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Considerable Evidence (considerable + evidence)
Selected AbstractsHomer proteins shape Xenopus optic tectal cell dendritic arbor development in vivoDEVELOPMENTAL NEUROBIOLOGY, Issue 11 2008Kendall R. Van Keuren-Jensen Abstract Considerable evidence suggests that the Homer family of scaffolding proteins contributes to synaptic organization and function. We investigated the role of both Homer 1b, the constitutively expressed, and developmentally regulated form of Homer, and Homer 1a, the activity-induced immediate early gene, in dendritic arbor elaboration and synaptic function of developing Xenopus optic tectal neurons. We expressed exogenous Homer 1a or Homer 1b in developing Xenopus tectal neurons. By collecting in vivo time lapse images of individual, EGFP-labeled and Homer-expressing neurons over 3 days, we found that Homer 1b leads to a significant decrease in dendritic arbor growth rate and arbor size. Synaptic transmission was also altered in developing neurons transfected with Homer 1b. Cells expressing exogenous Homer 1b over 3 days had a significantly greater AMPA to NMDA ratios, and increased AMPA mEPSC frequency. These data suggest that increasing Homer 1b expression increases excitatory synaptic inputs, increases synaptic maturation, and slows dendritic arbor growth rate. Exogenous Homer 1a expression increases AMPA mEPSC frequency, but did not significantly affect tectal cell dendritic arbor development. Changes in the ratio of Homer 1a to Homer 1b may signal the neuron that overall activity levels in the cell have changed, and this in turn could affect protein interactions at the synapse, synaptic transmission, and structural development of the dendritic arbor. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] The role of the dorsomedial striatum in instrumental conditioningEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2005Henry H. Yin Abstract Considerable evidence suggests that, in instrumental conditioning, rats learn the relationship between actions and their specific consequences or outcomes. The present study examined the role of the dorsomedial striatum (DMS) in this type of learning after excitotoxic lesions and reversible, muscimol-induced inactivation. In three experiments, rats were first trained to press two levers for distinct outcomes, and then tested after training using a variety of behavioural assays that have been established to detect action-outcome learning. In Experiment 1, pre-training lesions of the posterior DMS abolished the sensitivity of rats' instrumental performance to both outcome devaluation and contingency degradation when tested in extinction, whereas lesions of the anterior DMS had no effect. In Experiment 2, both pre-training and post-training lesions of the posterior DMS were equally effective in reducing the sensitivity of performance both to devaluation and degradation treatments. In Experiment 3, the infusion of muscimol into the posterior DMS selectively abolished sensitivity of performance to devaluation and contingency degradation without impairing the ability of rats to discriminate either the instrumental actions performed or the identity of the earned outcomes. Taken together, these results suggest that the posterior region of the DMS is a crucial neural substrate for the acquisition and expression of action,outcome associations in instrumental conditioning. [source] Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse controlEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2005Catharine A. Winstanley Abstract Although the subthalamic nucleus (STN) is involved in regulating motor function, and inactivation of this structure relieves the motor symptoms in Parkinsonian patients, recent data indicate that corticosubthalamic connections are involved in both the regulation of attention and the ability to withhold from responding. Considerable evidence suggests that the neural circuitry underlying such behavioural disinhibition or impulsive action can be at least partially dissociated from that implicated in impulsive decision-making and it has been suggested that the tendency to choose impulsively is related to the ability to form and use Pavlovian associations. To explore these hypotheses further, STN-lesioned rats were tested on the delay-discounting model of impulsive choice, where impulsivity is defined as the selection of a small immediate over a larger delayed reward, as well as in a rodent autoshaping paradigm. In contrast to previous reports of increased impulsive action, STN lesions decreased impulsive choice but dramatically impaired the acquisition of the autoshaping response. When the STN was lesioned after the establishment of autoshaping behaviour, lesioned subjects were more sensitive to the omission of reward, indicative of a reduction in the use of Pavlovian associations to control autoshaping performance. These results emphasize the importance of the STN in permitting conditioned stimulus,unconditioned stimulus associations to regulate goal-seeking, a function which may relate to the alterations in impulsive choice observed in the delay-discounting task. These data bear a striking similarity to those observed after lesions of the orbitofrontal cortex and are suggestive of an important role for corticosubthalamic connections in complex cognitive behaviour. [source] Obesity,hypertension: an ongoing pandemicINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2007E. A. Francischetti Summary Considerable evidence has suggested that excessive weight gain is the most common cause of arterial hypertension. This association has been observed in several populations, in different regions of the world. Obesity,hypertension, a term that underscores the link between these two deleterious conditions, is an important public health challenge, because of its high frequency and concomitant risk of cardiovascular and kidney diseases. The obesity,hypertension pandemic imposes a considerable economic burden on societies, directly reflecting on healthcare system costs. Increased renal sodium reabsorption and blood volume expansion are central features in the development of obesity,hypertension. Overweight is also associated with increased sympathetic activity. Leptin, a protein expressed in and secreted by adipocytes, is the main factor linking obesity, increased sympathetic nervous system activity and hypertension. The renin,angiotensin,aldosterone system has also been causally implicated in obesity,hypertension, because angiotensinogen is expressed in and secreted by adipose tissue. Hypoadiponectinemia, high circulating levels of free fatty acids and increased vascular production of endothelin-1 (ET-1) have been reported as potential mechanisms for obesity,hypertension. Lifestyle changes are effective in obesity,hypertension control, though pharmacological treatment is frequently necessary. Despite the consistency of the mechanistic approach in explaining the causal relation between hypertension and obesity, there is yet no evidence that one class of drug is superior to the others in controlling obesity,hypertension. In this review, we present the current knowledge and research in obesity,hypertension, exploring the epidemiologic evidence of the association, its probable pathophysiological mechanisms and treatment issues. [source] Ras signaling in prostate cancer progressionJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2004Michael J. Weber Abstract When prostate cancer is first detected it generally is dependent on the presence of androgens for growth, and responds to androgen ablation therapies. However, the disease often recurs in a disseminated and apparently androgen independent (AI) form, and in this state is almost invariably fatal. Considerable evidence indicates that the Androgen receptor (AR) continues to be required even in androgen independent (AI) disease. Thus, a key to understanding hormone independent prostate cancer is to determine the mechanism(s) by which the AR can function even in the absence of physiologic levels of androgen. In this article, we argue that growth factors and receptors that utilize Ras family members drive prostate cancer progression to a state of androgen hypersensitivity; and that post-translational modifications (e.g., phosphorylations) of transcriptional cofactors might be responsible for modulating the function of the AR so that it is active even at low concentrations of androgen. © 2003 Wiley-Liss, Inc. [source] Relationship of resident characteristics, attitudes, prior training and clinical knowledge to communication skills performanceMEDICAL EDUCATION, Issue 1 2006Toni Suzuki Laidlaw Purpose, A substantial body of literature demonstrates that communication skills in medicine can be taught and retained through teaching and practice. Considerable evidence also reveals that characteristics such as gender, age, language and attitudes affect communication skills performance. Our study examined the characteristics, attitudes and prior communication skills training of residents to determine the relationship of each to patient,doctor communication. The relationship between communication skills proficiency and clinical knowledge application (biomedical and ethical) was also examined through the use of doctor-developed clinical content checklists, as very little research has been conducted in this area. Methods, A total of 78 first- and second-year residents across all departments at Dalhousie Medical School participated in a videotaped 4-station objective structured clinical examination presenting a range of communication and clinical knowledge challenges. A variety of instruments were used to gather information and assess performance. Two expert raters evaluated the videotapes. Results, Significant relationships were observed between resident characteristics, prior communication skills training, clinical knowledge and communication skills performance. Females, younger residents and residents with English as first language scored significantly higher, as did residents with prior communication skills training. A significant positive relationship was found between the clinical content checklist and communication performance. Gender was the only characteristic related significantly to attitudes. Conclusions, Gender, age, language and prior communication skills training are related to communication skills performance and have implications for resident education. The positive relationship between communication skills proficiency and clinical knowledge application is important and should be explored further. [source] Orchid mycorrhiza: implications of a mycophagous life styleOIKOS, Issue 3 2009Hanne N. Rasmussen Orchid mycorrhiza probably affects about 25,000 plant species and thus roughly one tenth of all higher plants. Histologically, this symbiosis resembles other kinds of endomycorrhiza, the fungal hyphae growing within living plant cells. Considerable evidence, however, suggests that it is not a two-way exchange relationship and thus not potentially mutualistic, such as the wide-spread endomycorrhiza between plants and Glomalean fungi, known as arbuscular mycorrhiza. During the achlorophyllous seedling stage orchids are obligately dependent on the fungi; some species remain so through life, while others establish photosynthesis but to varying degrees remain facultatively dependent of /responsive to fungal infection as adults. None of the fungi involved are so far known to depend on the symbiosis with orchids. Transfer of organic carbon compounds from hyphae to the orchid has been demonstrated repeatedly, but it is not clear to what extent this takes place during a biotrophic phase while the intracellular hyphae remain intact, or during the subsequent extensive degradation of the hyphal coils. The advantage of viewing orchid mycorrhiza basically as a unilateral mycophagous relationship, in spite of hypothetical beneficial spin-offs to the mycobiont, is that it provides a conceptual framework similar to that of other parasitic or fungivore relationships; mechanisms known in such relationships could be searched for in future studies of the orchid,fungus symbiosis. These could include mechanisms for recognition, attraction and selection of fungi, physiological regulation of internal hyphal growth, breakdown, and material transfer, nutritional consequences of the plant's preference(s) and trophic changes, fungal avoidance mechanisms, and consequences at population and ecosystem levels. A whole range of possible life strategies becomes apparent that could support divergent evolution and lead to the proliferation of species that has indeed occurred in the orchid family. We outline some of the possible physiological mechanisms and ecological implications of this approach. [source] Presidential Coattails and Legislative FragmentationAMERICAN JOURNAL OF POLITICAL SCIENCE, Issue 1 2006Matt Golder Considerable evidence suggests that legislative fragmentation can negatively affect the survival of democratic presidential regimes. While there is a vast literature examining the determinants of legislative fragmentation, one factor that has traditionally been overlooked is the impact of presidential elections. Do presidential elections increase or decrease legislative fragmentation? Does it matter if presidents are elected by plurality rule or by runoff? Using a new dataset that covers all democratic legislative and presidential elections between 1946 and 2000, I find that presidential coattails can reduce, increase, or have no effect on legislative fragmentation depending on the number of presidential candidates. I also find strong evidence that social heterogeneity increases the number of presidential candidates when runoff systems are employed. Taken together, these results suggest that the widespread adoption of runoffs by newly democratic presidential regimes will likely increase legislative fragmentation, thereby putting their democratic survival at increased risk. [source] The effect of strength training on the force of twitches evoked by corticospinal stimulation in humansACTA PHYSIOLOGICA, Issue 2 2009T. J. Carroll Abstract Aim:, Although there is considerable evidence that strength training causes adaptations in the central nervous system, many details remain unclear. Here we studied neuromuscular responses to strength training of the wrist by recording electromyographic and twitch responses to transcranial magnetic stimulation (TMS) and cervicomedullary stimulation of the corticospinal tract. Methods:, Seventeen participants performed 4 weeks (12 sessions) of strength training for the radial deviator (RD) muscles of the wrist (n = 8) or control training without external load (n = 9). TMS recruitment curves were constructed from stimuli at five to eight intensities ranging between 15% below resting motor threshold and maximal stimulator output, both at rest and during isometric wrist extension (EXT) and RD at 10% and 50% of maximal voluntary contraction (MVC). Responses to weak TMS and cervicomedullary stimulation (set to produce a response of 10% maximal M wave amplitude during 10% MVC EXT contraction) were also compared at contraction strengths ranging from 10% to 75% MVC. Results:, Isometric strength increased following strength training (10.7% for the RD MVC, 8.8% for the EXT MVC), but not control training. Strength training also significantly increased the amplitude of TMS- and cervicomedullary-evoked twitches during low-force contractions. Increases in the force-generating capacity of the wrist extensor muscles are unlikely to account for this finding because training did not affect the amplitude of twitches elicited by supra-maximal nerve stimulation. Conclusion:, The data suggest that strength training induces adaptations that increase the net gain of corticospinal-motor neuronal projections to the trained muscles. [source] Overexpression of the transcription factor Msx1 is insufficient to drive complete regeneration of refractory stage Xenopus laevis hindlimbsDEVELOPMENTAL DYNAMICS, Issue 6 2009Donna M. Barker Abstract Xenopus laevis tadpoles are capable of hindlimb regeneration, although this ability declines with age. Bmp signaling is one pathway known to be necessary for successful regeneration to occur. Using an inducible transgenic line containing an activated version of the Bmp target Msx1, we assessed the ability of this transcription factor to enhance regeneration in older limbs. Despite considerable evidence correlating msx1 expression with regenerative success in vertebrate regeneration models, we show that induction of msx1 during hindlimb regeneration fails to induce complete regeneration. However, we did observe some improvement in regenerative outcome, linked to morphological changes in the early wound epithelium and a corresponding increase in proliferation in the underlying distal mesenchyme, neither of which are maintained later. Additionally, we show that Msx1 is not able to rescue limb regeneration in a Bmp signalling-deficient background, indicating that additional Bmp targets are required for regeneration in anuran limbs. Developmental Dynamics 238:1366,1378, 2009. © 2009 Wiley-Liss, Inc. [source] Inadequacies of absolute threshold levels for diagnosing prediabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2010Michael Bergman Abstract Prediabetes comprising Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT) represents an intermediate stage of altered glucose metabolism between normal glucose levels and type 2 diabetes mellitus and is associated with an increased risk for the development of diabetes and cardiovascular disease. There is considerable evidence that glucose levels lower than those meeting the current definition of prediabetes may also be associated with similar risks particularly in high-risk individuals. Prediabetes is often unrecognized and therefore constitutes a major public health concern suggesting the need for earlier intervention than is currently recommended. Copyright © 2010 John Wiley & Sons, Ltd. [source] Genetic aspects of pathological gambling: a complex disorder with shared genetic vulnerabilitiesADDICTION, Issue 9 2009Daniela S. S. Lobo ABSTRACT Aims To summarize and discuss findings from genetic studies conducted on pathological gambling (PG). Methods Searches were conducted on PubMed and PsychInfo databases using the keywords: ,gambling and genes', ,gambling and family' and ,gambling and genetics', yielding 18 original research articles investigating the genetics of PG. Results Twin studies using the Vietnam Era Twin Registry have found that: (i) the heritability of PG is estimated to be 50,60%; (ii) PG and subclinical PG are a continuum of the same disorder; (iii) PG shares genetic vulnerability factors with antisocial behaviours, alcohol dependence and major depressive disorder; (iv) genetic factors underlie the association between exposure to traumatic life-events and PG. Molecular genetic investigations on PG are at an early stage and published studies have reported associations with genes involved in the brain's reward and impulse control systems. Conclusions Despite the paucity of studies in this area, published studies have provided considerable evidence of the influence of genetic factors on PG and its complex interaction with other psychiatric disorders and environmental factors. The next step would be to investigate the association and interaction of these variables in larger molecular genetic studies with subphenotypes that underlie PG. Results from family and genetic investigations corroborate further the importance of understanding the biological underpinnings of PG in the development of more specific treatment and prevention strategies. [source] Temporal lobe epilepsy surgery and the quest for optimal extent of resection: A reviewEPILEPSIA, Issue 8 2008Johannes Schramm Summary The efficacy of surgery to treat drug-resistant temporal lobe epilepsy (TLE) has been demonstrated in a prospective randomized trial. It remains controversial which resection method gives best results for seizure freedom and neuropsychological function. This review of 53 studies addressing extent of resection in surgery for TLE identified seven prospective studies of which four were randomized. There is considerable variability between the intended resection and the volumetrically assessed end result. Even leaving hippocampus or amygdalum behind can result in seizure freedom rates around 50%. Most authors found seizure outcome in selective amygdalohippocampectomy (SAH) to be similar to that of lobectomy and there is considerable evidence for better neuropsychological outcome in SAH. Studies varied in the relationship between extent of mesial resection and seizure freedom, most authors finding no positive correlation to larger mesial resection. Electrophysiological tailoring saw no benefit from larger resection in 6 of 10 studies. It must be concluded that class I evidence concerning seizure outcome related to type and extent of resection of mesial temporal lobe structures is rare. Many studies are only retrospective and do not use MRI volumetry. SAH appears to have similar seizure outcome and a better cognitive outcome than TLR. It remains unclear whether a larger mesial resection extent leads to better seizure outcome. [source] Chronic interleukin-6 alters the level of synaptic proteins in hippocampus in culture and in vivoEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007Elly J. F. Vereyken Abstract There is now considerable evidence that the level of expression of the proinflammatory cytokine, interleukin-6 (IL-6), is increased in the central nervous system (CNS) during neuroinflammatory conditions such as occurs in neurological disorders and in disease and injury. However, our understanding of the consequences of increased expression of IL-6 on the CNS is still limited, especially with respect to the developing nervous system, which is known to be particularly vulnerable to environmental factors. To address this issue, we investigated the properties of cultured hippocampal neurons exposed chronically to IL-6 during the main period of morphological and physiological development, which occurs during the first 2 weeks of culture. IL-6 was tested at 500 U/mL, considered to reflect a pathophysiologic concentration. The morphological features of neuronal development in the control and IL-6-treated cultures appeared similar. However, Western blot analysis showed a significant reduction in the level of Group-II metabotropic receptors (mGluR2/3) and L-type Ca2+ channels in the IL-6-treated cultures. A similar reduction in mGluR2/3 and L-type Ca2+ channel protein was observed in transgenic mice that over-express IL-6 in the CNS through astrocyte production starting early in development. Analysis of Ca2+ signals produced by spontaneous synaptic network activity in the hippocampal cultures and effects of a mGluR2/3 agonist and antagonist showed that the reduced levels of mGluR2/3 impact on the functional properties of hippocampal synaptic network activity. These results have important implications relative to the mechanisms responsible for altered CNS function during conditions associated with increased levels of IL-6 in the CNS. [source] Ascending visceral regulation of cortical affective information processingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2003Gary G. Berntson Abstract Over a century ago, William James proposed that strong emotions represent the perceptual consequences of somato-visceral feedback. Although the strong form of this conception is no longer viable, considerable evidence has accumulated indicating a range of visceral influences on higher neurobehavioural processes. This literature has only recently begun to consolidate, because earlier reports generally remained at the demonstration level, and pathways and mechanisms for such influences were uncertain. Recently, specific effects of visceral feedback have become apparent on cortical activity, cerebral auditory-evoked responses, anxiety, memory and behavioural aspects of immunological sickness. Moreover, considerable progress has been made recently in determining the specific neural pathways and systems underlying these actions, especially the role of noradrenergic projections from the nucleus of the tractus solitarius and the locus coeruleus to the amygdala in memory processes, and to the basal forebrain in the processing of anxiety-related information. The present paper highlights selected recent findings in this area, and outlines relevant structures and pathways involved in the ascending visceral influence on higher neurobehavioural processes. [source] New visions of dental tissue research: Tooth development, chemistry, and structureEVOLUTIONARY ANTHROPOLOGY, Issue 5 2008Tanya M. Smith Abstract Teeth are one of the best preserved and most commonly recovered elements in primate fossil assemblages. Taxonomic, functional, and phylogenetic hypotheses often rely on dental characters, despite considerable evidence of homoplasy in tooth form and large variation in tooth size within and among primates.1,2 Recent studies have led to new areas of research centered on incremental tooth development, chemical composition, and internal structure. Due to rapid technological developments in imaging and elemental sampling, these new approaches have the potential to increase our understanding of developmental biology, including not only changes in the pace of growth and reproduction, but also our assessments of diets, migration patterns, environments, and taxonomy. The integration of these temporal, chemical, and structural approaches heralds a bright future for the role of dental tissue research in evolutionary anthropology. © 2008 Wiley-Liss, Inc. [source] Circadian rhythm disturbances in depression,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2008Anne Germain Abstract Objective The aim of this article is to review progress in understanding the mechanisms that underlie circadian and sleep rhythms, and their role in the pathogenesis and treatment of depression. Methods Literature was selected principally by Medline searches, and additional reports were identified based on ongoing research activities in the authors' laboratory. Results Many physiological processes show circadian rhythms of activity. Sleep and waking are the most obvious circadian rhythms in mammals. There is considerable evidence that circadian and sleep disturbances are important in the pathophysiology of mood disorders. Depressed patients often show altered circadian rhythms, sleep disturbances, and diurnal mood variation. Chronotherapies, including bright light exposure, sleep deprivation, and social rhythm therapies, may be useful adjuncts in non-seasonal and seasonal depression. Antidepressant drugs have marked effects on circadian processes and sleep. Conclusions Recent progress in understanding chronobiological and sleep regulation mechanisms may provide novel insights and avenues into the development of new pharmacological and behavioral treatment strategies for mood disorders. Copyright © 2008 John Wiley & Sons, Ltd. [source] Cigarette smoking, endothelial injury and cardiovascular diseaseINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2000Michael Pittilo Despite the fact that the epidemiological evidence linking cigarette smoking with cardiovascular disease is overwhelming, the precise components of cigarette smoke responsible for this relationship and the mechanisms by which they exert their effect have not yet been elucidated. There are however, some promising pointers as a result of recent developments and this review concentrates on new evidence since earlier reviews of this topic. It is now known that the endothelium has a vastly more important role than was ever thought to be the case a decade ago. Its role in health and disease is increasingly understood, as is the relationship between endothelial injury and the development of atherosclerosis. There is considerable evidence that cigarette smoking can result in both morphological and biochemical disturbances to the endothelium both in vivo and in cell culture systems. Cigarette smoke is a complex mixture and only a few components have been extensively studied. Nicotine and carbon monoxide are much less damaging than is whole smoke. However the free radical components of cigarette smoke have been shown to cause damage in model systems. Further work will be necessary to consolidate the evidence base but the data reported in this review suggest that the free radical components of cigarette smoke may be responsible for the morphological and functional damage to endothelium that has been observed in model systems. [source] Social capital and children's wellbeing: a critical synthesis of the international social capital literatureINTERNATIONAL JOURNAL OF SOCIAL WELFARE, Issue 1 2006Kristin M. FergusonArticle first published online: 13 JAN 200 Drawing on social capital literature from the international realm, this article presents a critical synthesis of this social resource in relation to children's and youth's wellbeing. Although considerable evidence indicates that social capital can have a positive impact on future outcomes for children and youth, no prior comprehensive review exists of the literature on social capital and children's wellbeing. Adopting the systematic review method (SR), the author explores how social capital has been conceptualised and operationalised as an explanatory variable in research on individual and collective wellbeing with children and youth. Oft-cited indicators of family social capital and community social capital are identified, together with common control variables, such as human and financial capital. The author concludes by examining several social capital trends in relation to children's wellbeing and offering recommendations for future research using a social capital theoretical framework to explore additional outcomes related to children's and youth's wellbeing. [source] On the Phosphorus Limitation Paradigm for LakesINTERNATIONAL REVIEW OF HYDROBIOLOGY, Issue 4-5 2008Robert W. Sterner stern007@umn.edu Abstract Lakes are often said to be primarily phosphorus limited, but this paradigm has been described in numerous ways and there is considerable evidence that algae in lakes are often limited by other elements too. Crucial whole-ecosystem experiments that support the paradigm of the primacy of P limitation are few in number and have been limited to naturally oligotrophic lakes. A large amount of observational and experimental data seems to contradict the phosphorus limitation paradigm and instead indicates that most lakes are co-limited by N and P as well as, perhaps, by Fe and other resources. The biogeochemical theory behind the phosphorus limitation paradigm is that mechanisms can supplement cycles of C and N (and, discussed here, perhaps Fe) so that ultimately it is P that limits production and biomass. However, no mechanism has been proposed for ecosystems to overshoot this endpoint, meaning one might logically expect to see frequent occurrence of co-limitation by P, N and other resources over short, but still ecologically meaningful time scales that influence, for example, biodiversity patterns in lakes. One point of view has been that small-scale experimentation is simply misleading. However, an alternative is that even if P is ultimately limiting over multi-annual time scales, over shorter but still meaningful time scales, co-limitation of multiple nutrients is expected, and indeed is very common. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] A composite poly-hydroxybutyrate,glial growth factor conduit for long nerve gap repairsJOURNAL OF ANATOMY, Issue 6 2003P.-N. Mohanna Abstract There is considerable evidence that peripheral nerves have the potential to regenerate in an appropriate microenvironment. We have developed a novel artificial nerve guide composed of poly 3-hydroxybutyrate (PHB) filled with glial growth factor (GGF) suspended in alginate hydrogel. Gaps of 2,4 cm in rabbit common peroneal nerve were bridged using a PHB conduit containing either GGF in alginate hydrogel (GGF) or alginate alone (Alginate), or with an empty PHB conduit (Empty). Tissues were harvested 21, 42 and 63 days post-operatively. Schwann cell and axonal regeneration were assessed using quantitative immunohistochemistry. At 21 days, addition of GGF increased significantly the distance of axonal and Schwann cells regeneration in comparison with that observed in Alginate and Empty conduits for both gap lengths. The axons bridged the 2-cm GGF conduits gap by 63 days, with a comparable rate of regeneration seen in 4-cm conduits. Schwann cells and axonal regeneration quantity was similar for both gap lengths in each group. However, at all time points the quantity of axonal and Schwann cells regeneration in GGF grafts was significantly greater than in both Alginate and Empty conduits, the latter showing better regeneration than Alginate conduits. The results indicate an inhibitory effect of alginate on regeneration, which is partially reversed by the addition of GGF to the conduits. In conclusion, GGF stimulates a progressive and sustainable regeneration increase in long nerve gap conduits. [source] THE CAPITAL STRUCTURE CHOICE: NEW EVIDENCE FOR A DYNAMIC TRADEOFF MODELJOURNAL OF APPLIED CORPORATE FINANCE, Issue 1 2002Armen Hovakimian Most academic insights about corporate capital structure decisions come from models that focus on the trade-off between the tax benefits and financial distress costs of debt financing. But empirical tests of corporate capital structure indicate that actual debt ratios are considerably different from those predicted by the models, casting doubt on whether most companies have leverage targets at all. In particular, there is considerable evidence that corporate leverage ratios reflect in large part the tendency of profitable companies to use their excess cash flow to pay down debt, while unprofitable companies build up higher leverage ratios. Such behavior is consistent with a competing theory of capital structure known as the "pecking order" model, in which management's main objectives are to preserve financing flexibility and avoid issuing equity. The results of the authors' recent study suggest that although past profits are an important predictor of observed debt ratios at any given time, companies nevertheless often make financing and stock repurchase decisions designed to offset the effects of past profitability and move their debt ratios toward their target capital structures. This evidence provides support for a compromise theory called the dynamic tradeoff model, which says that although companies often deviate from their leverage targets, over the longer run they take measures to close the gap between their actual and targeted leverage ratios. [source] Habitat utilisation during staging affects body condition in a long distance migrant, Branta bernicla hrota: potential impacts on fitness?JOURNAL OF AVIAN BIOLOGY, Issue 6 2008R. Inger There is considerable evidence to suggest that an animal's ability to access the appropriate resources at one time of year may profoundly restrict its performance at another. For migrants, wintering and breeding periods are often connected by refuelling or staging periods, critical (particularly for females) in attaining the body reserves required to ensure successful breeding. However in many instances there are differences in the extent to which different individuals gain access to the highest quality resources. Here we demonstrate how body condition in brent geese Branta bernicla hrota, during spring staging is related to differences in marine and terrestrial habitat utilisation (inferred from stable isotope analysis). Female birds with high fat scores feed to a greater extent on marine resources. Body mass and condition are also higher in individuals utilising more marine resources. Given that body mass at spring staging is correlated with reproductive success, the extent of marine habitat maybe critical to this population. Combining this with data from previous studies of dark-bellied brent geese Branta bernicla bernicla, we predict the potential impacts of spring staging resource utilisation on future breeding success. Although staging is of short duration compared to the other components of annual cycles of migratory species, our results suggest that the quality of staging grounds may be vitally important to population processes. [source] MINERVA-DM and subadditive frequency judgmentsJOURNAL OF BEHAVIORAL DECISION MAKING, Issue 5 2004J. Neil Bearden Abstract There is considerable evidence that frequency (and probability) judgments are often subadditive. That is, the frequency judgment assigned to an event is often less than the sum of the frequency judgments assigned to the mutually exclusive component events that together form it. Explanations for subadditive judgments have typically relied on relatively high-level cognitive constructs such as the availability and representativeness heuristics. A lower-level explanation of subadditivity is presented in this paper through a model of memory and judgment processes, MINERVA-DM. Under MINERVA-DM, subadditivity is influenced by the similarity of the representations of the judged component events in memory to one another and by the placement of decision criteria. Results from two experiments support the model predictions. The first examines the effects of component event similarity on subadditivity. The second replicates the first and also provides support for the model's prediction of the effects of payoffs on similarity criteria. Copyright © 2004 John Wiley & Sons, Ltd. [source] Role of Wavelength Adaptation in the Initiation, Maintenance, and Pharmacologic Suppression of ReentryJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2001STEVEN D. GIROUARD Ph.D. Wavelength Adaptation and Reentry.Introduction: The stability of reentry is thought to depend on a critical balance between the spatial extent of refractory tissue in a reentrant wave (i.e., wavelength ,) and the reentrant path length. Because considerable evidence suggests that , changes continuously in space and time during abrupt rate changes associated with the onset of tachycardia, we hypothesized that beat-by-beat adaptation of , to the dimensions of the reentrant path plays a central role in the mechanism of initiation of reentry. Methods and Results: To investigate the dynamic relationship between , and path length during initiation of reentry, optical mapping with voltage-sensitive dyes was used in a guinea pig model of reentrant ventricular tachycardia (VT). In this model, a computer-guided laser obstacle precisely controlled the position and dimensions of the reentrant path. Under control perfusion and after addition of 15 , M d-sotalol, , was monitored during steady-state pacing, premature stimulation, and the initiating beats leading to nonsustained and sustained VT. During control perfusion, reentrant VT was reproducibly induced in 8 of 8 hearts, whereas in the presence of d-sotalol, reentry could only be initiated in 1 of 8 hearts due primarily to the failure of , to adapt to the reentrant path length. During successful initiation of VT, a consistent sequence was observed. The sequence was characterized by antidromic and orthodromic propagation around both sides of the anatomic obstacle, followed by unidirectional block of the antidromic impulse and persistence of reentry only if the , of the orthodromic impulse adapted to the reentrant path (, < path length). d-Sotalol prevented initiation of VT by altering , adaptation of the orthodromic wave; however, it failed to terminate ongoing VT because reverse use-dependence developed after several beats of tachycardia. Conclusion: In an experimental model where ,, path length, and cellular action potentials were monitored during initiation of reentry, we found that, in contrast to termination, the initiation of reentry and the transition from nonsustained to sustained VT is strongly dependent on beat-to-beat adaptation of , to the dimensions of the reentrant path. [source] Cell death mechanisms in neurodegenerationJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2001K. A. Jellinger Abstract Progressive cell loss in specific neuronal populations often associated with typical cytoskeletal protein aggregations is a pathological hallmark of neurodegenerative disorders, but the nature, time course and molecular causes of cell death and their relation to cytoskeletal pathologies are still unresolved. Apoptosis or alternative pathways of cell death have been discussed in Alzheimer's disease and other neurodegenerative disorders. Apoptotic DNA fragmentation in human brain as a sign of neuronal injury is found too frequent as to account for continous neuron loss in these slowly progressive processes. Morphological studies revealed extremely rare apoptotic neuronal death in Alzheimer's disease but yielded mixed results for Parkinson's disease and other neurodegenerative disorders. Based on recent data in human brain, as well as in animal and cell culture models, a picture is beginning to emerge suggesting that, in addition to apoptosis, other forms of programmed cell death may participate in neurodegeneration. Better understanding of the molecular players will further elucidate the mechanisms of cell death in these disorders and their relations to cytoskeletal abnormalities. Susceptible cell populations in a proapoptotic environment show increased vulnerability towards multiple noxious factors discussed in the pathogenesis of neurodegeneration. In conclusion, although many in vivo and in vitro data are in favor of apoptosis involvement in neurodegenerative processes, there is considerable evidence that very complex events may contribute to neuronal death with possible repair mechanisms, the elucidation of which may prove useful for future prevention and therapy of neurodegenerative disorders. [source] Phytotherapeutics: an evaluation of the potential of 1000 plantsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2010G. Cravotto MD Summary Objective:, The aim of this review is to evaluate and summarize the available scientific information on the commonest plant extracts marketed in Western countries. In view of the intense, ongoing search for new plant extracts with powerful anti-inflammatory activity, we paid particular attention to this topic. The aim is to provide broad coverage of as many potentially useful plants as possible and then to focus on those with the greatest therapeutic potential. Methods:, Our bibliographic sources were the SciFinder databases: CAPLUS, MEDLINE, REGISTRY, CASREACT, CHEMLIST, CHEMCATS (update to October 2007). In order to assess the value of clinical trials, we focused a specific search on clinical investigations concerning nine plants with the most trial data, viz., Althaea officinalis, Calendula officinalis, Centella asiatica, Echinacea purpurea, Passiflora incarnata, Punica granatum, Vaccinium macrocarpon, Vaccinium myrtillus, Valeriana officinalis. This was carried out in several databases (update to June 2008): ISI Web of KnowledgeSM (ISI WoK), SciFinder (CAPLUS, MEDLINE, REGISTRY, CASREACT, CHEMLIST, CHEMCATS) and PubMed (indexed for MEDLINE). Results:, Our survey covers roughly a 1000 plants, although clinical trials have been published only for 156 plants supporting specific pharmacological activities and therapeutic applications. However, for about half of the plants, in vitro and in vivo studies provide some support for therapeutic use. For one-fifth of the plants included in our search, only phytochemical studies were found. Their properties and indications were often attributed to the presence of certain compounds, but no evidence concerning the activities of the whole extracts was presented. We found that for about 12% of the plants, currently available on the Western market, no substantial studies on their properties had been published, while there was strong evidence that 1 in 200 were toxic or allergenic, so that their use ought to be discouraged or forbidden. Nine plants had considerable evidence of therapeutic effect, viz., A. officinalis, Calendula officinalis, Centella asiatica, E. purpurea, Passiflora incarnata, Punica granatum, Vaccinium macrocarpon, Vaccinium myrtillus, Valeriana officinalis. Conclusion:, The present review provides a baseline on the level of evidence available on many herbal preparations and should be of help to those intending to research further on these topics. [source] The endocannabinoid system and rimonabant: a new drug with a novel mechanism of action involving cannabinoid CB1 receptor antagonism , or inverse agonism , as potential obesity treatment and other therapeutic useJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2007S. Xie Pharm D student Summary There is considerable evidence that the endocannabinoid (endogenous cannabinoid) system plays a significant role in appetitive drive and associated behaviours. It is therefore reasonable to hypothesize that the attenuation of the activity of this system would have therapeutic benefit in treating disorders that might have a component of excess appetitive drive or over-activity of the endocannabinoid system, such as obesity, ethanol and other drug abuse, and a variety of central nervous system and other disorders. Towards this end, antagonists of cannabinoid receptors have been designed through rational drug discovery efforts. Devoid of the abuse concerns that confound and impede the use of cannabinoid receptor agonists for legitimate medical purposes, investigation of the use of cannabinoid receptor antagonists as possible pharmacotherapeutic agents is currently being actively investigated. The compound furthest along this pathway is rimonabant, a selective CB1 (cannabinoid receptor subtype 1) antagonist, or inverse agonist, approved in the European Union and under regulatory review in the United States for the treatment of obesity. This article summarizes the basic science of the endocannabinoid system and the therapeutic potential of cannabinoid receptor antagonists, with emphasis on the treatment of obesity. [source] Temporal and spatial genetic variation in a metapopulation of the annual Erysimum cheiranthoides on stony river banksJOURNAL OF ECOLOGY, Issue 1 2009Olivier Honnay Summary 1Metapopulation dynamics , the recurrent extinction and colonization in spatially discrete habitats , is expected to strongly affect within and between population genetic diversity. So far, however, accounts of true plant metapopulations are extremely scarce. 2We monitored the colonization and extinction dynamics of an assemblage of populations of the annual Erysimum cheiranthoides on stony river banks during three consecutive years. Each year, winter flooding drives some populations to extinction, while vacant banks may become colonized. We describe the dynamics of these ephemeral populations using amplified fragment length polymorphism (AFLP) markers to quantify changes in the metapopulation genetic structure over time, and assessing the direction and relative amount of migration and colonization events. 3Average extinction and colonization rates were high (0.39 and 0.34, respectively). While population genetic differentiation (FST) tripled from 0.06 in 2005 to 0.17 in 2007, total metapopulation genetic diversity remained fairly constant through the years. Genetic assignment analyses allowed assigning more than 50% of the genotyped individuals to populations extant the year before. Colonizing individuals originated from different source populations (, << 1) and there was considerable evidence of upstream seed dispersal. 4The degree and pattern of spatial genetic structure varied between years and was related to variation in the flooding intensity of the Meuse River through the years. Possibly, activation of the soil seed bank also played a role in structuring the genetic make-up of the populations. 5Because migration and colonization events were qualitatively equal, and colonizing individuals originated from different sources, the increase in FST was in agreement with previous theoretical work. Very high migration and colonization rates, and the short monitoring period, may explain why there was no loss of genetic diversity from the metapopulation through recurrent extinction and colonization events. 6Synthesis. This study gives one of the first accounts of the dynamics of a true plant metapopulation. Temporal monitoring of genetic variation gave evidence of extensive and bidirectional seed dispersal, highly variable and increasing genetic differentiation, and rather constant within population genetic diversity. An important suggestion from this research is to include a dormant seed stage in further theoretical work on (meta) population genetics. [source] The evolutionary significance of parasitism: do parasite-driven genetic dynamics occur ex silico?JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 1 2002T. J. Little It has long been recognized that reciprocal antagonism might lock host and parasite populations into a process of constant change, adapting and reacting in open-ended coevolution. A significant body of theory supports this intuition: dynamic genetic polymorphisms are a common outcome of computer simulations of host,parasite coevolution. These in silico experiments have also shown that dynamical interactions could be responsible for high levels of genetic diversity in host populations, and even be the principle determinant of rates of genetic recombination and sexuality. The evolutionary significance of parasitism depends on the strength and prevalence of parasite-mediated selection in nature. Here I appraise whether parasitism is a pervasive agent of evolutionary change by detailing empirical evidence for selection. Although there is considerable evidence of genetic variation for resistance, and hence the potential for selection, direct observation of parasite-driven genetic change is lacking. [source] | |||||||||||||||||||||||||||||||||||||