bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of insect pathogenic soil fungi and ectomycorrhizal inoculation of birch seedlings on the survival of Otiorhynchus larvae
Authors: Oddsdottir Edda S. , Eilenberg Jørgen , Sen Robin , Halldorsson Gudmundur
Published: May 2010

Weevil larvae of the genus Otiorhynchus are a serious problem in agriculture and forestry, causing damage to a wide range of plant species, primarily by larval feeding on roots. Otiorhynchus larvae are a serious pest in forest plantations in Iceland, causing 10–20% mortality of newly‐planted seedlings.

We studied the effects of soil fungi on the survival of Otiorhynchus sulcatus larvae. The larvae were introduced into pots with birch seedlings grown in: (i) nursery peat; (ii) nursery peat inoculated with three different species of ectomycorrhizal fungi; (iii) nursery peat inoculated with insect pathogenic fungi; (iv) nursery peat inoculated with ectomycorrhizal fungi and insect pathogenic fungi; and (v) nursery peat inoculated with natural forest soil from Icelandic birch woodland.

Larval survival was negatively affected by inoculation of: (i) the ectomycorrhizal fungus Laccaria laccata; (ii) the ectomycorrhizal fungus Cenococcum geophylum; (iii) the insect pathogenic fungus Metarhizium anisopliae; and (iv) forest soil. Inoculation with the ectomycorrhizal fungus Phialophora finlandia did not have any significant effect on larval survival. No significant synergistic effect was found between insect pathogenic and ectomycorrhizal fungi.

It is concluded that ectomycorrhizal and insect pathogenic fungi have a significant potential in biological control of Otiorhynchus larvae in afforestation areas in Iceland. Further studies are needed to establish the effect of these fungi in the field and to analyse how mycorrhizal fungi affect root‐feeding larvae.
Spatio‐temporal analysis of plant pests in a greenhouse using a Bayesian approach
Authors: Poncet Christine , Lemesle Valérie , Mailleret Ludovic , Bout Alexandre , Boll Roger , Vaglio Joelle
Published: May 2010

The present study aimed to propose a method that can improve our understanding of pest outbreaks and spatio‐temporal development in greenhouse crops.

The experiment was carried out in a greenhouse rose crop grown under integrated pest management (IPM) for 21 months. The main pests observed were powdery mildew, two‐spotted spider mites and western flower thrips. A quick visual sampling method was established to provide continuous monitoring of overall crop health.

A Bayesian inferential approach was then used to analyse temporal and spatial heterogeneity in the occurrence of pests. Interactions between pest dynamics and properties of spatial evolutions were exhibited revealing the influence of biotic and abiotic factors on crop health.

In the context of IPM, this information could be used to improve monitoring strategies by identifying periods or locations at risk. It could also facilitate the implementation of the whole IPM procedure through the identification of key factors that have a negative impact on overall crop health.
Conditional Rights, Benefit Reform, and Drug Users: Reducing Dependency?
Authors: Harris Neville
Published: May 2010

United Kingdom government policy to increase social security claimants' entry to the labour market through conditions attached to unemployed, sickness and incapacity benefits now includes additional measures to activate particular groups such as lone parents and drug users. The latter are a prime target because of their high level of dependency on benefits and because social security rules are seen as having the potential to modify the behaviour of individuals with a lifestyle regarded as being at odds with the moral obligations of citizenship and incompatible with the government's realization of its wider economic and social goals. There are strict procedures for the identification of drug‐user claimants, enabling additional conditions to be attached to their benefit rights. This article discusses the general trend in benefit reform towards increased conditionality and evaluates the reforms affecting drug users, considering human rights and other implications. It concludes by reflecting on the status of conditional rights to social security as social rights.
‘Consumer’ versus ‘Customer’: The Devil in the Detail
Authors: Akman Pinar
Published: May 2010

According to the European Commission, the objective of EU competition rules is enhancing ‘consumer welfare’. In EU competition law, however, ‘consumer’ means ‘customer’ and encompasses intermediate customers as well as final consumers. Under Article 102TFEU, harming intermediate ‘customers’ is generally presumed to harm ‘consumers’ and where intermediate customers are not competitors of the dominant undertaking, there is no requisite to assess the effects of conduct on users further downstream. Using advances in economics of vertical restraints and, in particular, non‐linear pricing, this article shows that there are instances where the effect on ‘customer welfare’ does not coincide with the effect on ‘consumer welfare’ and the presumption can potentially lead to decisional errors. Thus, if the law is to serve the interests of ‘consumers’, the Commission should reconsider this presumption and its interpretation of the ‘consumer’ in ‘consumer welfare’; otherwise, it remains questionable whose interests EU competition law serves.
Cartel Laws Undermined: Corruption, Social Norms, and Collectivist Business Cultures
Authors: Stephan Andreas
Published: May 2010

The combination of leniency programmes, high sanctions, complaints from customers and private actions for damages, has proven very successful at uncovering and punishing cartel agreements in United States Antitrust Law. Countless jurisdictions are being encouraged to adopt these ‘conventional’ enforcement tools, in the absence of an international competition authority. This paper identifies three issues which may undermine the universal efficacy of these cartel laws: (i) corruption and organized crime; (ii) social norms that are sympathetic to collusive practices; (iii) collectivist business cultures built on personal relationships.
Seed‐based expression systems for plant molecular farming
Authors: Boothe Joseph , Nykiforuk Cory , Shen Yin , Zaplachinski Steven , Szarka Steven , Kuhlman Philip , Murray Elizabeth , Morck Douglas , Moloney Maurice M.
Published: May 2010

The evolution of the seed system provides enormous adaptability to the gymnosperms and angiosperms, because of the properties of dormancy, nutrient storage and seedling vigour. Many of the unique properties of seeds can be exploited in molecular farming applications, particularly where it is desirable to produce large quantities of a recombinant protein. Seeds of transgenic plants have been widely used to generate a raw material for the extraction and isolation of proteins and polypeptides, which can be processed into valuable biopharmaceuticals. The factors that control high‐level accumulation of recombinant proteins in seed are reviewed in the following paragraphs. These include promoters and enhancers, which regulate transcript abundance. However, it is shown that subcellular trafficking and targeting of the desired polypeptides or proteins play a crucial role in their accumulation at economically useful levels. Seeds have proven to be versatile hosts for recombinant proteins of all types, including peptides or short and long polypeptides as well as complex, noncontiguous proteins like antibodies and other immunoglobulins. The extraction and recovery of recombinant proteins from seeds is greatly assisted by their dormancy properties, because this allows for long‐term stability of stored products including recombinant proteins and a decoupling of processing from the growth and harvest cycles. Furthermore, the low water content and relatively low bioload of seeds help greatly in designing cost‐effective manufacturing processes for the desired active pharmaceutical ingredient. The development of cGMP processes based on seed‐derived materials has only been attempted by a few groups to date, but we provide a review of the key issues and criteria based on interactions with Food and Drug Administration and European Medicines Agency. This article uses ‘case studies’ to highlight the utility of seeds as vehicles for pharmaceutical production including: insulin, human growth hormone, lysozyme and lactoferrin. These examples serve to illustrate the preclinical and, in one case, clinical information required to move these plant‐derived molecules through the research phase and into the regulatory pathway en route to eventual approval.
Transgenic expression of trehalulose synthase results in high concentrations of the sucrose isomer trehalulose in mature stems of field‐grown sugarcane
Authors: Hamerli Dénes , Birch Robert G.
Published: May 2010

Sugarcane plants were developed that produce the sucrose isomers trehalulose and isomaltulose through expression of a vacuole‐targeted trehalulose synthase modified from the gene in ‘Pseudomonas mesoacidophila MX‐45’ and controlled by the maize ubiquitin (Ubi‐1) promoter. Trehalulose concentration in juice increased with internode maturity, reaching about 600 mm, with near‐complete conversion of sucrose in the most mature internodes. Plants remained vigorous, and trehalulose production in selected lines was retained over multiple vegetative generations under glasshouse and field conditions.
Multisensory information boosts numerical matching abilities in young children
Authors: Jordan Kerry E. , Baker Joseph
Published: May 2010

This study presents the first evidence that preschool children perform more accurately in a numerical matching task when given multisensory rather than unisensory information about number. Three‐ to 5‐year‐old children learned to play a numerical matching game on a touchscreen computer, which asked them to match a sample numerosity with a numerically equivalent choice numerosity. Samples consisted of a series of visual squares on some trials, a series of auditory tones on other trials, and synchronized squares and tones on still other trials. Children performed at chance on this matching task when provided with either type of unisensory sample, but improved significantly when provided with multisensory samples. There was no speed–accuracy tradeoff between unisensory and multisensory trial types. Thus, these findings suggest that intersensory redundancy may improve young children’s abilities to match numerosities.
Elevated amygdala response to faces following early deprivation
Authors: Tottenham N. , Hare T.A. , Millner A. , Gilhooly T. , Zevin J.D. , Casey B.J.
Published: May 2010

A functional neuroimaging study examined the long‐term neural correlates of early adverse rearing conditions in humans as they relate to socio‐emotional development. Previously institutionalized (PI) children and a same‐aged comparison group were scanned using functional magnetic resonance imaging (fMRI) while performing an Emotional Face Go/Nogo task. PI children showed heightened activity of the amygdala, a region that supports emotional learning and reactivity to emotional stimuli, and corresponding decreases in cortical regions that support perceptual and cognitive functions. Amygdala activity was associated with decreased eye‐contact as measured by eye‐tracking methods and during a live dyadic interaction. The association between early rearing environment and subsequent eye‐contact was mediated by amygdala activity. These data support the hypothesis that early adversity alters human brain development in a way that can persist into childhood, and they offer insight into the socio‐emotional disturbances in human behavior following early adversity.
Twelve‐month‐olds privilege words over other linguistic sounds in an associative learning task
Authors: MacKenzie Heather , Graham Susan A. , Curtin Suzanne
Published: May 2010

We examined whether 12‐month‐old infants privilege words over other linguistic stimuli in an associative learning task. Sixty‐four infants were presented with sets of either word–object, communicative sound–object, or consonantal sound–object pairings until they habituated. They were then tested on a ‘switch’ in the sound to determine whether they were able to associate the word and/or sound with the novel objects. Infants associated words, but not communicative sounds or consonantal sounds, with novel objects. The results demonstrate that infants exhibit a preference for words over other linguistic stimuli in an associative word learning task. This suggests that by 12 months of age, infants have developed knowledge about the nature of an appropriate sound form for an object label and will privilege this form as an object label.
Garbage‐Can Decision Making and the Accommodation of Uncertainty in New Drug Development Work
Authors: Styhre Alexander , Wikmalm Leena , Olilla Sanne , Roth Jonas
Published: May 2010

Innovation processes are sometimes described as a series of sequential activities, smoothly transforming into one another. However, in real‐life settings, innovation work is characterized by uncertainty, risk taking, politics and time pressure, and consequently much decision making in innovation work deviates from such rationalist models. Instead, decisions are made in the form of garbage‐can decision making, demonstrating a variety of non‐linear elements. Such characteristics are especially pronounced in industries based on science‐based innovation, operating under genuine uncertainty. This article reports a study of the clinical trial work in a major multinational pharmaceutical company and suggests that decision making includes at least four coping strategies for dealing with non‐linear and migrating decision‐making processes.
Managing for Innovation: The Two Faces of Tension in Creative Climates
Authors: Isaksen Scott G. , Ekvall Göran
Published: May 2010

Part of managing for innovation is creating the appropriate climate so that people can share and build upon each other's ideas and suggestions. Yet, there are increasing pressures and potential unproductive levels of tension within organizations. This article points out the distinction between two forms of tension that appear within the research on organizational climates for creativity as well as the conflict management literature. The Debate dimension is described as reflecting a more productive idea tension and the Conflict dimension suggests a more non‐productive personal tension. A series of studies, across multiple levels of analysis, are summarized and a new study is reported in order to highlight the finding that relatively higher levels of Debate, and lower levels of Conflict are more conducive to organizational creativity and innovation. A practical model for the constructive use of differences is shared, along with a few strategies for reducing the negative tension associated with Conflict and increasing the positive aspects associated with Debate.
The Impact of Technology on Creativity in Design: An Enhancement?
Authors: Bonnardel Nathalie , Zenasni Franck
Published: May 2010

Technology may be considered as an interface between individuals and the products they create, but we have to determine whether the use of new systems effectively enhance individuals' creative activities. In this paper, we present a new angle of reflection that we illustrate in the field of creative design, since it is a constant challenge for designers to introduce creativity in the projects they work on. The approach we propose is centred on designers' cognitive processes. We argue that both the development of new CAD (computer‐aided design) systems and their assessment should be conducted on the basis of a deep understanding of designers' cognitive processes. In accordance with this view, we present three empirical studies that were conducted in order to analyse the impact of new design support systems on designers' cognitive processes. Therefore, the results we present contribute to further our knowledge of whether new CAD technologies effectively facilitate designers' activities and enhance their creativity.
Work and employment in distribution and exchange: moments in the circuit of capital
Authors: Newsome Kirsty
Published: May 2010

This article examines the ‘politics of production’ within grocery warehousing and distribution. In doing so, it highlights the complex linkages between logistics companies and their dominant supermarket customers. Building on the work of Glucksmann and the notion of the ‘total social organisation of labour’, the article reveals how an understanding of employment change within grocery distribution necessarily involves mapping these linkages, thereby examining how they impact on the labour process. Drawing on case‐study evidence from two third‐party grocery distribution companies, it examines empirically the nature of the linkages between these organisations and their effects on the labour process. It also explores the extent to which organised labour within these interconnected distribution companies is able to mediate and re‐shape the requirements placed upon them by their customers. It concludes by highlighting how the power of the retailers and the corresponding ‘logistics revolution’ has reshaped the politics of production. In addition, it calls for an understanding of work and employment in warehousing and distribution, which engages with the complex articulation between production, distribution and exchange.
The removal of workplace partnership in the UK Civil Service: a trade union perspective
Authors: Martin Douglas
Published: May 2010

Despite extensive research on the impact of social partnership in the workplace, limited investigation has been undertaken around its removal. This article examines, from a trade union perspective, the removal of the partnership agreement by the Department for Work and Pensions and the Public and Commercial Services Union.
Treatment of human head lice infestations in a single application with a new galenic lotion
Authors: Militão de Sousa F. , Vasconcelos A. W. , De Nadon J. , Duhot P‐Y.
Published: May 2010

Synopsis

To evaluate the efficiency and safety of a new galenic meta‐emulsion for the treatment of human head lice (Pediculus capitis) in a single application. A controlled clinical study was conducted comparing lice infestation and nit hatching observed before and after a treatment in a single application. Eighty‐two of the 87 children included completed the study. An infestation control was performed on 36 and 46 children, 8 and 24 h respectively after application. Five days later, a meticulous hair examination was carried out to check that the lice infestation was completely cured. After a single application of the lotion being tested, an examination of the scalp with a head lice detection comb, as well as an examination of the rinsing water and the towel used for drying after washing, showed that out of the total 1285 lice, there were no live lice. The percentage of nits hatching before treatment was close to 70%. In comparison, after an 8‐h treatment (t+8), the percentage of nits hatching was 2.1%, with only 0.35% of living nymphs. After a 24‐h treatment (t+24), 1.9% hatched with 0.38% living nymphs. Nymphs were revealed to be non‐viable. After 5 days (t+120), no living adult or immature lice were found on the subjects tested. Moreover, observation of tolerance levels to this treatment at days 1, 5 and 12 showed no side effects. The specific galenic lotion completely cured head lice infestation in the population studied in a single application. The lotion, a patented meta‐emulsion, has a mechanical action that asphyxiates lice and nits. Considering the advantages of the single application, the possibility of complete concomitant therapeutics for a whole school population within only 1 day and the high level of tolerance to this treatment, this approach seems simple and promising.
Gamma irradiation, rheological and microbiological analysis of cosmetic products
Authors: Santos‐Oliveira R. , De Jesus Andreoli Pinto T. , Satiko Kikuchi I. , Gonçalves Mothè C.
Published: May 2010

Synopsis

In this study, we aimed to use gamma irradiation for decontamination of cosmetic product (gel) achieve the acceptable microbiological limits. Cosmetic product vials were irradiated (10–100 kGy) and physicochemical, microbiological and biological properties of these samples were evaluated in normal conditions. Decontamination dose for all samples was found to be about 10 kGy or below. A pseudoplastic feature was induced in the gel after irradiation suggesting a large applicability of gamma radiation to this purpose.
No association between the 2D:4D fetal testosterone marker and multidimensional attentional abilities in children with ADHD
Authors: LEMIERE JURGEN , BOETS BART , DANCKAERTS MARINA
Published: May 2010

Aim  It has been suggested that high levels of prenatal testosterone exposure are implied in the aetiology of attention‐deficit–hyperactivity disorder (ADHD). This study examined the association between the ratio of the length of the second and fourth digits (2D:4D ratio), a marker of fetal testosterone exposure, and the presence of ADHD‐related cognitive and behavioural problems in children with ADHD and in typically developing comparison individuals.

Method  A clinically referred group of 64 children who fulfilled DSM‐IV‐TR criteria for ADHD (47 males, 17 females; mean age 8y 8mo, SD 1y 8mo, range 7–12y) and 46 comparison children (25 males, 21 females; mean age 9y 2mo; SD 1y 10mo, range 7–12y) were included in the study. The length of the second and fourth digits was measured by two independent raters. The Child Behaviour Checklist (CBCL) and the Test of Everyday Attention for Children (TEA‐Ch) were used to assess behavioural problems and different aspects of attention.

Results  No group differences in 2D:4D ratio were observed between children with (combined, inattentive, or hyperactive‐impulsive subtype of) ADHD and comparison children. The ratio did not show the postulated relation with cognitive and behavioural aspects of ADHD.

Interpretation  These findings challenge the hypothesis that fetal testosterone exposure plays a prominent role in the aetiology of ADHD.
Paroxysmal disorders in infancy and their risk factors in a population‐based cohort: the Generation R Study
Authors: VISSER ANNEMARIE M , JADDOE VINCENT WV , ARENDS LIDIA R , TIEMEIER HENNING , HOFMAN ALBERT , MOLL HENRIETTE A , STEEGERS ERIC AP , BRETELER MONIQUE MB , ARTS WILLEM FM
Published: May 2010

Aim  To examine the incidence of paroxysmal epileptic and non‐epileptic disorders and the associated prenatal and perinatal factors that might predict them in the first year of life in a population‐based cohort.

Method  This study was embedded in the Generation R Study, a population‐based prospective cohort study from early fetal life onwards. Information about the occurrence of paroxysmal events, defined as suddenly occurring episodes with an altered consciousness, altered behaviour, involuntary movements, altered muscle tone, and/or a changed breathing pattern, was collected by questionnaires at the ages of 2, 6, and 12 months. Information on possible prenatal and perinatal determinants was obtained by measurements and questionnaires during pregnancy and after birth.

Results  Information about paroxysmal events in the first year of life was available in 2860 participants (1410 males, 1450 females). We found an incidence of paroxysmal disorders of 8.9% (n=255) in the first year of life. Of these participants, 17 were diagnosed with febrile seizures and two with epilepsy. Non‐epileptic events included physiological events, apnoeic spells, loss of consciousness by causes other than epileptic seizures or apnoeic spells, parasomnias, and other events. Preterm birth (p<0.001) and low Apgar score at 1 minute (p<0.05) were significantly associated with paroxysmal disorders in the first year of life. Continued maternal smoking during pregnancy and preterm birth were significantly associated with febrile seizures in the first year of life (p<0.05).

Interpretation  Paroxysmal disorders are frequent in infancy. They are associated with preterm birth and a low Apgar score. Epileptic seizures only form a minority of the paroxysmal events in infancy. In this study, children whose mothers continued smoking during pregnancy had a higher reported incidence of febrile seizures in the first year of life. These findings may generate various hypotheses for further investigations.
Recurrence of breech presentation in consecutive pregnancies
Authors: Ford JB , Roberts CL , Nassar N , Giles W , Morris JM
Published: May 2010

Please cite this paper as: Ford J, Roberts C, Nassar N, Giles W, Morris J. Recurrence of breech presentation in consecutive pregnancies. BJOG 2010;117:830–836.

Objective  To investigate the recurrence risk of breech presentation at term, and to assess the risk factors that contribute to its recurrence.

Design  Cohort study.

Setting  New South Wales, Australia.

Population  Women with their first two (n = 113 854) and first three (n = 21 690) consecutive singleton term pregnancies, in the period 1994–2002.

Methods  Descriptive statistics including rates, relative risks and adjusted relative risks, as determined from logistic regression and Poisson analyses.

Main outcome measures  Rates and risks of occurrence and recurrence of breech presentation at birth in each pregnancy, and maternal and infant risk factors associated with breech recurrence.

Results  First‐time breech presentation at term occurred in 4.2% of first pregnancy deliveries, 2.2% of second pregnancies and 1.9% of third pregnancies. The rate of breech recurrence in a second consecutive pregnancy was 9.9%, and in a third consecutive pregnancy (after two prior breech deliveries) was 27.5%. The relative risk of breech recurrence in a second pregnancy was 3.2 (95% CI 2.8–3.6), and in a third consecutive breech pregnancy was 13.9 (95% CI 8.8–22.1). First pregnancy factors associated with recurrence included placenta praevia [adjusted relative risk (aRR) 2.2; 95% CI 1.3–3.7], maternal diabetes (aRR 1.4; 95% CI 1.0–2.1) and a maternal age of ≥35 years (aRR 1.2; 95% CI 0.9–1.6). Second pregnancy factors included birth defects (aRR 2.5; 95% CI 1.4–4.2), placenta praevia (aRR 2.5; 95% CI 1.5–4.1) and a female infant (aRR 1.2; 95% CI 1.0–1.5).

Conclusions  The increased recurrence risk of breech presentations suggests that women with a history of breech delivery should be closely monitored in the latter stages of pregnancy.
How to interpret randomised trials of test–treatment combinations: a critical evaluation of research on uterine Doppler test to predict, and aspirin to prevent, pre‐eclampsia
Authors: Fox C , Khan KS , Coomarasamy A
Published: May 2010

Please cite this paper as: Fox C, Khan K, Coomarasamy A. How to interpret randomised trials of test–treatment combinations: a critical evaluation of research on uterine Doppler test to predict, and aspirin to prevent, pre‐eclampsia. BJOG 2010;117:801–808.

The methodology to evaluate either a test or treatment is well developed and understood. However, the design, conduct and interpretation of a combination of a test and a treatment in a single study are fraught with complexities. There are two distinct study designs to evaluate test–treatment combinations, with randomisation occurring either before or after the test. We present critical issues that need to be considered when evaluating and appraising test–treatment combinations, using the example of research on the uterine artery Doppler test to predict, and aspirin to prevent, pre‐eclampsia.
Discordant patterns of population structure for two co‐distributed snake species across a fragmented Ontario landscape
Authors: DiLeo Michelle F. , Row Jeffrey R. , Lougheed Stephen C.
Published: May 2010

Aim The goal of our study was to investigate the effects of a fragmented landscape on the genetic population structure of two sympatric snake species that differ in habitat preference. The eastern garter snake (Thamnophis sirtalis sirtalis) is a common, habitat generalist, whereas the endangered eastern foxsnake (Mintonius[Elaphe] gloydi) is rarer, geographically restricted, and a marsh‐specialist. We were most interested in comparing the genetic population structure of both species and identifying any natural and human‐created features of the landscape that overlap with genetic disjunctions.

Location Southwestern Ontario, Canada, surveying over half of the remaining range of the eastern foxsnake.

Methods We utilized DNA microsatellite markers to examine genetic population structure of both species. The number of genetically distinct clusters for each species was determined using both Bayesian spatial assignment and spatial principal component analyses (sPCA). Genetic clusters were overlaid onto a habitat map to deduce possible physiognomic barriers to gene flow.

Results Spatial assignment revealed three genetic clusters for garter snakes and five for foxsnakes. Each individual garter snake had a near equal probability of membership to two or more clusters with no cluster mapping onto a discrete geographic region, indicating that garter snakes comprise a single genetic population. The identified foxsnake clusters correspond to geographically circumscribed locations on the landscape, roughly coincident with isolated patches of suitable habitat. sPCAs revealed significant global allelic structure for foxsnakes, but not for garter snakes. No significant local structure was found for either species.

Main Conclusions Our results imply that foxsnakes and garter snakes are differentially impacted by the same landscape or have dramatically different effective population sizes. Unsuitable intervening habitat such as agricultural tracts and roads between existing populations of foxsnakes appears to act as barriers to gene flow, while garter snake movement appears unrestricted by these features. Our findings have important implications for the management of eastern foxsnakes.
Tracking greenery across a latitudinal gradient in central Asia – the migration of the saiga antelope
Authors: Singh N. J. , Grachev I. A. , Bekenov A. B. , Milner‐Gulland E. J.
Published: May 2010

Aim Long‐distance migrations of terrestrial animals, driven by needs such as food, water and escaping predators and harsh climatic conditions, are widely known phenomena. The saiga antelope (Saiga tatarica tatarica) migrates over long distances in the semi‐arid rangelands of Central Asia. Both the saiga’s range and its populations have been severely affected by socio‐political and land use changes over the last century, related to the formation and dissolution of the Soviet Union. We identified ecological drivers of saiga migration, compared four populations in terms of differences in the geographical characteristics of their ranges and the factors affecting habitat selection within the seasonal ranges.

Location Kazakhstan and pre‐Caspian Russia.

Methods Using 40 years of direct observations, we tested for differences between the four saiga populations’ ranges in terms of precipitation, seasonal productivity and topographical variables using discriminant analyses. We tested hypotheses concerning the drivers of migration to their seasonal ranges and assessed the impact of peak and average values and the predictability of drivers of habitat use within the seasonal ranges using logistic regressions.

Results Three of the four populations migrate in a similar way, following a latitudinal gradient driven by seasonal changes in productivity, which is closely related to broad‐scale differences in precipitation. Intermediate productivity and its low interannual variability determine habitat selection within the seasonal ranges of all the populations.

Main conclusions Migration of all four populations is driven by productivity and precipitation. The migrations in Kazakhstan are still intact despite major recent disruption to the populations, whereas their status in the pre‐Caspian region is unknown. All four populations are under severe threat from habitat loss, poaching, lack of protection and gaps in ecological knowledge. A better understanding of the drivers of saiga migration at multiple scales is a key step towards addressing these threats.
A role for the Werner syndrome protein in epigenetic inactivation of the pluripotency factor Oct4
Authors: Smith Johanna A. , Ndoye Abibatou M. N. , Geary Kyla , Lisanti Michael P. , Igoucheva Olga , Daniel René
Published: May 2010

Werner syndrome (WS) is an autosomal recessive disorder, the hallmarks of which are premature aging and early onset of neoplastic diseases (Orren, 2006; Bohr, 2008). The gene, whose mutation underlies the WS phenotype, is called WRN. The protein encoded by the WRN gene, WRNp, has DNA helicase activity (Gray et al., 1997; Orren, 2006; Bohr, 2008; Opresko, 2008). Extensive evidence suggests that WRNp plays a role in DNA replication and DNA repair (Chen et al., 2003; Hickson, 2003; Orren, 2006; Turaga et al., 2007; Bohr, 2008). However, WRNp function is not yet fully understood. In this study, we show that WRNp is involved in de novo DNA methylation of the promoter of the Oct4 gene, which encodes a crucial stem cell transcription factor. We demonstrate that WRNp localizes to the Oct4 promoter during retinoic acid‐induced differentiation of human pluripotent cells and associates with the de novo methyltransferase Dnmt3b in the chromatin of differentiating pluripotent cells. Depletion of WRNp does not affect demethylation of lysine 4 of the histone H3 at the Oct4 promoter, nor methylation of lysine 9 of H3, but it blocks the recruitment of Dnmt3b to the promoter and results in the reduced methylation of CpG sites within the Oct4 promoter. The lack of DNA methylation was associated with continued, albeit greatly reduced, Oct4 expression in WRN‐deficient, retinoic acid‐treated cells, which resulted in attenuated differentiation. The presented results reveal a novel function of WRNp and demonstrate that WRNp controls a key step in pluripotent stem cell differentiation.
Sustained morphine‐mediated pain sensitization and antinociceptive tolerance are blocked by intrathecal treatment with Raf‐1‐selective siRNA
Authors: Tumati S , Roeske WR , Largent‐Milnes T , Wang R , Vanderah TW , Varga EV
Published: May 2010

BACKGROUND AND PURPOSELong‐term morphine treatment enhances pain neurotransmitter [such as calcitonin gene‐related peptide (CGRP)] levels in the spinal cord. It has been suggested previously that increased spinal CGRP may contribute to sustained morphine‐mediated paradoxical pain sensitization and antinociceptive tolerance. Previousin vitrostudies from our group indicated that Raf‐1 kinase‐mediated adenylyl cyclase superactivation played a crucial role in sustained morphine‐mediated augmentation of basal and evoked CGRP release from cultured primary sensory neurons. The present study was aimed to evaluate the physiological significance of this molecular mechanismin vivo, in rats.

EXPERIMENTAL APPROACHRats were intrathecally (i.th) injected with a Raf‐1‐selective small interfering RNA (siRNA) mixture for 3 days and were subsequently infused with saline or morphine, s.c. for 7 days. Thermal and mechanical sensory thresholds of the animals were assessed by daily behavioural tests. After final behavioural testing (day 6), spinal cords were isolated from each animal group and spinal CGRP and Raf‐1 protein levels were measured usingelisaand immunohistochemistry.

KEY RESULTSSelective knockdown of spinal Raf‐1 protein levels by i.th Raf‐1‐selective siRNA pretreatment significantly attenuated sustained morphine‐mediated up‐regulation of CGRP immunoreactivity in the spinal cord of rats and prevented the development of thermal hyperalgesia, mechanical allodynia and antinociceptive tolerance.

CONCLUSIONS AND IMPLICATIONSRaf‐1 played a significant role in sustained morphine‐mediated paradoxical pain sensitization and antinociceptive tolerancein vivo. These findings suggest novel pharmacological approaches to improve the long‐term utility of opioids in the treatment of chronic pain.
Regional enhancement of cannabinoid CB1 receptor desensitization in female adolescent rats following repeated Δ9‐tetrahydrocannabinol exposure
Authors: Burston James J , Wiley Jenny L , Craig Abimbola A , Selley Dana E , Sim‐Selley Laura J
Published: May 2010

BACKGROUND AND PURPOSE Disruption of the substantial re‐organization of the brain during adolescence may be induced by persistent abuse of marijuana. The aim of this study was to determine whether adolescent and adult rats exhibit differential adaptation of brain cannabinoid (CB1) receptors after repeated exposure to Δ9‐tetrahydrocannabinol (THC).

EXPERIMENTAL APPROACH Rats of both ages and sexes were dosed with 10 mg kg−1 THC or vehicle twice daily for 9.5 days. Subsequently, CB1 receptor function and density were assessed.

KEY RESULTS In all brain regions, THC treatment produced desensitization and down‐regulation of CB1 receptors. While the magnitude of down‐regulation did not differ across groups, greater desensitization was evident in the brains of THC‐treated female adolescent rats for most regions. Adolescent females showed greater desensitization than adult females in the prefrontal cortex, hippocampus, periaqueductal gray (PAG) and ventral midbrain. In contrast, adolescent males exhibited less desensitization in the prefrontal cortex, hippocampus and PAG, an effect opposite to that seen in females. With the exception of the PAG, sex differences were seen only in adolescents, with greater desensitization in the prefrontal cortex, striatum, hippocampus, PAG, and ventral midbrain of females.

CONCLUSIONS AND IMPLICATIONS These results suggest that the brains of adolescent females may be particularly vulnerable to disruption of CB1 receptor signalling by marijuana abuse. Alternatively, increased desensitization may reflect protective adaptation. Given the extensive re‐organization of the brain during adolescence, this disruption has potential long‐term consequences for maturation of the endocannabinoid system.
Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway
Authors: Li Feng , Rajendran Peramaiyan , Sethi Gautam
Published: May 2010

BACKGROUND AND PURPOSE Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) pathway is frequently encountered in several human cancers including multiple myeloma (MM). Thus, agents that suppress STAT3 phosphorylation have a potential for treatment of MM. In the present report, we investigated whether thymoquinone (TQ), the main component isolated from the medicinal plant Nigella sativa, modulated the STAT3 signalling pathway in MM cells.

EXPERIMENTAL APPROACH The effect of TQ on both constitutive and IL‐6‐induced STAT3 activation, associated protein kinases, STAT3‐regulated gene products involved in proliferation, survival and angiogenesis, cellular proliferation and apoptosis in MM cells, was investigated.

KEY RESULTS We found that TQ inhibited both constitutive and IL‐6‐inducible STAT3 phosphorylation which correlated with the inhibition of c‐Src and JAK2 activation. Vanadate reversed the TQ‐induced down‐regulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that TQ can induce the expression of Src homology‐2 phosphatase 2 that correlated with suppression of STAT3 activation. TQ also down‐regulated the expression of STAT3‐regulated gene products, such as cyclin D1, Bcl‐2, Bcl‐xL, survivin, Mcl‐1 and vascular endothelial growth factor. Finally, TQ induced the accumulation of cells in sub‐G1 phase, inhibited proliferation and induced apoptosis, as indicated by poly ADP ribose polymerase cleavage. TQ also significantly potentiated the apoptotic effects of thalidomide and bortezomib in MM cells.

CONCLUSIONS AND IMPLICATIONS Our study has identified STAT3 signalling as a target of TQ and has thus raised its potential application in the prevention and treatment of MM and other cancers.
β‐Arrestin 1 and 2 stabilize the angiotensin II type I receptor in distinct high‐affinity conformations
Authors: Sanni SJ , Hansen JT , Bonde MM , Speerschneider T , Christensen GL , Munk S , Gammeltoft S , Hansen JL
Published: May 2010

BACKGROUND AND PURPOSE The angiotensin II type 1 (AT1) receptor belongs to family A of 7 transmembrane (7TM) receptors. The receptor has important roles in the cardiovascular system and is commonly used as a drug target in cardiovascular diseases. Interaction of 7TM receptors with G proteins or β‐arrestins often induces higher binding affinity for agonists. Here, we examined interactions between AT1A receptors and β‐arrestins to look for differences between the AT1A receptor interaction with β‐arrestin1 and β‐arrestin2.

EXPERIMENTAL APPROACH Ligand‐induced interaction between AT1A receptors and β‐arrestins was measured by Bioluminescence Resonance Energy Transfer 2. AT1A‐β‐arrestin1 and AT1A‐β‐arrestin2 fusion proteins were cloned and tested for differences using immunocytochemistry, inositol phosphate hydrolysis and competition radioligand binding.

KEY RESULTS Bioluminescence Resonance Energy Transfer 2 analysis showed that β‐arrestin1 and 2 were recruited to AT1A receptors with similar ligand potencies and efficacies. The AT1A‐β‐arrestin fusion proteins showed attenuated G protein signalling and increased agonist binding affinity, while antagonist affinity was unchanged. Importantly, larger agonist affinity shifts were observed for AT1A‐β‐arrestin2 than for AT1A‐β‐arrestin1.

CONCLUSION AND IMPLICATIONS β‐Arrestin1 and 2 are recruited to AT1A receptors with similar ligand pharmacology and stabilize AT1A receptors in distinct high‐affinity conformations. However, β‐arrestin2 induces a receptor conformation with a higher agonist‐binding affinity than β‐arrestin1. Thus, this study demonstrates that β‐arrestins interact with AT1A receptors in different ways and suggest that AT1 receptor biased agonists with the ability to recruit either of the β‐arrestins selectively, would be possible to design.
Darbepoetin‐mediated cardioprotection after myocardial infarction involves multiple mechanisms independent of erythropoietin receptor–common β‐chain heteroreceptor
Authors: Kanellakis Peter , Pomilio Giovanna , Agrotis Alex , Gao Xiaoming , Du Xiao‐Jun , Curtis David , Bobik Alexander
Published: May 2010

BACKGROUND AND PURPOSE

Darbepoetin, a long‐acting erythropoietin derivative, attenuates cardiomyocyte apoptosis and improves short‐term (3 days) cardiac function, but the mechanisms responsible are unknown. We investigated potential mechanisms by which darbepoetin exerts cardioprotection following myocardial infarction in mice and the significance of the erythropoietin receptor (EPOR)–common β‐chain (c‐β‐chain) heteroreceptor.

EXPERIMENTAL APPROACH

Mice underwent 60 min coronary occlusion followed by treatment with vehicle or a single dose of darbepoetin. Effects on gene expression, apoptosis and neutrophil accumulation in infarcted left ventricle were assessed 24 h later. Cardiac function, effects on vascularization and fibrosis were assessed 28 days later. The significance of EPOR–c‐β‐chain heteroreceptor was examined 28 days after infarction using mice deficient in c‐β‐chain.

KEY RESULTS

Twenty‐four hours after darbepoetin, mRNAs encoding haeme oxygenase‐1 (HO‐1), iNOS and brain natriuretic peptide (BNP) were markedly elevated only in infarcted regions, and the frequency of apoptotic cells attenuated. Inflammation was also attenuated with reductions in neutrophil numbers. Darbepoetin also elevated mRNAs encoding angiogenic factors: placental growth factor, monocyte chemoattractant protein‐1 and interleukin‐1β. Twenty‐eight days after treatment, CD31+ vessels in the infarct zone doubled and fibrosis reduced. Cardiac haemodynamics were improved. Darbepoetin also improved cardiac haemodynamics in c‐β‐chain‐deficient mice, increased HO‐1 and iNOS expression and vessel numbers and attenuated fibrosis.

CONCLUSIONS AND IMPLICATIONS

Darbepoetin stimulates expression of haeme oxygenase, iNOS, BNP and angiogenic factors specifically in infarcted left ventricle that attenuates inflammation, apoptosis and fibrosis; elevate vessel numbers; and improve cardiac function. The EPOR–c‐β‐chain heteroreceptor is not essential for these effects.
Frequency of Headaches in Children is Influenced by Headache Status in the Mother
Authors: Arruda Marco A. , Guidetti Vincenzo , Galli Federica , Albuquerque Regina C.A.P. , Bigal Marcelo E.
Published: May 2010

(Headache 2010;50:973‐980)

Background.— Migraine aggregates within families. Nonetheless the familial aggregation of chronic daily headaches (CDH) and of episodic headaches of different frequencies has been very poorly studied. Accordingly herein we test the hypothesis that frequency of primary headaches aggregates in the family.

Methods.— Sample consisted of 1994 children (5‐12 years) identified in the population. Validated questionnaires were used to interview the parents. Crude and adjusted prevalences of low‐frequency (1‐4 headache days/month), intermediate‐frequency (5‐9 days/month), high‐frequency (10‐14 headache days/month), and CDH (15 or more headache days/month) in children were calculated as a function of headaches in the mother.

Results.— Frequency of headaches in the mother predicted frequency of headaches in the children; when the mother had low frequency headaches, the children had an increased chance to have low or intermediate headache frequency (relative risk = 1.4, 1.2‐1.6) but not CDH. When the mother had CDH, risk of CDH in the children was increased by almost 13‐fold, but the risk of infrequent headaches was not increased. In multivariate models, headaches in the children were independently predicted by headaches in the mother (P < .001); headache frequency in the children was also predicted by frequency in the mother (P < .001).

Conclusions.— Frequency of headaches in children is influenced by frequency of headaches in the mother and seems to aggregate in families. Future studies should focus on the determinants of headache aggregation, including genetic and non‐genetic factors.
The Renin–Angiotensin System Mediates the Effects of Stretch on Conduction Velocity, Connexin43 Expression, and Redistribution in Intact Ventricle
Authors: HUSSAIN WAJID , PATEL PRAVINA M. , CHOWDHURY RASHEDA A. , CABO CANDIDO , CIACCIO EDWARD J. , LAB MAX J. , DUFFY HEATHER S. , WIT ANDREW L. , PETERS NICHOLAS S.
Published: May 2010

Effect of Stretch on Conduction and Cx43. Introduction: In disease states such as heart failure, myocardial infarction, and hypertrophy, changes in the expression and location of Connexin43 (Cx43) occur (Cx43 remodeling), and may predispose to arrhythmias. Stretch may be an important stimulus to Cx43 remodeling; however, it has only been investigated in neonatal cell cultures, which have different physiological properties than adult myocytes. We hypothesized that localized stretch in vivo causes Cx43 remodeling, with associated changes in conduction, mediated by the renin–angiotensin system (RAS).

Methods and Results: In an open‐chest canine model, a device was used to stretch part of the right ventricle (RV) by 22% for 6 hours. Activation mapping using a 312‐electrode array was performed before and after stretch. Regional stretch did not change longitudinal conduction velocity (post‐stretch vs baseline: 51.5 ± 5.2 vs 55.3 ± 8.1 cm/s, P = 0.24, n = 11), but significantly reduced transverse conduction velocity (28.7 ± 2.5 vs 35.4 ± 5.4 cm/s, P < 0.01). It also reduced total Cx43 expression, by Western blotting, compared with nonstretched RV of the same animal (86.1 ± 32.2 vs 100 ± 19.4%, P < 0.02, n = 11). Cx43 labeling redistributed to the lateral cell borders. Stretch caused a small but significant increase in the proportion of the dephosphorylated form of Cx43 (stretch 9.95 ± 1.4% vs control 8.74 ± 1.2%, P < 0.05). Olmesartan, an angiotensin II blocker, prevented the stretch‐induced changes in Cx43 levels, localization, and conduction.

Conclusion: Myocardial stretch in vivo has opposite effects to that in neonatal myocytes in vitro. Stretch in vivo causes conduction changes associated with Cx43 remodeling that are likely caused by local stretch‐induced activation of the RAS. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1276‐1283, November 2010)