bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity of canopy transpiration to altered precipitation in an upland oak forest: evidence from a long‐term field manipulation study
Authors: WULLSCHLEGER STAN D. , HANSON PAUL J.
Published: December 2005

Climate‐induced changes in regional precipitation could have important implications for the carbon, water, and nutrient cycles of forest ecosystems. However, few studies have examined the response of deciduous forests to increases or decreases in precipitation. Therefore, the throughfall displacement experiment (TDE) was established in 1993 near Oak Ridge, Tennessee to examine the sensitivity of an upland oak (Quercus spp.) forest to ambient, wet (+33%), and dry (−33%) precipitation regimes. Sap flux measurements on co‐occurring tree species were scaled using species‐specific estimates of stand sapwood area to derive daily and seasonal rates of canopy transpiration (EC) from 2000 to 2003. With the exception of 2003, which was an extremely wet year, daily EC in the dry plot, and occasionally during extended droughts in the ambient and wet plots, declined as water potential in the upper 0.35 m soil profile approached ‐3.0 MPa. Seasonal patterns of soil water potential and treatment‐specific differences in EC were dependent on precipitation frequency and intensity. Supplemental precipitation added to the wet plot increased seasonal EC on average by 9% (range −1% to 19%), whereas extended periods of drought on the dry plot in 2000, 2001, and 2002 were sufficient to reduce seasonal EC by 26–30% compared with the ambient plot. There was a strong correlation between seasonal EC and the water stress integral, a cumulative index of drought severity and duration. A polynomial fitted to these data indicated that reductions in seasonal EC on the order of 40% were possible given TDE‐imposed reductions in soil water potential. Application of this equation to all years of the TDE (1994–2003) revealed considerable interannual and treatment‐specific variation in canopy transpiration. In general, a 33% removal of throughfall on the dry plot during 1995, 1998, and 2002 resulted in a 23–32% reduction in seasonal EC compared with the ambient plot. While droughts in deciduous forests are often limited in duration and tend to occur late in the growing season, soil water deficits of the magnitude observed in this study have the potential to impact local and regional forest water budgets.
On the variability of respiration in terrestrial ecosystems: moving beyondQ10
Authors: DAVIDSON ERIC A. , JANSSENS IVAN A. , LUO YIQI
Published: December 2005

Respiration, which is the second most important carbon flux in ecosystems following gross primary productivity, is typically represented in biogeochemical models by simple temperature dependence equations. These equations were established in the 19th century and have been modified very little since then. Recent applications of these equations to data on soil respiration have produced highly variable apparent temperature sensitivities. This paper searches for reasons for this variability, ranging from biochemical reactions to ecosystem‐scale substrate supply. For a simple membrane‐bound enzymatic system that follows Michaelis–Menten kinetics, the temperature sensitivities of maximum enzyme activity (Vmax) and the half‐saturation constant that reflects the affinity of the enzyme for the substrate (Km) can cancel each other to produce no net temperature dependence of the enzyme. Alternatively, when diffusion of substrates covaries with temperature, then the combined temperature sensitivity can be higher than that of each individual process. We also present examples to show that soluble carbon substrate supply is likely to be important at scales ranging from transport across membranes, diffusion through soil water films, allocation to aboveground and belowground plant tissues, phenological patterns of carbon allocation and growth, and intersite differences in productivity. Robust models of soil respiration will require that the direct effects of substrate supply, temperature, and desiccation stress be separated from the indirect effects of temperature and soil water content on substrate diffusion and availability. We speculate that apparentQ10values of respiration that are significantly above about 2.5 probably indicate that some unidentified process of substrate supply is confounded with observed temperature variation.
Comparison of measured and EF5‐r‐derived N2O fluxes from a spring‐fed river
Authors: CLOUGH TIM J. , BERTRAM JANET E. , SHERLOCK ROBERT R. , LEONARD ROBERT L. , NOWICKI BARBARA L.
Published: December 2005

There is considerable uncertainty in the estimates of indirect N2O emissions as defined by the Intergovernmental Panel on Climate Change's (IPCC) methodology. Direct measurements of N2O yields and fluxes in aquatic river environments are sparse and more data are required to determine the role that rivers play in the global N2O budget.

The objectives of this research were to measure the N2O fluxes from a spring‐fed river, relate these fluxes to the dissolved N2O concentrations and NO3‐N loading of the river, and to try to define the indirect emission factor (EF5‐r) for the river.

Gas bubble ebullition was observed at the river source with bubbles containing 7.9 μL N2O L−1. River NO3‐N and dissolved N2O concentrations ranged from 2.5 to 5.3 mg L−1 and 0.4 to 1.9 μg N2O‐N L−1, respectively, with N2O saturation reaching 404%. Floating headspace chambers were used to sample N2O fluxes. N2O‐N fluxes were significantly related to dissolved N2O‐N concentrations (r2=0.31) but not to NO3‐N concentrations. The N2O‐N fluxes ranged from 38 to 501 μg m−2 h−1, averaging 171 μg m−2 h−1 (±SD 85) overall. The measured N2O‐N fluxes equated to an EF5‐r of only 6.6% of that calculated using the IPCC methodology, and this itself was considered to be an overestimate because of the degassing of antecedent dissolved N2O present in the groundwater that fed the river.
Focal epithelial hyperplasia (Heck's disease): report of a case in a girl of Brazilian Indian descent
Authors: MARTINS W. D. , DE LIMA A. A. S. , VIEIRA S.
Published: December 2005

Summary. Background.  This report describes the case of a patient with focal epithelial hyperplasia (FEH), a rare but distinctive entity of viral aetiology with characteristic clinical and histopathological features.

Case report. The condition is usually seen in children and adolescents of American Indian and Eskimo background. Surgical removal of papillomatous lesions is the treatment of choice, either for aesthetic reasons, or when the lesions interfere with function or are readily traumatized. Recurrence and the site of new lesions are unpredictable, and continued review of the patient is often necessary. The patient described here has been followed for 24 months without recurrences or changes in the aspect of the remaining lesions.

Conclusion.  This case highlights a possible genetic predilection for FEH, since the patient is a descent of a Brazilian Xavante Indian.
Differences in methodologies of measuring the prevalence of oral mucosal lesions in children and adolescents
Authors: FURLANETTO D. L. C. , CRIGHTON A. , TOPPING G. V. A.
Published: December 2005

Summary. Aim. This review offers a brief summary of three of the more commonly surveyed and reported oral mucosal conditions found in children, and an appraisal of the variation between selected elements of prevalence study methodologies.

Design. Searches of electronic databases (i.e. MEDLINE, CINAHL, EMBASE and EBM Reviews) were conducted to find publications related to oral mucosal conditions in children. Studies were included and reviewed if they contained data on the prevalence of any of the following oral mucosal conditions: geographical tongue, oral ulceration and herpes labialis in children or adolescents (up to the age of 19 years).

Results. A total of 29 articles out of 333 met the inclusion criteria and were reviewed. Of these 29 reports, 18 considered geographical tongue, 12 herpes labialis and 10 oral ulceration, although a number of the surveys reported on more than one condition. The approaches used in these studies varied on a number of the potentially important areas associated with validity, comparability, and whether or not the findings may be extrapolated beyond the study population, such as the sampling frame, diagnostic criteria, training and calibration, and examination features.

Conclusion. Although there were a number of surveys relating to the prevalence of geographical tongue, herpes labialis and oral ulcers in children and adolescents, reported prevalences varied and few studies were directly comparable in terms of the methodology applied. In particular, there was substantial variation between surveys in terms of the diagnostic criteria and method of detection employed although, in many instances, there was inadequate detail to allow full appraisal of the methodology. There is a need for more good‐quality epidemiological studies in this area.
CD36 expression and its relationship with obesity in blood cells from people with and without Prader–Willi syndrome
Authors: Webb T , Whittington J , Holland AJ , Soni S , Boer H , Clarke D , Horsthemke B
Published: December 2005

Although Prader–Willi syndrome (PWS) has been linked to the loss of function of imprinted genes in 15q11q13, very little is known about the pathogenesis. Using quantitative real‐time PCR, we have confirmed the previous observation of an abnormality of CD36 expression in cells with maternal uniparental disomy 15, obtained from a proband with mosaicism for PWS, by demonstrating reduced expression levels in blood cells from a series of non‐mosaic probands with PWS. Furthermore, we have extended these observations to show that CD36 expression in a non‐PWS population is inversely correlated with body mass index but that this correlation does not hold in PWS. CD36 which maps to 7q11.2 is the first gene outside the 15q11q13 region whose level of expression appears to be reduced in people with PWS. Low CD36 expression levels in PWS point to an abnormal control of lipid and glucose homeostasis which may explain the insatiable hunger in these patients.
Comorbid ADHD is associated with altered patterns of neuronal activation in adolescents with bipolar disorder performing a simple attention task
Authors: Adler Caleb M , DelBello Melissa P , Mills Neil P , Schmithorst Vince , Holland Scott , Strakowski Stephen M
Published: December 2005

Objective:  Bipolar disorder is increasingly recognized as a significant source of psychiatric morbidity in children and adolescents. Younger bipolar patients symptomatically differ from adults, and frequently present with comorbid disorders, particularly attention‐deficit hyperactivity disorder (ADHD). The neurophysiological relationship between these two disorders, however, remains unclear. In this study we utilized functional magnetic resonance imaging (fMRI) to compare activation patterns during performance of a simple attention task between bipolar adolescents with and without ADHD.

Methods:  Eleven bipolar adolescents with comorbid ADHD and 15 bipolar adolescents without comorbidity were recruited to participate in fMRI scans. A single‐digit continuous performance task alternated with a control task in a block‐design paradigm. between‐group comparisons were made using voxel‐by‐voxel analysis. Follow‐up correlations were made between performance and activation.

Results:  Group performance did not significantly differ in percentage correct (p = 0.36) or discriminability (p = 0.11). ADHD comorbidity was associated with less activation in the ventrolateral prefrontal cortex (Brodmann 10) and anterior cingulate, and greater activation in posterior parietal cortex and middle temporal gyrus. Comorbid ADHD was associated with substantial differences in patterns of correlation between performance and voxel‐by‐voxel activation.

Conclusions:  Our findings suggest that comorbid ADHD in bipolar adolescents is associated with activation of alternative pathways during performance of a simple attention task. The pattern of differences suggests that bipolar adolescents with comorbid ADHD demonstrate decreased activation of prefrontal regions, compared with bipolar adolescents without ADHD, and preferentially recruit portions of posterior parietal and temporal cortex.
History of suicide attempts in pediatric bipolar disorder: factors associated with increased risk
Authors: Goldstein Tina R , Birmaher Boris , Axelson David , Ryan Neal D , Strober Michael A , Gill Mary Kay , Valeri Sylvia , Chiappetta Laurel , Leonard Henrietta , Hunt Jeffrey , Bridge Jeffrey A , Brent David A , Keller Martin
Published: December 2005

Background:  Despite evidence indicating high morbidity associated with pediatric bipolar disorder (BP), little is known about the prevalence and clinical correlates of suicidal behavior among this population.

Objective:  To investigate the prevalence of suicidal behavior among children and adolescents with BP, and to compare subjects with a history of suicide attempt to those without on demographic, clinical, and familial risk factors.

Methods:  Subjects were 405 children and adolescents aged 7–17 years, who fulfilled DSM‐IV criteria for BPI (n = 236) or BPII (n = 29), or operationalized criteria for BP not otherwise specified (BP NOS; n = 140) via the Schedule for Affective Disorders and Schizophrenia for School‐Aged Children. As part of a multi‐site longitudinal study of pediatric BP (Course and Outcome of Bipolar Youth), demographic, clinical, and family history variables were measured at intake via clinical interview with the subject and a parent/guardian.

Results:  Nearly one‐third of BP patients had a lifetime history of suicide attempt. Attempters, compared with non‐attempters, were older, and more likely to have a lifetime history of mixed episodes, psychotic features, and BPI. Attempters were more likely to have a lifetime history of comorbid substance use disorder, panic disorder, non‐suicidal self‐injurious behavior, family history of suicide attempt, history of hospitalization, and history of physical and/or sexual abuse. Multivariate analysis found that the following were the most robust set of predictors for suicide attempt: mixed episodes, psychosis, hospitalization, self‐injurious behavior, panic disorder, and substance use disorder.

Conclusions:  These findings indicate that children and adolescents with BP exhibit high rates of suicidal behavior, with more severe features of BP illness and comorbidity increasing the risk for suicide attempt. Multiple clinical factors emerged distinguishing suicide attempters from non‐attempters. These clinical factors should be considered in both assessment and treatment of pediatric BP.
Negatively condition dependent predation cost of a positively condition dependent sexual signalling
Authors: Lindström L. , Ahtiainen J. J. , Mappes J. , Kotiaho J. S. , Lyytinen A. , Alatalo R. V.
Published: December 2005

Predation is considered as an important factor constraining the expression of sexual signals. Nevertheless, direct quantitative evidence for predation provoking significant viability costs on individuals signalling at high rates is scarce. Moreover, it is unclear whether high rate signallers are able to balance presumably increased predation costs. We examined whether a condition dependent audible sexual signal, drumming, makes Hygrolycosa rubrofasciata male spiders more prone to predation by pied flycatchers (Ficedula hypoleuca), and whether sexual signalling rate is related to escaping ability once attacked. When birds were given a choice between two spider males manipulated to drum either one or three bouts per minute using playbacks, naïve birds attacked the males randomly regardless of the drumming rate. However, experienced birds chose significantly more often the males with high signalling rate. When spiders were allowed to escape, males with high sexual signalling rate tended to be better at escaping attacks than males with low sexual signalling rate. This study provides evidence that high signalling rate increases the risk of predation, but simultaneously males with high mobility, which correlates positively with signalling rate seemed to be better at compensating this cost.
Fitness conflicts and the costs of sociality in communal egg layers: a theoretical model and empirical tests
Authors: Loeb M. L. G. , Zink A. G.
Published: December 2005

Individuals within complex social groups often experience reduced reproduction owing to coercive or suppressive actions of other group members. However, the nature of social and ecological environments that favour individual acceptance of such costs of sociality is not well understood. Taxa with short periods of direct social interaction, such as some communal egg layers, are interesting models for study of the cost of social interaction because opportunities to control reproduction of others are limited to brief periods of reproduction. To understand the conditions under which communal egg layers are in fitness conflict and thus likely to influence each other's reproduction, we develop an optimality model involving a brood guarding ‘host’ and a nonguarding disperser, or ‘egg dumper’. The model shows that when, where intermediate-sized broods have highest survival, lifetime inclusive fitnesses of hosts and dumpers are often optimized with different numbers of dumped eggs. We hypothesize that resolution of this conflict may involve attempts by one party to manipulate the other's reproduction. To test model predictions we used a lace bug (Heteroptera: Tingidae) that shows both hosts and egg dumpers as well as increased offspring survival in response to communal egg laying. We found that egg-dumping lace bugs oviposit a number of eggs that very closely matches predicted fitness optimum for hosts rather than predicted optimum of dumpers. This result suggests that dumpers pay a social cost for communal egg laying, a cost that may occur through host suppression of dumper reproduction. Although dumper allocation of eggs is thus sub-optimal for dumpers, previous models show that the decision to egg dump is nevertheless evolutionarily stable, possibly because hosts permit just enough dumper oviposition to encourage commitment to the behaviour.
Do mothers producing large offspring have to sacrifice fecundity?
Authors: Fischer K. , Bot A. N. M. , Brakefield P. M. , Zwaan Bas J.
Published: December 2005

We artificially selected on egg size in a butterfly to study the consequences for fecundity, reproductive effort and offspring fitness. Correlated responses in either pupal mass, larval or pupal development time were virtually absent. Offspring size was positively related to fitness, but only partly traded off against fecundity. Rather, total reproductive effort (measured as fresh mass), egg water content and the decline of egg size with female age increased in the large-egg selected lines compared to either small-egg or control lines. Accounting for these effects showed that reproductive investment (in dry mass) was in fact similar across lines. Such mechanisms may enable increased investment in (early) offspring without a reduction in their number, revealing a much more complex picture than a simple trade-off between offspring size and number. Substantial variation among replicates suggests that there are different underlying mechanisms for change, rather than any single, unitary pathway.
Asymmetric gene flow and constraints on adaptation caused by sex ratio distorters
Authors: Telschow A. , Engelstädter J. , Yamamura N. , Hammerstein P. , Hurst G.D.D.
Published: December 2005

Asymmetric gene flow is generally believed to oppose natural selection and potentially impede adaptation. Whilst the cause of asymmetric gene flow has been seen largely in terms of variation in population density over space, asymmetric gene flow can also result from varying sex ratios across subpopulations with similar population sizes. We model the process of adaptation in a scenario in which two adjacent subpopulations have different sex ratios, associated with different levels of infection with maternally inherited endosymbionts that selectively kill male hosts. Two models are analyzed in detail. First, we consider one host locus with two alleles, each of which possesses a selective advantage in one of the subpopulations. We found that local adaptation can strongly be impeded in the subpopulation with the more female biased population sex ratio. Second, we analyze host alleles that provide resistance against the male-killing (MK) endosymbionts and show that asymmetric gene flow can prevent the spread of such alleles under certain conditions. These results might have important implications for the coevolution of MK bacteria and their hosts.
The costs and benefits in an unusual symbiosis: experimental evidence that bitterling fish (Rhodeus sericeus) are parasites of unionid mussels in Europe
Authors: Reichard M. , Ondračková M. , Przybylski M. , Liu H. , Smith C.
Published: December 2005

Interspecific symbiotic relationships involve a complex network of interactions, and understanding their outcome requires quantification of the costs and benefits to both partners. We experimentally investigated the costs and benefits in the relationship between European bitterling fish (Rhodeus sericeus) and freshwater mussels that are used by R. sericeus for oviposition. This relationship has hitherto been thought mutualistic, on the premise that R. sericeus use mussels as foster parents of their embryos while mussels use R. sericeus as hosts for their larvae. We demonstrate that R. sericeus is a parasite of European mussels, because it (i) avoids the cost of infection by mussel larvae and (ii) imposes a direct cost on mussels. Our experiments also indicate a potential coevolutionary arms race between bitterling fishes and their mussel hosts; the outcome of this relationship may differ between Asia, the centre of distribution of bitterling fishes, and Europe where they have recently invaded.
Glacial refugia and the phylogeography of Steller's sea lion (Eumatopias jubatus) in the North Pacific
Authors: Harlin-cognato A. , Bickham J. W. , Loughlin T. R. , Honeycutt R. L.
Published: December 2005

Mitochondrial DNA sequence data were used to examine the phylogeographic history of Steller's sea lions (Eumetopias jubatus) in relation to the presence of Plio-Pleistocene insular refugia. Cytochrome b and control region sequences from 336 Steller's sea lions reveal phylogenetic lineages associated with continental refugia south of the ice sheets in North America and Eurasia. Phylogenetic analysis suggests the genetic structure of E. jubatus is the result of Pleistocene glacial geology, which caused the elimination and subsequent reappearance of suitable rookery habitat during glacial and interglacial periods. The cyclic nature of geological change produced a series of independent population expansions, contractions and isolations that had analogous results on Steller's sea lions and other marine and terrestrial species. Our data show evidence of four glacial refugia in which populations of Steller's sea lions diverged. These events occurred from approximately 60 000 to 180 000 years BP and thus preceded the last glacial maximum.
Sediment greenhouse gases (methane and carbon dioxide) in the Lobo‐Broa Reservoir, São Paulo State, Brazil: Concentrations and diffuse emission fluxes for carbon budget considerations
Authors: Abe Donato S. , Adams Donald D. , Galli Corina V. Sidagis , Sikar Elizabeth , Tundisi José G.
Published: December 2005

Carbon gases (methane, CH4, and carbon dioxide, CO2) were measured for the first time in sediments of the Lobo‐Broa Reservoir, near São Carlos in São Paulo State, Brazil. It is believed these are the first measurements of this kind in any of the many reservoirs located in Brazil. Even though the Lobo‐Broa Reservoir is classified as oligotrophic, the sediment gas concentrations were exceedingly high, ranging from 0.4–3 mmol L−1 for CH4 and 1–9 mmol L−1 for CO2. Both gases exceeded their in situ gas saturation values at these shallow water depths (7 m in central basin; 11 m at dam), resulting in numerous sediment bubbles. Organic matter was highly concentrated in the reservoir sediments, averaging 25.5% loss on ignition (LOI) (dam) to 26.9% LOI (central basin) for the 0–12 cm depth interval, with values as high as 29–30% LOI (12% organic carbon) in the surface 0–5 mm layer. The theoretical flux of dissolved pore water carbon gases to the sediment–water interface (SWI) averaged 3.4 mmol L−1 m−2 day−1 CH4 and 7.3 mmol L−1 m−2 day−1 CO2 for the surface 0–10 mm. From gas emission measurements at the water surface, it was calculated that 90% of CH4 is consumed either at the SWI or in the water column, resulting in a loss of 0.31 mmol L−1 m−2 day−1 of CH4 to the atmosphere. However, only 20% of the total CO2 gas transported across the water–atmosphere interface (36.3 mmol L−1 m−2 day−1, or 1600 mg CO2 m−2 day−1) was produced in the sediments. The remaining 80% of CO2 probably comes from other carbon sources. With CH4 oxidation in the aerobic water column, close to 30% of the carbon gas flux to the atmosphere could be accounted for by gas production of CO2 and CH4 in the sediments and their diffuse transport to the water column.
The role of prefrontal cortex in object‐in‐place learning in monkeys
Authors: Browning Philip G. F. , Easton Alexander , Buckley Mark J. , Gaffan David
Published: December 2005

Previous ablation studies in monkeys suggest that prefrontal cortex is involved in a wide range of learning and memory tasks. However, monkeys with crossed unilateral lesions of frontal and temporal cortex are unimpaired at concurrent object–reward association learning but are impaired at conditional learning and the implementation of memory‐based performance rules. We trained seven monkeys preoperatively on an associative learning task that required them to associate objects embedded in unique complex scenes with reward. Three monkeys then had crossed unilateral lesions of frontal and inferior temporal cortex and the remaining monkeys had bilateral prefrontal cortex ablation. Both groups were severely impaired postoperatively. These results show that both bilateral prefrontal cortex ablation and frontal–temporal disconnection impair associative learning for objects embedded in scenes. The results provide evidence that the function of frontal–temporal interactions in memory is not limited to conditional learning tasks and memory‐dependent performance rules. We propose that rapid object‐in‐place learning requires the interaction of frontal cortex with inferotemporal cortex because visual object and contextual information which is captured over multiple saccades must be processed as a unique complex event that is extended in time. The present results suggest a role for frontal–temporal interaction in the integration of visual information over time.
Late N‐methyl‐d‐aspartate receptor blockade rescues hippocampal neurons from excitotoxic stress and death after 4‐aminopyridine‐induced epilepsy
Authors: Ayala Gabriela X. , Tapia Ricardo
Published: December 2005

The intrahippocampal perfusion of 4‐aminopyridine (4‐AP) in the rat produces immediate seizures and delayed neuronal death, due to the overactivation of N‐methyl‐d‐aspartate (NMDA) receptors by endogenous glutamate released from nerve endings. With the same time course, 4‐AP also induces the expression of the cell stress marker heat shock protein 70 (HSP70) in the contralateral non‐damaged hippocampus. We have used this experimental model to study the mechanisms of the delayed neuronal stress and death. The NMDA receptor antagonist (+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo(a,d)cyclohepten‐5,10‐imine maleate (MK‐801), administered intraperitoneally 30 or 60 but not 120 min after 4‐AP perfusion, when animals show intense electroencephalography epileptiform activity, prevented the delayed neurodegeneration whereas the seizures continued for about 3 h as in the control animals. With an identical time window, MK‐801 treatment also modified the pattern of HSP70 expression; the protein was expressed in the protected perfused hippocampus but no longer in the undamaged contralateral hippocampus. The possible role of Ca2+ in the delayed cell death and HSP70 expression was also studied by coperfusing the intracellular Ca2+ chelator 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetra‐acetic acid tetrakis(acetoxymethyl ester) with 4‐AP. This treatment resulted in protective and HSP70 effects very similar to those of MK‐801. These results suggest that the seizures are not linked to neurodegeneration and that NMDA receptors need to be continuously overactivated by endogenous glutamate for at least 60 min in order to induce delayed neuronal stress and death, which are dependent on Ca2+ entry through the NMDA receptor channel.
A postnatal switch in GABAergic control of spinal cutaneous reflexes
Authors: Hathway Gareth , Harrop Emily , Baccei Mark , Walker Suellen , Moss Andrew , Fitzgerald Maria
Published: December 2005

GABAergic signalling exerts powerful inhibitory control over spinal tactile and nociceptive processing, but during development GABA can be depolarizing and the functional consequences of this upon neonatal pain processing is unknown. Here we show a postnatal switch in tonic GABAA receptor (GABAAR) modulation of cutaneous tactile and nociceptive reflexes from excitation to inhibition, but only in the intact spinal cord. Neonatal and 21‐day‐old (P21) rats were intrathecally treated with one of the GABAAR antagonists bicuculline and gabazine, with both compounds dose‐dependently decreasing hindpaw mechanical and thermal withdrawal thresholds in P21 rats but increasing them in P3 neonates. Intrathecal gabazine also produced an increase in the cutaneous evoked electromyography (EMG) response of the biceps femoris in P21 rates but lowering the response in neonates. Injections of 3H‐gabazine in the L4–L5 region at P3 confirmed that gabazine binding was restricted to the lumbar spinal cord. Spinalization of P3 neonates at the upper thoracic level prior to drug application reversed the behavioural and EMG responses to GABA antagonists so that they resembled those of P21 rats. The effects of spinalization were consistent with gabazine facilitation of ventral root potentials observed in isolated neonatal spinal cord. These data show a marked postnatal developmental switch in GABAergic control of neonatal nociception that is mediated by supraspinal structures and illustrate the importance of studying developmental circuits in the intact nervous system.
ATP activates both receptor and sustentacular supporting cells in the olfactory epithelium of Xenopus laevis tadpoles
Authors: Czesnik Dirk , Kuduz Josko , Schild Detlev , Manzini Ivan
Published: December 2005

Nucleotides and amino acids are acknowledged categories of water‐borne olfactory stimuli. In previous studies it has been shown that larvae of Xenopus laevis are able to sense amino acids. Here we report on the effect of ATP in the olfactory epithelium (OE) of Xenopus laevis tadpoles. First, ATP activates a subpopulation of cells in the OE. The ATP‐sensitive subset of cells is almost perfectly disjoint from the subset of amino acid‐activated cells. Both responses are not mediated by the well‐described cAMP transduction pathway as the two subpopulations of cells do not overlap with a third, forskolin‐activated subpopulation. We further show that, in contrast to amino acids, which act exclusively as olfactory stimuli, ATP appears to feature a second role. Surprisingly it activated a large number of sustentacular supporting cells (SCs) and, to a much lower extent, olfactory receptor neurons. The cells of the amino acid‐ and ATP‐responding subsets featured differences in shape, size and position in the OE. The latencies to activation upon stimulus application differed markedly in these subsets. To obtain these results two technical points were important. We used a novel dextran‐tetramethylrhodamine‐backfilled slice preparation of the OE and we found out that an antibody to calnexin, a known molecular chaperone, also labels SCs. Our findings thus show a strong effect of ATP in the OE and we discuss some of the possible physiological functions of nucleotides in the OE.
Quantifying the roles of immigration and chance in shaping prokaryote community structure
Authors: Sloan William T. , Lunn Mary , Woodcock Stephen , Head Ian M. , Nee Sean , Curtis Thomas P.
Published: December 2005

Naturally occurring populations of bacteria and archaea are vital to life on the earth and are of enormous practical significance in medicine, engineering and agriculture. However, the rules governing the formation of such communities are still poorly understood, and there is a need for a usable mathematical description of this process. Typically, microbial community structure is thought to be shaped mainly by deterministic factors such as competition and niche differentiation. Here we show, for a wide range of prokaryotic communities, that the relative abundance and frequency with which different taxa are observed in samples can be explained by a neutral community model (NCM). The NCM, which is a stochastic, birth–death immigration process, does not explicitly represent the deterministic factors and therefore cannot be a complete or literal description of community assembly. However, its success suggests that chance and immigration are important forces in shaping the patterns seen in prokaryotic communities.
Expression of calcineurin and its interacting proteins in epileptic fowl
Authors: Lakshmikuttyamma Ashakumary , Selvakumar Ponniah , Charavaryamath Chandrashekhar , Singh Baljit , Tuchek John , Sharma Rajendra K.
Published: December 2005

Calcineurin (CaN), a Ca2+–calmodulin (CaM)‐dependent protein phosphatase, is important for Ca2+‐mediated signal transduction. The main objective of this study was to examine the potential role of CaN in epileptic brain and its involvement in neuronal apoptosis. We investigated CaN expression and its interaction with various signaling molecules in normal, carrier and epileptic brain tissues of chicken. Our results revealed higher Ca2+–CaM‐dependent phosphatase activity of CaN and a correspondingly strong immunoreactive band of CaN A in epileptic and carrier brain samples compared with normal brain. Furthermore, immunohistochemical analysis showed a higher level of expression of CaN in epileptic brain tissue. However, the intensity of immunoreactivity was less in carrier than epileptic brain. We observed that the interaction of CaN with m‐calpain and µ‐calpain was strong in carrier and epileptic chickens compared with that in normal birds. In addition, the interaction of CaN with Bcl‐2, caspase‐3 and p53 was greater in carrier and epileptic fowl than in normal chickens. The greater interaction of CaN with various apoptotic factors in epileptic chickens adds to our understanding of the mechanism of CaN signaling in neuronal apoptosis.
Decreased GTP‐stimulated adenylyl cyclase activity in HPRT‐deficient human and mouse fibroblast and rat B103 neuroblastoma cell membranes
Authors: Pinto Cibele S. , Seifert Roland
Published: December 2005

Defect of the purine salvage enzyme, hypoxanthine phosphoribosyl transferase (HPRT), results in Lesch–Nyhan disease (LND). It is unknown how the metabolic defect translates into the severe neuropsychiatric phenotype characterized by self‐injurious behavior, dystonia and mental retardation. There are abnormalities in GTP, UTP and CTP concentrations in HPRT‐deficient cells. Moreover, GTP, ITP, XTP, UTP and CTP differentially support Gs‐protein‐mediated adenylyl cyclase (AC) activation. Based on these findings we hypothesized that abnormal AC regulation may constitute the missing link between HPRT deficiency and the neuropsychiatric symptoms in LND. To test this hypothesis, we studied AC activity in membranes from primary human skin and immortalized mouse skin fibroblasts, mouse Neuro‐2a neuroblastoma cells and rat B103 neuroblastoma cells. In B103 control membranes, GTP, ITP, XTP and UTP exhibited profound stimulatory effects on basal AC activity that approached the effects of hydrolysis‐resistant nucleotide analogs. In HPRT–membranes, the stimulatory effects of GTP, ITP, XTP and UTP were strongly reduced. Similarly, in human and mouse skin fibroblast membranes we also observed a decrease in GTP‐stimulated AC activity in HPRT‐deficient cells compared with the respective controls. In mouse Neuro‐2a neuroblastoma membranes, AC activity in the presence of GTP was below the detection limit of the assay. We discuss several possibilities to explain the abnormalities in AC regulation in HPRT deficiency that encompass various species and cell types.
Type A monoamine oxidase is the target of an endogenous dopaminergic neurotoxin, N‐methyl(R)salsolinol, leading to apoptosis in SH‐SY5Y cells
Authors: Yi Hong , Akao Yukihiro , Maruyama Wakako , Chen Kavin , Shih Jean , Naoi Makoto
Published: December 2005

Mitochondrial monoamine oxidase (MAO) has been considered to be involved in neuronal degeneration either by increased oxidative stress or protection with the inhibitors of type B MAO (MAO‐B). In this paper, the role of type A MAO (MAO‐A) in apoptosis was studied using human neuroblastoma SH‐SY5Y cells, where only MAO‐A is expressed. An endogenous dopaminergic neurotoxin, N‐methyl(R)salsolinol, an MAO‐A inhibitor, reduced membrane potential, ΔΨm, in isolated mitochondria, and induced apoptosis in the cells, which 5‐hydroxytryptamine, an MAO‐A substrate, prevented. In contrast, β‐phenylethylamine, an MAO‐B substrate, did not suppress the ΔΨm decline by N‐methyl(R)salsolinol. The binding of N‐methyl(R)salsolinol to mitochondria was inhibited by clorgyline, a MOA‐A inhibitor, but not by (–)deprenyl, an MAO‐B inhibitor. RNA interference targeting MAO‐A significantly reduced the binding of N‐methyl(R)salsolinol with simultaneous reduction in the MAO activity. To examine the intervention of MAO‐B in the apoptotic process, human MAO‐B was transfected to SH‐SY5Y cells, but the sensitivity to N‐methyl(R)salsolinol was not affected, even although the activity and protein of MAO increased markedly. These results demonstrate a novel function of MAO‐A in the binding of neurotoxins and the induction of apoptosis, which may account for neuronal cell death in neurodegenerative disorders, including Parkinson's disease.
Vesicular storage and secretion of l‐glutamate from glucagon‐like peptide 1‐secreting clonal intestinal L cells
Authors: Uehara Shunsuke , Jung Sun‐Kyung , Morimoto Riyo , Arioka Shigeo , Miyaji Takaaki , Juge Narinobu , Hiasa Miki , Shimizu Kahori , Ishimura Akinori , Otsuka Masato , Yamamoto Akitsugu , Maechler Pierre , Moriyama Yoshinori
Published: December 2005

Vesicular glutamate transporter (VGLUT) is responsible for the vesicular storage of l‐glutamate, and plays an essential role in glutamate‐mediated intercellular signal transmission in the CNS and in some neuroendocrine cells. Intestinal L cells are the glucose‐responsive neuroendocrine cells responsible for the secretion of glucagon‐like peptide 1 (GLP‐1). We have shown that intestinal L cells express VGLUT2, a VGLUT isoform, which suggests that L cells secrete l‐glutamate. In the present study, we investigated this possibility using GLUTag mouse clonal L cells. RT–PCR and northern blot analyses revealed expression of the VGLUT1 and VGLUT2 genes, but not of the VGLUT3 gene. Western blot analysis revealed immunological counterparts for VGLUT2, whereas an immunological counterpart of VGLUT1 was not detected. Indirect immunofluorescence microscopy revealed a punctate distribution of VGLUT2 immunoreactivity throughout the cells, which co‐localized with GLP‐1. Double‐labeling immunoelectronmicroscopy confirmed the association of VGLUT2 with GLP‐1‐containing secretory granules. The membrane fraction exhibited ATP‐dependent l‐glutamate uptake, which was sensitive to bafilomycin A1 (a vacuolar proton ATPase inhibitor) and Evans blue (a VGLUT inhibitor) but insensitive to d,l‐aspartate. Upon depolarization with KCl, GLUTag cells secreted appreciable amounts of l‐glutamate and GLP‐1. d‐Glucose and methyl‐α‐d‐glucopyranoside, stimulators of exocytosis of GLP‐1, also triggered the secretion of l‐glutamate. The l‐glutamate secretion was partially dependent on Ca2+ and sensitive to bafilomycin A1. These results demonstrated that GLUTag cells stored l‐glutamate in secretory granules and secreted it with GLP‐1 by exocytosis. As GLUTag cells and intestinal L cells express kainate receptors and plasma membrane glutamate transporters, these results support the concept of l‐glutamate‐mediated intercellular signaling in the vicinity of intestinal L cells.
Semaphorin 3A and neurotrophins: a balance between apoptosis and survival signaling in embryonic DRG neurons
Authors: Ben‐Zvi Ayal , Yagil Zohar , Hagalili Yamit , Klein Hagit , Lerman Omer , Behar Oded
Published: December 2005

Large numbers of neurons are eliminated by apoptosis during nervous system development. For instance, in the mouse dorsal root ganglion (DRG), the highest incidence of cell death occurs between embryonic days 12 and 14 (E12–E14). While the cause of cell death and its biological significance in the nervous system is not entirely understood, it is generally believed that limiting quantities of neurotrophins are responsible for neuronal death. Between E12 and E14, developing DRG neurons pass through tissues expressing high levels of axonal guidance molecules such as Semaphorin 3A (Sema3A) while navigating to their targets. Here, we demonstrate that Sema3A acts as a death‐inducing molecule in neurotrophin‐3 (NT‐3)‐, brain‐derived neurotrophic factor (BDNF)‐ and nerve growth factor (NGF)‐dependent E12 and E13 cultured DRG neurons. We show that Sema3A most probably induces cell death through activation of the c‐Jun N‐terminal kinase (JNK)/c‐Jun signaling pathway, and that this cell death is blocked by a moderate increase in NGF concentration. Interestingly, increasing concentrations of other neurotrophic factors, such as NT‐3 or BDNF, do not elicit similar effects. Our data suggest that the number of DRG neurons is determined by a fine balance between neurotrophins and Semaphorin 3A, and not only by neurotrophin levels.
Polyphenol amentoflavone affords neuroprotection against neonatal hypoxic‐ischemic brain damage via multiple mechanisms
Authors: Shin Dong Hoon , Bae Young Chul , Kim‐Han Jeong Sook , Lee Ji Hyun , Choi In Young , Son Kun Ho , Kang Sam Sik , Kim Won‐Ki , Han Byung Hee
Published: December 2005

Flavonoids are naturally occurring polyphenolic compounds that have many biological properties, including antioxidative, anti‐inflammatory and neuroprotective effects. Here, we report that amentoflavone significantly reduced cell death induced by staurosporine, etoposide and sodium nitroprusside in neuroblastoma SH‐SY5Y cells. In post‐natal day 7 rats, hypoxic‐ischemic (H‐I) brain damage induced by unilateral carotid ligation and hypoxia resulted in distinct features of neuronal cell death including apoptosis and necrosis. In this model, a systemic administration of amentoflavone (30 mg/kg) markedly reduced the H‐I‐induced brain tissue loss with a wide therapeutic time window up to 6 h after the onset of hypoxia. Amentoflavone blocked the activation of caspase 3, characteristic of apoptosis, and the proteolytic cleavage of its substrates following H‐I injury. Amentoflavone also reduced the excitotoxic/necrotic cell death after H‐I injury in vivo and after oxygen/glucose deprivation in mouse mixed cultures in vitro. Treatment of mouse microglial cells with amentoflavone resulted in a significant decrease in the lipopolysaccharide‐induced production of nitric oxide and induction of inducible nitric oxide synthase and cyclo‐oxygenase‐2. Furthermore, amentoflavone decreased the inflammatory activation of microglia after H‐I injury when assessed by the microglial‐specific marker OX‐42. These data demonstrate for the first time that amentoflavone strongly protects the neonatal brain from H‐I injury by blocking multiple cellular events leading to brain damage.
Role of metalloproteinase‐dependent EGF receptor activation in α1‐adrenoceptor‐stimulated MAP kinase phosphorylation in GT1‐7 neurons
Authors: Shah Bukhtiar H. , Shah Farzana B. , Catt Kevin J.
Published: December 2005

Adrenoceptors (ARs) are involved in the regulation of gonadotropin‐releasing hormone (GnRH) release from native and immortalized hypothalamic (GT1‐7) neurons. However, the AR‐mediated signaling mechanisms and their functional significance in these cells are not known. Stimulation of GT1‐7 cells with the α1‐AR agonist, phenylephrine (Phe), causes phosphorylation of extracellular signal‐regulated kinases 1 and 2 (ERK1/2) mitogen‐activated protein (MAP) kinases that is mediated by protein kinase C (PKC)‐dependent transactivation of the epidermal growth factor receptor (EGF‐R). Phe stimulation causes shedding of the soluble ligand, heparin‐binding EGF (HB‐EGF), as a consequence of matrix metalloproteinase (MMP) activation. Phe‐induced phosphorylation of the EGF‐R, and subsequently of Shc and ERK1/2, was attenuated by inhibition of MMP or HB‐EGF with the selective inhibitor, CRM197, or by a neutralizing antibody. In contrast, phosphorylation of the EGF‐R, Shc and ERK1/2 by EGF and HB‐EGF was independent of PKC and MMP activity. Moreover, inhibition of Src attenuated ERK1/2 responses by Phe, but not by HB‐EGF and EGF, indicating that Src acts upstream of the EGF‐R. Consistent with a potential role of reactive oxygen species (ROS), Phe‐induced phosphorylation of EGF‐R was attenuated by the antioxidant, N‐acetylcysteine. These data suggest that activation of the α1‐AR causes phosphorylation of ERK1/2 through activation of PKC, ROS and Src, and shedding of HB‐EGF, which binds to and activates the EGF‐R.
Erythropoietin protects against 6‐hydroxydopamine‐induced dopaminergic cell death
Authors: Signore Armando P. , Weng Zhongfang , Hastings Teresa , Van Laar Amber D. , Liang Qinghua , Lee Yong J. , Chen Jun
Published: December 2005

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the death of midbrain dopaminergic neurons. In the present study, erythropoietin, a trophic factor that has both hematopoietic and neural protective characteristics, was investigated for its capacity to protect dopaminergic neurons in experimental Parkinson's disease. Using both the dopaminergic cell line, MN9D, and primary dopamine neurons, we show that erythropoietin (1–3 U/mL) is neuroprotective against the dopaminergic neurotoxin, 6‐hydroxydopamine. Protection was mediated by the erythropoietin receptor, as neutralizing anti‐erythropoietin receptor antibody abrogated the protection. Activation of Akt/protein kinase B (PKB), via the phosphoinositide 3‐kinase pathway, is a critical mechanism in erythropoietin‐induced protection, while activation of extracellular signal‐regulated kinase (ERK)1/2 contributes only moderately. Indeed, transfection of constitutively active Akt/PKB into dopaminergic cells was sufficient to protect against cell death. Furthermore, erythropoietin diminished markers of apoptosis in MN9D cells, including caspase 9 and caspase 3 activation and internucleosomal DNA fragmentation, suggesting that erythropoietin interferes with the apoptosis–execution process. When erythropoietin was administered to mice unilaterally lesioned with 6‐hydroxydopamine, it prevented the loss of nigral dopaminergic neurons and maintained striatal catecholamine levels for at least 8 weeks. Erythropoietin‐treated mice also had significantly reduced behavioral asymmetries. These studies suggest that erythropoietin can be an effective neuroprotective agent for dopaminergic neurons, and may be useful in reversing behavioral deficits associated with Parkinson's disease.