bluuebunny/crossref_metadata_2025 huggingface dataset:
Isoliquiritigenin, a natural anti‐oxidant, selectively inhibits the proliferation of prostate cancer cells
Authors: Zhang Xiaoyu , Yeung Eddie D , Wang Jingying , Panzhinskiy Evgeniy E , Tong Chao , Li Wenguang , Li Ji
Published: April 2010

1. Isoliquiritigenin (ISL) is a simple chalcone‐type flavonoid derived from liquorice compounds. It has been reported to have anti‐oxidative and antitumour activities. The aim of the present study was to investigate the antitumour effect of ISL on prostate cancer cells and to explore the possible signalling mechanisms involved.

2. Cell viability was assessed using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The fluorescent probe 2′,7′‐dichlorofluorescein diacetate (H2DCF‐DA) was used to measure intracellular levels of reactive oxygen species (ROS). Mitochondrial membrane potential (Ψm) was measured using the mitochondrial probe 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethyl‐benzimidazolylcarbocyanine iodide (JC‐1).

3. Isoliquiritigenin treatment (10–100 μmol/L for 24 h) markedly inhibited the proliferation of both C4‐2 and LNCaP prostate cancer cells in a dose‐dependent manner. Intriguingly, ISL treatment (10–100 μmol/L for 24 h) had no effect on the viability of IEC‐6 normal epithelial cells. Treatment of C4‐2 and IEC‐6 cells with 87.0 μmol/L ISL significantly decreased ROS levels and the Ψm of C4‐2 cells, but had no effect on either parameter in IEC‐6 cells. Furthermore, AMP‐activated protein kinase (AMPK) and extracellular‐signal regulated kinase (ERK) levels were three to fourfold higher in IEC‐6 cells than in C4‐2 cells (P < 0.05).

4. The results of the present study suggest that ISL, a natural anti‐oxidant, selectively inhibits the proliferation of prostate cancer C4‐2 cells, which may be attributed, in part, to defective AMPK and ERK signalling pathways in C4‐2 compared with IEC‐6 cells.
Functional impact of the hyperpolarization‐activated current on the excitability of myelinated A‐type vagal afferent neurons in the rat
Authors: Zhou Yu‐Hong , Sun Li‐Hua , Liu Zhen‐Hong , Bu Guixue , Pang Xiao‐Ping , Sun Shi‐Chao , Qiao Guo‐Fen , Li Bai‐Yan , Schild John H
Published: April 2010

1. The hyperpolarization‐induced, cation‐selective current Ih is widely observed in peripheral sensory neurons of the vagal and dorsal root ganglia, but the peak magnitude and voltage‐ and time‐dependent properties of this current vary widely across afferent fibre type.

2. Using patch clamp investigations of rat isolated vagal ganglion neurons (VGN) identified as myelinated A‐type afferents, we established a compendium of functional correlates between changes in membrane potential and the dynamic discharge properties of these sensory neurons as a result of the controlled recruitment of Ih using the current clamp technique.

3. Two robust reponses were observed in response to hyperpolarizing step currents: (i) upon initiation of the negative step current, there was a rapid hyperpolarization of membrane potential followed by a depolarizing voltage sag (DVS) towards a plateau in membrane potential as a result of steady state recruitment of Ih; and (ii) upon termination of the negative step current, there was a rapid return to the pretest resting membrane potential that often led to spontaneous action potential discharge. These data were strongly correlated (r2 > 0.9) with a broad compendium of dynamic discharge characteristics in these A‐type VGN.

4. In response to depolarizing step currents of increasing magnitude, the discharge frequency of the A‐type VGN responded with increases in the rate of sustained repetitive discharge. Upon termination of the depolarizing step current, there was a post‐excitatory membrane hyperpolarization of a magnitude that was strongly correlated with action potential discharge rate (r2 > 0.9).

5. Application of the selective hyperpolarization‐activated cyclic nucleotide gated (HCN) channel blockers ZD7288 (10 μmol/L) or CsCl (1.0 mmol/L) abolished Ih and all of the aforementioned functional correlates. In addition to reducing the excitability of the A‐type VGN to step depolarizing currents.

6. Because there is increasing evidence that the HCN channel current may represent a valid target for pharmacological intervention, the quantitative relationships described in the present study could potentially help guide the molecular and/or chemical modification of HCN channel gating properties to effect a particular outcome in VGN discharge properties, ideally well beyond merely selective blockade of a particular HCN channel subtype.
Leucocyte apoptosis in patients with acute ischaemic stroke
Authors: Tsai Nai‐Wen , Chang Wen‐Neng , Shaw Chen‐Fu , Jan Chung‐Ren , Lu Cheng‐Hsien
Published: April 2010

1. Inflammation and activated leucocytes are involved in the pathogenesis of acute ischaemic stroke. Leucocyte apoptosis is critical for the efficient resolution of inflammation. Little is known about the correlation between leucocyte apoptosis and acute ischaemic stroke (AIS). The objective of the present study was to evaluate the role of leucocyte apoptosis in patients with AIS.

2. Serial changes in leucocyte apoptosis and the apoptosis of leucocyte subsets (i.e. neutrophils, monocytes and lymphocytes), as determined by flow cytometry, were examined prospectively at various time‐points in 50 patients with AIS and 50 controls using the APO 2.7 antibody.

3. Leucocyte apoptosis and the apoptosis of leucocyte subsets were significantly lower in stroke patients than in the control group (P < 0.01). The percentage apoptosis of total leucocytes and neutrophils was significantly lower in the group with large‐artery disease than in the group with small‐atery disease (P < 0.01). Leucocyte apoptosis was lowest during the acute stage of ischaemic stroke and increased thereafter.

4. Leucocyte apoptosis may reflect the inflammatory status after AIS. A better understanding of the mechanisms underlying leucocyte apoptosis in ischaemic stroke may lead to the development of new strategies to improve the outcome for stroke patients.
Developmental changes in the geometry, function and responsiveness of the mouse heart to β‐adrenergic stimulation as determined by high‐resolution echocardiography
Authors: Xiao Han , Zhang You‐Yi , Du Xiao‐Jun , Lu Zhi‐Zhen
Published: April 2010

1. The mouse is the preferred species for gene targeting as a tool for research into the heart and heart development. The developmental features of the geometry and function of the heart in young mice are not well defined and cardiac functional responses following stimulation of β‐adrenoceptors have not been investigated.

2. Using the VisualSonic (Toronto, ON, Canada) high‐resolution ultrasound system, we investigated male C57BL/6 mice at 0.5–18 weeks of age. Echocardiography was performed at baseline and repeated after administration of the β‐adrenoceptor agonist isoproterenol (4 μg/kg).

3. The geometry of the left ventricle became mature 2 weeks after birth. A significant decline in left ventricular contractile function occurred at 2–3 weeks of age.

4. Inotropic and chronotropic responses to isoproterenol were significantly weaker in mice at a weaning age < 2 weeks compared with adult mice (heart rate increment 3 ± 3% vs 32 ± 4%, respectively; fractional shortening increment 19 ± 5% vs 78 ± 8%, respectively;P < 0.001).

5. In conclusion, significant changes occur in mice from birth until weaning with respect to the topography, function and β‐adrenoceptor responsiveness of the heart. The results of the present study provide a reference point for future studies in genotyping cardiac function during the postnatal phase in genetically engineered mice.
Visfatin is associated with lipid metabolic abnormalities in Lyon hypertensive rats
Authors: Wang Pei , Bai Chong , Xu Quan‐Yi , Xu Tian‐Ying , Su Ding‐Feng , Sassard Jean , Miao Chao‐Yu
Published: April 2010

1. Visfatin (also known as nicotinamide phosphoribosyltransferase or Nampt) is a novel adipokine associated with metabolic abnormalities in obesity and diabetes. The aim of the present study was to determine whether visfatin levels in the circulation and visfatin expression in fat tissues are altered in Lyon hypertensive (LH) rats, a hypertensive strain with numerous metabolic abnormalities, and, if so, to explore the possible correlations between blood visfatin levels and the metabolic abnormalities in LH rats.

2. Male 18–20‐week‐old LH rats and their control, Lyon normotensive (LN) rats, were used. Blood pressure was recorded in conscious, unrestrained rats. Fat tissue weight was determined. Serum visfatin concentrations were determined by enzyme immunoassay, whereas visfatin expression in fat tissues was determined by western blotting. Relationships between two parameters were evaluated by linear regression analysis.

3. The LH rats had significantly higher bodyweight and fat tissue weight compared with LN rats. Serum lipid levels of total cholesterol (TC), high‐density lipoprotein–cholesterol (HDL‐C), low‐density lipoprotein–cholesterol (LDL‐C) and triglyceride (TG) were all significantly higher in LH rats than in LN rats. Moreover, serum visfatin levels were higher in LH rats than in LN rats and were positively correlated with bodyweight, fat tissue weight and serum lipid levels (i.e. TC, HDL‐C, LDL‐C, TG and the TG:HDL‐C ratio). There were no significant differences in serum glucose and insulin concentrations, or in the whole‐body insulin resistance index, between LN and LH rats, and serum visfatin levels were not correlated with any of these parameters. Visfatin expression in visceral fat tissue, but not in subcutaneous fat tissue, was markedly upregulated in LH compared with LN rats.

4. In conclusion, the results of the present study demonstrate that serum visfatin levels in LH rats are elevated and are associated with lipid metabolic abnormalities.
Arginine‐vasopressin and the regulation of aggression in female Syrian hamsters (Mesocricetus auratus)
Authors: Gutzler Stephanie J. , Karom Mary , Erwin W. D. , Albers H. E.
Published: April 2010

Arginine‐vasopressin (AVP) is critical for the expression of a variety of social behaviors in many species. Previous studies have demonstrated that AVP regulates behaviors such as social communication and aggression in Syrian hamsters through the V1a receptor subtype. In male hamsters, AVP injected into the anterior hypothalamus (AH) stimulates aggression, while injection of a V1a receptor antagonist inhibits the behavior. The purpose of the present studies was to determine whether AVP influences aggression by its action in the AH in female hamsters. In the first experiment, we were surprised to find that injection of the V1a receptor antagonist, Manning compound, into the AH of intact female hamsters increased aggression. The second experiment confirmed the ability of the V1a receptor antagonist to increase aggression and found that the largest effects of the antagonist occurred at intermediate concentrations of the compound. The next experiment found that injection of AVP into the AH significantly reduced the latency to attack and the duration of aggression. Finally, we examined whether the effects of AVP and the V1a receptor antagonist on aggression differed in hamsters exposed to long ‘summer‐like’ photoperiods or short ‘winter‐like’ photoperiods, and found that their effects on aggression were not photoperiod dependent. In summary, contrary to what is observed in males, these data suggest that AVP in the AH may play an inhibitory role on aggression in female Syrian hamsters.
Threshold and rate sensitivity of low‐threshold thermal nociception
Authors: Green Barry G. , Akirav Carol
Published: April 2010

Previous studies have shown that sensations of burning, stinging or pricking can be evoked by warming or cooling the skin to innocuous temperatures [low‐threshold thermal nociception (LTN)] below the thresholds of cold‐ and heat‐sensitive nociceptors. LTN implies that some primary afferent fibers classically defined as warm and cold fibers relay stimulation to the nociceptive system. We addressed this question in humans by determining if different adaptation temperatures (ATs) and rates of temperature change would affect thermal sensation and LTN similarly. In Experiment 1 subjects rated the intensity of warmth, cold and nociceptive sensations produced by increasing steps in temperature (±0.5°C increments) from ATs of 35, 33 and 31°C for cooling, and 30, 32 and 34°C for heating. Depending upon the AT, thresholds for nociceptive and thermal sensations estimated from the rating data differed by as little as −1.0°C for cooling and +1.5°C for heating. Thresholds of thermal and nociceptive sensations shifted by similar amounts across the three ATs during cooling, whereas during heating the nociceptive threshold was significantly affected only between ATs of 32 and 34°C. In Experiment 2, increasing the rate of temperature change from 0.5 to 4.0°C/s increased the intensity of thermal and nociceptive sensations significantly but the effect was greatest for nociceptive sensations during heating. The results of both experiments are consistent with the mediation of LTN by low‐threshold thermoreceptors, although LTN caused by heating may depend on a subset of fibers that express less sensitive TRP channels than those that serve sensations of warmth at the mildest temperatures.
Protein kinase Cγ is a signaling molecule required for the developmental speeding of α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate receptor kinetics
Authors: Patten Shunmoogum A. , Roy Birbickram , Cunningham Marcus E. , Stafford James L. , Ali Declan W.
Published: April 2010

A key step in the maturation of glutamate synapses is the developmental speeding of α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate receptor (AMPA‐R) kinetics, which occurs via a switch in receptor subtypes. However, the molecular components required for the switch in receptors are unknown. Here, we used the zebrafish preparation to show that activation of protein kinase C (PKC)γ is necessary for the developmental speeding of AMPA‐R kinetics. Targeted knockdown of PKCγ with an antisense morpholino oligonucleotide [PKCγ‐morpholino (PKCγ‐MO)], prevents the normal speeding up of AMPA‐R kinetics in Mauthner cells. PKCγ‐MO‐injected embryos are incapable of trafficking AMPA‐Rs following application of phorbol 12‐myristate 13‐acetate or PKCγ. PKCγ‐MO‐injected embryos do not hatch or exhibit the C‐start escape response. Increasing synaptic activity (33 h post‐fertilization embryos) by application of an elevated K+ medium or by application of N‐methyl‐d‐aspartate induces rapid PKCγ‐dependent trafficking of fast AMPA‐Rs to synapses. Our findings reveal that PKCγ is a molecular link underlying the developmental speeding of AMPA‐Rs in zebrafish Mauthner cells.
IGF‐I stimulates neurogenesis in the hypothalamus of adult rats
Authors: Pérez‐Martín M. , Cifuentes M. , Grondona J. M. , López‐Ávalos M. D. , Gómez‐Pinedo U. , García‐Verdugo J. M. , Fernández‐Llebrez P.
Published: April 2010

In the brain of adult rats neurogenesis persists in the subventricular zone of the lateral ventricles and in the dentate gyrus of the hippocampus. By contrast, low proliferative activity was observed in the hypothalamus. We report here that, after intracerebroventricular treatment with insulin‐like growth factor I (IGF‐I), cell proliferation significantly increased in both the periventricular and the parenchymal zones of the whole hypothalamus. Neurons, astrocytes, tanycytes, microglia and endothelial cells of the local vessels were stained with the proliferative marker 5‐bromo‐2′‐deoxyuridine (BrdU) in response to IGF‐I. Conversely, we never observed BrdU‐positive ciliated cubic ependymal cells. Proliferation was intense in the subventricular area of a distinct zone of the mid third ventricle wall limited dorsally by ciliated cubic ependyma and ventrally by tanycytic ependyma. In this area, we saw a characteristic cluster of proliferating cells. This zone of the ventricular wall displayed three cell layers: ciliated ependyma, subependyma and underlying tanycytes. After IGF‐I treatment, proliferating cells were seen in the subependyma and in the layer of tanycytes. In the subependyma, proliferating glial fibrillary acidic protein‐positive astrocytes contacted the ventricle by an apical process bearing a single cilium and there were many labyrinthine extensions of the periventricular basement membranes. Both features are typical of neurogenic niches in other brain zones, suggesting that the central overlapping zone of the rat hypothalamic wall could be considered a neurogenic niche in response to IGF‐I.
Emerging topics in Reelin function
Authors: Förster Eckart , Bock Hans H. , Herz Joachim , Chai Xuejun , Frotscher Michael , Zhao Shanting
Published: April 2010

Reelin signalling in the early developing cortex regulates radial migration of cortical neurons. Later in development, Reelin promotes maturation of dendrites and dendritic spines. Finally, in the mature brain, it is involved in modulating synaptic function. In recent years, efforts to identify downstream signalling events induced by binding of Reelin to lipoprotein receptors led to the characterization of novel components of the Reelin signalling cascade. In the present review, we first address distinct functions of the Reelin receptors Apoer2 and Vldlr in cortical layer formation, followed by a discussion on the recently identified downstream effector molecule n‐cofilin, involved in regulating actin cytoskeletal dynamics required for coordinated neuronal migration. Next, we discuss possible functions of the recently identified Reelin–Notch signalling crosstalk, and new aspects of the role of Reelin in the formation of the dentate radial glial scaffold. Finally, progress in characterizing the function of Reelin in modulating synaptic function in the adult brain is summarized. The present review has been inspired by a session entitled ‘Functions of Reelin in the developing and adult hippocampus’, held at the Spring Hippocampal Research Conference in Verona/Italy, June 2009.
Left temporal alpha band activity increases during working memory retention of pitches
Authors: Van Dijk Hanneke , Nieuwenhuis Ingrid L.C. , Jensen Ole
Published: April 2010

The functional role and regional specificity of ∼10 Hz alpha band activity remains of debate. Alpha band activity is strongly modulated in visual working memory tasks and it has been proposed to subserve resource allocation by disengaging task‐irrelevant regions. It remains unknown if alpha band activity plays a similar role during auditory working memory processing. In this study we applied whole‐head magnetoencephalography to investigate brain activity in a delayed‐match‐to‐sample task including pure tones, non‐harmonic complex tones and harmonic tones. The paradigm included a control condition in which no active auditory maintenance was required. We observed a bilateral increase in 5–12 Hz power during the perception of harmonic and non‐harmonic complex tones compared with the control tone. During the maintenance period a left‐lateralized increase in 5–12 Hz was found for all stimuli compared with the control condition. Using a beam‐forming approach we identified the sources in left temporal regions. Given that functional magnetic resonance imaging, positron emission tomography and lesion studies have identified right hemisphere regions to be engaged in memory of pitch, we propose that the 5–12 Hz activity serves to functionally disengage left temporal regions. Our findings support the notion that alpha activity is a general mechanism for disengaging task‐irrelevant regions.
Electrophysiological evidence of mediolateral functional dichotomy in the rat nucleus accumbens during cocaine self‐administration II: phasic firing patterns
Authors: Fabbricatore Anthony T. , Ghitza Udi E. , Prokopenko Volodymyr F. , West Mark O.
Published: April 2010

In the cocaine self‐administering rat, individual nucleus accumbens (NAcc) neurons exhibit phasic changes in firing rate within minutes and/or seconds of lever presses (i.e. slow phasic and rapid phasic changes, respectively). To determine whether neurons that demonstrate these changes during self‐administration sessions are differentially distributed in the NAcc, rats were implanted with jugular catheters and microwire arrays in different NAcc subregions (core, dorsal shell, ventromedial shell, ventrolateral shell, or rostral pole). Neural recording sessions were typically conducted on days 13–17 of cocaine self‐administration (0.77 mg/kg per 0.2‐mL infusion; fixed‐ratio 1 schedule of reinforcement; 6‐h daily sessions). Pre‐press rapid phasic firing rate changes were greater in lateral accumbal (core and ventrolateral shell) than in medial accumbal (dorsal shell and rostral pole shell) subregions. Slow phasic pattern analysis revealed that reversal latencies of neurons that exhibited change + reversal patterns differed mediolaterally: medial NAcc neurons exhibited more early reversals and fewer progressive/late reversals than lateral NAcc neurons. Comparisons of firing patterns within individual neurons across time bases indicated that lateral NAcc pre‐press rapid phasic increases were correlated with tonic increases. Tonic decreases were correlated with slow phasic patterns in individual medial NAcc neurons, indicative of greater pharmacological sensitivity of neurons in this region. On the other hand, the bias of the lateral NAcc towards increased pre‐press rapid phasic activity, coupled with a greater prevalence of tonic increase firing, may reflect particular sensitivity of these neurons to excitatory afferent signaling and perhaps differential pharmacological influences on firing rates between regions.
TO JOIN OR NOT TO JOIN? DO BANKS THAT ARE PART OF A FINANCIAL HOLDING COMPANY PERFORM BETTER THAN BANKS THAT ARE NOT?
Authors: SHEN CHUNG‐HUA , CHANG YUAN
Published: April 2010

This study compares the performance of banks that are part of a financial holding company (FHC banks) with that of banks that are not (independent banks) using Taiwan data from 2002:Q1 to 2006:Q2. The comparisons are based on 14 performance ratios resulting from the concept of CAMEL (which is an acronym for Capital adequacy, Asset quality, Management efficiency, Earnings ability, and Liquidity sufficiency). To ensure that becoming part of an FHC is a random process, we used four matching methods to select the controlled banks so that the characteristic variables of banks in the two groups are statistically indifferent. By using the data before matching, it was found that FHC banks significantly defeat independent banks, regardless of their performance ratios. Conversely, when the sample was used after the matching, the results changed dramatically. Although FHC banks still beat the independent banks in terms of capital adequacy, asset quality, and liquidity sufficiency, FHC banks and independent banks are found to have equal profitability and management efficiency. Earlier studies that do not consider the endogeneity problem tend to overestimate the joining effect.(JELC21, G21)
The Fate of Former East German Police in Reunified Germany, 1990–1996: The Dialectics of Inclusion and Exclusion
Authors: CROSSLEY‐FROLICK KATY A.
Published: April 2010

This article analyzes the vetting of former East German police in Berlin and Brandenburg in the context of the former East Germany's transition to democracy and German unification. Police are one of the most critical and sensitive sectors of the civil service and typically, along with teachers, among the first groups to be vetted in the context of democratic transitions. The German case illustrates the often unpredictable and inconsistent approaches to vetting that led to very different outcomes throughout the East. It identifies several factors that influenced vetting and employment prospects for former East German police officers. These included political geography, who did the vetting, how a candidate's past was interpreted (whether aggravating or mitigating circumstances were weighed), the institutional arrangements for vetting, state‐mandated guidelines or criteria for determining suitability, and timing.
Progressive and regressive developmental changes in neural substrates for face processing: testing specific predictions of the Interactive Specialization account
Authors: Joseph Jane E. , Gathers Ann D. , Bhatt Ramesh S.
Published: April 2010

Face processing undergoes a fairly protracted developmental time course but the neural underpinnings are not well understood. Prior fMRI studies have only examined progressive changes (i.e. increases in specialization in certain regions with age), which would be predicted by both the Interactive Specialization (IS) and maturational theories of neural development. To differentiate between these accounts, the present study also examined regressive changes (i.e. decreases in specialization in certain regions with age), which is predicted by the IS but not the maturational account. The fMRI results show that both progressive and regressive changes occur, consistent with IS. Progressive changes mostly occurred in occipital‐fusiform and inferior frontal cortex, whereas regressive changes largely emerged in parietal and lateral temporal cortices. Moreover, inconsistent with the maturational account, all of the regions involved in face viewing in adults were active in children, with some regions already specialized for face processing by 5 years of age and other regions activated in children but not specifically for faces. Thus, neurodevelopment of face processing involves dynamic interactions among brain regions including age‐related increases and decreases in specialization and the involvement of different regions at different ages. These results are more consistent with IS than maturational models of neural development.
An image is worth a thousand words: why nouns tend to dominate verbs in early word learning
Authors: McDonough Colleen , Song Lulu , Hirsh‐Pasek Kathy , Golinkoff Roberta Michnick , Lannon Robert
Published: April 2010

Nouns are generally easier to learn than verbs (e.g.Bornstein, 2005;Bornstein et al., 2004;Gentner, 1982;Maguire, Hirsh‐Pasek & Golinkoff, 2006). Yet, verbs appear in children’s earliest vocabularies, creating a seeming paradox. This paper examines one hypothesis about the difference between noun and verb acquisition. Perhaps the advantage nouns have is not a function of grammatical form class but rather is related to a word’s imageability. Here, word imageability ratings and form class (nouns and verbs) were correlated with age of acquisition according to the MacArthur‐Bates Communicative Development Inventory (CDI;Fenson et al., 1994). CDI age of acquisition was negatively correlated with words’ imageability ratings. Further, a word’s imageability contributes to the variance of the word’s age of acquisition above and beyond form class, suggesting that at the beginning of word learning, imageability might be a driving factor.
REVERSIBLE JUMP MARKOV CHAIN MONTE CARLO METHODS AND SEGMENTATION ALGORITHMS IN HIDDEN MARKOV MODELS
Authors: Paroli R. , Spezia L.
Published: April 2010

We consider hidden Markov models with an unknown number of regimes for the segmentation of the pixel intensities of digital images that consist of a small set of colours. New reversible jump Markov chain Monte Carlo algorithms to estimate both the dimension and the unknown parameters of the model are introduced. Parameters are updated by random walk Metropolis–Hastings moves, without updating the sequence of the hidden Markov chain. The segmentation (i.e. the estimation of the hidden regimes) is a further aim and is performed by means of a number of competing algorithms. We apply our Bayesian inference and segmentation tools to digital images, which are linearized through the Peano–Hilbert scan, and perform experiments and comparisons on both synthetic images and a real brain magnetic resonance image.
COGNITIVE AND BEHAVIORAL MODEL ENSEMBLES FOR AUTONOMOUS VIRTUAL CHARACTERS
Authors: Whiting Jeffrey S. , Dinerstein Jonathan , Egbert Parris K. , Ventura Dan
Published: April 2010

Cognitive and behavioral models have become popular methods for creating autonomous self‐animating characters. Creating these models present the following challenges: (1) creating a cognitive or behavioral model is a time‐intensive and complex process that must be done by an expert programmer and (2) the models are created to solve a specific problem in a given environment and because of their specific nature cannot be easily reused. Combining existing models together would allow an animator, without the need for a programmer, to create new characters in less time and to leverage each model's strengths, resulting in an increase in the character's performance and in the creation of new behaviors and animations. This article provides a framework that can aggregate existing behavioral and cognitive models into an ensemble. An animator has only to rate how appropriately a character performs in a set of scenarios and the system then uses machine learning to determine how the character should act given the current situation. Empirical results from multiple case studies validate the approach.
When it Pays to Be Friendly: Employment Relationships and Emotional Labour in Hairstyling
Authors: Cohen Rachel Lara
Published: April 2010

This article examines worker-client relationships in hairstyling. Data are drawn from interviews with 15 hourly-paid and 32 self-employed hairstylists and a self-administered survey. Relations of employment are found to be central to the deployment of emotional labour. Self-employed owner-operators are highly dependent on clients, rely on deep-acting, enact favours, and are prone to emotional breaking points when they fail to realise their ‘congealed service’. In contrast, hourly-paid stylists perform surface acting, resist unpaid favours and experience fewer breaking points. Methodologically this article demonstrates the importance of comparative employment relations analysis (CERA) for exposing the relationship between employment structures and labour process experiences.
Education and Egalitarianism: The Culture of the Norwegian Middle Class
Authors: Skarpenes Ove , Sakslind Rune
Published: April 2010

It is well documented that educational achievement in Western societies is related to family background. Yet we know less about how people who have completed university degrees experience the importance of their education. How is education related to the different culturally embedded structures of nation states? How do highly educated people perceive the pertinence of their education? Such questions are rarely posed in the literature on social class, but recent research on the middle class in Britain offers a background for comparisons. Based on results from interviews with a sample of people having higher educational diplomas, the article discusses the particularities of the Norwegian case. We find much ambivalence over class identification and there is a remarkable tendency to downplay the importance of education. Our findings indicate that the Norwegian middle class has internalized egalitarian values embedded in Norwegian culture and thus, compared to the British case, more often hesitates to set up boundaries between itself and other classes. We argue that such findings diverge from conventional typifications of western ‘middle-classes’ and have wider methodological implications for the study of class systems.
Social Capital, Educational Aspirations and Young Pakistani Muslim Men and Women in Bradford, West Yorkshire
Authors: Thapar-Bjorkert Suruchi , Sanghera Gurchathen
Published: April 2010

Drawing on research with the Pakistani Muslim ‘community’ in inner-city Bradford, West Yorkshire, this paper critically engages with relevant debates on social capital and educational aspirations. It examines the processes and mechanisms in the accumulation of social capital within the family and the immediate community, to demonstrate how three sets of interpersonal relationships (parent-child, child–child and between co-ethnic peers) facilitate educational aspirations among a group that has traditionally been portrayed as under-achieving.
Does ‘Race’ Matter? A Study of ‘Mixed Race’ Siblings' Identifications
Authors: Song Miri
Published: April 2010

‘Mixed’ people comprise one of the fastest growing populations in Britain today, and their growth refutes the idea that there exist distinct, ‘natural’ races among people in multiethnic societies, such as Britain. In recent years, a large body of scholarship, both in the US and Britain, has begun to investigate the diverse social experiences and racial identifications of mixed people. In this article, I investigate the ways in which mixed siblings perceive and think about race and differences in racial, ethnic, and religious identification within their families. What role do race and the recognition of difference play in sibling relationships and in family life more generally? I draw upon a small number of cases to illustrate the diverse ways in which understandings of race, ethnicity, and religion are (or are not) regarded as important in these families. I also consider whether there are group differences in terms of how disparate types of mixed siblings may perceive pressures to identify in particular ways.
Whole‐word shape effect in dyslexia
Authors: Lavidor Michal
Published: April 2010

The research question here was whether whole‐word shape cues might facilitate reading in dyslexia following reports of how normal‐reading children benefit from using this cue when learning to read. We predicted that adults with dyslexia would tend to rely more on orthographic rather than other cues when reading, and therefore would be more affected by word shape manipulations. This prediction was tested in a lexical decision task on words with a flat or a non‐flat outline (i.e. without or with letters with ascending/descending features). We found that readers with dyslexia were significantly faster when reading non‐flat compared with flat words, while typical readers did not benefit from whole‐word shape cues. The interaction of participants' group and word shape was not modulated by word frequency; that is word outline shape facilitated reading for both rare and frequent words. Our results suggest that enhanced sensitivity to orthographic cues is developed in some cases of dyslexia when normal, phonology‐based word recognition processing is not exploited.
Mother–child joint writing in Chinese kindergarteners: metalinguistic awareness, maternal mediation and literacy acquisition
Authors: Lin Dan , McBride‐Chang Catherine , Aram Dorit , Levin Iris
Published: April 2010

The present study examined the relations of Chinese word reading and writing to both maternal mediation of writing and a number of metalinguistic and cognitive skills in 63 Hong Kong Chinese kindergarteners. The whole process of maternal mediation of writing, in which mothers individually facilitated their children's writing of 12 two‐character words in their own ways, was videotaped. This study replicated and extended previous work on the cognitive strategies mothers use to help children in writing Chinese words. Mothers' typical mediation strategies were positively and significantly associated with both children's independent word reading and writing. In addition, maternal mediation of writing was uniquely associated with Chinese word reading, but not word writing, even with metalinguistic and cognitive skills, including phonological awareness, morphological awareness, orthographic processing and visual knowledge, statistically controlled. Findings underscore the importance of mothers' early scaffolding in facilitating children's literacy acquisition.
Association of polymorphisms in the BDNF, DRD1 and DRD3 genes with tobacco smoking in schizophrenia
Authors: Novak Gabriela , LeBlanc Martha , Zai Clement , Shaikh Sajid , Renou Julien , DeLuca Vincenzo , Bulgin Natalie , Kennedy James L. , Le Foll Bernard
Published: April 2010

Emerging evidence indicates that the DRD1‐BDNF‐DRD3 cluster plays an important role in nicotine addiction. We have performed an association analysis of 42 SNPs within these genes with cigarette consumption in a group of 341 schizophrenia patients. The ACCG haplotype consisting of four BDNF markers (Val66Met (rs6265), rs11030104, rs2049045 and rs7103411) showed an association with the risk of smoking (p = 0.0002). Both DRD1 markers tested (rs4532 and rs686) and the DRD3 marker (rs1025398) showed association with quantity of tobacco smoked (p = 0.01, 0.005 and 0.002, respectively). Our findings are preliminary; however, they support the involvement of the DRD1, BDNF and DRD3 genes in smoking behaviour.
Why do British Indian children have an apparent mental health advantage?
Authors: Goodman Anna , Patel Vikram , Leon David A.
Published: April 2010

Background:  Previous studies document a mental health advantage in British Indian children, particularly for externalising problems. The causes of this advantage are unknown.

Methods:  Subjects were 13,836 White children and 361 Indian children aged 5–16 years from the English subsample of the British Child and Adolescent Mental Health Surveys. The primary mental health outcome was the parent Strengths and Difficulties Questionnaire (SDQ). Mental health was also assessed using the teacher and child SDQs; diagnostic interviews with parents, teachers and children; and multi‐informant clinician‐rated diagnoses. Multiple child, family, school and area factors were examined as possible mediators or confounders in explaining observed ethnic differences.

Results:  Indian children had a large advantage for externalising problems and disorders, and little or no difference for internalising problems and disorders. This was observed across all mental health outcomes, including teacher‐reported and diagnostic interview measures. Detailed psychometric analyses provided no suggestion of information bias. The Indian advantage for externalising problems was partly mediated by Indian children being more likely to live in two‐parent families and less likely to have academic difficulties. Yet after adjusting for these and all other covariates, the unexplained Indian advantage only reduced by about a quarter (from 1.08 to .71 parent SDQ points) and remained highly significant (p < .001). This Indian advantage was largely confined to families of low socio‐economic position.

Conclusion:  The Indian mental health advantage is real and is specific to externalising problems. Family type and academic abilities mediate part of the advantage, but most is not explained by major risk factors. Likewise unexplained is the absence in Indian children of a socio‐economic gradient in mental health. Further investigation of the Indian advantage may yield insights into novel ways to promote child mental health and child mental health equity in all ethnic groups.
Social and non‐social visual attention patterns and associative learning in infants at risk for autism
Authors: Bhat A.N. , Galloway J.C. , Landa R.J.
Published: April 2010

Background:  Social inattention is common in children with autism whereas associative learning capabilities are considered a relative strength. Identifying early precursors of impairment associated with autism could lead to earlier identification of this disorder. The present study compared social and non‐social visual attention patterns as well as associative learning in infant siblings of children with autism (AU sibs) and low‐risk (LR) infants at 6 months of age.

Methods:  Twenty‐five AU sibs and 25 LR infants were observed in a novel social‐object learning task, within which attention to social and non‐social cues was contrasted. Video recorded data were coded for percent duration of gaze to objects or caregiver. Movement rates to activate the toy within the associative learning task were also quantified.

Results:  Both groups learned the association between moving a switch and activating a cause–effect toy. AU sibs spent less time looking at caregivers and more time looking at the toy or joystick when their caregivers made no attempts to engage their attention. However, response to caregiver‐initiated social bids was comparable for both groups.

Conclusions:  Infrequent self‐initiated socially directed gaze may be an early marker of later social and communication delays.
FROM MEDICAL RATIONING TO RATIONALIZING THE USE OF HUMAN RESOURCES FOR AIDS CARE AND TREATMENT IN AFRICA: A CASE FOR TASK SHIFTING
Authors: PRICE JESSICA , BINAGWAHO AGNES
Published: April 2010

With a global commitment to scaling up AIDS care and treatment in resource‐poor settings for some of the most HIV‐affected countries in Africa, availability of antiretroviral treatment is no longer the principal obstacle to expanding access to treatment. A shortage of trained healthcare personnel to initiate treatment and manage patients represents a more challenging barrier to offering life‐saving treatment to all patients in need. Physician‐centered treatment policies accentuate this challenge. Despite evidence that task shifting for nurse‐centered AIDS patient care is effective and can alleviate severe physician shortages that currently obstruct treatment scale‐up, political commitment and policy action to support task shifting models of care has been slow to absent. In this paper we review the evidence in support of task shifting for AIDS treatment in Africa and argue that continued policy inaction amounts to unwarranted healthcare rationing and as such is ethically untenable.
New drugs for neglected infectious diseases: Chagas' disease
Authors: Machado Fabiana S , Tanowitz Herbert B , Teixeira Mauro M
Published: April 2010

Chagas' disease (CD) is caused by the protozoan Trypanosoma cruzi (Tc) and remains an important cause of morbidity and mortality. Most researchers in the field now agree that chronic low grade parasite persistence in tissue drives tissue damage and the autoimmune component of CD. Current therapy relies on two compounds: benznidazole and nifurtimox. Despite their long history in the treatment of CD, both compounds induce significant side‐effects. In the current issue of the BJP, two contributions demonstrate that NO‐donors are active, especially in combination with benznidazole, against Tc in vitro and in experimental models in vivo. The basic concept used by the authors to develop novel anti‐Tc compounds relied on the demonstrated ability of nitric oxide to kill the parasite. There are several issues still to be resolved but the reported studies are a clear advance to the field and should be considered for further pre‐clinical development.

This article is a commentary on Silva et al., pp. 260–269 and Guedes et al., pp. 270–282 of this issue. To view these papers visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00524.x and http://dx.doi.org/10.1111/j.1476‐5381.2010.00576.x
Disruption of cellular cholesterol transport and homeostasis as a novel mechanism of action of membrane‐targeted alkylphospholipid analogues
Authors: Carrasco María P , Jiménez‐López José M , Ríos‐Marco Pablo , Segovia Josefa L , Marco Carmen
Published: April 2010

Background and purpose:  Alkylphospholipid (APL) analogues constitute a new class of synthetic anti‐tumour agents that act directly on cell membranes. We have previously demonstrated that hexadecylphosphocholine (HePC) alters intracellular cholesterol traffic and metabolism in HepG2 cells. We now extended our studies to analyse the effects of other clinically relevant APLs, such as edelfosine, erucylphosphocholine and perifosine on intracellular cholesterol homeostasis.

Experimental approach:  Using radiolabelled substrates we determined the effect of APLs on cholesterol metabolism and cholesterol traffic from the plasma membrane to the endoplasmic reticulum (ER). Protein levels and gene expression of the main proteins involved in cholesterol homeostasis were analysed by Western blot and RT‐PCR respectively. Membrane raft and non‐raft fractions were isolated from HepG2 cells by a detergent‐free method.

Key results:  All APLs inhibited the transport of cholesterol from the plasma membrane to the ER, which induced a significant cholesterogenic response in HepG2 cells. This response involved an increased gene expression and higher levels of several proteins related to the biosynthesis and the receptor‐mediated uptake of cholesterol. Cell exposure to the APL‐representative HePC enhanced the content of cholesterol mainly in the membrane raft fractions, compared with the untreated cells.

Conclusions and implications:  Membrane‐targeted APLs exhibited a novel and common mechanism of action, through disruption of cholesterol homeostasis, which in turn affected specific lipid microdomains of cellular membranes.
Investigating the interaction of McN‐A‐343 with the M1muscarinic receptor using its nitrogen mustard derivative and ACh mustard
Authors: Figueroa KW , Suga H , Ehlert FJ
Published: April 2010

Background and purpose: We investigated how McN‐A‐343 inhibited the alkylation of the M1muscarinic receptor by its nitrogen mustard derivative and that of ACh to identify whether it interacts allosterically or orthosterically.

Experimental approach: We incubated the M1muscarinic receptor expressed in Chinese hamster ovary cells with ACh mustard for various periods of time in the presence of McN‐A‐343 or known allosteric and orthosteric ligands. After stopping the reaction and removing unreacted ligands, unalkylated receptors were measured using [3H]N‐methylscopolamine. Analogous experiments were done using a nitrogen mustard analog of McN‐A‐343. Affinity constants, cooperativity values for allosteric interactions and rate constants for receptor alkylation were estimated using a mathematical model.

Key results: The kinetics of receptor alkylation by the nitrogen mustard derivatives of ACh and McN‐A‐343 were consistent with a two‐step model in which the aziridinium ion rapidly forms a reversible receptor complex, which converts to a covalent complex at a slower rate. The inhibition of receptor alkylation by acetycholine,N‐methylscopolamine and McN‐A‐343 was consistent with competitive inhibition, whereas that caused by gallamine was consistent with allosterism. Affinity constants estimated from alkylation kinetics agreed with those measured by displacement of [3H]N‐methylscopolamine binding.

Conclusions and implications: Our results suggest that McN‐A‐343 and its nitrogen mustard derivative interact competitively with ACh andN‐methylscopolamine at the orthosteric site on the M1muscarinic receptor. Measuring how drugs modulate the kinetics of receptor alkylation by an irreversible ligand is a powerful approach for distinguishing between negative allosteric modulators and competitive inhibitors.