bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium movement in nerve fibres
Authors: Requena J. , Mullins L. J.
Published: March 2009

Given the existence of a difference in electrical potential between the interior of a nerve cell and the media surrounding it, where the cytoplasm is some 70 mV negative (Hodgkin, 1958), it must be expected that any positively charged ion to which the cell membrane is permeable is more concentrated in the cell interior. For monovalent cations such as Na and divalent cations such as Ca and Mg this is not the case in the majority of the cells such as the squid giant axon. In other words, nerve cells maintain a lower intracellular concentration of these ions, as compared with their concentration in the extracellular fluid. For Mg, Ca and Na ions, this lower internal concentration must, in the steady state, be effected by some membrane based mechanism which consumes energy.
Heteronuclear three-dimensional NMR spectroscopy of isotopically labelled biological macromolecules
Authors: Fesik Stephen W. , Zuiderweg Erik R. P.
Published: March 2009

Due to the development of two-dimensional Fourier transformation techniques (for reviews see Bax, 1982; Ernst et al. 1987), NMR spectroscopy has become a powerful tool for determining the 3D structures of small proteins (MW ≤ 10 kDa); for reviews see Wüthrich, 1986; Clore & Gronenborn, 1987. For larger molecules, however, the amount of detailed structural information that can be obtained using homonuclear 2D NMR techniques is limited because of the vast number of overlapping signals. In order to extend the capabilities of NMR to the study of larger systems, new approaches are required.
Biochemistry and measurement of Environmental lead intoxication
Authors: Eisinger Josef
Published: March 2009

Lead is probably the oldest and most widely distributed environmental intoxicant, but unlike many of the synthetic agents which cause the greatest concern in industrial societies today, it occurs naturally at low levels in the environment and was present during evolutionary times. Galena (PbS), the most important lead-bearing mineral, is abundant and it is readily smelted. The metal is easily shaped and does not corrode and its compounds have found innumerable uses, particularly as pigments. This explains, in brief, why lead has had great economic importance since ancient times and why lead disease has plagued civilized societies for thousands of years and continues to be a serious concern to health authorities today. (Grandjean, 1975; Eisinger, 1977).
The biochemistry of toxic elements
Authors: Wood J. M. , Fanchiang Y. -T. , Ridley W. P.
Published: March 2009

In 1968 it was discovered that mercury could be biomethylated to give methylmercury as the major product (Wood, Kennedy & Rosen, 1968; Jensen & Jernelöv, 1969). This discovery has proved to be important in two respects: (a) it provided us with the recognition that biological systems are capable of synthesizing very toxic organometallic compounds from relatively innocuous inorganic precursors, and (b) it opened the door to the study of organometallic compounds produced by biological mechanisms in the aqueous environment.
DNA structural forms
Authors: Hartmann Brigitte , Lavery Richard
Published: March 2009

In the years that have passed since the publication of Wolfram Saenger's classic book on nucleic acid structure (Saenger, 1984), a considerable amount of new data has been accumulated on the range of conformations which can be adopted by DNA. Many unusual species have joined the DNA zoo, including new varieties of two, three and four stranded helices. Much has been learnt about intrinsic DNA curvature, dynamics and conformational transitions and many types of damaged or deformed DNA have been investigated. In this article, we will try to summarise this progress, pointing out the scope of the various experimental techniques used to study DNA structure, and, where possible, trying to discern the rules which govern the behaviour of this subtle macromolecule. The article is divided into six major sections which begin with a general discussion of DNA structure and then present successively, B-DNA, DNA deformations, A-DNA, Z-DNA and DNARNA hybrids. An extensive set of references is included and should serve the reader who wishes to delve into greater detai.
Biped gait generation based on parametric excitation by knee-joint actuation
Authors: Harata Yuji , Asano Fumihiko , Luo Zhi-Wei , Taji Kouichi , Uno Yoji
Published: March 2009

Restoration of mechanical energy dissipating on impact at the ground is necessary for sustainable gait generation. Parametric excitation is one approach to restore the mechanical energy. Asano et al. (“Parametric excitation mechanisms for dynamic bipedal walking,” IEEE International Conference on Robotics and Automation (2005) pp. 611–617.) applied parametric excitation to a biped robot with telescopic-legs, in which up-and-down motion restores total mechanical energy like playing on the swing. In this paper, parametric excitation principle is applied to a kneed biped robot with only knee actuation and it is shown that the robot walks successively without hip actuation. We also examine influences of several parameters and reference trajectory on walking performance.
The effect of vaccination on undetected persistence of foot-and-mouth disease virus in cattle herds and sheep flocks
Authors: SCHLEY D. , PATON D. J. , COX S. J. , PARIDA S. , GUBBINS S.
Published: March 2009

The importance of carrier animals (those in whom virus persists after recovery from disease or acute infection) and their potential role in the spread of disease remain open questions within foot-and-mouth disease epidemiology. Using simple probabilistic models we attempt to quantify the effect of emergency vaccination – and especially the time of application – on the likely number of such animals, using data from challenge experiments on both cattle and sheep to determine the probability of persistence in diseased and subclinically infected animals. We show that the number of persistently infected animals in a group is predominantly determined by the number of animals initially infected on premises – the high variability of which ultimately limits the accuracy of any predictions of carrier numbers based upon transmission models. Furthermore, results suggest that, within a cattle herd, carrier numbers may be increased if challenge occurs shortly after vaccination. We show that the quality of inspection is the principal factor influencing whether or not carrier herds occur and that, by reducing clinical signs, the application of vaccination in regularly checked stock also results in an increase in undetected persistently infected animals. Where clinical detection would be poor regardless of the use of vaccination (i.e. particularly in sheep), vaccination will result in a reduction in the probability of a group containing undetected carriers: otherwise there is a benefit only if vaccination is applied sufficiently far in advance of any challenge. The implications of the results for serosurveillance are discussed, including the requisite test sensitivity and practices for successful implementation.
Of Colored Numbers and Numbered Colors
Authors: Gebuis Titia , Nijboer Tanja C.W. , van der Smagt Maarten J.
Published: March 2009

Grapheme-color synesthetes experience a specific color when they see a grapheme but they do not report to perceive a grapheme when a color is presented. In this study, we investigate whether color can still evoke number-processes even when a vivid number experience is absent. We used color-number and number-color priming, both revealing faster responses in congruent compared to incongruent conditions. Interestingly, the congruency effect was of similar magnitude for both conditions, and a numerical distance effect was present only in the color-number priming task. In addition, a priming task in which synesthetes had to judge the parity of a colored number revealed faster responses in parity congruent than in parity incongruent trials. These combined results demonstrate that synesthesia is indeed bi-directional and of similar strength in both directions. Furthermore, they illustrate the precise nature of these interactions and show that the direction of these interactions is determined by task demands, not by the more vividly experienced aspect of the stimulus.
Conflict-Frequency Affects Flanker Interference
Authors: Wendt Mike , Luna-Rodriguez Aquiles
Published: March 2009

Performance in choice reaction time tasks deteriorates when an irrelevant stimulus feature is associated with an incorrect response (conflict condition). Such interference effects are reduced under conditions of increased conflict-frequency. Although models of cognitive control account for this modulation in terms of conflict-related attentional focusing on the target stimulus dimension, it is possible that the effect reflects practice with specific stimulus ensembles or stimulus feature-response contingencies. Using an Eriksen flanker task, we deconfounded the frequency of conflict trials and the frequency of specific stimulus ensembles (i.e., target-flanker conjunctions). In Experiments 1 and 2, flanker interference varied inversely with the frequency of conflict trials, irrespective of practice with specific target-flanker conjunctions, thereby disputing a stimulus ensemble learning account. In Experiment 3, however, flanker interference was reduced for specific flanker stimuli which occurred predominantly in conflict trials. Taken together, the findings are consistent with flanker-specific attentional adjustment or associative flanker-response priming.
Impact of climate and land use change on the hydrology of a large‐scale agricultural catchment
Authors: van Roosmalen Lieke , Sonnenborg Torben O. , Jensen Karsten H.
Published: March 2009

This paper presents a quantitative comparison of plausible climate and land use change impacts on the hydrology of a large‐scale agricultural catchment. An integrated, distributed hydrological model was used to simulate changes in the groundwater system and its discharge to rivers and drains for two climate scenarios (2071–2100). Annual groundwater recharge increased significantly (especially the B2 scenario), giving higher groundwater heads and stream discharges and amplifying the seasonal dynamics significantly. Owing to drier summers, irrigation volumes increased by up to 90% compared to current values. Changing the land use from grass to forest had a minor effect on groundwater recharge, whereas CO2 effects on transpiration resulted in a relatively large increase in recharge. This study has shown that climate change has the most substantial effect on the hydrology in this catchment, whereas other factors such as irrigation, CO2 effects on transpiration, and land use changes affect the water balance to a lesser extent.
Model of the spume sea spray generation
Authors: Kudryavtsev V. N. , Makin V. K.
Published: March 2009

A model of the spume spray generation function (SGF) is suggested. Spume droplets are produced by the wind tearing off breaking crests of the equilibrium range wind waves. The injection occurs in the form of a jet which is pulverized into droplets that have a range of sizes with a distribution proportional to the radius to the power 2. Breaking of the equilibrium range wind waves takes place on crests of dominant wind waves, therefore spume droplets are injected into the air at the altitude of the dominant wave crest. A reasonable agreement with the empirical SGFs is found.
Surface shortwave aerosol radiative forcing during the Atmospheric Radiation Measurement Mobile Facility deployment in Niamey, Niger
Authors: McFarlane S. A. , Kassianov E. I. , Barnard J. , Flynn C. , Ackerman T. P.
Published: March 2009

The Atmospheric Radiation Measurement (ARM) Program's Mobile Facility (AMF) was deployed to Niamey, Niger, during 2006. Niamey, which is located in sub‐Saharan Africa, is affected by both dust and biomass burning emissions. Column aerosol optical properties were derived from multifilter rotating shadowband radiometer, measurements and the vertical distribution of aerosol extinction was derived from a micropulse lidar during the two observed dry seasons (January–April and October–December). Mean aerosol optical depth (AOD) and single scattering albedo (SSA) at 500 nm during January–April were 0.53 ± 0.4 and 0.94 ± 0.05, while during October–December mean AOD and SSA were 0.33 ± 0.25 and 0.99 ± 0.01. Aerosol extinction profiles peaked near 500 m during the January–April period and near 100 m during the October–December period. Broadband shortwave surface fluxes and heating rate profiles were calculated using retrieved aerosol properties. Comparisons for noncloudy periods indicated that the remote sensing retrievals provided a reasonable estimation of the aerosol optical properties, with mean differences between calculated and observed fluxes of less than 5 W m−2 and RMS differences less than 25 W m−2. Sensitivity tests showed that the observed fluxes could be matched with variations of <10% in the inputs to the radiative transfer model. The calculated 24‐h averaged SW instantaneous surface aerosol radiative forcing (ARF) was −21.1 ± 14.3 W m−2 and was estimated to account for 80% of the total radiative forcing at the surface. The ARF was larger during January–April (−28.5 ± 13.5 W m−2) than October–December (−11.9 ± 8.9 W m−2).
Experimental evidence of the anisotropy of tracer dispersion in rough fractures with sheared walls
Authors: Boschan A. , Auradou H. , Ippolito I. , Chertcoff R. , Hulin J. P.
Published: March 2009

Dispersion experiments are compared for two model fractures with identical complementary rough walls but with a relative shear displacement δ parallel (δ ∥ U) or perpendicular (δ ⊥ U) to the flow velocity U. The flowing fluid is a shear thinning polymer solution with a Newtonian behavior at low shear rates. For δ ⊥ U, the mixing fronts display large structures well reproduced by assuming parallel channels of conductance deduced from the aperture field. This model also explains the amplification of the structures in the shear thinning regime and the distribution of the local transit times (x, y). For δ ∥ U, the front is much flatter. The local thickness of the front is characterized by a dispersivity α(x, y): its distribution is narrow enough to define an effective value α(Pe) only for δ ∥ U, and, in this case, α(Pe) has a Taylor‐Aris‐like variation with Pe.
Fundamentals of Food Reaction Technology
Authors: Earle Richard , Earle Mary
Published: March 2009

Food processing has moved on from being a craft to a modern technology. In order to meet the sensory quality, safety, nutrition, health, economy and novelty demanded of food products by consumers, it is necessary to improve food processing operations. This improvement involves better prediction and control of the changes that occur during the processing of food materials, and the rates of changes and the factors that influence them. This book introduces the methods of reaction technology, illustrating what has been and can be applied in real situations. It builds a framework for the application of reaction technology, and uses this in a straightforward way, with understandable examples set within an industrial context. The book starts by setting out the general principles governing change in the nature and chemistry of a food constituent, and extends this to include the dynamics of the reactions of the many chemical constituents of food raw materials and ingredients. Fundamentals of Food Reaction Technology is intended for those working in process design, organisation and control, and will give technical managers an overall view of how the application of reaction technology in the future can lead to a "high tech" food industry. It will also be a valuable guide for students, lecturers and practitioners in development and process technology and engineering.
Culturally and Linguistically Diverse Populations: Serving GLBT Families in Our Schools
Authors: Frazier Ashley M.
Published: March 2009

School speech-language pathologists (SLPs) are increasingly likely to serve children of gay, lesbian, bisexual, and transgender (GLBT) parents or GLBT students as cultural and societal changes create growth in the population and increased willingness to disclose sexual orientation. The American Speech-Language-Hearing Association (ASHA) has a progressive nondiscrimination statement that includes sexual orientation as a protected status and strongly urges the membership to develop cultural competence as a matter of ethical service delivery. The purpose of this article is to describe cultural competence in relation to GLBT culture, discuss GLBT parent and student cultural issues as they are important in parent-school or student-school relations, and to provide suggestions for increasing sensitivity in these types of interactions. A list of resources is provided.
A Space to Care, a Space of Care: Public Housing, Belonging, and Care in Inner Newcastle, Australia
Authors: Mee Kathleen
Published: March 2009

Public housing places are often examined in academic literature through an entry point of social exclusion. The entry point of this paper is, in contrast, belonging. In public housing, belonging is not guaranteed by the provision of a dwelling. Belonging is an active process created by tenants through interactions within households, with neighbours, and with housing providers. Central to these interactions, and the primary focus of this paper, are interactions based on care. The paper draws on results from a survey of public housing tenants in inner Newcastle, Australia. It is argued that a range of forms of care were critical to developing belonging for public housing tenants. The entry point of belonging allows an appreciation of the active of role of tenants in creating their everyday lives and the caring possibilities of public housing tenancy. The care needs and bonds of public housing tenants are explored, as well as perceptions of care deficits that make the achievement of belonging more challenging.
Northern Belongings: Frontiers, Fences, and Identities in Australia's Urban North
Authors: Instone Lesley
Published: March 2009

The importance of the frontier in shaping northern Australia continues to arouse interest and debate among scholars. This paper contributes to this scholarship through the exploration of the mutual constitution of frontier and belonging in suburban backyards in Australia's urban north. The focus of the paper is the angry and indignant resistance to the introduction of mandatory pool fencing in the Northern Territory in 2002–04. Adopting an attitude of ‘witnessing’ small and ordinary happenings, I explore the spontaneous outbursts of identity and belonging expressed by antifence residents of Darwin, with particular emphasis on their creative enactment of frontier tropes of freedom, vigilance, risk, and self-reliance in defence of unfenced pools. By exploring an apparently ordinary event I reflect on the unconscious, subtle, and pervasive reach of the frontier in shaping performances of belonging in the urban north.
An adrenal β-arrestin 1-mediated signaling pathway underlies angiotensin II-induced aldosterone production in vitro and in vivo
Authors: Lymperopoulos Anastasios , Rengo Giuseppe , Zincarelli Carmela , Kim Jihee , Soltys Stephen , Koch Walter J.
Published: March 2009

Aldosterone produces a multitude of effects in vivo, including promotion of postmyocardial infarction adverse cardiac remodeling and heart failure progression. It is produced and secreted by the adrenocortical zona glomerulosa (AZG) cells after angiotensin II (AngII) activation of AngII type 1 receptors (AT1Rs). Until now, the general consensus for AngII signaling to aldosterone production has been that it proceeds via activation of Gq/11-proteins, to which the AT1R normally couples. Here, we describe a novel signaling pathway underlying this AT1R-dependent aldosterone production mediated by β-arrestin-1 (βarr1), a universal heptahelical receptor adapter/scaffolding protein. This pathway results in sustained ERK activation and subsequent up-regulation of steroidogenic acute regulatory protein, a steroid transport protein regulating aldosterone biosynthesis in AZG cells. Also, this βarr1-mediated pathway appears capable of promoting aldosterone turnover independently of G protein activation, because treatment of AZG cells with SII, an AngII analog that induces βarr, but not G protein coupling to the AT1R, recapitulates the effects of AngII on aldosterone production and secretion. In vivo, increased adrenal βarr1 activity, by means of adrenal-targeted adenoviral-mediated gene delivery of a βarr1 transgene, resulted in a marked elevation of circulating aldosterone levels in otherwise normal animals, suggesting that this adrenocortical βarr1-mediated signaling pathway is operative, and promotes aldosterone production and secretion in vivo, as well. Thus, inhibition of adrenal βarr1 activity on AT1Rs might be of therapeutic value in pathological conditions characterized and aggravated by hyperaldosteronism.
MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment
Authors: Pitroda Sean P. , Khodarev Nikolai N. , Beckett Michael A. , Kufe Donald W. , Weichselbaum Ralph R.
Published: March 2009

The mucin 1 (MUC1) oncoprotein is aberrantly overexpressed in human breast cancers. Although MUC1 modulates the activity of estrogen receptor α (ER), there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for breast cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of genes involved in cholesterol and fatty acid metabolism. A 38-gene set of experimentally derived MUC1-induced genes associated with lipid metabolism was applied to the analysis of ER+breast cancer patients treated with tamoxifen. The results obtained from 2 independent databases demonstrate that patients overexpressing MUC1 and the lipid metabolic pathways are at significantly higher risk for death and recurrence/distant metastasis. By contrast, these genes were not predictive in untreated patients. Furthermore, a positive correlation was found between expression of the 38-gene set and the ER signaling pathway. These findings indicate that (i) MUC1 regulates cholesterol and fatty acid metabolism, and (ii) activation of these pathways in ER+breast cancers predicts failure to tamoxifen treatment.
Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in
KCNJ10
Authors: Scholl Ute I. , Choi Murim , Liu Tiewen , Ramaekers Vincent T. , Häusler Martin G. , Grimmer Joanne , Tobe Sheldon W. , Farhi Anita , Nelson-Williams Carol , Lifton Richard P.
Published: March 2009

We describe members of 4 kindreds with a previously unrecognized syndrome characterized by seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (hypokalemia, metabolic alkalosis, and hypomagnesemia). By analysis of linkage we localize the putative causative gene to a 2.5-Mb segment of chromosome 1q23.2–23.3. Direct DNA sequencing of
KCNJ10
, which encodes an inwardly rectifying K
+
channel, identifies previously unidentified missense or nonsense mutations on both alleles in all affected subjects. These mutations alter highly conserved amino acids and are absent among control chromosomes. Many of these mutations have been shown to cause loss of function in related K
+
channels. These findings demonstrate that loss-of-function mutations in
KCNJ10
cause this syndrome, which we name SeSAME.
KCNJ10
is expressed in glia in the brain and spinal cord, where it is believed to take up K
+
released by neuronal repolarization, in cochlea, where it is involved in the generation of endolymph, and on the basolateral membrane in the distal nephron. We propose that
KCNJ10
is required in the kidney for normal salt reabsorption in the distal convoluted tubule because of the need for K
+
recycling across the basolateral membrane to enable normal activity of the Na
+
-K
+
-ATPase; loss of this function accounts for the observed electrolyte defects. Mice deficient for
KCNJ10
show a related phenotype with seizures, ataxia, and hearing loss, further supporting
KCNJ10
's role in this syndrome. These findings define a unique human syndrome, and establish the essential role of basolateral K
+
channels in renal electrolyte homeostasis.
Comparisons of stuttering frequency during and after speech initiation in unaltered feedback, altered auditory feedback and choral speech conditions
Authors: Saltuklaroglu Tim , Kalinowski Joseph , Robbins Mary , Crawcour Stephen , Bowers Andrew
Published: March 2009

Background: Stuttering is prone to strike during speech initiation more so than at any other point in an utterance. The use of auditory feedback (AAF) has been found to produce robust decreases in the stuttering frequency by creating an electronic rendition of choral speech (i.e., speaking in unison). However, AAF requires users to self‐initiate speech before it can go into effect and, therefore, it might not be as helpful as true choral speech during speech initiation.

Aims: To examine how AAF and choral speech differentially enhance fluency during speech initiation and in subsequent portions of utterances.

Methods & Procedures: Ten participants who stuttered read passages without altered feedback (NAF), under four AAF conditions and under a true choral speech condition. Each condition was blocked into ten 10 s trials separated by 5 s intervals so each trial required ‘cold’ speech initiation. In the first analysis, comparisons of stuttering frequencies were made across conditions. A second, finer grain analysis involved examining stuttering frequencies on the initial syllable, the subsequent four syllables produced and the five syllables produced immediately after the midpoint of each trial.

Outcomes & Results: On average, AAF reduced stuttering by approximately 68% relative to the NAF condition. Stuttering frequencies on the initial syllables were considerably higher than on the other syllables analysed (0.45 and 0.34 for NAF and AAF conditions, respectively). After the first syllable was produced, stuttering frequencies dropped precipitously and remained stable. However, this drop in stuttering frequency was significantly greater (approximately 84%) in the AAF conditions than in the NAF condition (approximately 66%) with frequencies on the last nine syllables analysed averaging 0.15 and 0.05 for NAF and AAF conditions, respectively. In the true choral speech condition, stuttering was virtually (approximately 98%) eliminated across all utterances and all syllable positions.

Conclusions & Implications: Altered auditory feedback effectively inhibits stuttering immediately after speech has been initiated. However, unlike a true choral signal, which is exogenously initiated and offers the most complete fluency enhancement, AAF requires speech to be initiated by the user and ‘fed back’ before it can directly inhibit stuttering. It is suggested that AAF can be a viable clinical option for those who stutter and should often be used in combination with therapeutic techniques, particularly those that aid speech initiation. The substantially higher rate of stuttering occurring on initiation supports a hypothesis that overt stuttering events help ‘release’ and ‘inhibit’ central stuttering blocks. This perspective is examined in the context of internal models and mirror neurons.
The barriers perceived to prevent the successful implementation of evidence‐based practice by speech and language therapists
Authors: O'Connor Siobhan , Pettigrew Catharine M.
Published: March 2009

Background: There is currently a paucity of research investigating what speech and language therapists, in particular, perceive are the greatest barriers to implementing evidence‐based practice.

Aims: The purpose of this study was to investigate the perceived barriers that are faced by speech and language therapists in southern Ireland when attempting to implement evidence‐based practice.

Methods & Procedures: A 34‐item questionnaire was sent to 39 therapists working in several counties in southern Ireland. The survey received an 82.1% (n = 32) response rate.

Outcomes & Results: The results of the study indicated that certain barriers are perceived to prevent evidence‐based practice being implemented successfully. The most significant barrier affecting evidence‐based practice implementation was reported to be a lack of time to read research (71.9%). Additional barriers that were found to be the most significant were the research having methodological inadequacies (62.5%) and insufficient time to implement new ideas (59.4%). Other important factors identified as being significant barriers to the implementation of evidence‐based practice were those associated with the quality and presentation of the research, workplace setting, and lack of skills of the therapist. Associations between specific barriers and workplace setting or grade were also investigated. Some possible reasons for these barriers and the implications for clinical practice are also discussed.

Conclusions & Implications: This small study suggests that therapists agreed that evidence‐based practice is essential to the practice of speech and language therapy. There are, however, barriers in place that are perceived to prevent its successful implementation. It is hoped that because these barriers have been identified, individual clinicians and organizations can be proactive in aiming to provide an evidence‐based service to their clients.
Functional asymmetry in a simple coincidence‐anticipation task: Effects of handedness
Authors: Rodrigues Paula Cristina , Vasconcelos Olga , Barreiros João , Barbosa Ricardo , Trifilio Fábio
Published: March 2009

Right‐ and left‐handed performance presents different degrees of manual functional asymmetry, because left‐handers usually present lower asymmetry in several tasks. Thus, we asked 27 right‐handed and 33 left‐handed male and female adolescents to perform a coincidence‐anticipation task. Absolute, constant, and variable errors were calculated for each participant, for the preferred and non‐preferred hand, as well as the performance asymmetry index. Results demonstrated that: (i) right‐ and left‐handers performed to a similar level; (ii) both right‐ and left‐handers were less variable when using their left hand; (iii) males were more accurate and less variable than their female counterparts. Although handedness failed to show a significant effect, our results demonstrate that both performing hand and gender have an influence on coincidence timing ability. The gender‐related effect lends support to the idea that differences exist in the neural mechanisms of visuospatial processing between the sexes, and the performing hand‐related effect is supposed to reflect the right hemisphere advantage in movement planning.
A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
Authors: Lu Albert , Tebar Francesc , Alvarez-Moya Blanca , López-Alcalá Cristina , Calvo Maria , Enrich Carlos , Agell Neus , Nakamura Takeshi , Matsuda Michiyuki , Bachs Oriol
Published: March 2009

Ras proteins are small guanosine triphosphatases involved in the regulation of important cellular functions such as proliferation, differentiation, and apoptosis. Understanding the intracellular trafficking of Ras proteins is crucial to identify novel Ras signaling platforms. In this study, we report that epidermal growth factor triggers Kirsten Ras (KRas) translocation onto endosomal membranes (independently of calmodulin and protein kinase C phosphorylation) through a clathrin-dependent pathway. From early endosomes, KRas but not Harvey Ras or neuroblastoma Ras is sorted and transported to late endosomes (LEs) and lysosomes. Using yellow fluorescent protein–Raf1 and the Raichu-KRas probe, we identified for the first time in vivo–active KRas on Rab7 LEs, eliciting a signal output through Raf1. On these LEs, we also identified the p14–MP1 scaffolding complex and activated extracellular signal-regulated kinase 1/2. Abrogation of lysosomal function leads to a sustained late endosomal mitogen-activated protein kinase signal output. Altogether, this study reveals novel aspects about KRas intracellular trafficking and signaling, shedding new light on the mechanisms controlling Ras regulation in the cell.
TopBP1 and DNA polymerase-α directly recruit the 9-1-1 complex to stalled DNA replication forks
Authors: Yan Shan , Michael W. Matthew
Published: March 2009

TopBP1 and the Rad9–Rad1–Hus1 (9-1-1) complex activate the ataxia telangiectasia mutated and Rad3-related (ATR) protein kinase at stalled replication forks. ATR is recruited to stalled forks through its binding partner, ATR-interacting protein (ATRIP); however, it is unclear how TopBP1 and 9-1-1 are recruited so that they may join ATR–ATRIP and initiate signaling. In this study, we use Xenopus laevis egg extracts to determine the requirements for 9-1-1 loading. We show that TopBP1 is required for the recruitment of both 9-1-1 and DNA polymerase (pol)-α to sites of replication stress. Furthermore, we show that pol-α is also directly required for Rad9 loading. Our study identifies an assembly pathway, which is controlled by TopBP1 and includes pol-α, that mediates the loading of the 9-1-1 complex onto stalled replication forks. These findings clarify early events in the assembly of checkpoint signaling complexes on DNA and identify TopBP1 as a critical sensor of replication stress.
Gaussian process regression bootstrapping: exploring the effects of uncertainty in time course data
Authors: Kirk Paul D. W. , Stumpf Michael P. H.
Published: March 2009

Motivation: Although widely accepted that high-throughput biological data are typically highly noisy, the effects that this uncertainty has upon the conclusions we draw from these data are often overlooked. However, in order to assign any degree of confidence to our conclusions, we must quantify these effects. Bootstrap resampling is one method by which this may be achieved. Here, we present a parametric bootstrapping approach for time-course data, in which Gaussian process regression (GPR) is used to fit a probabilistic model from which replicates may then be drawn. This approach implicitly allows the time dependence of the data to be taken into account, and is applicable to a wide range of problems.

Results: We apply GPR bootstrapping to two datasets from the literature. In the first example, we show how the approach may be used to investigate the effects of data uncertainty upon the estimation of parameters in an ordinary differential equations (ODE) model of a cell signalling pathway. Although we find that the parameter estimates inferred from the original dataset are relatively robust to data uncertainty, we also identify a distinct second set of estimates. In the second example, we use our method to show that the topology of networks constructed from time-course gene expression data appears to be sensitive to data uncertainty, although there may be individual edges in the network that are robust in light of present data.

Availability: Matlab code for performing GPR bootstrapping is available from our web site: http://www3.imperial.ac.uk/theoreticalsystemsbiology/data-software/

Contact:  paul.kirk@imperial.ac.uk, m.stumpf@imperial.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
A method and program for estimating graphical models for linkage disequilibrium that scale linearly with the number of loci, and their application to gene drop simulation
Authors: Thomas Alun
Published: March 2009

Motivation: Efficient models for genetic linkage disequilibrium (LD) are needed to enable appropriate statistical analysis of the dense, genome-wide single nucleotide polymorphism assays currently available.

Results: Estimation of graphical models for LD within a restricted class of decomposable models is shown to be possible using computer time and storage that scale linearly with the number of loci. Programs for estimation and for simulating from these models on a whole-genome basis are described and provided.

Availability: Java classes and source code for IntervalLD and GeneDrops are freely available over the internet at http://bioinformatics.med.utah.edu/∼alun.

Contact:  alun@genepi.med.utah.edu
A concanavalin A-like lectin domain in the CHS1/LYST protein, shared by members of the BEACH family
Authors: Burgess Agathe , Mornon Jean-Paul , de Saint-Basile Geneviève , Callebaut Isabelle
Published: March 2009

CHS1/LYST, the causative protein of the Chediak–Higashi syndrome (CHS), belongs to the BEACH (named after BEige And Chediak–Higashi) family, which includes various large proteins sharing the same C-terminal domain architecture [a PH (Pleckstrin homology)–BEACH domain followed by WD repeats). Members of the BEACH family are generally defined as vesicle-trafficking regulatory proteins, but their functions remain to be determined at the molecular level.

Here, using a panel of sensitive methods of sequence analysis, we show that the N-terminal regions of BEACH proteins contain an as yet not described domain, which shares striking similarities with clostridial neurotoxins and defines a novel family within the concanavalin A (ConA)-like lectin superfamily. These results suggest that the BEACH ConA-like lectin domain could be involved in oligosaccharide binding associated with protein traffic and sorting along the secretory pathway, especially in relation with components of the vesicle fusion machinery.

Contact:  isabelle.callebaut@impmc.jussieu.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Clinical efficacies of topical agents for the treatment of seborrheic dermatitis of the scalp: A comparative study
Authors: SHIN Hyoseung , KWON Oh Sang , WON Chong Hyun , KIM Beom Joon , LEE Yang Won , CHOE Yong Beom , AHN Kyu Joong , EUN Hee Chul
Published: March 2009

Previous studies have shown that topical steroid and shampoo containing zinc pyrithione provide clinical benefits for treatment of scalp seborrheic dermatitis. But the clinical efficacy of topical tacrolimus, a newly developed calcineurin inhibitor on seborrheic dermatitis, is not well investigated yet. We wanted to compare the clinical efficacy of topical tacrolimus with that of conventional treatment (zinc pyrithione shampoo and topical betamethasone) for treatment of seborrheic dermatitis of the scalp. Patients with seborrheic dermatitis of the scalp were randomly allocated to receive topical betamethasone, topical tacrolimus or zinc pyrithione shampoo. Some patients were instructed to continue the treatments for 8 weeks and the others to discontinue the treatments at week 4. We evaluated the efficacy using a clinical severity score, dandruff score and sebum secretion at baseline, week 4 and week 8. All treatment groups showed significant improvements in clinical assessment after 4 weeks. While the patients treated by zinc pyrithione improved continuously even after cessation of the treatment, the patients treated by betamethasone lotion or tacrolimus ointment were aggravated clinically. Topical tacrolimus was as effective as topical betamethasone, and showed more prolonged remission than topical betamethasone. To treat seborrheic dermatitis of the scalp, we think that the combination therapy of topical steroid or topical tacrolimus, and zinc pyrithione is recommended.
Candidate genes for cannabis use disorders: findings, challenges and directions
Authors: Agrawal Arpana , Lynskey Michael T.
Published: March 2009

Aim Twin studies have shown that cannabis use disorders (abuse/dependence) are highly heritable. This review aims to: (i) review existing linkage studies of cannabis use disorders and (ii) review gene association studies, to identify potential candidate genes, including those that have been tested for composite substance use disorders and (iii) to highlight challenges in the genomic study of cannabis use disorders.

Methods Peer‐reviewed linkage and candidate gene association studies are reviewed.

Results Four linkage studies are reviewed: results from these have homed in on regions on chromosomes 1, 3, 4, 9, 14, 17 and 18, which harbor candidates of predicted biological relevance, such as monoglyceride lipase (MGLL) on chromosome 3, but also novel genes, includingELTD1[epidermal growth factor (EGF), latrophilin and seven transmembrane domain containing 1] on chromosome 1. Gene association studies are presented for (a) genes posited to have specific influences on cannabis use disorders:CNR1,CB2,FAAH,MGLL,TRPV1andGPR55and (b) genes from various neurotransmitter systems that are likely to exert a non‐specific influence on risk of cannabis use disorders, e.g.GABRA2,DRD2andOPRM1.

Conclusions There are challenges associated with (i) understanding biological complexity underlying cannabis use disorders (including the need to study gene–gene and gene–environment interactions), (ii) using diagnostic versus quantitative phenotypes, (iii) delineating which stage of cannabis involvement (e.g. use versus misuse) genes influence and (iv) problems of sample ascertainment.
Influence of experimental warming and shading on host–parasitoid synchrony
Authors: KLAPWIJK MAARTJE J. , GRÖBLER B. CHRIS , WARD KIMBERLEY , WHEELER DAVID , LEWIS OWEN T.
Published: March 2009

As the climate warms, many species are showing altered phenology patterns, potentially disrupting synchrony between interacting species. Recent studies have documented disrupted synchrony in plant–herbivore and predator–prey interactions. However, studies investigating climate‐related asynchrony in host–parasitoid interactions and exploring the relative responses of interacting hosts and parasitoids to climate change are lacking. This is an important gap in knowledge given the ubiquity of insect parasitoids and their importance in influencing the abundance and dynamics of their hosts. In the threatened marsh fritillary butterflyEuphydryas aurinia(Lepidoptera: Nymphalidae) and its specialized parasitoid,Cotesia bignellii(Hymenoptera: Braconidae) phenological synchrony (and consequently population fluctuations) are thought to be weather‐dependent. To assess the likely influence of climate and microenvironment change on synchrony betweenE. auriniaandC. bignellii, we experimentally manipulated the exposure of sensitive‐stage host larvae and parasitoid pupae to temperature (ambient or elevated) and shading (shaded or unshaded) regimes. We also analysed a 20‐year population dynamic dataset from the United Kingdom forE. auriniato investigate whether population variations could be explained by interannual variations in the thermal and sunshine environment. Development times were affected significantly by the experimental temperature and shading treatments forE. auriniabut not forC. bignellii. However, the contrasting responses were insufficient to significantly affect host availability for parasitoids. In the field, thermal and sunshine conditions did not influence population fluctuations, and population variations across a large (UK‐wide) scale were uncorrelated. Changes to the thermal and sunshine environment of the magnitude investigated in our experiment and within the range experienced by wildE. auriniapopulations over the last 20‐years thus seem unlikely to cause breakdown in host–parasitoid synchrony. We suggest that experiments investigating the mechanistic responses of interacting species to environmental change are needed to support the analysis and interpretation of observational data on species' phenology.
Physiological responses and statistical models of the environmental niche: a comparative study of two co‐occurring Eucalyptus species
Authors: Austin Michael P. , Smith Thomas M. , Van Niel Kimberley P. , Wellington A. Bruce.
Published: March 2009

Our objectives were as follows: (i) to quantify the realized environmental niche of two co‐occurring species and their differences and (ii) to examine whether differences in the species niches relate to differences in water and light use efficiency and growth responses to light and water.

Statistical models of the environmental niches of two Eucalyptus species were derived from presence/absence records and from environmental variables (mean annual temperature, mean summer rainfall, mean summer daily radiation) and three factors (topographic position, lithology and a nutrient index) for 10 577 plots from south‐eastern New South Wales, Australia. Generalized additive models (GAM) were fitted in a backwards stepwise procedure using Aikake's Information Criterion (AIC) for model selection.

Seedlings were used in two experiments: (i) a water supply gradient with 20 treatments from 10 mL per day to 1000 mL per day and (ii) a light gradient with five treatments from 3% to 100% (full) sunlight.

After controlling for lithology and nutrients, the principal differences in niche between species were as follows: (i) Eucalyptus mannifera was insensitive to mean summer daily radiation, (ii) it had a higher probability of occurrence in gullies and (iii) the two species differed in response shape and breadth of response to temperature, and temperature of maximum occurrence. Both species had a similar response to mean summer rainfall.

Eucalyptus mannifera showed a monotonic increase in total biomass along the water supply gradient, consistently outperforming Eucalyptus dives, which showed little further increase above 440 mL per day. Consistent differences between species were found for leaf area, specific leaf area and allocation to leaves and stems.

Diurnal measurements of conductance, transpiration, carbon dioxide assimilation and water use efficiency (WUE) showed differences between species along both the water and light gradients. Eucalyptus dives exhibits conservative responses to increasing resources and relatively higher WUE while E. mannifera has lower WUE.

Synthesis. Species differences in ecophysiological strategies are consistent with their co‐occurrence and with their realized environmental niche responses except for their temperature responses. The combination of statistical niche models and ecophysiological gradient experiments focuses attention on important unresolved environmental processes controlling distributions.
Geographical distribution of cryptic genetic types in the planktonic foraminifer Globigerinoides ruber
Authors: AURAHS RALF , GRIMM GUIDO W. , HEMLEBEN VERA , HEMLEBEN CHRISTOPH , KUCERA MICHAL
Published: March 2009

We present SSU rDNA data resolving the seasonal and geographical distribution of ‘cryptic’ genetic types of the planktonic foraminifer morphospecies Globigerinoides ruber in the eastern Atlantic Ocean and the Mediterranean Sea. Analysis of 262 sequences revealed the presence of five genetic types belonging to two distinct lineages. Although the morphospecies G. ruber occurs throughout the investigated region, its constituent ‘cryptic’ genetic types show a pattern of widespread exclusion, which is difficult to reconcile with the concept of ubiquitous dispersal. One of the newly discovered genetic types was exclusively found at stations in the Mediterranean Sea, possibly representing the smallest‐scale example of endemism known in planktonic foraminifera. In general, our results suggest that the geographical scale of mutual exclusion between the genotypes is negatively correlated with their phylogenetic relatedness: the most similar and most recently diverged pair of siblings showed the strongest evidence for small‐scale competitive exclusion. This pattern is consistent with the concept of niche partitioning, implying decreasing level of competition between genetic types with increasing degree of genetic divergence.