bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscarine activates the sodium–calcium exchanger via M3 receptors in basal forebrain neurons
Authors: Xu Changqing , Wu Min , Morozova Elena , Alreja Meenakshi
Published: October 2006

Neurons of the medial septum/diagonal band of Broca (MSDB) project to the hippocampus. Muscarinic cholinergic mechanisms within the MSDB are potent modulators of hippocampal functions; intraseptal scopolamine disrupts and intraseptal carbachol facilitates hippocampus‐dependent learning and memory tasks, and the associated hippocampal theta rhythm. In earlier work, we demonstrated that, within the MSDB, the septohippocampal GABAergic but not cholinergic neurons are the primary target of muscarinic manipulations and that muscarinic activation of septohippocampal GABAergic neurons is mediated directly via M3 receptors. In the present study, we examined the ionic mechanism(s) underlying the excitatory actions of muscarine in these neurons. Using whole‐cell patch‐clamp recording techniques in rat brain slices, we demonstrated that M3 receptor‐mediated muscarinic activation of MSDB neurons is dependent on external Na+ and is also reduced by bath‐applied Ni2+ and KB‐R7943 as well as by replacing external Na+ with Li+, suggesting a primary involvement of the Na+–Ca2+ exchanger. We conclude that the M3 receptor‐mediated muscarinic activation of MSDB septohippocampal GABA‐type neurons, that is important for cognitive functioning, is mediated via activation of the Na+–Ca2+ exchanger.
A comparison of methods for mapping species ranges and species richness
Authors: Graham Catherine H. , Hijmans Robert J.
Published: October 2006

Aim  Maps of species richness are the basis for applied research and conservation planning as well as for theoretical research investigating patterns of richness and the processes shaping these patterns. The method used to create a richness map could influence the results of such studies, but differences between these methods have been insufficiently evaluated. We investigate how different methods of mapping species ranges can influence patterns of richness, at three spatial resolutions.

Location  California, USA.

Methods  We created richness maps by overlaying individual species range maps for terrestrial amphibians and reptiles. The methods we used to create ranges included: point‐to‐grid maps, obtained by overlaying point observations of species occurrences with a grid and determining presence or absence for each cell; expert‐drawn maps; and maps obtained through species distribution modelling. We also used a hybrid method that incorporated data from all three methods. We assessed the correlation and similarity of the spatial patterns of richness maps created with each of these four methods at three different resolutions.

Results  Richness maps created with different methods were more correlated at lower spatial resolutions than at higher resolutions. At all resolutions, point‐to‐grid richness maps estimated the lowest species richness and those derived from species distribution models the highest. Expert‐drawn maps and hybrid maps showed intermediate levels of richness but had different spatial patterns of species richness from those derived with the other methods.

Main conclusions  Even in relatively well‐studied areas such as California, different data sources can lead to rather dissimilar maps of species richness. Evaluating the strengths and weaknesses of different methods for creating a richness map can provide guidance for selecting the approach that is most appropriate for a given application and region.
Is the Rapoport effect widespread? Null models revisited
Authors: Ribas Carla R. , Schoereder José H.
Published: October 2006

Aim To test the Rapoport effect using null models and data sets taken from the literature. We propose an improvement on an existing method, testing the Rapoport effect in elevational and latitudinal distributions when distributions are restricted by sampling.

Location Global.

Methods First, we hypothesized that real range size distributions are similar to those expected by null assumptions (expected by only imposing boundaries to species distributions). When these distributions were different from those expected under the null assumptions, we tested the hypothesis that these distributions correspond to those expected when a Rapoport effect occurs. We used two simulation methods, random and pseudo‐random, which differed only in that the latter one assumes fixed species mid‐points, coinciding with real mid‐points. Observed correlations between range size and mid‐point were compared with the frequency distribution of 1000 simulations, using both simulation methods. We compared the correlation curves generated by 1000 simulations with those of the observed distributions, testing whether correlations indicated a Rapoport effect.

Results Several significant patterns of correlations between range size and mid‐point were observed in the data sets when compared with random and pseudo‐random simulations. However, few of these correlations were consistent with a Rapoport effect.

Main conclusions Although some recent studies are consistent with a Rapoport effect, our results suggest that the Rapoport effect is not a widespread pattern in global ecology.
The foundations of psychological understanding
Authors: Goswami Usha
Published: October 2006

In this paper, I review some recent submissions to Developmental Science that advance our understanding of psychological development. More and more submissions to the journal explore the origins of knowledge and, for psychological knowledge, such origins are multiple. Here I consider the contribution of mechanisms such as contingency detection, gaze following and gaze monitoring, social referencing and joint attention to emergent psychological understanding. I also consider infant understanding of goal‐directed action, and the intimate connection between language acquisition and psychological development. The centrality of intention‐reading skills to both language and social cognition is highlighted.
Physiological and behavioral parameters of infants’ categorization: changes in heart rate and duration of examining across trials
Authors: Elsner Birgit , Pauen Sabina , Jeschonek Susanna
Published: October 2006

This report investigates the relations between duration of examining and heart rate (HR) across several trials of an object‐examination task. A total of N= 20 11‐month‐olds were familiarized with a sequence of 10 different exemplars from the same global category (animals or furniture) before they received an exemplar from the contrasting category at test. Consistent with previous findings, HR was lower during states of focused attention (i.e. examining) than during states of casual attention (i.e. looking) or non‐looking. Over the familiarization trials, examining stayed about the same, while mean HR increased. At test, examining increased and mean HR decreased, indicating that infants focused their attention on the out‐of‐category object. Psychophysiological and behavioral measures of attention were systematically related over trials, suggesting that heart rate provides a suitable objective measure to study infants’ categorization performance in object‐examination tasks.
Two‐year‐olds grasp the intentional structure of pretense acts
Authors: Rakoczy Hannes , Tomasello Michael
Published: October 2006

Twenty‐two‐ and 27‐month‐old children were tested for their understanding of pretending as a specific intentional action form. Pairs of superficially similar behaviors – pretending to perform an action and trying to perform that action – were demonstrated to children. The 27‐month‐olds, and to some degree the 22‐month‐olds, showed in their responses that they understood the intentional structure of both kinds of behaviors: after pretense models, they themselves performed appropriate inferential pretense acts, whereas after the trying models they properly performed the action or tried to perform it with novel means. These findings are discussed in the light of recent debates about children's developing understanding of pretense and theory of mind.
Imitation of hierarchical action structure by young children
Authors: Whiten Andrew , Flynn Emma , Brown Katy , Lee Tanya
Published: October 2006

To provide the first systematic test of whether young children will spontaneously perceive and imitate hierarchical structure in complex actions, a task was devised in which a set of 16 elements can be modelled through either of two different, hierarchically organized strategies. Three‐year‐old children showed a strong and significant tendency to copy whichever of the two hierarchical approaches they witnessed an adult perform. Responses to an element absent in demonstrations, but present at test, showed that children did not merely copy the chain of events they had witnessed, but acquired hierarchically structured rules to which the new element was assimilated. Consistent with this finding, children did not copy specific sequences of actions at lower hierarchical levels.
Context sensitivity in children's reasoning about ability across the elementary school years
Authors: Heyman Gail D. , Compton Brian J.
Published: October 2006

Children's sensitivity to context when making inferences about ability was investigated. In three studies, elementary school children (ages 5 to 10, total N = 332) were asked to reason about the relation between academic ability and the speed with which characters completed puzzle tasks. Participants were primed to interpret the characters’ task completion rates with reference to either (1) the character's perceptions of the difficulty of the task, or (2) the character's level of effort on the task. Children who were primed to consider the perceived difficulty of the task were more likely to view ability as a static quality, a pattern of reasoning that included a tendency to associate task completion rates with ability, and to agree that not all individuals are capable of achieving high levels of success. These results provide evidence that even early elementary school children are sensitive to subtle contextual cues when making inferences about ability, and are consistent with the possibility that children make use of implicit cues available to them in their social environment to derive meaning from achievement situations.
Brain–behavior relationships in reading acquisition are modulated by socioeconomic factors
Authors: Noble Kimberly G. , Wolmetz Michael E. , Ochs Lisa G. , Farah Martha J. , McCandliss Bruce D.
Published: October 2006

Functional neuroimaging may provide insights into the achievement gap in reading skill commonly observed across socioeconomic status (SES). Brain activation during reading tasks is known to be associated with individual differences in children's phonological language skills. By selecting children of equivalent phonological skill, yet diverse socioeconomic backgrounds, we use functional magnetic resonance imaging (fMRI) to demonstrate that a child's experience, as operationalized by SES, can systematically modulate the relationship between phonological language skills and reading‐related brain activity in left fusiform and perisylvian regions. Specifically, at lower socioeconomic levels, individual differences in skill result in large differences in brain activation. In contrast, as SES increases, this relationship between phonological language skill and activation is attenuated. Socioeconomic background factors are thus found to modulate brain–behavior relationships in reading, indicating that cognitive, social, and neurobiological influences on reading development are fundamentally intertwined.
Multiple Directorships and Corporate Performance in Australian Listed Companies*
Authors: Kiel Geoffrey C. , Nicholson Gavin J.
Published: October 2006

How many directorships are too many? Globally, normative advice emphasises the importance of limiting the number of directorships any individual should hold due to the workloads they entail. However, there is little empirical evidence to support this view. Rather, there is a strong tradition of supporting multiple directorships as a mechanism for the firm to co‐opt external resources. To explore the issue of director workloads and multiple directorships, we first consider the issues related to multiple directorships and outline the conclusions of extant international and Australian studies into multiple directorships. We then detail our objectives in undertaking this research and our approach to data collection.

Our findings indicate that the incidence of multiple directorships in Australian listed companies is low. We also find that many of the apparent examples of multiple directorships are due to related entities, which share common directors and, due to the nature of these entities, have much lower workload requirements. Further, there does not appear to be any relationship between holding multiple directorships and firm financial performance. Finally, we discuss the implications for boards and those interested in governance, particularly the need to ensure governance recommendations and guidelines reflect empirical findings. We offer one solution to address the concerns of boards, investors, other stakeholders and the community regarding multiple directorships: board and individual director evaluations.
Corporate Governance and Corporate Identity*
Authors: Parum Eva
Published: October 2006

The aim of this paper is to discuss and analyse whether recommendations on corporate governance have led to more transparency and well‐defined corporate identities for listed small and medium‐sized companies through their external communication on corporate governance. The paper focuses on the task and responsibility of the board and discusses the effect of external communication on management, transparency and corporate identity. The paper also analyses results from two empirical studies on communication on corporate governance from 60 Danish listed companies. It can be concluded that communication through corporate governance has led to more transparency in how companies are managed. There is room for improvement, however, before external communication leads to well‐defined company identities.
Corporate Governance Options for the Local Subsidiaries of Multinational Enterprises*
Authors: Kiel Geoffrey C. , Hendry Kevin , Nicholson Gavin J.
Published: October 2006

While the corporate governance literature generally focuses on the parent legal entity, many organisations are now multinational enterprises (MNEs) with subsidiaries that are most often legal entities in their host countries. Despite the strengthening of corporate governance regimes internationally, the boards of these subsidiaries are in many instances perfunctory. This paper examines the question of whether developments in corporate governance theory and practice can add value for the local subsidiaries of MNEs.

This paper provides a theoretical basis for evaluating governance models in MNEs. The paper commences with a review of the key concepts from the MNE and conglomerates literature with respect to core MNE strategies. The paper then discusses what the “governance roles” are that must be performed in MNE subsidiaries. We propose four governance frameworks for subsidiary corporations. These frameworks are: (1) Direct Control; (2) Dual Reporting; (3) Advisory Board; (4) Local Board. We consider the strengths and weaknesses of each model in relation to international strategy theory. We conclude with recommendations for the conditions under which the various models may be appropriate and practical guidelines for the utilisation of corporate governance theory to improve MNE performance.
Boards of Directors and Firm Performance: is there an expectations gap?
Authors: Brennan Niamh
Published: October 2006

Reflecting investor expectations, most prior corporate governance research attempts to find a relationship between boards of directors and firm performance. This paper critically examines the premise on which this research is based. An expectations gap approach is applied for the first time to implicit expectations which assume a relationship between firm performance and company boards. An expectations gap has two elements: a reasonableness gap and a performance gap. Seven aspects of boards are identified as leading to a reasonableness gap. Five aspects of boards are identified as leading to a performance gap. The paper concludes by suggesting avenues for empirically testing some of the concepts discussed in this paper.
Semiparametric Estimation by Model Selection for Locally Stationary Processes
Authors: Van Bellegem Sébastien , Dahlhaus Rainer
Published: October 2006

Over recent decades increasingly more attention has been paid to the problem of how to fit a parametric model of time series with time-varying parameters. A typical example is given by autoregressive models with time-varying parameters. We propose a procedure to fit such time-varying models to general non-stationary processes. The estimator is a maximum Whittle likelihood estimator on sieves. The results do not assume that the observed process belongs to a specific class of time-varying parametric models. We discuss in more detail the fitting of time-varying AR(p) processes for which we treat the problem of the selection of the order p, and we propose an iterative algorithm for the computation of the estimator. A comparison with model selection by Akaike's information criterion is provided through simulations.
The Complex Bingham Quartic Distribution and Shape Analysis
Authors: Kent J. T. , Mardia K. V. , McDonnell P.
Published: October 2006

The complex Bingham distribution was introduced by Kent as a tractable model for landmark-based shape analysis. It forms an exponential family with a sufficient statistic which is quadratic in the data. However, the distribution has too much symmetry to be widely useful. In particular, under high concentration it behaves asymptotically as a normal distribution, but where the covariance matrix is constrained to have complex symmetry. To overcome this limitation and to provide a full range of asymptotic normal behaviour, we introduce a new ‘complex Bingham quartic distribution’ by adding a selection of quartic terms to the log-density. In the simplest case this new distribution corresponds to Kent's FB5-distribution. Asymptotic and saddlepoint methods are developed for the normalizing constant to facilitate maximum likelihood estimation. Examples are given to show the usefulness of this new distribution.
Network Delay Tomography using Flexicast Experiments
Authors: Lawrence Earl , Michailidis George , Nair Vijayan N.
Published: October 2006

Estimating and monitoring the quality of service of computer and communications networks is a problem of considerable interest. The paper focuses on estimating link level delay distributions from end-to-end path level data collected by using active probing experiments. This is an interesting large scale statistical inverse (deconvolution) problem. We describe a flexible class of probing experiments (‘flexicast’) for data collection and develop conditions under which the link level delay distributions are identifiable. Maximum likelihood estimation using the EM algorithm is studied. It does not scale well for large trees, so a faster algorithm based on solving for local maximum likehood estimators and combining their information is proposed. The usefulness of the methods is illustrated on real voice over Internet protocol data that were collected from the University of North Carolina campus network.
A Functional Wavelet–Kernel Approach for Time Series Prediction
Authors: Antoniadis Anestis , Paparoditis Efstathios , Sapatinas Theofanis
Published: October 2006

We consider the prediction problem of a time series on a whole time interval in terms of its past. The approach that we adopt is based on functional kernel nonparametric regression estimation techniques where observations are discrete recordings of segments of an underlying stochastic process considered as curves. These curves are assumed to lie within the space of continuous functions, and the discretized time series data set consists of a relatively small, compared with the number of segments, number of measurements made at regular times. We estimate conditional expectations by using appropriate wavelet decompositions of the segmented sample paths. A notion of similarity, based on wavelet decompositions, is used to calibrate the prediction. Asymptotic properties when the number of segments grows to ∞ are investigated under mild conditions, and a nonparametric resampling procedure is used to generate, in a flexible way, valid asymptotic pointwise prediction intervals for the trajectories predicted. We illustrate the usefulness of the proposed functional wavelet–kernel methodology in finite sample situations by means of a simulated example and two real life data sets, and we compare the resulting predictions with those obtained by three other methods in the literature, in particular with a smoothing spline method, with an exponential smoothing procedure and with a seasonal autoregressive integrated moving average model.
Separating Between- and Within-Cluster Covariate Effects by Using Conditional and Partitioning Methods
Authors: Neuhaus John M. , McCulloch Charles E.
Published: October 2006

We consider the situation where the random effects in a generalized linear mixed model may be correlated with one of the predictors, which leads to inconsistent estimators. We show that conditional maximum likelihood can eliminate this bias. Conditional likelihood leads naturally to the partitioning of the covariate into between- and within-cluster components and models that include separate terms for these components also eliminate the source of the bias. Another viewpoint that we develop is the idea that many violations of the assumptions (including correlation between the random effects and a covariate) in a generalized linear mixed model may be cast as misspecified mixing distributions. We illustrate the results with two examples and simulations.
First organise, then automate: a modern socio‐technical view on ERP systems and teamworking
Authors: Benders Jos , Hoeken Paul , Batenburg Ronald , Schouteten Roel
Published: October 2006

Previous empirical work demonstrated that self‐managing teamwork and Enterprise Resource Planning (ERP) systems are difficult to combine in practice, and have called for the development of templates for configuring ERP systems to support teamworking. This requires a view on organisation design, dealing with both in an integrated fashion. ‘Modern Socio‐technology’ provides such a view. We discuss its underlying principles and show how it relates to ERP.
Bashing the Migrant Climbers: Interethnic Classification Struggles in German City Neighborhoods
Authors: SUTTERLÜTY FERDINAND , NECKEL SIGHARD
Published: October 2006

This article examines the symbolic order of the relationships between various social groups in disadvantaged neighborhoods and shows that ethnicity is the main reference point of derogatory designations or ‘negative classifications’. Using two districts in German cities as examples, the semantic patterns of mutual negative classifications among autochthonous individuals and their Turkish neighbors are reconstructed. Upwardly mobile individuals of Turkish origin are the most frequent targets of stigmatization. This fact is explained by the existence of a deep symbolic dimension of social inequality that conceives of ethnicity in terms of kinship relations. The socially inclusive or exclusive effects of negative interethnic classifications and the related classification struggles depend on three factors: the internal, i.e. gradual or categorical logic of the classification patterns; the form and process of conflict resolution; and the social contexts in which negative classifications are used. While the disintegrating effects of negative classifications are curbed by institutionalized norms in local politics and economic life, there only exist informal performative norms of interaction in the life‐world, and here these classifications can more easily lead to social exclusion and ethnic separation.
Chronic Tension-Type Headache Treated with Acupuncture, Physical Training and Relaxation Training. Between-Group Differences
Authors: Söderberg E , Carlsson J , Stener-Victorin E
Published: October 2006

The aim of this study was to compare acupuncture, relaxation training and physical training in the treatment of chronic tension-type headache (CTTH). The study comprised 90 consecutive patients with CTTH who were randomly allocated to acupuncture, relaxation training or physical training. Headache intensity, headache-free days and headache-free periods were registered using a visual analogue scale and a headache diary. The measurements were made 4 weeks before, immediately after, and 3 and 6 months after the treatment period. Immediately after the last treatment, the number of headache-free periods and of headache-free days was higher in the relaxation group compared with the acupuncture group. There were no other significant differences between the groups at any time point. The clinical implications of our findings are that relaxation training induced the most pronounced effects directly after the treatment period, compared with acupuncture and physical training.
Reliability of Recalled Self-Report on Headache Intensity: Investigation using Ecological Momentary Assessment Technique
Authors: Kikuchi H , Yoshiuchi K , Miyasaka N , Ohashi K , Yamamoto Y , Kumano H , Kuboki T , Akabayashi A
Published: October 2006

Recalled evaluation of headache intensity is often affected by several factors. Recently, computerized ecological momentary assessment (EMA) has been developed to avoid such problems as recall bias. Here, we compared recalled headache intensity with momentary headache intensity using EMA in tension- type headache (TTH). Forty patients with TTH wore watch-type computers for 1 week to record momentary headache intensity and also rated their headache intensities by recall. We calculated intraclass correlation coefficients between recalled headache intensity and indices from EMA recordings in the whole study population and in two subgroups divided by variability of momentary headache intensity. The results showed that consistency and agreement of momentary and recalled headache intensity were low, and this was especially marked in the subjects whose headache varied widely. These observations suggested that variability of headache intensity may affect recall of headache intensity and this should be taken into consideration in both clinical and research settings.
Living with psoriasis
Authors: Wolkenstein P
Published: October 2006

Background  Psoriasis has a strong impact on quality of life and the viewpoints of patients and physicians are necessary for satisfactory therapy.

Aim  To inform dermatologists on what represents ‘living with psoriasis’.

Methods  We conducted a research using Medline with the following keywords: psoriasis, quality of life. Forty‐one papers were selected from a total of 369 papers.

Results  As with other major medical chronic disorders, psoriasis has a severe impact on the life of patients. Patients with palmoplantar, pustular and arthropathic psoriasis are more likely to have a poorer quality of life. Emotionally charged body regions, e.g. the scalp, face, neck, forearms, hands and genital region, have a specific and significant impact. Living with psoriasis is to live with its symptoms, especially pruritus, and to live in vulnerable social isolation.

Conclusions  As psoriasis has a strong impact on quality of life because of extensive skin involvement, clinical management should take these two criteria into account when making therapeutic decisions. The strong impact of new treatments on patient‐related outcomes probably leads to the conclusion that they improve life with psoriasis. Nevertheless, it is important to highlight that even a successful treatment does not impact on the psychological distress of the patients, the patients’ beliefs about psoriasis or their coping with the disease.
Patient‐based medicine
Authors: Dubertret L
Published: October 2006

Every day, we have to solve two questions:

The first question is how to evaluate the severity of diseases affecting mainly the quality of life (psoriasis, acne, vitiligo, atopic dermatitis, genedermatosis …). This severity (the main information for selecting more appropriate treatments) is assessed by the patient but unfortunately the patient rarely has the expertise to make such assessments.

The second question is to find a method to adjust the knowledge from the ‘evidence based medicine’, which is obtained by statistical population studies, to an individual patient, who will always be different and specific.

The so‐called “Patient Based Medicine” is the association of clinical techniques which can make it possible to solve these two questions.

Patient Based Medicine unfolds in four phases: questions, explanations, negotiation (the most important step) and prescription. The goal of these successive phases is to take into account in the therapeutic choice all the aspects of the patient's characteristics: way of life, co‐morbidities and associated treatments, previous experiences of the patient with different treatments, personal evaluation by the patient of his quality of life and of the impact on his quality of life of the disease and of the treatments. The goal of the negotiation is to involve the patient in the therapeutic choice. Patient Based Medicine is necessary for the efficient treatment of chronic diseases. Patient Based Medicine is a therapeutic revolution with a strong impact on patient/doctor relationships, medical education, and development of new drugs as well as on the awareness of the rights and the duty of patients.
Fluid inclusion constraints on the origin of the brines responsible for Pb–Zn mineralization at Pine Point and coarse non‐saddle and saddle dolomite formation in southern Northwest Territories
Authors: GLEESON S. A. , TURNER W. A.
Published: October 2006

The Pine Point region is a classic metallogenic mining camp that produced over 58 million short tons of Zn–Pb ore from approximately 40 base‐metal mineralized deposits hosted by Middle Devonian carbonates. The ore deposits are localized in paleokarstic features found in the epigenetic ‘Presqu'ile’ dolomite that preferentially replaced some of the upper barrier limestones. The main ore‐stage sulfides include galena, sphalerite, marcasite, and pyrite. A bulk fluid inclusion chemistry study was carried out on sulfide, coarse non‐saddle and saddle dolomite and calcite samples from the Pine Point and Great Slave Reef deposits, and unmineralized coarse non‐saddle and saddle dolomite samples from Hay West, Windy Point and Qito areas. Molar Cl/Br ratio data from Pine Point indicate the presence of four fluids at different stages of the paragenesis. The fluids trapped in sulfides and ore‐stage dolomites predominately consist of a Br‐rich fluid with a composition similar to that of evaporated seawater (fluid A), and a very Br‐enriched fluid of unknown origin (fluid B). Both these fluids are CaCl2–NaCl (Na to Ca ratios of 1:10)‐rich brines and have compositions unlike the modern formation waters in the Devonian aquifers in the basin today. A third, relatively Cl‐rich (or Br‐poor), fluid (fluid C) was identified in two samples and may have acquired some chlorinity by dissolving halide minerals. Mixing between the Br‐rich fluid A and a dilute fluid also occurred in the later stages of the paragenesis, resulting in the formation of calcite and native sulfur. Saddle and coarse dolomites not associated with significant sulfide mineralization have a narrow range of halogen compositions similar to fluid A. There is no evidence of fluid B or C in the unmineralized samples. Relative to a modern‐day seawater compositions all the fluids have had some modification of their cation compositions. There is some weak evidence for interactions with clastic units or crystalline basement rocks. It is also possible however, that the evaporative brines could have formed from a relatively CaCl2‐rich, NaCl‐depleted Devonian seawater, unlike the composition of modern‐day seawater.
Endoscopic investigation of the internal organs of a 15th‐century child mummy from Yangju, Korea
Authors: Kim Seok Bae , Shin Jeong Eun , Park Sung Sil , Bok Gi Dae , Chang Young Pyo , Kim Jaehyup , Chung Yoon Hee , Yi Yang Su , Shin Myung Ho , Chang Byung Soo , Shin Dong Hoon , Kim Myeung Ju
Published: October 2006

Our previous reports on medieval mummies in Korea have provided information on their preservation status. Because invasive techniques cannot easily be applied when investigating such mummies, the need for non‐invasive techniques incurring minimal damage has increased among researchers. Therefore, we wished to confirm whether endoscopy, which has been used in non‐invasive and minimally invasive studies of mummies around the world, is an effective tool for study of Korean mummies as well. In conducting an endoscopic investigation on a 15th‐century child mummy, we found that well‐preserved internal organs remained within the thoracic, abdominal and cranial cavities. The internal organs – including the brain, spinal cord, lung, muscles, liver, heart, intestine, diaphragm and mesentery – were easily investigated by endoscopy. Even the stool of the mummy, which accidentally leaked into the abdominal cavity during an endoscopic biopsy, was clearly observed. In addition, unusual nodules were found on the surface of the intestines and liver. Our current study therefore showed that endoscopic observation could provide an invaluable tool for the palaeo‐pathological study of Korean mummies. This technique will continue to be used in the study of medieval mummy cases in the future.
Micro‐anatomical response of cartilage‐on‐bone to compression: mechanisms of deformation within and beyond the directly loaded matrix
Authors: Thambyah Ashvin , Broom Neil
Published: October 2006

The biomechanical function of articular cartilage relies crucially on its integration with both the subchondral bone and the wider continuum of cartilage beyond the directly loaded contact region. This study was aimed at visualizing, at the microanatomical level, the deformation response of cartilage including that of the non‐directly loaded continuum. Cartilage‐on‐bone samples from bovine patellae were loaded in static compression until a near‐equilibrium deformation was achieved, and then chemically fixed in this deformed state. Full‐depth cartilage–bone sections, incorporating the indentation profile and beyond, were studied in their fully hydrated state using differential interference contrast microscopy. Morphometric measurements of the indented profile were used in combination with a force analysis of the tangential layer to investigate the extent to which the applied force is attenuated in moving away from the directly loaded region. This study provides microscopic evidence of a structure‐related response in the transitional zone of the cartilage matrix. It is manifested as an intense chevron‐type shear discontinuity arising from the constraints provided by both the strain‐limiting articular surface and the osteochondral attachment. The discontinuity persists well into the non‐directly loaded continuum of cartilage and is proposed as a force attenuation mechanism. The structural and biomechanical analyses presented in this study emphasize the important role of the complex microanatomy of cartilage, highlighting the interconnectivity and optimal recruitment of the load‐bearing elements throughout the zonally differentiated cartilage depth.
Spatial separation of endothelial small‐ and intermediate‐conductance calcium‐activated potassium channels (KCa) and connexins: possible relationship to vasodilator function?
Authors: Sandow Shaun L. , Neylon Craig B. , Chen Mao X. , Garland Christopher J.
Published: October 2006

Activation of endothelial cell small‐ (S) and intermediate‐ (I) conductance calcium‐activated potassium channels (KCa) and current or molecular transfer via myoendothelial gap junctions underlies endothelium‐derived hyperpolarization leading to vasodilation. The mechanism underlying the KCa component of vasodilator activity and the characteristics of gap junctions are targets for the selective control of vascular function. In the rat mesenteric artery, where myoendothelial gap junctions and connexin (Cx) 40 are critical for the transmission of the endothelial cell hyperpolarization to the smooth muscle, SKCa and IKCa provide different facets of the endothelium‐derived hyperpolarization response, being critical for the hyperpolarization and repolarization phases, respectively. The present study addressed the question of whether this functional separation of responses may be related to the spatial localization of the associated channels? The distribution of endothelial SKCa and IKCa and Cx subtype(s) were examined in the rat mesenteric artery using conventional confocal and high‐resolution ultrastructural immunohistochemistry. At the internal elastic lamina–smooth muscle cell interface at internal elastic lamina holes (as potential myoendothelial gap junction sites), strong punctate IKCa, Cx37 and Cx40 expression was present. SKCa, Cx37, Cx40 and Cx43 were localized to adjacent endothelial cell gap junctions. High‐resolution immunohistochemistry demonstrated IKCa and Cx37‐conjugated gold to myoendothelial gap junction‐associated endothelial cell projections. Clear co‐localization of KCa and Cxs suggests a causal relationship between their activity and the previously described differential functional activation of SKCa and IKCa. Such precise localizations may represent a selective target for control of vasodilator function and vascular tone.
Keystones in lymph node development
Authors: Blum Katrin S. , Pabst Reinhard
Published: October 2006

New molecular markers are constantly increasing our knowledge of developmental processes. In this review article we have attempted to summarize the keystones of lymphoid tissue development in embryonic and pathological conditions. During embryonic lymph node development in the mouse, cells from the anterior cardinal vein start to bud and sprout, forming a lymph sac at defined sites. The protrusion of mesenchymal tissue into the lymph sacs forms the environment, where so‐called ‘lymphoid tissue inducer cells’ and ‘mesenchymal organizer cells’ meet and interact. Defects of molecules involved in the recruitment and signalling cascades of these cells lead to primary immunodeficiency diseases. A comparison of molecules involved in the development of secondary lymphoid organs and tertiary lymphoid organs, e.g. in autoimmune diseases, shows that the same molecules are involved in both processes. This has led to the hypothesis that the development of tertiary lymphoid organs is a recapitulation of embryonic lymphoid tissue development at ectopic sites.
The prevalence of mental health problems in children 1½ years of age – the Copenhagen Child Cohort 2000
Authors: Skovgaard Anne Mette , Houmann Tine , Christiansen Eva , Landorph Susanne , Jørgensen Torben ,   CCC 2000 Study Team, Olsen E.M. , Heering K. , Kaas‐Nielsen S. , Samberg V. , Lichtenberg A.
Published: October 2006

Background:  The Copenhagen Child Cohort, CCC 2000, was established to investigate developmental psychopathology prospectively from birth in a general population.

Methods:  A random sample of 211 children from the CCC 2000 was investigated when the children were 1½ years of age. The prevalence and associates of mental health problems and psychopathology were studied by clinical and standardised strategies, including videotape recordings, parent interviews and the following instruments: The Child Behavior Check List 1½–5 (CBCL 1½–5), The Infant Toddler Symptom Check List (ITSCL), Checklist for Autism in Toddlers (CHAT), Bayley Scales of Infant Development II (BSID II), The Parent Child Early Relationship Assessment (PC ERA) and Parent Infant Relationship Global Assessment Scale (PIR‐GAS).

Results:  Mental health problems according to International Classification of Diseases (ICD‐10) and Diagnostic Classification Zero to Three (DC 0–3) diagnoses were found in 16–18% of 1½‐year‐old children. Most common were disturbances of emotion, behaviour and eating and the DC 0–3 diagnosis of regulatory disorder. Parent–child relationship disturbances were found in 8%. High psychosocial risk was significantly associated with emotional and behavioural disorders (OR 3.1 95% (1.2–8.1)) and disturbed parent–child relationship (OR 5.0 95% (1.6–16.0)). The strongest association of risk was found between relationship disorders and emotional and behavioural disorders (OR 11.6 95% (3.8–37.5)).

Conclusions:  The prevalence and distribution of psychopathology in 1½‐year‐old children seem to correspond to the distributions among older children. Disturbances in parent–child relationship have a key position in the risk mechanisms in early child psychopathology.
Is there an epidemic of child or adolescent depression?
Authors: Jane Costello E. , Erkanli Alaattin , Angold Adrian
Published: October 2006

Background:  Both the professional and the general media have recently published concerns about an ‘epidemic’ of child and adolescent depression. Reasons for this concern include (1) increases in antidepressant prescriptions, (2) retrospective recall by successive birth cohorts of adults, (3) rising adolescent suicide rates until 1990, and (4) evidence of an increase in emotional problems across three cohorts of British adolescents.

Methods:  Epidemiologic studies of children born between 1965 and 1996 were reviewed and a meta‐analysis conducted of all studies that used structured diagnostic interviews to make formal diagnoses of depression on representative population samples of participants up to age 18. The effect of year of birth on prevalence was estimated, controlling for age, sex, sample size, taxonomy (e.g., DSM vs. ICD), measurement instrument, and time‐frame of the interview (current, 3 months, 6 months, 12 months).

Results:  Twenty‐six studies were identified, generating close to 60,000 observations on children born between 1965 and 1996 who had received at least one structured psychiatric interview capable of making a formal diagnosis of depression. Rates of depression showed no effect of year of birth. There was little effect of taxonomy, measurement instrument, or time‐frame of interview. The overall prevalence estimates were: under 13, 2.8% (standard error (SE) .5%); 13–18 5.6% (SE .3%); 13–18 girls: 5.9% (SE .3%); 13–18 boys: 4.6% (SE .3%).

Conclusions:  When concurrent assessment rather than retrospective recall is used, there is no evidence for an increased prevalence of child or adolescent depression over the past 30 years. Public perception of an ‘epidemic’ may arise from heightened awareness of a disorder that was long under‐diagnosed by clinicians.
Chronic lithium administration to FTDP‐17 tau and GSK‐3β overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre‐formed neurofibrillary tangles do not revert
Authors: Engel Tobias , Goñi‐Oliver Paloma , Lucas José J. , Avila Jesús , Hernández Félix
Published: October 2006

Glycogen synthase kinase‐3 (GSK‐3) has been proposed as the main kinase able to aberrantly phosphorylate tau in Alzheimer's disease (AD) and related tauopathies, raising the possibility of designing novel therapeutic interventions for AD based on GSK‐3 inhibition. Lithium, a widely used drug for affective disorders, inhibits GSK‐3 at therapeutically relevant concentrations. Therefore, it was of great interest to test the possible protective effects of lithium in an AD animal model based on GSK‐3 overexpression. We had previously generated a double transgenic model, overexpressing GSK‐3β in a conditional manner, using the Tet‐off system and tau protein carrying a triple FTDP‐17 (frontotemporal dementia and parkinsonism linked to chromosome 17) mutation. This transgenic line shows tau hyperphosphorylation in hippocampal neurones accompanied by neurofibrillary tangles (NFTs). We used this transgenic model to address two issues: first, whether chronic lithium treatment is able to prevent the formation of aberrant tau aggregates that result from the overexpression of FTDP‐17 tau and GSK‐3β; second, whether lithium is able to change back already formed NFTs in aged animals. Our data suggest that progression of the tauopathy can be prevented by administration of lithium when the first signs of neuropathology appear. Furthermore, it is still possible to partially reverse tau pathology in advanced stages of the disease, although NFT‐like structures cannot be changed. The same results were obtained after shut‐down of GSK‐3β overexpression, supporting the possibility that GSK‐3 inhibition is not sufficient to reverse NFT‐like aggregates.
A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a substrate of Parkin
Authors: Omura Tomohiro , Kaneko Masayuki , Okuma Yasunobu , Orba Yasuko , Nagashima Kazuo , Takahashi Ryosuke , Fujitani Noboru , Matsumura Satoshi , Hata Akihisa , Kubota Kyoko , Murahashi Karin , Uehara Takashi , Nomura Yasuyuki
Published: October 2006

It has been proposed that in autosomal recessive juvenile parkinsonism (AR‐JP), a ubiquitin ligase (E3) Parkin, which is involved in endoplasmic reticulum‐associated degradation (ERAD), lacks E3 activity. The resulting accumulation of Parkin‐associated endothelin receptor‐like receptor (Pael‐R), a substrate of Parkin, leads to endoplasmic reticulum stress, causing neuronal death. We previously reported that human E3 HRD1 in the endoplasmic reticulum protects against endoplasmic reticulum stress‐induced apoptosis. This study shows that HRD1 was expressed in substantia nigra pars compacta (SNC) dopaminergic neurons and interacted with Pael‐R through the HRD1 proline‐rich region, promoting the ubiquitylation and degradation of Pael‐R. Furthermore, the disruption of endogenous HRD1 by small interfering RNA (siRNA) induced Pael‐R accumulation and caspase‐3 activation. We also found that ATF6 overexpression, which induced HRD1, accelerated and caused Pael‐R degradation; the suppression of HRD1 expression by siRNA partially prevents this degradation. These results suggest that in addition to Parkin, HRD1 is also involved in the degradation of Pael‐R.
Glutamate pretreatment affects Ca2+ signaling in processes of astrocyte pairs
Authors: Padmashri Ragunathan , Sikdar Sujit Kumar
Published: October 2006

Simultaneous somatic patch‐pipette recording of a single astrocyte to evoke voltage‐gated calcium currents, and Ca2+ imaging, were used to study the spatial and temporal profiles of depolarization‐induced changes in intracellular Ca2+ ([Ca2+]i) in the processes of cultured rat cortical astrocytes existing as pairs. Transient Ca2+ changes locked to depolarization were observed as microdomains in the processes of the astrocyte pairs, and the responses were more pronounced in the adjoining astrocyte. Considering the functional significance of higher concentrations of glutamate observed in certain pathological conditions, Ca2+ transients were recorded following pretreatment of cells with glutamate (500 µm for 20 min). This showed distance‐dependent incremental scaling and attenuation in the presence of the metabotropic glutamate receptor (mGluR) antagonist, α‐methyl(4‐carboxy‐phenyl) glycine (MCPG). Estimation of local Ca2+ diffusion coefficients in the astrocytic processes indicated higher values in the adjoining astrocyte of the glutamate pretreated group. Intracellular heparin introduced into the depolarized astrocyte did not affect the Ca2+ transients in the heparin‐loaded astrocyte but attenuated the [Ca2+]i responses in the adjoining astrocyte, suggesting that inositol 1,4,5 triphosphate (IP3) may be the transfer signal. The uncoupling agent, 1‐octanol, attenuated the [Ca2+]i responses in both the control and glutamate pretreated astrocytes, indicating the role of gap junctional communication. Our studies indicate that individual astrocytes have distinct functional domains, and that the glutamate‐induced alterations in Ca2+ signaling involve a sequence of intra‐ and intercellular steps in which phospholipase C (PLC), IP3, internal Ca2+ stores, VGCC and gap junction channels appear to play an important role.