bluuebunny/crossref_metadata_2025 huggingface dataset:
Two phases of palmitate-induced insulin resistance in skeletal muscle: impaired GLUT4 translocation is followed by a reduced GLUT4 intrinsic activity
Authors: Alkhateeb Hakam , Chabowski Adrian , Glatz Jan F. C. , Luiken Joost F. P. , Bonen Arend
Published: June 2007

We examined, in soleus muscle, the effects of prolonged palmitate exposure (0, 6, 12, 18 h) on insulin-stimulated glucose transport, intramuscular lipid accumulation and oxidation, activation of selected insulin-signaling proteins, and the insulin-stimulated translocation of GLUT4. Insulin-stimulated glucose transport was progressively reduced after 6 h (−33%), 12 h (−66%), and 18 h (−89%) of palmitate exposure. These decrements were closely associated with concurrent reductions in palmitate oxidation at 6 h (−40%), 12 h (−60%), and 18 h (−67%). In contrast, intramuscular ceramide (+24%) and diacylglycerol (+32%) concentrations, insulin-stimulated AS160 (−36%) and PRAS40 (−33%) phosphorylations, and Akt (−40%), PKCθ (−50%), and GLUT4 translocation (−40%) to the plasma membrane were all maximally altered within the first 6 h of palmitate treatment. No further changes were observed in any of these parameters after 12 and 18 h of palmitate exposure. Thus, the intrinsic activity of GLUT4 was markedly reduced after 12 and 18 h of palmitate treatment. During this reduced GLUT4 intrinsic activity phase at 12 and 18 h, the reduction in glucose transport was twofold greater compared with the early phase (≤6 h), when only GLUT4 translocation was impaired. Our study indicates that palmitate-induced insulin resistance is provoked by two distinct mechanisms: 1) an early phase (≤6 h), during which lipid-mediated impairments in insulin signaling and GLUT4 translocation reduce insulin-stimulated glucose transport, followed by 2) a later phase (12 and 18 h), during which the intrinsic activity of GLUT4 is markedly reduced independently of any further alterations in intramuscular lipid accumulation, insulin signaling and GLUT4 translocation.
Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake
Authors: Wang ChuanFeng , Bomberg Eric , Levine Allen , Billington Charles , Kotz Catherine M.
Published: June 2007

Recent studies show that brain-derived neurotrophic factor (BDNF) decreases feeding and body weight after peripheral and ventricular administration. BDNF mRNA and protein, and its receptor TrkB, are widely distributed in the hypothalamus and other brain regions. However, there are few reports on specific brain sites of actions for BDNF. We evaluated the effect of BDNF, given into the ventromedial nucleus of the hypothalamus (VMH), on normal and deprivation- and neuropeptide Y (NPY)-induced feeding behavior and body weight. BDNF injected unilaterally or bilaterally into the VMH of food-deprived and nondeprived rats significantly decreased feeding and body weight gain within the 0- to 24-h and the 24- to 48-h postinjection intervals. Doses effectively producing inhibition of feeding behavior did not establish a conditioned taste aversion. BDNF-induced feeding inhibition was attenuated by pretreatment of the TrkB-Fc fusion protein that blocks binding between BDNF and its receptor TrkB. VMH-injected BDNF significantly decreased VMH NPY-induced feeding at 1, 2, and 4 h after injection. In summary, BDNF in the VMH significantly decreases food intake and body weight gain, by TrkB receptor-mediated actions. Furthermore, the anorectic effects of BDNF in this site appear to be mediated by NPY. These data suggest that the VMH is an important site of action for BDNF in its effects on energy metabolism.
Dopamine Induces a Slow Afterdepolarization in Lateral Amygdala Neurons
Authors: Yamamoto Ryo , Ueta Yoshifumi , Kato Nobuo
Published: June 2007

The amygdala and dopaminergic innervation thereunto are considered to cooperatively regulate emotional states and behaviors. The present experiments examined effects of dopamine on lateral amygdala (LA) neuron excitability by whole cell recordings. Bath application of dopamine induced slow afterdepolarization (sADP). This sADP lasted for >5 s, and its magnitude varied in a concentration-dependent manner. Co-application of the D1 receptor antagonist SKF83566 reduced its amplitude. The D1 receptor agonist SKF38393 , applied alone, induced sADP of a smaller amplitude. Induction of the full sADP required 5-HT2 and noradrenalin α1 receptor activation as well. D2 receptor activation or blockade did not affect sADP induction. The calcium channel blocker cadmium or intracellular calcium chelator bis-( o-aminophenoxy)- N, N, N′, N′ tetraacetic acid (BAPTA) blocked induction of the sADP, which was suggested to be triggered by calcium influx. Under voltage clamp, membrane conductance decreased at the peak of sADP current ( IsADP). IsADP was suppressed by cesium included in pipettes. The I-V curve of the net IsADP was shifted as the external concentration of potassium was raised, and the reversal potential was identical to that of potassium, suggesting that dopamine decreases potassium conductance to induce the sADP. The present sADP may serve as a positive-feedback regulator of excitability in LA neurons.
Multidigit Control of Contact Forces During Transport of Handheld Objects
Authors: Winges Sara A. , Soechting John F. , Flanders Martha
Published: June 2007

When an object is lifted vertically, the normal force increases and decreases in tandem with tangential (load) force to safely avoid slips. For horizontal object transport, horizontal forces at the contact surfaces can be decomposed into manipulation forces (producing acceleration/deceleration) and grasping forces. Although the grasping forces must satisfy equilibrium constraints, it is not clear what determines their modulation across time, nor the extent to which they result from active muscle contraction or mechanical interactions of the digits with the moving object. Grasping force was found to increase in an experimental condition where the center of mass was below the contact plane, compared with when it was in the contact plane. This increase may be aimed at stabilizing object orientation during translation. In another experimental condition, more complex moments were introduced by allowing the low center of mass to swing around a pivot point. Electromyographic (EMG) activity recorded from several intrinsic and extrinsic hand muscles failed to reveal active feedback regulation of contact force in this situation. Instead, in all experimental conditions, EMG data revealed a strategy of feedforward stiffness modulation. Multiple regression analysis revealed that muscle activity at remote digits (e.g., the index and ring fingers) was highly correlated with the contact force measured at another digit (e.g., the thumb). The data suggest that to maintain grasp stability during horizontal translation, predictable as well as somewhat unpredictable inertial forces are compensated for by controlling the stiffness of the hand through cocontraction and modulation of hand muscle activity.
Identification of the circadian transcriptome in adult mouse skeletal muscle
Authors: McCarthy John J. , Andrews Jessica L. , McDearmon Erin L. , Campbell Kenneth S. , Barber Brigham K. , Miller Brooke H. , Walker John R. , Hogenesch John B. , Takahashi Joseph S. , Esser Karyn A.
Published: June 2007

Circadian rhythms are approximate 24-h behavioral and physiological cycles that function to prepare an organism for daily environmental changes. The basic clock mechanism is a network of transcriptional-translational feedback loops that drive rhythmic expression of genes over a 24-h period. The objectives of this study were to identify transcripts with a circadian pattern of expression in adult skeletal muscle and to determine the effect of the Clock mutation on gene expression. Expression profiling on muscle samples collected every 4 h for 48 h was performed. Using COSOPT, we identified a total of 215 transcripts as having a circadian pattern of expression. Real-time PCR results verified the circadian expression of the core clock genes, Bmal1, Per2, and Cry2. Annotation revealed cycling genes were involved in a range of biological processes including transcription, lipid metabolism, protein degradation, ion transport, and vesicular trafficking. The tissue specificity of the skeletal muscle circadian transcriptome was highlighted by the presence of known muscle-specific genes such as Myod1, Ucp3, Atrogin1 ( Fbxo32), and Myh1 (myosin heavy chain IIX). Expression profiling was also performed on muscle from the Clock mutant mouse and sarcomeric genes such as actin and titin, and many mitochondrial genes were significantly downregulated in the muscle of Clock mutant mice. Defining the circadian transcriptome in adult skeletal muscle and identifying the significant alterations in gene expression that occur in muscle of the Clock mutant mouse provide the basis for understanding the role of circadian rhythms in the daily maintenance of skeletal muscle.
Diplomatic Cultures: Comparing Russia and the West in Terms of a 'Modern Model of Diplomacy'
Authors: Zonova Tatiana
Published: June 2007

Diplomacy is an international institution, although national and regional diplomatic services keep their own intrinsic identity. Existing differences occasionally interfere with mutual understanding as an essential requirement for overcoming today's instability. Comparative analysis of Western and Russian diplomacy enables deeper insight into some essential reasons for existing differences. The modern model of diplomacy was formed because of the Renaissance, which was characterized by a process of secularization. In Russia this process was delayed by the Byzantine tradition of 'symphony'. From Tsar Peter's era, however, a gradual rapprochement can be observed between the two systems of diplomacy — Western and Russian. However, within new parameters, the ghost of Byzantium appeared now and again. Even under Soviet-imposed atheism, diplomacy was viewed as a tool for a new Messianic universalism (as it was in pre-Petrine times), expressed in terms of 'proletarian internationalism'. New and dramatic events placed an urgent need for a qualitatively new type of diplomacy on the agenda: the European experience, with its emphasis on a solid juridical basis, rationalism and human rights; and the Russian experience, with its universalism that is attentive to existential problems and traditional values. Diplomacy of the future should be based on a synthesis of both European and Russian historical experiences.
Security through Disarmament: The Story of the Weapons of Mass Destruction Commission
Authors: Rydell Randy
Published: June 2007

The world has been trying to eliminate weapons of mass destruction (WMD) — nuclear, biological and chemical arms — for over half a century. Yet many such weapons remain, and progress in nuclear disarmament has been especially disappointing. The chronic failure to achieve agreed WMD disarmament mandates has prompted the creation of several independent international commissions to find some solutions. The WMD Commission created by Sweden in late 2003 was the latest such venture, and its 2006 report has received international acclaim. Chaired by Hans Blix, the Commission covered disarmament, non-proliferation and counter-terrorism issues, and did so from a variety of policy dimensions, from unilateral action through fully multilateral cooperation. Written by a member of the Commission's secretariat staff, this article tells the story of the Commission: how it conducted its work, what it proposed and what impacts it has had — and may yet have — in revitalizing WMD disarmament efforts.
Patterned Fluidities: (Re)Imagining the Relationship between Gender and Sexuality
Authors: Richardson Diane
Published: June 2007

This ar ticle examines the question of how the relationship between gender and sexuality has been theorized. Five strands of argument, which draw on different epistemological concerns, are identified.These have structured the study of gender and sexuality, providing a contested understanding of both the meaning of these categories and their relationship. A challenge for future work is to elaborate frameworks that allow more complex analyses of the dynamic, historically and socially specific relationship between sexuality and gender, as well as the gendered and sexualized nature of their interconnections. To achieve this we need to consider the question of the relationship of gender and sexuality at a number of levels of social analysis.These issues are explored by drawing on three areas of research: on transsexuality/transgender, homosexuality and heterosexuality. Finally, a new metaphor for (re)imagining how we think about the interconnections between gender and sexuality is proposed.
Methadone Maintenance Treatment and Making Up People
Authors: valentine kylie
Published: June 2007

This ar ticle considers the operations of methadone maintenance treatment through the use of concepts proposed by actor-network theor y and historical ontology. The former provokes a concern with the co-constitution of treatment regimes by various actors, including non-human actants.The latter provokes a concern with the creation of new identities. Analysis of methadone often examines treatment as a nether world, and clients as neither addicted nor autonomous.The analysis under taken here instead emphasizes what is produced in methadone maintenance treatment, rather than the inexactness of existing categories. It considers four identities produced through methadone treatment: the dissatisfied customer ; the stable user ; the individual in need of guidance; and the lay carer. This analysis enables a study of what and who is produced through treatment in terms that problematize simple distinctions between good and bad, addicted and independent, stable and chaotic.
Bureaucratic Effects: `Weberian' State Agencies and Poverty Reduction
Authors: Henderson Jeffrey , Hulme David , Jalilian Hossein , Phillips Richard
Published: June 2007

Evans and Rauch (1999) have demonstrated that there is a strong relationship between the `Weberianness' of a national state's bureaucratic capacities and its record on economic growth. Using their data set and the best available data sets on the incidence of income poverty, this article investigates whether there is a relationship between a Weberian notion of effective bureaucratic capacities and the state's ability to reduce poverty. Using the same time frame as Evans and Rauch (1970—90) and analysing data for 29 developing and middle income countries, the article concludes that, in general, there does indeed seem to be a relationship between states with effective `Weberian' public institutions and their ability to reduce poverty.
Epistemological Bricolage: How Practitioners Make Sense of Learning
Authors: Freeman Richard
Published: June 2007

How do policy makers come to know what they know? How do they think of learning? And how does that inform what they do? In this qualitative, empirical study, public health officials variously display scientific, institutional, and more socially situated epistemological strategies or rationalities. In turn, the study reveals that a key element of what they do is “piecing together,” assembling and literally making sense of different bits of information and experience, often creating something new from what they have acquired secondhand. It shows how much policy making is knowledge work, and how learning might be thought of as a process of epistemological bricolage.
Representative Bureaucracy, Ethnicity, and Public Schools
Authors: Pitts David W.
Published: June 2007

Demographic changes in the United States have led to challenges for public organizations that are tasked to serve shifting target populations. Many arguments exist for including greater numbers of ethnic minorities among an organization's personnel, under the guise that greater ethnic representation will result in greater competitiveness in the market or effectiveness in governance. This article tests this proposition empirically, using data from the public education policy setting. Results show that representativeness along ethnic lines leads to gains for the organization as a whole, but some segments of the target population appear to respond more positively to representativeness than others.
Affective Synchrony: Individual Differences in Mixed Emotions
Authors: Rafaeli Eshkol , Rogers Gregory M. , Revelle William
Published: June 2007

Most models of affect suggest either inverse or null associations between positivity and negativity. Recent work has highlighted situations that sometimes lead to mixed positive-negative affect. Focusing on the counterpart to these situational factors, the authors explore the individual-difference tendency toward mixed emotions, which they term affective synchrony . In five studies, the authors show that some individuals demonstrate affective synchrony (overlapping experience of positive and negative moods), others a-synchrony (positive and negative mood that fluctuate independently), and still others de-synchrony (positive and negative moods that function as bipolar opposites). These tendencies are stable over time within persons, vary broadly across individuals, and are associated with individual differences in cognitive representation of self and of emotions.
Through the Eyes of Hunter-Gatherers: participatory 3D modelling among Ogiek indigenous peoples in Kenya
Authors: Rambaldi Giacomo , Muchemi Julius , Crawhall Nigel , Monaci Laura
Published: June 2007

Describes a participatory process by which Ogiek indigenous people in the Mau Forest Complex in Kenya rendered their spatial memories through the making of a georeferenced three dimensional model covering part of their ancestral territory. The paper focuses on the course of action and related human dynamics which led to the production of the map legend via deep reflections and intense negotiations among elders of different clans. The 3D mapmaking process proved to be a catalyst in stimulating memory, articulating tacit knowledge and creating visible and tangible representations of the physical, biological and cultural landscapes of the area in the 1920s. Elaborating and negotiating agreement on the elements of the map legend allowed the participants to gain greater clarity on meanings and relationships between natural and cultural features. Once completed, the model selectively displayed both the tangible and the intangible heritage of the Ogiek people. The composition of the legend and the making of the model stimulated collegial learning and community cohesion. The process has been perceived as a milestone for Ogiek clans in terms of working together towards a common goal, and in realizing the value and potential authority of their spatial knowledge once it was collated, georeferenced, documented and visualized.
Generating Plausible Crop Distribution Maps for Sub-Saharan Africa Using a Spatial Allocation Model
Authors: You Liangzhi , Wood Stanley , Wood-Sichra Ulrike , Chamberlin Jordan
Published: June 2007

Agricultural production statistics are fundamental parameters for agriculture policy research. Information on acreage and yields of important crops is critical for understanding trends within what is the most important economic sector of many developing countries. Sub-national data — i.e. data organized by administrative units such as regions or districts — enable the analysis of patterns within countries that may highlight important policy issues, such as the need to allocate resources to underproductive areas. However, collecting sub-national data is difficult for developing countries with limited resources. Even with great effort, and often only on broad regional scales, enormous data gaps exist and are unlikely to be filled. As a result, information is often only available at national or very broad sub-national levels (such as provinces). Such geographically coarse data are unable to reflect important variations within countries and are insufficient for the spatial analysis of production patterns and trends. To fill these spatial data gaps we developed a model to disaggregate production data from coarser to finer spatial units. Using a cross-entropy approach, our spatial allocation model attempts to make plausible allocations of crop production from large reporting units such as a country or state, into smaller spatial units organized as cells of a regularly-spaced grid. In addition to more detailed information, the organization of production information in geographic grids allows for greater analytical possibilities through geographic information systems. The allocation model works on the basis of available evidence of mapped indicators of agricultural production, which include farming systems, land cover, crop biophysical suitability surfaces, commodity prices and local market access. This article describes the generation of crop distribution maps for Sub-Saharan Africa for the year 2000 using the spatial allocation model and discusses the importance of such maps for development analysis and planning.
Environmental Approaches to Poverty Mapping: an example from Uganda
Authors: Robinson Timothy , Emwanu Thomas , Rogers David
Published: June 2007

To be of real value to governments and development agencies, poverty maps should go beyond describing the distribution of poverty, to help explain and thence predict its spatial distribution. Poverty maps are traditionally produced by exploiting links between extensive census data and intensive socio-economic household survey data; relationships found within the survey data are extended to census data, through variables common to both data sets. Many of the dimensions of poverty are environmentally related; people are poor because they are unhealthy, or underfed, or without access to fuel and water etc. We suggest that a more useful approach to poverty mapping might be first to identify its (environmental) causes. In this analysis, we explore a novel approach that combines household survey data from Uganda with a suite of environmental variables that are either direct measures of key climatic variables (such as temperature), descriptor variables of key ingredients of poverty-generating processes (such as agricultural production systems) or proxies for constraints on the health and well-being of the human populations (such as disease-causing pathogens). This potentially allows us to move beyond description, to explain and then predict the distribution of poverty at the spatial resolution of the predictor variables. Whilst correlation obviously does not automatically imply causation, we suggest an environmental approach to poverty mapping is more likely to reveal causes than the traditional, small area approaches. This paper takes the first steps towards establishing the predictive accuracy of an environmental approach to poverty mapping.
Spatial Information Tools for Land Use Management Networks in Montane Mainland Southeast Asia
Authors: Saipothong Pornwilai , Thomas David
Published: June 2007

This paper describes a participatory watershed management project which uses GIS-based mapping as a basis for dialog and collaboration between local communities and partner institutions in Mae Chaem watershed, northern Thailand. Through the participatory mapping process, local communities were able to document local patterns of resource utilization and changes over time. This allowed outsiders to better understand the context of land use and more clearly see the potential of the area. Output maps from projects such as this are important information resources for communities, local watershed management networks, local governance, and other institutions. Such maps can also provide a basis for dialog in efforts to solve problems and conflicts regarding natural resources management at different scales.
Dietary habits of Welsh 12—13 year olds
Authors: Thomas Non-Eleri , Cooper Stephen-Mark , Graham Mike , Boobier Wyndham , Baker Julien , Davies Bruce
Published: June 2007

This study examined the dietar y habits of Welsh 12—13 year olds. A cohor t of 84 boys and 81 girls, age 12.9 SD 0.3 years; body mass 51.3 SD 12.6kg; and stature 1.54 SD 0.08m, completed a food frequency questionnaire and seven-day food diary. Mean daily kilocalories (kcal/d), and percentages of total fat, saturated fat, carbohydrate, and protein, as well as fibre intake were calculated. The mean daily intake of total fat for this cohor t was 34.7 percent, for saturated fat the value was 13.8 percent. The mean daily intake of carbohydrate and protein were 50.5 and 14.9 percent, respectively. The schoolchildren in this study repor ted a mean daily fibre intake of 12.3g. The absolute intake of kilocalories was significantly greater ( p ≤ 0.05) among boys than girls, but no other significant differences were repor ted. This study revealed that the diets of Welsh 12—13 year olds exceeded recommendations for fat, while at the same time did not meet the recommendations for fibre, and particularly fruit and vegetable intake. Our data indicated that, despite schools offering a range of healthy lunchtime foods, young people continue to consume an energy-dense and nutrient-poor diet, both at school and at home.
Young people's participation in National Curriculum Physical Education: A study of 15—16 year olds in North-West England and North-East Wales
Authors: Smith Andy , Thurston Miranda , Lamb Kevin , Green Ken
Published: June 2007

Drawing on data from a broader study which investigated the place of spor t and physical activity in the lives of 15—16 year olds in England and Wales, this paper examines a relatively neglected dimension of research in physical education, namely, young people's par ticipation in spor t and physical activity through National Curriculum Physical Education (NCPE). The paper repor ts upon data generated by questionnaires completed by 1010 15—16 year olds who attended six secondar y schools in the Nor th-West of England and one secondar y school in the Nor th-East of Wales during 2003 and 2004. The study revealed strong inter-school variations in the mixes of spor ts that pupils experienced within NCPE. More specifically, the findings revealed that NCPE was largely dominated by competitive team-based spor ts that tend to be gender-stereotyped, alongside more individualized and less-competitive physical activities. It was also clear, however, that the repor ted levels and forms of participation in different spor ts and physical activities in NCPE during Years 10 and 11 varied significantly and differentially according to gender, social class, the school which young people attended, specialist spor ts college status and whether youngsters studied GCSE PE. The paper concludes by suggesting that inter-school variations are probably explainable in terms of a combination of traditions, facilities and the enthusiasms and perceptions of PE teachers.
The fabric of Africanity
Authors: Sylvanus Nina
Published: June 2007

This article explores the global circulation of a commodity — African wax-prints, manufactured since the late 19th century in Europe for the West African market and increasingly reproduced today in China — by way of focusing on the idea of the `authentically African'. Exploring the biography of wax fabric, this article seeks to cross-examine what serves as a parameter of authenticity, both in international markets, in which the African signifier appears as a source of the renewal of identity, and in Africa, where wax fabric's integration into local structures of consumption as a status symbol is informed by the principles of simulation and imitation. I suggest that the notion of `Africanity' is a conceptual construction whose validation depends more on the observer's gaze than on the object of that gaze in the context of western consumption practices. I propose that the trajectory of wax-cloth, not only in Africa, but also in international markets, is based on the principle of reproduction and imitation which determines the notion of authenticity.
What is the `process' in cultural process and in processual archaeology?
Authors: Lyman R. Lee
Published: June 2007

The concept of `cultural process' has been of interest to anthropologists since the late 19th century. Franz Boas indicated that investigating cultural processes was central to anthropology, but his failure to define the concept set a disciplinary precedent. Process has seldom been discussed in theoretical detail because the basic notion is commonsensical. A.L. Kroeber provided a definition in 1948 and distinguished between short-term dynamics of how cultures operate and long-term dynamics resulting in cultural change. Leslie White conflated the two families of processes. Archaeologists working before 1960 focused on processes resulting in the diachronic evolution of cultures; many of these involved cultural transmission. Initially, processes involving the synchronic operation of a culture were conflated with diachronic evolutionary processes by processual archaeologists. In the late 1960s and early 1970s, Lewis Binford, David Clarke, and Frank Hole and Robert Heizer all discussed cultural processes within the framework of systems theory. Simultaneously, growing concern over the formational processes that created the archaeological record shifted attention from the original conception of cultural processes. Models of the temporal duration, scale, and magnitude of cultural processes illustrate their complexity and suggest avenues for further conceptualization.
Youth Justice?
Authors: McAra Lesley , McVie Susan
Published: June 2007

This article assesses the effectiveness of the Scottish model of youth justice in the context of a growing body of international research that is challenging the `evidence base' of policy in many western jurisdictions. Drawing on findings from the Edinburgh Study of Youth Transitions and Crime, it shows how labelling processes within agency working cultures serve to recycle certain categories of children into the youth justice system, whereas other serious offenders escape the tutelage of the formal system altogether. The deeper a child penetrates the formal system, the less likely he or she is to desist from offending. The article concludes that the key to reducing offending lies in minimal intervention and maximum diversion. Although the Scottish system should be better placed than most other western systems at delivering such an agenda (owing to its founding commitment to decriminalization and destigmatization), as currently implemented it appears to be failing many young people.
Review Article: Plasticity of Spinal Centers in Spinal Cord Injury Patients: New Concepts for Gait Evaluation and Training
Authors: Scivoletto Giorgio , Ivanenko Yuri , Morganti Barbara , Grasso Renato , Zago Mirka , Lacquaniti Francesco , Ditunno John , Molinari Marco
Published: June 2007

Recent data on spinal cord plasticity after spinal cord injury (SCI) were reviewed to analyze the influence of training on the neurophysiological organization of locomotor spinal circuits in SCI patients. In particular, the authors studied the relationship between central pattern generators (CPGs) and motor neuron pool activation during gait. An analysis of the relations between locomotor recovery and compensatory mechanisms focuses on the hierarchical organization of gait parameters and allows characterizing kinematic parameters that are highly stable during different gait conditions and in recovered gait after SCI. The importance of training characteristics and the use of robotic/automated devices in gait recovery is analyzed and discussed. The role of CPG in defining kinematic gait parameters is summarized, and spatio-temporal maps of EMG activity during gait are used to clarify the role of CPG plasticity in sustaining gait recovery.
The Relationship Between Balance, Disability, and Recovery After Stroke: Predictive Validity of the Brunel Balance Assessment
Authors: Tyson Sarah F. , Hanley Marie , Chillala Jay , Selley Andrea B. , Tallis Raymond C.
Published: June 2007

Objective. To examine the influence of balance disability on function and the recovery of function after stroke and consequently to assess the predictive validity of the Brunel Balance Assessment (BBA). Methods. Cross-sectional study of 102 patients admitted consecutively to 6 National Health Service hospitals with weakness 2 to 4 weeks after their first anterior circulation stroke; 75 of whom completed follow-up assessment at 3 months. The BBA was assessed during admission and compared to the Barthel Index and Rivermead Mobility Index at 3 months. Results. Balance disability was the strongest predictor of function (in terms of activities of daily living [ADLs] and mobility disability) in the acute stages. Weakness was also an independent predictor. Recovery of ADLs was independently predicted by balance disability, weakness, age, and premorbid disability, whereas recovery of mobility disability was predicted by balance and age alone. At 3 months, a minority of people with limited sitting balance (0%-22%) and standing balance (25%-50%) recovered independent functional mobility. Most people who could walk initially recovered independent functional mobility (66%-84%), but 16% suffered a decline in their mobility and 44% had enduring limitations in everyday mobility activities. Conclusion. Initial balance disability is a strong predictor of function and recovery after stroke. These results demonstrate the predictive validity of the BBA.
Ability for Basic Movement as an Early Predictor of Functioning Related to Activities of Daily Living in Stroke Patients
Authors: Hashimoto Keiji , Higuchi Kenji , Nakayama Yasuhide , Abo Masahiro
Published: June 2007

Background. Early functional outcomes for activities of daily living at an early stage after a stroke may enable clinicians to establish treatment-optimal training and goals. The objective of this study was to assess the relationship between the ability to perform basic movements at the bedside, which were measured using a new scale, the Ability for Basic Movement Scale, in the early stage after stroke and functional ability at discharge from the hospital. Methods . A total of 142 stroke patients participated in this prospective study. In addition to the Ability for Basic Movement Scale score, age, limb paresis as measured by the Brunnstrom stage, and functional ability as measured by the Barthel Index were also selected as predictor variables. Results . Pearson correlation coefficient analysis showed that the state of functional ability at discharge had significant positive correlations with total scores of the Ability for Basic Movement Scale and Brunnstrom stage at all stages of data collection. The results of linear stepwise regression analysis indicated that “turn over from supine position,” “remain sitting,” and “sit up” of the Ability for Basic Movement Scale at 10 days after onset, in addition to age at onset of stroke, the baseline Barthel Index, and the baseline Brunnstrom stage, were significant predictors (75.6%) of functional ability at discharge. Conclusions. This study provides evidence for the predictive value of the Ability for Basic Movement Scale with regard to functional ability in stroke patients.
Generation of FGF reporter transgenic zebrafish and their utility in chemical screens
Authors: Molina Gabriela A , Watkins Simon C , Tsang Michael
Published: June 2007

Background

Fibroblast Growth Factors (FGFs) represent a large family of secreted proteins that are required for proper development and physiological processes. Mutations in mouse and zebrafish FGFs result in abnormal embryogenesis and lethality. A key to understanding the precise role for these factors is to determine their spatial and temporal activity during embryogenesis.

Results

Expression of Dual Specificity Phosphatase 6 (dusp6, also known as Mkp3) is controlled by FGF signalling throughout development. The Dusp6 promoter was isolated from zebrafish and used to drive expression of destabilized green fluorescent protein (d2EGFP) in transgenic embryos (Tg(Dusp6:d2EGFP)). Expression of d2EGFP is initiated as early as 4 hours post-fertilization (hpf) within the future dorsal region of the embryo, where fgf3 and fgf8 are initially expressed. At later stages, d2EGFP is detected within structures that correlate with the expression of Fgf ligands and their receptors. This includes the mid-hindbrain boundary (MHB), pharyngeal endoderm, otic vesicle, hindbrain, and Kupffer's vesicle. The expression of d2EGFP is under the control of FGF signalling as treatment with FGF Receptor (FGFR) inhibitors results in the suppression of d2EGFP expression. In a pilot screen of commercially available small molecules we have evaluated the effectiveness of the transgenic lines to identify specific FGF inhibitors within the class of indolinones. These compounds were counter screened with the transgenic line Tg(Fli1:EGFP)

y1, that serves as an indirect read-out for Vascular Endothelial Growth Factor (VEGF) signalling in order to determine the specificity between related receptor tyrosine kinases (RTKs). From these assays it is possible to determine the specificity of these indolinones towards specific RTK signalling pathways. This has enabled the identification of compounds that can block specifically the VEGFR or the FGFR signalling pathway.

Conclusion

The generation of transgenic reporter zebrafish lines has allowed direct visualization of FGF signalling within the developing embryo. These FGF reporter transgenic lines provide a tool to screen for specific compounds that can distinguish between two conserved members of the RTK family.
Uptake and metabolism of ciclesonide and retention of desisobutyryl-ciclesonide for up to 24 hours in rabbit nasal mucosa
Authors: Sato Hideyuki , Nave Ruediger , Nonaka Takashi , Yoshihisa Nishibe , Atsuhiro Nagano , Mochizuki Tsutomu , Takahama Shigehiro , Kondo Shiro , Wingertzahn Mark
Published: June 2007

Background

The nasal tissue uptake and metabolism of ciclesonide, a new-generation corticosteroid under investigation for treatment of allergic rhinitis, to its active metabolite, desisobutyryl-ciclesonide (des-CIC), was evaluated when administered to rabbits in a hypotonic versus an isotonic ciclesonide suspension. Nasal mucosa extracts from normal Japanese white rabbits were evaluated by high-performance liquid chromatography with tandem mass spectrometry detection after a single 143-μg dose of ciclesonide. Retention and formation of fatty acid conjugates of des-CIC were also measured in nasal mucosa extracts postadministration of a hypotonic ciclesonide suspension (143-μg single dose).

Results

Versus an isotonic suspension, the hypotonic suspension achieved higher concentrations of des-CIC (5.6-fold, 11.4-fold, and 13.4-fold; p < 0.05 for all) and ciclesonide (25.3-fold, 34.2-fold [p = not significant], and 16-fold [p < 0.05]) at 30, 120, and 240 min postadministration. Additionally, when administered via a hypotonic suspension, des-CIC was retained up to 24 h postadministration (45.46 pmol/g tissue). Highest concentration of major fatty acid ester conjugate, des-CIC-oleate, was detected in nasal mucosa at 8 h postadministration.

Conclusion

These data suggest that a hypotonic ciclesonide suspension provides higher intracellular concentrations of des-CIC up to 24 h, thereby providing a rationale for investigation of ciclesonide as a convenient once-daily nasal spray for treatment of allergic rhinitis.
Imported Crimean-Congo hemorrhagic fever cases in Istanbul
Authors: Midilli Kenan , Gargılı Ayşen , Ergonul Onder , Şengöz Gönül , Ozturk Recep , Bakar Mehmet , Jongejan Frans
Published: June 2007

We described a series of imported cases of Crimean-Congo Hemorrhagic Fever (CCHF) in Istanbul and investigated the genetic diversity of the virus. All the suspected cases of CCHF, who were applied to the health centers in Istanbul, were screened for CCHF virus (CCHFv) infection by using semi-nested Polymerase Chain Reaction (PCR) following RT-PCR. Simultaneous blood samples were also sent to the national reference laboratory in Ankara for serologic investigation. In 10 out of 91 patients, CCHFv was detected by PCR, and among 9 out of 10, anti-CCHFv IgM antibodies were also positive. Clinical features were characterized by fever, myalgia, and hemorrhage. The levels of liver enzymes, creatinine phosphokinase, and lactate dehydrogenase were elevated, and bleeding markers were prolonged. All the cases were treated with ribavirin. There was no fatal case. All the strains clustered within the same group as other Europe/Turkey isolates.
Reconstruction of the kinetochore: a prelude to meiosis
Authors: Asakawa Haruhiko , Haraguchi Tokuko , Hiraoka Yasushi
Published: June 2007

In eukaryotic organisms, chromosomes are spatially organized within the nucleus. Such nuclear architecture provides a physical framework for the genetic activities of chromosomes, and changes its functional organization as the cell moves through the phases of the cell cycle. The fission yeast Schizosaccharomyces pombe provides a striking example of nuclear reorganization during the transition from mitosis to meiosis. In this organism, centromeres remain clustered at the spindle-pole body (SPB; a centrosome-equivalent structure in fungi) during mitotic interphase. In contrast, during meiotic prophase, centromeres dissociate from the SPB and telomeres cluster to the SPB. Recent studies revealed that this repositioning of chromosomes is regulated by mating pheromone signaling. Some centromere proteins disappear from the centromere in response to mating pheromone, leading to dissociation of centromeres from the SPB. Interestingly, mating pheromone signaling is also required for monopolar orientation of the kinetochore which is crucial for proper segregation of sister chromatids during meiosis. When meiosis is induced in the absence of mating pheromone signaling, aberrant chromosome behaviors are observed: the centromere proteins remain at the centromere; the centromere remains associated with the SPB; and sister chromatids segregate precociously in the first meiotic division. These aberrant chromosome behaviors are all normalized by activating the mating pheromone signaling pathway. Thus, action of mating pheromone on the centromere is important for coherent behavior of chromosomes in meiosis. Here we discuss repositioning and reconstruction of the centromere during the transition from mitosis to meiosis, and highlight its significance for proper progression of meiosis.
Risk factors for breast cancer characterized by the estrogen receptor alpha A908G (K303R) mutation
Authors: Conway Kathleen , Parrish Eloise , Edmiston Sharon N , Tolbert Dawn , Tse Chiu-Kit , Moorman Patricia , Newman Beth , Millikan Robert C
Published: June 2007

Introduction

Estrogen is important in the development of breast cancer, and its biological effects are mediated primarily through the two estrogen receptors alpha and beta. A point mutation in the estrogen receptor alpha gene, ESR1, referred to as A908G or K303R, was originally identified in breast hyperplasias and was reported to be hypersensitive to estrogen. We recently detected this mutation at a low frequency of 6% in invasive breast tumors of the Carolina Breast Cancer Study (CBCS).

Methods

In this report, we evaluated risk factors for invasive breast cancer classified according to the presence or absence of the ESR1 A908G mutation in the CBCS, a population-based case-control study of breast cancer among younger and older white and African-American women in North Carolina. Of the 653 breast tumors evaluated, 37 were ESR1 A908G mutation-positive and 616 were mutation-negative.

Results

ESR1 A908G mutation-positive breast cancer was significantly associated with a first-degree family history of breast cancer (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.15 to 6.28), whereas mutation-negative breast cancer was not. Comparison of the two case subgroups supported this finding (OR = 2.65, 95% CI = 1.15 to 6.09). There was also the suggestion that longer duration of oral contraceptive (OC) use (OR = 3.73, 95% CI = 1.16 to 12.03; Ptrend = 0.02 for use of more than 10 years) and recent use of OCs (OR = 3.63, 95% CI = 0.80 to 16.45; Ptrend = 0.10 for use within 10 years) were associated with ESR1 A908G mutation-positive breast cancer; however, ORs for comparison of the two case subgroups were not statistically significant. Hormone replacement therapy use was inversely correlated with mutation-negative breast cancer, but the effect on mutation-positive cancer was unclear due to the small number of postmenopausal cases whose tumors carried the mutation. Mutation-negative breast cancer was associated with several reproductive factors, including younger age at menarche (OR = 1.46, 95% CI = 1.09 to 1.94) and greater total estimated years of ovarian function (OR = 1.82, 95% CI = 1.21 to 2.74).

Conclusion

These preliminary results suggest that OCs may interact with the ESR1 A908G mutant receptor to drive the development of some breast tumors.
Red blood cell transfusions and the risk of acute respiratory distress syndrome among the critically ill: a cohort study
Authors: Zilberberg Marya D , Carter Chureen , Lefebvre Patrick , Raut Monika , Vekeman Francis , Duh Mei Sheng , Shorr Andrew F
Published: June 2007

Introduction

Recent data indicate that transfusion of packed red blood cells (pRBCs) may increase the risk for the development of acute respiratory distress syndrome (ARDS) in critically ill patients. Uncertainty remains regarding the strength of this relationship.

Methods

To quantify the association between transfusions and intensive care unit (ICU)-onset ARDS, we performed a cohort study within Crit, a multicenter, prospective, observational study of transfusion practice in the ICU which enrolled 4,892 critically ill patients in 284 ICUs in the United States. Diagnostic criteria for ARDS were prospectively defined, and we focused on subjects without ARDS at admission. The development of ARDS in the ICU served as the primary endpoint.

Results

Among the 4,730 patients without ARDS at admission, 246 (5.2%) developed ARDS in the ICU. At baseline, ARDS cases were younger, more likely to be in a surgical ICU, and more likely to be admitted with pneumonia or sepsis than controls without ARDS. Cases also were more likely to have a serum creatinine of greater than 2.0 mg/dl (23% versus 18%) and a serum albumin of less than or equal to 2.3 g/dl (54% versus 30%) and were more severely ill upon ICU admission as measured by either the APACHE II (Acute Physiology and Chronic Health Evaluation II) or SOFA (Sequential Organ Failure Assessment) score (p < 0.05 for all). Sixty-seven percent and 42% of cases and controls, respectively, had exposure to pRBC transfusions (p < 0.05), and the unadjusted odds ratio (OR) of developing ARDS in transfused patients was 2.74 (95% confidence interval [CI], 2.09 to 3.59; p < 0.0001) compared to those never transfused. After age, baseline severity of illness, admitting diagnosis, and process-of-care factors were adjusted for, the independent relationship between pRBC transfusions and ICU-onset ARDS remained significant (adjusted OR, 2.80; 95% CI, 1.90 to 4.12; p < 0.0001).

Conclusion

Development of ARDS after ICU admission is common, occurring in approximately 5% of critically ill patients. Transfusion of pRBCs is independently associated with the development of ARDS in the ICU.