Home About us Contact
|
Home About us Contact | ||
|
|
||
Underlie
Terms modified by Underlie Selected AbstractsMapping the Conservation LandscapeCONSERVATION BIOLOGY, Issue 1 2003Kent H. Redford To begin this process and to help build understanding and collaboration, we provide a conceptual map of 21 approaches currently being implemented by 13 conservation organizations. We examined each of these approaches according to (1) the nature of the conservation target,the object(s) of the conservation action; ( 2 ) whether the question addressed is where conservation should be done or how conservation should be done; ( 3 ) the scale ( both grain and extent ) of the approach; and (4 ) the principles that underlie the approach. These questions provide a good way of distinguishing between most of the approaches and reveal that there is less competition between them than is assumed. We conclude that only with explicit understanding can the conservation community and its supporters critically compare approaches and come to a consensus about a set of metrics for measuring and achieving global conservation. Resumen: Para que una colaboración bien fundamentada pueda llevarse a cabo, debe haber un proceso de entendimiento de los distintos enfoques utilizadas por diferentes organizaciones de conservación para preservar la biodiversidad. Para iniciar este proceso y ayudar a fomentar el conocimiento y la colaboración, proveemos un mapa conceptual de 21 enfoques utilizados actualmente por 13 organizaciones conservacionistas. Examinamos cada uno de estos enfoques según (1) la naturaleza del objetivo de conservación,el ( los ) objetos( s ) de las actividades de conservación; ( 2 ) la naturaleza de la pregunta a contestar, ya sea "dónde se debe llevar a cabo la conservación" o "cómo se debe llevar a cabo la conservación"; ( 3 ) la escala ( tanto a nivel de detalle como extensión ) del enfoque; (4 ) los principios que constituyen el fundamento del enfoque. Estas preguntas proveen una buena manera de diferenciar la mayoría de las metodologías y muestran que hay menos competencia entre los enfoques de lo que se cree. Concluimos que la comunidad conservacionista y sus seguidores solo podrán comparar los diversos enfoques de manera criteriosa si tienen un entendimiento explícito de los mismos, y de esa manera, podrá desarrollar, por consenso, una serie de variables para medir y lograr la conservación a nivel global. [source] Decoding epithelial signals: critical role for the epidermal growth factor receptor in controlling intestinal transport functionACTA PHYSIOLOGICA, Issue 1 2009D. F. McCole Abstract The intestinal epithelium engages in bidirectional transport of fluid and electrolytes to subserve the physiological processes of nutrient digestion and absorption, as well as the elimination of wastes, without excessive losses of bodily fluids that would lead to dehydration. The overall processes of intestinal ion transport, which in turn drive the secretion or absorption of water, are accordingly carefully regulated. We and others have identified the epidermal growth factor receptor (EGFr) as a critical regulator of mammalian intestinal ion transport. In this article, we focus on our studies that have uncovered the intricate signalling mechanisms downstream of EGFr that regulate both chloride secretion and sodium absorption by colonocytes. Emphasis will be placed on the EGFr-associated regulatory pathways that dictate the precise outcome to receptor activation in response to signals that may seem, on their face, to be quite similar if not identical. The concepts to be discussed underlie the ability of the intestinal epithelium to utilize a limited set of signalling effectors to produce a variety of outcomes suitable for varying physiological and pathophysiological demands. Our findings therefore are relevant not only to basic biological principles, but also may ultimately point to new therapeutic targets in intestinal diseases where ion transport is abnormal. [source] Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L -arginine and antioxidantsACTA PHYSIOLOGICA, Issue 4 2007M. P. Koeners Abstract Aim:, Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation. Methods:, Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. N, -nitro- l -arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic). Results:, Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 ± 4 vs. 33 ± 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 ± 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed. Conclusion:, Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation. [source] Development without Institutions: Ersatz Medicine and the Politics of Everyday Life in Rural North IndiaCULTURAL ANTHROPOLOGY, Issue 3 2004Sarah Pinto In north India, unregulated medical practice is considered by many to be a sign of the failure of institutional rationality and "backward" quality of rural life. However, the work of self-made doctors can also be seen to engage key elements of institutional rationality as it is interwoven with the structure and ethos of development. This article explores what these practitioners and their work suggest about the imagination of institutions in rural India and the kinds of power this invokes. Through mimesis of key practices (namely, forms of talk and use of injections), self-made doctors tap into the authority of legitimate institutions to occupy lacunae in state health structures and redress (even as they reproduce) effects of privatization and repeated temporary health measures. At the same time, everyday elements of these practices demonstrate that institutional legitimacy can only be borrowed by those already in positions of authority (on the basis of caste status and political leadership), challenging ideals of equality that underlie health-related development efforts. [source] Critical Thoughts on Teaching Standard EnglishCURRICULUM INQUIRY, Issue 2 2000Barbara L. Speicher This article exposes four assumptions that underlie most discussions of Standard English. First, spoken English equates to written English. Substantial evidence demonstrates that this equation is both misleading and false. Second, spoken and written English are equally amenable to standardization. This is also fallacious. We will use Prototype Theory (Rosch et al., 1976) and Standard Ideology (Milroy and Milroy, 1991) to explore how broadly shared notions about standard language have led to this belief. Third, Standard English is the language of the workplace and essential for social mobility. While we do not refute this assumption, we do explore the discrimination that stems from it. Fourth, Standard English is the language of the classroom. This assumption has never been systematically tested in the literature by examining the language that teachers use. Nor is it clear that teachers believe they do or should impose an idealized spoken form on their students. [source] A Design Theory Approach to Building Strategic Network-Based Customer Service Systems,DECISION SCIENCES, Issue 3 2009M. Kathryn Brohman ABSTRACT Customer service is a key component of a firm's value proposition and a fundamental driver of differentiation and competitive advantage in nearly every industry. Moreover, the relentless coevolution of service opportunities with novel and more powerful information technologies has made this area exciting for academic researchers who can contribute to shaping the design and management of future customer service systems. We engage in interdisciplinary research,across information systems, marketing, and computer science,in order to contribute to the service design and service management literature. Grounded in the design-science perspective, our study leverages marketing theory on the service-dominant logic and recent findings pertaining to the evolution of customer service systems. Our theorizing culminates with the articulation of four design principles. These design principles underlie the emerging class of customer service systems that, we believe, will enable firms to better compete in an environment characterized by an increase in customer centricity and in customers' ability to self-serve and dynamically assemble the components of solutions that fit their needs. In this environment, customers retain control over their transactional data, as well as the timing and mode of their interactions with firms, as they increasingly gravitate toward integrated complete customer solutions rather than single products or services. Guided by these design principles, we iterated through, and evaluated, two instantiations of the class of systems we propose, before outlining implications and directions for further cross-disciplinary scholarly research. [source] Factors regulating renal angiotensin-converting enzyme activity in the ratACTA PHYSIOLOGICA, Issue 1 2000Changes in angiotensin-converting enzyme (ACE) activity appear to be important in mediating the natriuresis which ensues after administration of an oral or gastric sodium load. In this study, we sought to determine the time course of the changes in ACE activity in the kidney which occur after sodium ingestion. In addition, we sought to investigate mechanisms which might underlie these changes. Angiotensin-converting enzyme activity was measured by generation of histidyl-leucine in homogenates of kidneys harvested at varying time-points after gastric sodium administration. The effects of intravenous sodium loading, solution osmolality and of changes in renal nerve activity were also investigated. Intragastric instillation of both the sodium-containing solution and its iso-osmotic urea control solution resulted in significant increases in renal ACE activity (NaCl: P < 0.0005; Urea: P < 0.01). The increase in renal ACE activity after gastric sodium loading was more prolonged than after the urea control (P < 0.025, NaCl vs. urea at 90 min). This prolonged increase in renal ACE activity appeared to reflect a response to absorbed sodium as intravenous sodium administration caused a significant increase in renal ACE activity at 90 min (P < 0.0005). In contrast to these stimuli which increased renal ACE activity, renal denervation caused a significant decrease in ACE activity in the kidney (P < 0.05). We conclude that gastric sodium loading increases renal ACE activity. This effect appears to be due initially to a response to an increase in gastric lumenal osmolality and later to absorbed sodium. These changes in renal ACE activity are not mediated by a decrease in renal nerve activity. [source] The expression of anger and its relationship to symptoms and cognitions in obsessive,compulsive disorderDEPRESSION AND ANXIETY, Issue 3 2005Stephen P. Whiteside Abstract We compared the association between obsessive,compulsive disorder (OCD) and the expression of anger in a sample of 71 patients and 71 college students. Some authors [Rubenstein et al., J Anxiety Disord 1995;9:1,9] have proposed that anger and hostility underlie the symptoms of OCD; however, there has been little empirical study of this relationship. One recent study [Whiteside and Abramowitz, Cog Therapy Res 2004;28:259,268] with college undergraduates found that the association between OCD symptoms and anger was attributable to depressive symptoms. In the present study, we compared the expression of anger in a sample of patients diagnosed with OCD and nonclinical volunteers. Consistent with the previous study, we found increased levels of anger in patients with OCD as compared to control participants; however, these differences could be attributed to between-group differences in general distress. These results were discussed within the framework of the cognitive theory of OCD. © 2005 Wiley-Liss, Inc. [source] Clinical trials and statistical analyses: what should dermatologists look for in a report?DERMATOLOGIC THERAPY, Issue 3 2009Mohamed Alosh ABSTRACT Clinicians need to evaluate the quality of individual clinical studies and synthesize the information from multiple clinical studies to provide insights in selecting appropriate therapies for patients. Understanding the key statistical principles that underlie a clinical trial and how they may be implemented can help clinicians properly interpret the efficacy and safety findings of clinical trials. Several factors should be considered when evaluating clinical studies reported in the literature, as important differences might exist among reported studies, thereby impacting the reliability of their findings. Studies vary in terms of study design, conduct, analysis, and presentation of findings. The key features to consider when evaluating clinical trials are inferential intent (exploratory versus confirmatory), choice of control group, randomization, extent of blinding, prespecification of analyses, appropriate handling of missing data, and multiple end points. Making comparisons across studies is extremely difficult and rarely statistically justified. However, this article will point out issues to keep in mind when evaluating multiple studies, such as variations in design and study populations. [source] White matter lesions in euthymic patients with bipolar disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2009A. J. Lloyd Objective:, We aimed to quantify both load and regional distributions of hyperintensities on magnetic resonance imaging (MRI) in prospectively verified euthymic bipolar patients and matched controls. Method:, Cerebral hyperintensities on T2, proton density and fluid-attenuated inversion recovery (FLAIR) MRI were compared between 48 bipolar and 47 control subjects using semi-quantitative rating scales. Results:, Bipolar subjects had more severe frontal deep white matter lesions (DWML). Hyperintensity load was independent of age in bipolar patients but increased with age in controls. Global prevalence and severity of hyperintensities did not differ between groups. Exploratory analysis showed DWML in excess in the left hemisphere in bipolar subjects but not in controls. Conclusion:, Findings are consistent with clinical, particularly some neurocognitive, features of bipolar disorder and implicate fronto-subcortical circuits in its neurobiology. They more probably reflect a trait abnormality or illness scar rather than a mood state-dependent finding. Processes other than ageing and vascular factors may underlie their development. [source] Expressional changes of ganglioside GM3 during ovarian maturation and early embryonic development in db/db miceDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 1 2003Dong Hoon Kwak Diabetes and obesity cause abnormal development of reproductive processes in a variety of species, but the mechanisms that underlie this effect have not been fully elucidated. This study examined the expressional changes of ganglioside GM3 during ovarian maturation, in vitro fertilization (IVF) and early embryonic development in diabetic/obese db/db mice. In high-performance thin-layer chromatography studies, GM3 expression was conspicuously low in the ovaries of db/db mice compared to non-diabetic db/+ mice. Signal detected by anti-GM3 monoclonal antibody was greatly reduced in the primary, secondary and graffian follicles of db/db mice compared to control mice. Results from IVF with ova and sperm from db/db mice showed that GM3 expression during early embryonic development was obviously decreased compared to db/+ mice. This study also elucidated the effects of high glucose (20 and 30 mm) on early embryonic development in ICR strain mice. High glucose caused a decrease in GM3 expression during early embryonic development. Taken together, the results of this study indicate decreased GM3 expression during ovarian maturation and embryonic development of db/db mice, suggesting that alteration of ganglioside expression induced by the diabetic condition may be implicated in the abnormal follicular embryonic development. [source] The search for autism disease genesDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2004Thomas H Wassink Abstract Autism is a heritable disorder characterized by phenotypic and genetic complexity. This review begins by surveying current linkage, gene association, and cytogenetic studies performed with the goal of identifying autism disease susceptibility variants. Though numerous linkages and associations have been identified, they tend to diminish upon closer examination or attempted replication. The review therefore explores challenges to current methodologies presented by the complexities of autism that might underlie some of the current difficulties, and finishes by describing emerging phenotypic, statistical, and molecular investigational approaches that offer hope of overcoming those challenges. © 2004 Wiley-Liss, Inc. MRDD Research Reviews 2004;10:272,283. [source] Role for retinoid signaling in left,right asymmetric digestive organ morphogenesisDEVELOPMENTAL DYNAMICS, Issue 8 2006Kristen Lipscomb Abstract The looping events that establish left,right asymmetries in the vertebrate gut tube are poorly understood. Retinoic acid signaling is known to impact left,right development in multiple embryonic contexts, although its role in asymmetric digestive organ morphogenesis is unknown. Here, we show that the genes for retinaldehyde dehydrogenase (RALDH2) and a retinoic acid hydroxylase (CYP26A1) are expressed in complementary patterns in the Xenopus gut during looping. A late-stage chemical genetic assessment reveals that agonists and antagonists of retinoid signaling generate abnormal gut looping topologies, digestive organ heterotaxias, and intestinal malrotations. Accessory organ deformities commonly associated with intestinal malrotation in humans, such as annular pancreas, pancreas divisum, and extrahepatic biliary tree malformations, are also induced by distinct retinoid receptor agonists. Thus, late-stage retinoic acid signaling is likely to play a critical role in asymmetric gut tube morphogenesis and may underlie the etiology of several clinically relevant defects in the digestive system. Developmental Dynamics 235:2266,2275, 2006. © 2006 Wiley-Liss, Inc. [source] Muscle fiber differentiation in fish embryos as shown by in situ hybridization of a large repertoire of muscle-specific transcriptsDEVELOPMENTAL DYNAMICS, Issue 2 2005F. Chauvigné Abstract Skeletal muscles are composed of different fiber types, largely defined by differential expression of protein isoforms involved in myofibrillogenesis or metabolism. To learn more about the gene activations that underlie the differentiation and the diversification of embryonic fish myotomal fibers, we investigated the developmental expression of 25 muscle genes in trout embryos by in situ hybridization of muscle-specific transcripts. The earliest event of muscle differentiation, at approximately the 25-somite stage, was the expression of a variety of muscle-specific genes, including slow-twitch and fast-twitch muscle isoforms. The activation of these muscle genes started in the deep somitic domain, where the slow muscle precursors (the adaxial cells) were initially located, and progressively spread laterally throughout the width of the myotome. This mediolateral progression of gene expression was coordinated with the lateral migration of slow adaxial cells, which specifically expressed the slow myosin light chain 1 and the SLIM1/FHL1 genes. Subsequently, the fast and slow skeletal muscle isoforms precociously expressed in the course of the mediolateral wave of muscle gene activation became down-regulated in the superficial slow fibers and the deep fast fibers, respectively. Finally, several muscle-specific genes, including troponins, a slow myosin-binding protein C, tropomodulins, and parvalbumin started their transcription only in late embryos. Taken together, these findings show in fish embryos that a common myogenic program is triggered in a mediolateral progression in all muscle cells. The acquisition of the slow phenotype involves the additional activation of several slow-specific genes in migrating adaxial muscle cells. These events are followed by sequential gene activations and repressions in fast and slow muscle cells. Developmental Dynamics 233:659,666, 2005. © 2005 Wiley-Liss, Inc. [source] Villin: A marker for development of the epithelial pyloric borderDEVELOPMENTAL DYNAMICS, Issue 1 2002Evan M. Braunstein Abstract In the adult gastrointestinal tract, the morphologic borders between esophagus and stomach and between stomach and small intestine are literally one cell thick. The patterning mechanisms that underlie the development of these sharp regional divisions from a once continuous endodermal tube are still obscure. In the embryonic endoderm of the developing gut, region-specific expression of certain genes (e.g., intestine-specific expression of the actin bundling protein villin) can be detected as early as 9.0 days post coitum, although the morphologic differentiation of the gut epithelium proper does not begin until 4 to 5 days later. By using a mouse model in which a ,-galactosidase marker has been inserted into the endogenous villin locus, we examined the development of the stomach/intestinal (pyloric) border during gut organogenesis. The data indicate that the border is not sharp from the outset. Rather, the initial border region is characterized by a decreasing gradient of villin/,-galactosidase expression that extends into the distal stomach. A sharp epithelial border of villin/,-galactosidase expression appears abruptly at day 16 and is further refined over the next 3 weeks to form the distinct one-cell-thick border characteristic of the adult. These results indicate that an important previously unrecognized patterning event occurs in the gut epithelium at 16 days; this event may define an epithelial compartment boundary between the stomach and the intestine. The villin/,-galactosidase mouse model characterized here provides an excellent substrate with which to further dissect the mechanisms involved in this patterning process. © 2002 Wiley-Liss, Inc. [source] Transient expression of serotonin 5-HT4 receptors in the mouse developing thalamocortical projectionsDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2010Erin R. Slaten Abstract The serotonin 5-HT4 receptor (5-HT4 -R) is an unusually complex G-protein coupled receptor that is likely to play important roles in brain development and that may underlie the comorbidity of central and peripheral abnormalities in some developmental disorders. We studied the expression of 5-HT4 -Rs in the developing mouse forebrain at embryonic days 13, 15, 17, and at postnatal days 3 and 14 by using immunohistochemistry, tract tracing, and quantitative RT-PCR. The developing thalamocortical projections transiently expressed 5-HT4 -Rs in the embryonic brain and the 5-HT4 -R expression in the forebrain changed from axonal to somatic around birth. From embryonic days 13,17, the forebrain mRNA levels of the 5-HT4(a) -R and 5-HT4(b) -R splice variants increased nine- and fivefold, respectively, whereas the levels of the 5-HT4(e) -R and 5-HT4(f) -R variants remained relatively low throughout the studied period of embryonic development. These results suggest that during development 5-HT4 -R expression undergoes a dynamic regulation and that this regulation may be important for the normal development of sensory and limbic processing. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2010. [source] Activation of a calcium entry pathway by sodium pyrithione in the bag cell neurons of AplysiaDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2004Ronald J. Knox Abstract The ability of sodium pyrithione (NaP), an agent that produces delayed neuropathy in some species, to alter neuronal physiology was accessed using ratiometric imaging of cytosolic free Ca2+ concentration ([Ca2+]i) in fura PE-filled cultured Aplysia bag cell neurons. Bath-application of NaP evoked a [Ca2+]i elevation in both somata and neurites with an EC50 of ,300 nM and a Hill coefficient of ,1. The response required the presence of external Ca2+, had an onset of 3,5 min, and generally reached a maximum within 30 min. 2-Methyl-sulfonylpyridine, a metabolite and close structural analog of NaP, did not elevate [Ca2+]i. Under whole-cell current-clamp recording, NaP produced a ,14 mV depolarization of resting membrane potential that was dependent on external Ca2+. These data suggested that NaP stimulates Ca2+ entry across the plasma membrane. To minimize the possibility that a change in cytosolic pH was the basis for NaP-induced Ca2+ entry, bag cell neuron intracellular pH was estimated with the dye 2,,7,-bis(carboxyethyl-5(6)-carboxy-fluorescein acetoxy methylester. Exposure of the neurons to NaP did not alter intracellular pH. The slow onset and sustained nature of the NaP response suggested that a cation exchange mechanism coupled either directly or indirectly to Ca2+ entry could underlie the phenomenon. However, neither ouabain, a Na+/K+ ATPase inhibitor, nor removal of extracellular Na+, which eliminates Na+/Ca2+ exchanger activity, altered the NaP-induced [Ca2+]i elevation. Finally, the possibility that NaP gates a Ca2+ -permeable ion channel in the plasma membrane was examined. NaP did not appear to activate two major forms of bag cell neuron Ca2+ -permeable ion channels, as Ca2+ entry was unaffected by inhibition of voltage-gated Ca2+ channels using nifedipine or by inhibition of a voltage-dependent, nonselective cation channel using a high concentration of tetrodotoxin. In contrast, two potential store-operated Ca2+ entry current inhibitors, SKF-96365 and Ni2+, attenuated NaP-induced Ca2+ entry. We conclude that NaP activates a slow, persistent Ca2+ influx in Aplysia bag cell neurons. © 2004 Wiley Periodicals, Inc. J Neurobiol 411,423, 2004 [source] Evidence for species differences in the pattern of androgen receptor distribution in relation to species differences in an androgen-dependent behaviorDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2002Brian K. Shaw Abstract Chickens (Gallus gallus domesticus) and Japanese quail (Coturnix japonica), two closely related gallinaceous bird species, exhibit a form of vocalization,crowing,which differs between the species in two components: its temporal acoustic pattern and its accompanying postural motor pattern. Previous work utilizing the quail-chick chimera technique demonstrated that the species-specific characteristics of the two crow components are determined by distinct brain structures: the midbrain confers the acoustic pattern, and the caudal hindbrain confers the postural pattern. Crowing is induced by androgens, acting directly on androgen receptors. As a strategy for identifying candidate neurons in the midbrain and caudal hindbrain that could be involved in crow production, we performed immunocytochemistry for androgen receptors in these brain regions in both species. We also investigated midbrain-to-hindbrain vocal-motor projections. In the midbrain, both species showed prominent androgen receptor immunoreactivity in the nucleus intercollicularis, as had been reported in previous studies. In the caudal hindbrain, we discovered characteristic species differences in the pattern of androgen receptor distribution. Chickens, but not quail, showed strong immunoreactivity in the tracheosyringeal division of the hypoglossal nucleus, whereas quail, but not chickens, possessed strong immunoreactivity in a region of the ventrolateral medulla. Some of these differences in hindbrain androgen receptor distribution may be related to the species differences in the postural component of crowing behavior. The results of the present study imply that the spatial distribution of receptor proteins can vary even between closely related species. Such variation in receptor distribution could underlie the evolution of species differences in behavior. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 203,220, 2002 [source] Olfactory association learning and brain-derived neurotrophic factor in an animal model of early deprivationDEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2009Betty Zimmerberg Abstract Animal models can serve to explore neural mechanisms underlying the effects of stressful early experiences on behaviors supporting attachment. Neonatal rats primarily use olfaction for attachment, and Brain-Derived Neurotrophic Factor (BDNF) may be a key transcription target in olfactory association learning. In this experiment, neonatal male and female rats were isolated individually for 3 hr daily in the first week of life while their dams were left with partial litters (Early Deprivation, ED) or remained undisturbed (Control). At 1 week of age, subjects were tested using a 2-day classical conditioning paradigm. The conditioned group (O/M) was exposed to a novel odor paired with a milk infusion. Three additional groups included an unpaired odor and milk exposure group (O/M unP), an odor exposure alone group (O/NM), and neither an odor nor a milk group (NO/NM). Learning the odor association, as revealed in a position preference for the novel odor, was accompanied by an increase in hippocampal BDNF in O/M subjects from undisturbed Control litters. BDNF levels were also positively related to degree of preference for the odor in the O/M Control group. ED subjects did not make the classically conditioned odor association and did not show an increase in hippocampal BDNF. ED increased BDNF levels in the olfactory bulb compared to Controls regardless of training group; individual levels were not correlated with performance because samples were pooled. These results suggest that changes in the transcription of BDNF may underlie some of the long-term consequences of the early stress of maternal separation. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 333,344, 2009. [source] Six-month-old infants use analog magnitudes to represent durationDEVELOPMENTAL SCIENCE, Issue 5 2006Kristy VanMarle While many studies have investigated duration discrimination in human adults and in nonhuman animals, few have investigated this ability in infants. Here, we report findings that 6-month-old infants are able to discriminate brief durations, and, as with other animal species, their discrimination function is characterized by Weber's Law: proportionate difference rather than absolute difference between stimuli determined successful discrimination. Importantly, paralleling results found with nonhuman animals, the Weber function that we found for infants' discrimination of time is the same as that found for their discrimination of number. Infants discriminated durations of an audiovisual event differing by a 1:2 ratio, but not those differing by a 2:3 ratio, over a range of durations. This suggests that (a) in human as in nonhuman animals, the same mental mechanism may underlie the ability to measure duration as to represent number, and (b) we may share this mental mechanism with other animal species. [source] Origins of a stereotype: categorization of facial attractiveness by 6-month-old infantsDEVELOPMENTAL SCIENCE, Issue 2 2004Jennifer L. Ramsey Like adults, young infants prefer attractive to unattractive faces (e.g. Langlois, Roggman, Casey, Ritter, Rieser-Danner & Jenkins, 1987; Slater, von der Schulenburg, Brown, Badenoch, Butterworth, Parsons & Samuels, 1998). Older children and adults stereotype based on facial attractiveness (Eagly, Ashmore, Makhijani & Longo, 1991; Langlois, Kalakanis, Rubenstein, Larson, Hallam & Smooth, 2000). How do preferences for attractive faces develop into stereotypes? Several theories of stereotyping posit that categorization of groups is necessary before positive and negative traits can become linked to the groups (e.g. Tajfel, Billig, Bundy & Flament, 1971; Zebrowitz-McArthur, 1982). We investigated whether or not 6-month-old infants can categorize faces as attractive or unattractive. In Experiment 1, we familiarized infants to unattractive female faces; in Experiment 2, we familiarized infants to attractive female faces and tested both groups of infants on novel faces from the familiar or novel attractiveness category. Results showed that 6-month-olds categorized attractive and unattractive female faces into two different groups of faces. Experiments 3 and 4 confirmed that infants could discriminate among the faces used in Experiments 1 and 2, and therefore categorized the faces based on their similarities in attractiveness rather than because they could not differentiate among the faces. These findings suggest that categorization of facial attractiveness may underlie the development of the ,beauty is good' stereotype. [source] Autophagic pathways and metabolic stressDIABETES OBESITY & METABOLISM, Issue 2010S. Kaushik Autophagy is an essential intracellular process that mediates degradation of intracellular proteins and organelles in lysosomes. Autophagy was initially identified for its role as alternative source of energy when nutrients are scarce but, in recent years, a previously unknown role for this degradative pathway in the cellular response to stress has gained considerable attention. In this review, we focus on the novel findings linking autophagic function with metabolic stress resulting either from proteins or lipids. Proper autophagic activity is required in the cellular defense against proteotoxicity arising in the cytosol and also in the endoplasmic reticulum, where a vast amount of proteins are synthesized and folded. In addition, autophagy contributes to mobilization of intracellular lipid stores and may be central to lipid metabolism in certain cellular conditions. In this review, we focus on the interrelation between autophagy and different types of metabolic stress, specifically the stress resulting from the presence of misbehaving proteins within the cytosol or in the endoplasmic reticulum and the stress following a lipogenic challenge. We also comment on the consequences that chronic exposure to these metabolic stressors could have on autophagic function and on how this effect may underlie the basis of some common metabolic disorders. [source] Preconditioning and postconditioning: new strategies for cardioprotectionDIABETES OBESITY & METABOLISM, Issue 6 2008D. J. Hausenloy Despite optimal therapy, the morbidity and mortality of coronary heart disease (CHD) remains significant, particularly in patients with diabetes or the metabolic syndrome. New strategies for cardioprotection are therefore required to improve the clinical outcomes in patients with CHD. Ischaemic preconditioning (IPC) as a cardioprotective strategy has not fulfilled it clinical potential, primarily because of the need to intervene before the index ischaemic event, which is impossible to predict in patients presenting with an acute myocardial infarction (AMI). However, emerging studies suggest that IPC-induced protection is mediated in part by signalling transduction pathways recruited at time of myocardial reperfusion, creating the possibility of harnessing its cardioprotective potential by intervening at time of reperfusion. In this regard, the recently described phenomenon of ischaemic postconditioning (IPost) has attracted great interest, particularly as it represents an intervention, which can be applied at time of myocardial reperfusion for patients presenting with an AMI. Interestingly, the signal transduction pathways, which underlie its protection, are similar to those recruited by IPC, creating a potential common cardioprotective pathway, which can be recruited at time of myocardial reperfusion, through the use of appropriate pharmacological agents given as adjuvant therapy to current myocardial reperfusion strategies such as thrombolysis and primary percutaneous coronary intervention for patients presenting with an AMI. This article provides a brief overview of IPC and IPost and describes the common signal transduction pathway they both appear to recruit at time of myocardial reperfusion, the pharmacological manipulation of which has the potential to generate new strategies for cardioprotection. [source] Atherosclerosis in diabetes and insulin resistanceDIABETES OBESITY & METABOLISM, Issue 4 2007Jane E.-B. Atherosclerosis and cardiovascular disease are the major causes of morbidity and mortality in patients with diabetes and those with insulin resistance and the metabolic syndrome. Both conditions profoundly accelerate the development of atherosclerosis and increase the morbidity and mortality of cardiovascular events. The question, therefore, is what are the molecular/biochemical mechanisms that underlie the potentiating influence of diabetes, the metabolic syndrome and/or insulin resistance on the development and progression of atherosclerosis? The following review will focus on the molecular mechanism whereby hyperglycaemia and/or hyperinsulinemia either directly or indirectly promote atherosclerosis. [source] The mechanisms that underlie glucose sensing during hypoglycaemia in diabetesDIABETIC MEDICINE, Issue 5 2008R. McCrimmon Abstract Hypoglycaemia is a frequent and greatly feared side-effect of insulin therapy, and a major obstacle to achieving near-normal glucose control. This review will focus on the more recent developments in our understanding of the mechanisms that underlie the sensing of hypoglycaemia in both non-diabetic and diabetic individuals, and how this mechanism becomes impaired over time. The research focus of my own laboratory and many others is directed by three principal questions. Where does the body sense a falling glucose? How does the body detect a falling glucose? And why does this mechanism fail in Type 1 diabetes? Hypoglycaemia is sensed by specialized neurons found in the brain and periphery, and of these the ventromedial hypothalamus appears to play a major role. Neurons that react to fluctuations in glucose use mechanisms very similar to those that operate in pancreatic B- and A-cells, in particular in their use of glucokinase and the KATP channel as key steps through which the metabolic signal is translated into altered neuronal firing rates. During hypoglycaemia, glucose-inhibited (GI) neurons may be regulated by the activity of AMP-activated protein kinase. This sensing mechanism is disturbed by recurrent hypoglycaemia, such that counter-regulatory defence responses are triggered at a lower glucose level. Why this should occur is not yet known, but it may involve increased metabolism or fuel delivery to glucose-sensing neurons or alterations in the mechanisms that regulate the stress response. [source] Maternal transmission of diabetesDIABETIC MEDICINE, Issue 2 2002J. C. Alcolado Abstract Type 2 diabetes mellitus represents a heterogeneous group of conditions characterized by impaired glucose homeostasis. The disorder runs in families but the mechanism underlying this is unknown. Many, but not all, studies have suggested that mothers are excessively implicated in the transmission of the disorder. A number of possible genetic phenomena could explain this observation, including the exclusively maternal transmission of mitochondrial DNA (mtDNA). It is now apparent that mutations in mtDNA can indeed result in maternally inherited diabetes. Although several mutations have been implicated, the strongest evidence relates to a point substitution at nucleotide position 3243 (A to G) in the mitochondrial tRNAleu(UUR) gene. Mitochondrial diabetes is commonly associated with nerve deafness and often presents with progressive non-autoimmune ,-cell failure. Specific treatment with Coenzyme Q10 or L-carnitine may be beneficial. Several rodent models of mitochondrial diabetes have been developed, including one in which mtDNA is specifically depleted in the pancreatic islets. Apart from severe, pathogenic mtDNA mutations, common polymorphisms in mtDNA may contribute to variations of insulin secretory capacity in normal individuals. Mitochondrial diabetes accounts for less than 1% of all diabetes and other mechanisms must underlie the maternal transmission of Type 2 diabetes. Possibilities include the role of maternally controlled environments, imprinted genes and epigenetic phenomena. [source] Neuronal plasticity: implications in epilepsy progression and managementDRUG DEVELOPMENT RESEARCH, Issue 8 2007Sherifa A. HamedArticle first published online: 12 FEB 200 Abstract Epilepsy is a common neurological disease. A growing number of research studies provide evidence regarding the progressive neuronal damage induced by prolonged seizures or status epilepticus (SE), as well as recurrent brief seizures. Importantly, seizure is only one aspect of epilepsy. However, cognitive and behavioral deficits induced by progressive seizures or antiepileptic treatment can be detrimental to individual function. The neurobiology of epilepsy is poorly understood involving complex cellular and molecular mechanisms. The brain undergoes changes in its basic structure and function, e.g., neural plasticity with an increased susceptibility in neuronal synchronization and network circuit alterations. Some of these changes are transient, while others are permanent with an involvement of both glutamatergic and ,-aminobutyric acid (GABA)ergic systems. Recent data suggest that impaired neuronal plasticity may underlie the cognitive impairment and behavioral changes associated with epilepsy. Many neurologists recognize that the prevention or suppression of seizures by the use of antiepileptic drugs (AEDs) alone is insufficient without clear predictions of disease outcome. Hence, it is important to understand the molecular mechanisms underlying epileptogenesis because this may allow the development of innovative strategies to prevent or cure this condition. In addition, this realization would have significant impact in reducing the long-term adverse consequences of the disease, including neurocognitive and behavioral adverse effects. Drug Dev Res 68:498,511, 2007. © 2008 Wiley-Liss, Inc. [source] Dichotic listening deficits in children with dyslexiaDYSLEXIA, Issue 1 2008Deborah W. Moncrieff Abstract Several auditory processing deficits have been reported in children with dyslexia. In order to assess for the presence of a binaural integration type of auditory processing deficit, dichotic listening tests with digits, words and consonant,vowel (CV) pairs were administered to two groups of right-handed 11-year-old children, one group diagnosed with developmental dyslexia and an age-matched control group. Dyslexic children performed more poorly than controls from their left ears when listening to digits and words and from their right ears when listening to CVs. Direction of ear advantage varied across individuals in both groups when tested with digits and CVs, but ear advantage was stable with words. Several factors that may have contributed to inconsistencies in direction of ear advantage are discussed. When the children were tested in a directed response mode, degree of ear advantage differed significantly between groups with both words and digits. More dyslexic than control children demonstrated clinically significant reductions in dichotic listening performance, but no uniform pattern of deficit emerged. Only the double correct score and the left ear score with CV pairs were predictive of word recognition performance in dyslexic children. Binaural integration deficits are present in some children with dyslexia. Auditory processing disorder assessment may help delineate factors that underlie or are associated with reading impairment in this population. Copyright © 2007 John Wiley & Sons, Ltd. [source] The magnocellular theory of developmental dyslexiaDYSLEXIA, Issue 1 2001John Stein Abstract Low literacy is termed ,developmental dyslexia' when reading is significantly behind that expected from the intelligence quotient (IQ) in the presence of other symptoms,incoordination, left,right confusions, poor sequencing,that characterize it as a neurological syndrome. 5,10% of children, particularly boys, are found to be dyslexic. Reading requires the acquisition of good orthographic skills for recognising the visual form of words which allows one to access their meaning directly. It also requires the development of good phonological skills for sounding out unfamiliar words using knowledge of letter sound conversion rules. In the dyslexic brain, temporoparietal language areas on the two sides are symmetrical without the normal left-sided advantage. Also brain ,warts' (ectopias) are found, particularly clustered round the left temporoparietal language areas. The visual magnocellular system is responsible for timing visual events when reading. It therefore signals any visual motion that occurs if unintended movements lead to images moving off the fovea (,retinal slip'). These signals are then used to bring the eyes back on target. Thus, sensitivity to visual motion seems to help determine how well orthographic skill can develop in both good and bad readers. In dyslexics, the development of the visual magnocellular system is impaired: development of the magnocellular layers of the dyslexic lateral geniculate nucleus (LGN) is abnormal; their motion sensitivity is reduced; many dyslexics show unsteady binocular fixation; hence poor visual localization, particularly on the left side (left neglect). Dyslexics' binocular instability and visual perceptual instability, therefore, can cause the letters they are trying to read to appear to move around and cross over each other. Hence, blanking one eye (monocular occlusion) can improve reading. Thus, good magnocellular function is essential for high motion sensitivity and stable binocular fixation, hence proper development of orthographic skills. Many dyslexics also have auditory/phonological problems. Distinguishing letter sounds depends on picking up the changes in sound frequency and amplitude that characterize them. Thus, high frequency (FM) and amplitude modulation (AM) sensitivity helps the development of good phonological skill, and low sensitivity impedes the acquisition of these skills. Thus dyslexics' sensitivity to FM and AM is significantly lower than that of good readers and this explains their problems with phonology. The cerebellum is the head ganglion of magnocellular systems; it contributes to binocular fixation and to inner speech for sounding out words, and it is clearly defective in dyslexics. Thus, there is evidence that most reading problems have a fundamental sensorimotor cause. But why do magnocellular systems fail to develop properly? There is a clear genetic basis for impaired development of magnocells throughout the brain. The best understood linkage is to the region of the Major Histocompatibility Complex (MHC) Class 1 on the short arm of chromosome 6 which helps to control the production of antibodies. The development of magnocells may be impaired by autoantibodies affecting the developing brain. Magnocells also need high amounts of polyunsaturated fatty acids to preserve the membrane flexibility that permits the rapid conformational changes of channel proteins which underlie their transient sensitivity. But the genes that underlie magnocellular weakness would not be so common unless there were compensating advantages to dyslexia. In developmental dyslexics there may be heightened development of parvocellular systems that underlie their holistic, artistic, ,seeing the whole picture' and entrepreneurial talents. Copyright © 2001 John Wiley & Sons, Ltd. [source] Does disturbance of self underlie social cognition deficits in schizophrenia and other psychotic disorders?EARLY INTERVENTION IN PSYCHIATRY, Issue 2 2009Barnaby Nelson Abstract Aim: Although the different approaches to psychosis research have made significant advances in their own fields, integration between the approaches is often lacking. This paper attempts to integrate a strand of cognitive research in psychotic disorders (specifically, social cognition research) with phenomenological accounts of schizophrenia and other psychotic disorders. Method: The paper is a critical investigation of phenomenological models of disturbed selfhood in schizophrenia in relation to cognitive theories of social cognition in psychotic disorders. Results: We argue that disturbance of the basic sense of self, as articulated in the phenomenological literature, may underlie the social cognition difficulties present in psychotic disorders. This argument is based on phenomenological thinking about self-presence (,ipseity') being the primary or most basic ground for the intentionality of consciousness , that is, the directedness of consciousness towards others and the world. A disruption in this basic ground of conscious life has a reverberating effect through other areas of cognitive and social functioning. We propose three routes whereby self-disturbance may compromise social cognition, including dissimilarity, disruption of lived body and disturbed mental coherence. Conclusions: If this model is supported, then social cognition difficulties may be thought of as a secondary index or marker of the more primary disturbance of self in psychotic disorders. Further empirical work examining the relationship between cognitive and phenomenological variables may be of value in identifying risk markers for psychosis onset, thus contributing to early intervention efforts, as well as in clarifying the essential psychopathological features of schizophrenia and other psychotic disorders. [source] | ||||||||||||||||||||||||||||||||||||||||