 12 genes or regions experience detectable levels of heterozygote advantage in any one condition and as many as 25 overall. Thus, balancing selection is widespread and is likely to play an important role in maintaining genetic variability.
Understanding the shapes of bacteria just got more complicated
Authors: Beveridge Terry J.
Published: August 2006

The paper by Briegel et al. in this issue of Molecular Microbiology uses advanced cryo‐transmission electron microscopy (cryoTEM) techniques to reveal four separate locations of cytoplasmic filament bundles in Caulobacter crescentus. Intuitively, these filaments should be rather rigid protein structures and composed of previously identified shape‐forming proteins, such as crescentin or MreB. Yet, deletion mutants lacking these proteins still possessed filaments and still possessed wild‐type morphology. These results suggest that a complex combination of protein structures, including those of crescentin, MreB and these newly identified bundles, in combination with the cell envelope help maintain the complicated shape of C. crescentus. Other bacteria might have similar architectural proteins to assist in maintaining the cell contours during growth and division.
Molecular genotyping to distinguish between recrudescents and new infections in treatment trials of Plasmodium falciparum malaria conducted in Sub‐Saharan Africa: adjustment of parasitological outcomes and assessment of genotyping effectiveness
Authors: Mugittu Kefas , Adjuik Martin , Snounou Georges , Ntoumi Francine , Taylor Walter , Mshinda Hassan , Olliaro Piero , Beck Hans‐Peter
Published: August 2006

Molecular genotyping of baseline and post‐treatment recurrent Plasmodium falciparum is recommended to distinguish recrudescent from new infections. However, genotyping performance and adjustment of treatment outcomes have not been evaluated in large field trials. Parasitological outcomes were assessed in nine double‐blinded trials of uncomplicated P. falciparum malaria in African children treated with artesunate/placebo plus standard monotherapies. Day 28 failure rates were adjusted by stepwise genotyping the P. falciparum glutamate rich protein (glurp), merozoite surface protein 1 (msp1) and 2 (msp2). We calculated overall and laboratory genotyping performance and compared unadjusted (crude) and PCR‐adjusted outcomes. 3455 (93.6%) of 3691 enrolled patients were evaluable by Day 28. 767 (22%) had post‐Day 14 recurrent parasitemias of which 686 could be genotyped: 246 were recrudescences, 286 new infections and 154 unresolved. The overall and laboratory genotyping performance were 69 (12–100)% and 78 (50–100)%, respectively. The mean Day 28 crude parasitological failure rate was 44 (range 3–87)%. PCR‐adjusted rates were 36 (range 2–86)% if unresolved infections were counted as failures or 33 (range 2–86)% if excluded from analysis. The overall difference between crude Day 28 and Day 14 failure rates was 22% (95% CI 20.3, 24.6) but decreased to 14% (95% CI 12.1, 16.3) if unresolved infections are counted as failures, or to 11% (95% CI 9.8, 16.3) if unresolved infections are excluded from the analysis. Genotyping refined treatment outcomes but diligence is needed in sample collection and analysis to improve its performance. Our findings support the WHO recommendation of PCR genotyping in malaria clinical trials and suggest that stepwise genotyping of only two loci (msp2 and msp1 or glurp) can reliably discriminate recrudescences from new infections.
Surveillance of the efficacy of artesunate and mefloquine combination for the treatment of uncomplicated falciparum malaria in Cambodia
Authors: Denis Mey Bouth , Tsuyuoka Reiko , Poravuth Yi , Narann Top Sophoan , Seila Suon , Lim Chim , Incardona Sandra , Lim Pharath , Sem Rithy , Socheat Duong , Christophel Eva Maria , Ringwald Pascal
Published: August 2006

Artesunate and mefloquine combination treatment has been used since 2000 in Cambodia as the first‐line drug for the treatment of uncomplicated falciparum malaria. In order to assess its efficacy and safety, the national malaria control programme conducted 14 therapeutic efficacy studies with the drug combination between 2001 and 2004 at nine sites. In 2001 and 2002, co‐blister packs of artesunate and mefloquine were used, whereas in 2003 and 2004, drugs were given individually from a bulk pack at a total dose of 12 mg/kg of artesunate and 25 mg/kg of mefloquine over 3 days. A total of 1025 patients were enrolled over the 4 years and 977 were follow‐up during the period of 28 days. The PCR‐corrected cure rates ranged from 85.7% to 100% with an overall cure rate of 95.8% (920/960). The studies in 2002 showed also that co‐blister packs used on the basis of age and not on the basis of weight could lead to underdosed regimens but without any detectable effect on the treatment outcome. The follow‐up period was extended from 28 to 42 days in three sites in 2004. A total of 219 among 255 were follow‐up until day 42. The cure rate decreased but not significantly from 90.1% (73/81) with 28 days follow‐up to 79.3% (46/58) with 42 days follow‐up in Pailin, whereas the cure rate remained at 100% in the two other sites. Side effects were common, especially dizziness, but were mild and transient and patients recovered without any medical intervention.
The evolution of trans‐generational altruism: kin selection meets niche construction
Authors: LEHMANN L.
Published: August 2006

A cornerstone result of sociobiology states that limited dispersal can induce kin competition to offset the kin selected benefits of altruism. Several mechanisms have been proposed to circumvent this dilemma but all assume that actors and recipients of altruism interact during the same time period. Here, this assumption is relaxed and a model is developed where individuals express an altruistic act, which results in posthumously helping relatives living in the future. The analysis of this model suggests that kin selected benefits can then feedback on the evolution of the trait in a way that promotes altruistic helping at high rates under limited dispersal. The decoupling of kin competition and kin selected benefits results from the fact that by helping relatives living in the future, an actor is helping individuals that are not in direct competition with itself. A direct consequence is that behaviours which actors gain by reducing the common good of present and future generations can be opposed by kin selection. The present model integrates niche‐constructing traits with kin selection theory and delineates demographic and ecological conditions under which altruism can be selected for; and conditions where the ‘tragedy of the commons’ can be reduced.
Effects of B chromosomes and supernumerary segments on morphometric traits and adult fitness components in the grasshopper, Dichroplus elongatus (Acrididae)
Authors: ROSETTI N. , VILARDI J. C. , REMIS M. I.
Published: August 2006

The South American species, Dichroplus elongatus, is polymorphic for B chromosomes and supernumerary segments in chromosome pairs M6 (SS6), S9 (SS9) and S10 (SS10). Both forms of supernumerary heterochromatin shape chiasma frequency and distribution and B chromosomes also affect male fertility. Here, we analysed the effects of these polymorphisms on morphometric traits (total, 3rd femur, 3rd tibia, thorax and tegmen lengths) and several adult fitness components, including male and female mating success, and female reproductive potential. B chromosomes tend to decrease, and SS6 segments to increase the body size of carriers. The analysis of reproductive potential suggested that B chromosome carrying females have higher numbers of embryos per clutch and ovarioles per ovary. The uni‐ and multivariate analysis of mating success revealed that sexual selection favours larger individuals of both sexes and males with standard karyotype. B chromosomes may have accumulation mechanisms, which involve preferential transmission of B chromosomes to germ cells or functional gametes. The maintenance of Bs might be explained by interactions among accumulation mechanisms and trade‐offs between detrimental and favourable effects on different fitness components.
Changed environmental conditions weaken sexual selection in sticklebacks
Authors: CANDOLIN U. , SALESTO T. , EVERS M.
Published: August 2006

Environmental heterogeneity can cause the intensity and direction of selection to vary in time and space. Yet, the effects of human‐induced environmental changes on sexual selection and the expression of mating traits of native species are poorly known. Currently, the breeding habitats of the three‐spined sticklebackGasterosteus aculeatus are changing in the Baltic Sea because of eutrophication and increased growth of algae. Here we show that enhanced growth of filamentous algae increases the costs of mating by inducing an increase in the time and energy spent on courtship and mate choice. This is not followed by a concomitant increase in mate attraction, but instead the strength of selection on male red nuptial coloration and courtship activity is relaxed. Thus, the high investment into the costly sexually selected traits is maladaptive under the new conditions, and the mating system mediates a negative effect of the environmental change on the population. We attribute these environmentally induced changes in the benefit of the mating traits and in the strength of sexual selection to reduced visibility in dense vegetation. Anthropogenic disturbances hence affect the selection pressures that mould the species, which could have long‐term effects on the viability and evolution of the populations.
A Study of the Transfer of Tetracycline Resistance Genes Between Escherichia coli in the Intestinal Tract of a Mouse and a Chicken Model
Authors: Hart W. S. , Heuzenroeder M. W. , Barton M. D.
Published: August 2006

Experiments to demonstrate the transfer of genes within a natural environment are technically difficult because of the unknown numbers and strains of bacteria present, as well as difficulties designing adequate control experiments. The results of such studies should be viewed within the limits of the experimental design. Most experiments to date have been based on artificial models, which only give approximations of the real‐life situation. The current study uses more natural models and provides information about tetracycline resistance as it occurs in wild‐type bacteria within the environment of the normal intestinal tract of an animal. Tetracycline sensitive, nalidixic acid resistant Escherichia coli isolates of human origin were administered to mice and chicken animal models. They were monitored for acquisition of tetracycline resistance from indigenous or administered donor E. coli. Five sets of in vivo experiments demonstrated unequivocal transfer of tetracycline resistance to tetracycline sensitive recipients. The addition of tetracycline in the drinking water of the animals increased the probability of transfer between E. coli strains originating from the same animal species. The co‐transfer of unselected antibiotic resistance in animal models was also demonstrated.
Analysis of the Presence ofail,ystAandystBGenes inYersinia enterocoliticaStrains Isolated from Aborting Sows and Aborted Fetuses
Authors: Platt‐Samoraj A. , Ugorski M. , Szweda W. , Szczerba‐Turek A. , Wojciech K. , Procajło Z.
Published: August 2006

Forty‐fiveYersinia enterocoliticastrains isolated from aborted fetuses and placentas and from vaginal and rectal swabs of aborting sows were subjected to serotyping, biochemical typing and polymerase chain reaction multiplex analyses to detect the presence of theail,yst AandystBgenes. The isolates were recovered from the internal organs (tonsil, lung, liver, spleen, kidney, mesentheric lymph nodes, small intestine and rectal intestine) of 18 (18.6%) of 97 aborted fetuses examined, two (8%) of 25 aborted placentas and 27 (15.8%) of 172 examined aborting sows. Serotyping ofY. enterocoliticarevealed that only six (13.3%) of the examined isolates belonged to serotype O:3, with a considerable number of isolates (31.1%) having serotype O:5, while biochemical studies showed that as many as 40 of the 45 strains belonged to biotype 1A. As expected, theY. enterocoliticastrains of bioserotype 4/O:3 containedailandystAgenes, while strains of biotype 1A contained only theystBgene.
Diagnostic Evaluation of a Real‐Time RT‐PCR assay for Routine Diagnosis of Classical Swine Fever in Wild Boar
Authors: Depner K. , Bunzenthal C. , Heun‐Münch B. , Strebelow G. , Hoffmann B. , Beer M.
Published: August 2006

The aim of the study was to evaluate a real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) assay for routine diagnosis of classical swine fever (CSF) in wild boar by using 1000 spleen homogenates that were tested previously negative by virus isolation and 26 homogenates from which CSF virus could be isolated. All 26 positive samples in the virus isolation assay also were found to be positive in real‐time RT‐PCR. Additionally further 10 samples were detected by real‐time RT‐PCR out of the 1000 negative samples in the virus isolation. With a commercial CSF antigen‐ELISA only 14 out of the 36 real‐time RT‐PCR positive samples could be detected. The sequence analysis of all ten samples that tested positive by real‐time RT‐PCR and negative by virus isolation revealed CSF virus‐specific sequences. Based on the assumption that all samples with a CSF virus‐specific sequence or positive in the virus isolation test originated from truly CSF virus‐infected wild boar, the following sensitivity values were calculated as antigen‐ELISA, 39%; virus isolation, 72% and real‐time RT‐PCR, 100%. The use of real‐time RT‐PCR instead of antigen‐ELISA and virus isolation as a routine tool for control and eradication of CSF in wild boar populations is recommended.
‘Motor Magic’: Evaluation of a community capacity‐building approach to supporting the development of preschool children (Part 2)
Authors: Priest Naomi , Waters Elizabeth
Published: August 2006

Background and Aims:  This paper is the second in a series of two that presents and discusses an exploratory evaluation study of the ‘Motor Magic’ program conducted in Adelaide, South Australia.

Methods:  A realist evaluation approach was used, and two focus groups (one with parents and one with kindergarten staff) were held to identify program outcomes and to develop and refine key hypotheses about how these outcomes occurred.

Results and Conclusions:  Results for kindergarten staff involved in the program are presented and discussed in this paper, including improved early identification and early intervention for children with, or at risk of, fine motor developmental difficulties; increased confidence in the effectiveness of their practice with these children; improved practice of kindergarten staff with both targeted and all children; improved empathy with, and support for, parents; and increased interagency links and ongoing advocacy for further resources. These results suggest that the program provides an effective model for building the capacity of kindergarten staff to support children with, or at risk of, developmental difficulties.
The effect of first year mental health fieldwork on attitudes of occupational therapy students towards people with mental illness
Authors: Beltran Ruth O. , Scanlan Justin Newton , Hancock Nicola , Luckett Tim
Published: August 2006

Background and Aims:  Despite recent initiatives to reduce stigma towards people with mental illness, negative attitudes persist both in the community and among health professionals. Fieldwork experience has been identified as the most powerful way of modifying the attitudes of health professional students. Research to date suggests that later placements tend to have a more positive effect on attitudes than do earlier placements. However, inconsistencies within the literature suggest that it is the nature of the fieldwork experience that is the critical factor. We set out to investigate whether a program of fieldwork that included a tutorial component would bring about positive attitudinal change in first year occupational therapy students.

Methods:  We conducted secondary analysis of data collected from first year students before and after first year fieldwork experience in mental health settings. Student statements were rated to identify positive versus negative attitudes, and attitudinal themes were analysed.

Results:  Quantitative analysis revealed that students made significantly more statements reflecting positive attitudes following fieldwork than they did before. From pre‐ to post‐fieldwork, attitudinal themes changed from: people with mental illness as different, fear of people with mental illness, and a deficit focus of mental illness, to: the ‘ordinariness’ of people with mental illness, students’ understanding of people with mental illness, and an enabling approach to people with mental illness.

Conclusions:  A program of fieldwork that includes a structured tutorial component can bring about positive changes in the attitudes of first year students towards people with mental illness.
Expression of transforming acidic coiled‐coil containing protein 3 is a novel independent prognostic marker in non‐small cell lung cancer
Authors: Jung Chan Kwon , Jung Ji Han , Park Gyeong Sin , Lee Ahwon , Kang Chang Suk , Lee Kyo Young
Published: August 2006

Transforming acidic coiled‐coil containing protein 3 (TACC3) is known to be involved in the control of normal cell growth and differentiation and in mechanisms of unregulated growth leading to tumorigenesis. The aim of the present paper was to determine the rate of TACC3 expression in a non‐small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters. A total of 163 NSCLC were analyzed immunohistochemically using a polyclonal TACC3 antibody and monoclonal p53 and Ki‐67 antibodies on NSCLC tissue microarrays. A high level of TACC3 expression was observed in 14.8% of cases, preferentially squamous cell carcinomas. Patients whose tumors had a high TACC3 expression had a significantly shorter median survival time. In the Cox regression‐based multivariate analysis, TACC3 expression proved to be an independent prognostic parameter (P = 0.031). TACC3 expression was correlated with p53 expression, and patient whose tumors highly expressed TACC3 and p53 had a significantly poorer prognosis than patients whose tumors had low‐level expression for both immunostainings (P = 0.006). It is suggested that increase in TACC3 may impart a proliferative advantage to NSCLC and contribute to tumor progression, and that TACC3 expression is a strong prognostic indicator of clinical outcome in NSCLC.
Muco‐epidermoid carcinoma of the breast
Authors: Horii Rie , Akiyama Futoshi , Ikenaga Motoko , Iwase Takuji , Sakamoto Goi
Published: August 2006

A very rare case of muco‐epidermoid carcinoma of the breast is reported. A 54‐year‐old woman noticed a breast lump and consulted the Cancer Institute Hospital, Tokyo. Physical examination revealed a mass with an unclear margin in the upper outer area of the left breast. Both mammography and ultrasonography showed an irregularly shaped mass, suggesting invasive carcinoma. Aspiration cytology revealed solid clusters of two types of cancer cells: ones with mucus in the cytoplasm, and others without mucus. Cytological features resembled muco‐epidermoid carcinoma of the salivary gland but it was not possible to establish a diagnosis of the histological type because muco‐epidermoid carcinoma of the breast had not previously been encountered by the authors. After incisional biopsy, left mastectomy with axillary lymph node dissection was performed. Histologically the tumor was surrounded by a fibrous pseudocapsule and was composed of intraductal carcinoma foci and invasive cancer nests. Intraductal carcinoma foci were the low papillary type. Stromal invasion showed many solid nests composed of mucus‐containing and squamoid cancer cells. There was no common invasive ductal carcinoma component in this tumor. These histological features confirmed the diagnosis as muco‐epidermoid carcinoma of the breast. This is the first report of muco‐epidermoid carcinoma of the breast in Japan.
6‐Shogaol, a natural product, reduces cell death and restores motor function in rat spinal cord injury
Authors: Kyung Kang Soo , Gon Jeon Hyo , Geun Kim Yong , Sup Jung Jin , Suk Woo Jae , Ho Kim Jae
Published: August 2006

Spinal cord injury (SCI) results in progressive waves of secondary injuries, which via the activation of a barrage of noxious pathological mechanisms exacerbate the injury to the spinal cord. Secondary injuries are associated with edema, inflammation, excitotoxicity, excessive cytokine release, caspase activation and cell apoptosis. This study was aimed at investigating the possible neuroprotective effects of 6‐shogaol purified from Zingiber officinale by comparing an experimental SCI rat group with SCI control rats. Shogaol attenuated apoptotic cell death, including poly(ADP‐ribose) polymerase activity, and reduced astrogliosis and hypomyelination which occurs in areas of active cell death in the spinal cords of SCI rats. The foremost protective effect of shogaol in SCI would therefore be manifested in the suppression of the acute secondary apoptotic cell death. However, it does not attenuate active microglia and macrophage infiltration. This finding is supported by a lack of histopathological changes in the areas of the lesion in the shogaol‐treated SCI rats. Moreover, shogaol‐mediated neuroprotection has been linked with shogaol's attenuation of p38 mitogen‐activated protein kinase, p‐SAPK/JNK and signal transducer, and with transcription‐3 activation. Our results demonstrate that shogaol administrated immediately after SCI significantly diminishes functional deficits. The shogaol‐treated group recovered hindlimb reflexes more rapidly and a higher percentage of these rats regained responses compared with the untreated injured rats. The overall hindlimb functional improvement of hindlimbs, as measured by the Basso, Beattie and Bresnahan scale, was significantly enhanced in the shogaol‐treated group relative to the SCI control rats. Our data show that the therapeutic outcome of shogaol probably results from its comprehensive effects of blocking apoptotic cell death, resulting in the protection of white matter, oligodendrocytes and neurons, and inhibiting astrogliosis. Our finding that the administration of shogaol prevents secondary pathological events in traumatic SCIs and promotes recovery of motor functions in an animal model raises the issue of whether shogaol could be used therapeutically in humans after SCI.
Up‐regulation of PK11195 binding in areas of axonal degeneration coincides with early microglial activation in mouse brain
Authors: Pedersen Mads D. , Minuzzi Luciano , Wirenfeldt Martin , Meldgaard Michael , Slidsborg Carina , Cumming Paul , Finsen Bente
Published: August 2006

Increased binding of the peripheral benzodiazepine binding site (PBBS) ligand [3H]PK11195 in the central nervous system of patients suffering from acute and chronic neuropathology has been associated with reactive microgliosis. However, it remains uncertain which stages of microglial activation occur in conjunction with the increased [3H]PK11195 binding. We used quantitative autoradiography for [3H]PK11195 and quantitative polymerase chain reaction for PBBS mRNA and markers of early and late microglial activation to investigate the time‐course of cellular responses in the hippocampus of mice with degeneration of the entorhinal‐hippocampal perforant path. The axonal lesion evoked an increase in the Bmax for [3H]PK11195 in hippocampus which peaked at 2 days post‐lesion, remained elevated at day 5 and began to decline at 10 days post‐lesion. These changes occurred in the absence of significant changes in affinity in vitro. Quantitative polymerase chain reaction analysis of isolated hippocampi using exon‐specific primers indicated the presence of several splice variants of PBBS mRNA, which appeared to be affected differentially by the lesion. The changes in PBBS mRNA and CD11b mRNA levels correlated with the Bmax for [3H]PK11195 during 10 days post‐lesion, suggesting that microglial activation couples with increases in mRNA levels for these markers. In addition, the onset of changes in PBBS mRNA levels coincided with the significantly elevated tumor necrosis factor mRNA levels present during early microglial activation at 2 days post‐lesion. We conclude that up‐regulation of [3H]PK11195 binding and PBBS mRNA levels coincided with early microglial activation, characterized by concomitantly increased microglial tumor necrosis factor mRNA levels, and persisted throughout the period with reactive microgliosis.
Cognitive modulation of emotion anticipation
Authors: Erk Susanne , Abler Birgit , Walter Henrik
Published: August 2006

Anticipating salient emotions is a vital function related to attention, self control and other cognitive mechanisms. Expecting affective events can trigger regulatory processes that prepare an organism, for example, to cope with possible threat. However, there are situations, like waiting at the dentist's or preparing for a public appearance, in which down‐regulation of especially negative emotions linked with the upcoming event is necessary or favorable. A strategy to achieve this is cognitive distraction, a process with up to now barely known neural mechanisms. We used graded cognitive distraction during the anticipation of subsequent negative emotions in order to induce down‐regulation of the emotional response in an event‐related fMRI design. Accordingly, we found down‐regulation of anterior rostral medial prefrontal cortex and amygdala activation during anticipatory cognitive distraction with the anterior medial prefrontal cortex being negatively correlated with the lateral prefrontal cortex. Furthermore, we demonstrated that anticipatory distraction does not influence subsequent emotion processing, i.e. does not reduce subsequent activation in emotion‐processing brain areas. We conclude that effortful anticipatory cognitive distraction effectively down‐regulates emotion processing during anticipation but not subsequent emotion information processing. These results help in the understanding of general mechanisms of emotion regulation and have implications for applied fields like cognitive behavioral therapy.
Temporal and spatial alterations in GPi neuronal encoding might contribute to slow down movement in Parkinsonian monkeys
Authors: Leblois Arthur , Meissner Wassilios , Bezard Erwan , Bioulac Bernard , Gross Christian E. , Boraud Thomas
Published: August 2006

Although widely investigated, the exact relationship between changes in basal ganglia neuronal activity and parkinsonian symptoms has not yet been deciphered. It has been proposed that bradykinesia (motor slowness) is related either to a modification of the activity of the globus pallidus internalis (GPi), the main output structure, or to a loss of spatial selectivity of the extrapyramidal motor system. Here we investigate the relationship between movement initiation and GPi activity in parkinsonian non‐human primates. We compare neuronal encoding of movement in the normal and pathological conditions. After dopamine depletion, we observe an increased number of neurons responding to movement, with a less specific somato‐sensory receptive field and a disruption of the selection mechanism. Moreover, the temporal order of the response of GPi neurons in parkinsonian animals is reversed. Indeed, whereas muscle activity and movement are delayed in parkinsonian animals, GPi neuronal responses to movement occur earlier and are prolonged, compared with normal conditions. Parkinsonian bradykinesia could thus result from an impairment of both temporal and spatial specificity of the GPi response to movement.
Tonic GABAA receptor‐mediated currents in human brain
Authors: Scimemi Annalisa , Andersson Anna , Heeroma Joost H. , Strandberg Joakim , Rydenhag Bertil , McEvoy Andrew W. , Thom Maria , Asztely Fredrik , Walker Matthew C.
Published: August 2006

GABAA receptors can mediate both phasic (synaptic) and tonic (extrasynaptic) forms of inhibition. It has been proposed that tonic inhibition plays a critical part in controlling neuronal and network excitability. Although tonic GABAA receptor‐mediated currents have been well characterized in rodents, their existence in human tissue has yet to be demonstrated. Here we show that tonic currents can be recorded from human tissue obtained from patients undergoing temporal lobectomies. Tonic GABAA receptor‐mediated currents were present in pyramidal cells and interneurons in layer V‐VI of temporal neocortex and granule cells in the dentate gyrus. These tonic currents have cell type‐specific pharmacologies, opening up the possibility of targeted therapeutics.
Peripheral antinociceptive effect of pertussis toxin: activation of the arginine/NO/cGMP/PKG/ ATP‐sensitive K+ channel pathway
Authors: Brito Gerly A. C. , Sachs Daniela , Cunha Fernando Q. , Vale Mariana L. , Lotufo Celina M. C. , Ferreira Sérgio H. , Ribeiro Ronaldo. A.
Published: August 2006

The aim of the present study was to determine the effect of pertussis toxin (PTX) on inflammatory hypernociception measured by the rat paw pressure test and to elucidate the mechanism involved in this effect. In this test, prostaglandin E2 (PGE2) administered subcutaneously induces hypernociception via a mechanism associated with neuronal cAMP increase. Local intraplantar pre‐treatment (30 min before), and post‐treatment (5 min after) with PTX (600 ng/paw1, in 100 µL) reduced hypernociception induced by prostaglandin E2 (100 ng/paw, in 100 µL, intraplantar). Furthermore, local intraplantar pre‐treatment (30 min before) with PTX (600 ng/paw, in 100 µL) reduced hypernociception induced by DbcAMP, a stable analogue of cAMP (100 µg/paw, in 100 µL, intraplantar), which indicates that PTX may have an effect other than just Gi/G0 inhibition. PTX‐induced analgesia was blocked by selective inhibitors of nitric oxide synthase (L‐NMMA), guanylyl cyclase (ODQ), protein kinase G (KT5823) and ATP‐sensitive K+ channel (Kir6) blockers (glybenclamide and tolbutamide). In addition, PTX was shown to induce nitric oxide (NO) production in cultured neurons of the dorsal root ganglia. In conclusion, this study shows a peripheral antinociceptive effect of pertussis toxin, resulting from the activation of the arginine/NO/cGMP/PKG/ATP‐sensitive K+ channel pathway.
Isolation and gene quantification of heterotrophic N2‐fixing bacterioplankton in the Baltic Sea
Authors: Boström Kjärstin H. , Riemann Lasse , Kühl Michael , Hagström Åke
Published: August 2006

Cyanobacteria are regarded as the main N2‐fixing organisms in marine waters. However, recent clone libraries from various oceans show a wide distribution of the dinitrogenase reductase gene (nifH) originating from heterotrophic bacterioplankton. We isolated heterotrophic N2‐fixing bacteria from Baltic Sea bacterioplankton using low‐nitrogen plates and semi‐solid diazotroph medium (SSDM) tubes. Isolates were analysed for the nitrogenase (nifH) gene and active N2 fixation by nested polymerase chain reaction (PCR) and acetylene reduction respectively. A primer‐probe set targeting the nifH gene from a γ‐proteobacterial isolate, 97% 16S rDNA similarity to Pseudomonas stutzeri, was designed for measuring in situ dynamics using quantitative real‐time PCR. This nifH gene sequence was detected at two of 11 stations in a Baltic Proper transect at abundances of 3 × 104 and 0.8 × 103 copies per litre seawater respectively. Oxygen requirements of isolates were examined by cultivation in SSDM tubes where oxygen gradients were determined with microelectrodes. Growth, and thereby N2 fixation, was observed as horizontal bands formed at oxygen levels of 0–6% air saturation. The apparent microaerophilic or facultative anaerobic nature of the isolates explains why the SSDM approach is the most appropriate isolation method. Our study illustrates how combined isolation, functional analyses and in situ quantification yielded insights into the oxygen requirements of heterotrophic N2‐fixing bacterioplankton isolates, which were confirmed to be present in situ.
RELIGIOUS REASONS AND POLITICAL ARGUMENTATION
Authors: Moran Jon
Published: August 2006

InEvangelium VitaePope John Paul II calls for a renewal of culture to combat the culture of death. He criticizes various aspects of a pluralistic, liberal society—a type of society that he claims is based on moral relativism and a view of democracy that becomes a substitute for moral law. He maintains that such a view trivializes moral choice. In this essay I argue that John Rawls's notion of a liberal society as an overlapping consensus of comprehensive doctrines can avoid relativism while allowing for reasonable debate among opposed positions. While Rawls maintains that comprehensive doctrines, including religions, should employ a form of public reason that is not a unique feature of any one comprehensive doctrine, I argue that this requirement is too strong. One is often justified in appealing to features of comprehensive doctrines other than one's own, features that are unique to the doctrines themselves. Such an appeal does not pretend to be neutral as public reason would seem to be. In the final section of the paper I discuss some suggestions made by the Pope regarding actions in civil society that are independent of debates about legal change and suggest some ways in which they might contribute to desired cultural transformation.
GOD IN THE CAVE
Authors: Wetzel James
Published: August 2006

When Finite and Infinite Goods was published in 1999, it took its place as one of the few major statements of a broadly Augustinian ethical philosophy of the past century. By “broadly Augustinian” I refer to the disposition to combine a Platonic emphasis on a transcendent source of value with a traditionally theistic emphasis on the value‐creating capacities of absolute will. In the form that this disposition takes with Robert Merrihew Adams, it is the resemblance between divine and a finite excellence that makes the finite excellence objectively of value, and it is the correspondence of an obligation to a divine command that makes the obligation objectively obligatory. I look closely at the complexity of this ethical division of labor—between the good and the right—mainly as it appears in the context of Finite and Infinite Goods, but also with attention to the broader corpus of Adams's writings, particularly his work on Leibniz and the essays of his that have been gathered together in The Virtue of Faith. I argue that there is a creative tension in his work between his desire to secure an objective basis for ethics and his affirmation of the value of grace, a love that is not proportioned to the excellence of its object. This tension, I further argue, ought to be resolved in the direction of grace.
Time Series Modelling of Two Millennia of Northern Hemisphere Temperatures: Long Memory or Shifting Trends?
Authors: Mills Terence C.
Published: August 2006

The time series properties of the temperature reconstruction of Moberg and co-workers are analysed. It is found that the record appears to exhibit long memory characteristics that can be modelled by an autoregressive fractionally integrated moving average process that is both stationary and mean reverting, so that forecasts will eventually return to a constant underlying level. Recent research has suggested that long memory and shifts in level and trend may be confused with each other, and fitting models with slowly changing trends is found to remove the evidence of long memory. Discriminating between the two models is difficult, however, and the strikingly different forecasts that are implied by the two models point towards some intriguing research questions concerning the stochastic process driving this temperature reconstruction.
On the Spectral Density of the Wavelet Coefficients of Long‐Memory Time Series with Application to the Log‐Regression Estimation of the Memory Parameter
Authors: Moulines E. , Roueff F. , Taqqu M. S.
Published: August 2006

Abstract.  In recent years, methods to estimate the memory parameter using wavelet analysis have gained popularity in many areas of science. Despite its widespread use, a rigorous semi‐parametric asymptotic theory, comparable with the one developed for Fourier methods, is still lacking. In this article, we adapt to the wavelet setting, the classical semi‐parametric framework introduced by Robinson and his co‐authors for estimating the memory parameter of a (possibly) non‐stationary process. Our results apply to a class of wavelets with bounded supports, which include but are not limited to Daubechies wavelets. We derive an explicit expression of the spectral density of the wavelet coefficients and show that it can be approximated, at large scales, by the spectral density of the continuous‐time wavelet coefficients of fractional Brownian motion. We derive an explicit bound for the difference between the spectral densities. As an application, we obtain minimax upper bounds for the log‐scale regression estimator of the memory parameter for a Gaussian process and we derive an explicit expression of its asymptotic variance.
“Health Courts” and Accountability for Patient Safety
Authors: MELLO MICHELLE M. , STUDDERT DAVID M. , KACHALIA ALLEN B. , BRENNAN TROYEN A.
Published: August 2006

Proposals that medical malpractice claims be removed from the tort system and processed in an alternative system, known as administrative compensation or ‘health courts,’ attract considerable policy interest during malpractice ‘crises,’ including the current one. This article describes current proposals for the design of a health court system and the system's advantages for improving patient safety. Among these advantages are the cultivation of a culture of transparency regarding medical errors and the creation of mechanisms to gather and analyze data on medical injuries. The article discusses the experiences of foreign countries with administrative compensation systems for medical injury, including their use of claims data for research on patient safety; choices regarding the compensation system's relationship to physician disciplinary processes; and the proposed system's possible limitations.
Epistatic Interactions between Genomic Regions Containing the COL1A1 Gene and Genes Regulating Osteoclast Differentiation may Influence Femoral Neck Bone Mineral Density
Authors: Yang Tie‐Lin , Shen Hui , Xiong Dong‐Hai , Xiao Peng , Guo Yan , Guo Yan‐fang , Liu Yao‐Zhong , Recker Robert R. , Deng Hong‐Wen
Published: August 2006

Bone mineral density (BMD) is a primary risk indicator of osteoporotic fractures, which are largely determined by the actions of multiple genes. Genetic linkage studies have seldom explored epistatic interaction of genes for BMD. To evaluate potential genetic interactions for BMD at the femoral neck (FN) we conducted a variance component linkage analysis, to test epistatic effects between the genomic region containing the COL1A1 (collagen type I alpha 1) gene and the genomic regions containing genes regulating osteoclast differentiation (e.g. TNFRSF11A encoding RANK (receptor for activation of nuclear factor kappa B), TNFSF11 encoding RANKL (RANK ligand), IL1A (interleukin‐1 alpha), IL6 (interleukin‐6), etc) in 3998 Caucasian subjects from 434 pedigrees. We detected significant epistatic interactions between the regions containing COL1A1 with IL6 (p = 0.004) and TNFRSF1B encoding TNFR2 (tumor necrosis factor receptor 2) (p = 0.003), respectively. In summary, we identified the epistatic effects on BMD between regions containing several prominent candidate genes. Our results suggested that the IL6 and TNFRSF1B genes may regulate FN BMD variation through interactions with the COL1A1 gene, which should be substantiated by other, or population‐based, association studies.
Commercial considerations in tissue engineering
Authors: Mansbridge Jonathan
Published: August 2006

Tissue engineering is a field with immense promise. Using the example of an early tissue‐engineered skin implant, Dermagraft, factors involved in the successful commercial development of devices of this type are explored. Tissue engineering has to strike a balance between tissue culture, which is a resource‐intensive activity, and business considerations that are concerned with minimizing cost and maximizing customer convenience. Bioreactor design takes place in a highly regulated environment, so factors to be incorporated into the concept include not only tissue culture considerations but also matters related to asepsis, scaleup, automation and ease of use by the final customer. Dermagraft is an allogeneic tissue. Stasis preservation, in this case cryopreservation, is essential in allogeneic tissue engineering, allowing sterility testing, inventory control and, in the case of Dermagraft, a cellular stress that may be important for hormesis following implantation. Although the use of allogeneic cells provides advantages in manufacturing under suitable conditions, it raises the spectre of immunological rejection. Such rejection has not been experienced with Dermagraft. Possible reasons for this and the vision of further application of allogeneic tissues are important considerations in future tissue‐engineered cellular devices. This review illustrates approaches that indicate some of the criteria that may provide a basis for further developments. Marketing is a further requirement for success, which entails understanding of the mechanism of action of the procedure, and is illustrated for Dermagraft. The success of a tissue‐engineered product is dependent on many interacting operations, some discussed here, each of which must be performed simultaneously and well.
Noxp20 and Noxp70, two new markers of early neuronal differentiation, detected in teratocarcinoma‐derived neuroectodermic precursor cells
Authors: Boucquey M. , De Plaen E. , Locker M. , Poliard A. , Mouillet‐Richard S. , Boon T. , Kellermann O.
Published: August 2006

The murine 1C11 cell line, derived from F9 pluripotent teratocarcinoma cells, exhibits features of a bipotential neuronal precursor as it converts into serotonergic or catecholaminergic neurons under appropriate induction. In order to point out molecular markers expressed in this early neuroectodermic commitment, we used a cDNA subtractive hybridization method. The 105 different isolated cDNAs represented 75 known genes, expressed sequence tags (EST) or genomic fragments. A majority of known proteins encoded by these sequences are involved in cellular mobility or migration. We characterized two sequences showing identities with ESTs and we called them Noxp20 and Noxp70. The Noxp20 transcript encodes a putative protein with a predicted caspase recruitment domain and the Noxp70 transcript encodes a putative protein displaying a Zn‐finger domain. Consistent with their roles in neuronal cell development, in situ hybridization showed that Noxp20 and Noxp70 are over‐expressed in brain. At embryonic days 12 and 15, Noxp20 is strongly expressed in the ventricular and intermediate zones of the brain and of the spinal cord. At embryonic day 15, Noxp70 was found to be strongly expressed in the ventricular zone around the telencephalic ventricle, and to a lower extent in the thalamus and hypothalamus. At post‐natal day 10, Noxp20 mRNA was detected in the dentate gyrus, the hippocampus, the cerebellum and the olfactory bulb.