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Medical Sciences33%
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Chemistry5%
Psychology5%
Humanities and Social Sciences4%
Earth and Environmental Science4%
Polymers and Materials Science2%
6 Other Domains7%
Distribution within Life Sciences
Neuroscience14%
Ecology & Organismal Biology5%
40 Other Subdomains81%

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    Selected Abstracts

    Bank Mergers and Small Firm Finance: Evidence from Lender Liability

    FINANCIAL MARKETS, INSTITUTIONS & INSTRUMENTS, Issue 2 2008
    James E. McNulty
    As a merger approaches, the value of repeat business for the target bank can drop sharply, so loan relationships between this bank and small businesses are often disrupted. Small firms sometimes experience serious value destruction as a consequence of this sudden lack of credit. This paper shows that lender liability may result from bank mergers and bankers involved in mergers often engage in aggressive, scorched-earth defense tactics to discourage further litigation. I summarize six lender liability cases to illustrate these points. Bank mergers have been shown to reduce credit availability in a number of studies. Since small firms depend on credit for their daily existence, owners of small firms do have a reason to fear a merger of their bank with a larger institution. Analyzing merger effects with survey data of firms obtained after a bank merger, an empirical strategy used in a number of studies, raises problems since the only firms considered are the ones that survived the bank merger. Suggesting that the problem will cure itself in the long run, an argument advanced in other studies, ignores small firms' daily dependence on credit. In the long run we are all dead. Bank examiners need to evaluate an institution's litigation experience and measure a bank's organizational architecture , its ethical climate. Banks which are repeatedly involved in lender liability lawsuits should be denied future mergers until there is a change in organizational architecture. To assist in evaluating organizational architecture, banks should be required to report their litigation expense on their call reports. Furthermore, regulators should seriously consider the recent suggestion of Carow, Kane and Narayanan (2006) that they take steps to ensure that participants in bank mergers preserve target bank relationships. Otherwise negative effects on small business lending and economic growth will continue as bank consolidation proceeds. [source]

    The eyewitness post-identification feedback effect: What is the function of flexible confidence estimates for autobiographical events?

    APPLIED COGNITIVE PSYCHOLOGY, Issue 8 2009
    Gary L. Wells
    Suggesting to eyewitnesses who mistakenly identify someone from a lineup that they identified the right person leads them to recall having been more certain, having a better view during witnessing, and having paid closer attention during witnessing. The post-identification feedback effect is robust and has profound forensic implications because the courts relay on witnesses' answers to these questions to make decisions about the reliability of the identification. The effect seems to occur because there is not an accessible memory trace formed about these retrospective judgments, thereby making witnesses rely on an inference process that responds to the feedback. We speculate on the function served by a cognitive system that does not form accessible memory traces for these judgments. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Etiology, pathogenesis and prevention of neural tube defects

    CONGENITAL ANOMALIES, Issue 2 2006
    Rengasamy Padmanabhan
    ABSTRACT Spina bifida, anencephaly, and encephalocele are commonly grouped together and termed neural tube defects (NTD). Failure of closure of the neural tube during development results in anencephaly or spina bifida aperta but encephaloceles are possibly post-closure defects. NTD are associated with a number of other central nervous system (CNS) and non-neural malformations. Racial, geographic and seasonal variations seem to affect their incidence. Etiology of NTD is unknown. Most of the non-syndromic NTD are of multifactorial origin. Recent in vitro and in vivo studies have highlighted the molecular mechanisms of neurulation in vertebrates but the morphologic development of human neural tube is poorly understood. A multisite closure theory, extrapolated directly from mouse experiments highlighted the clinical relevance of closure mechanisms to human NTD. Animal models, such as circle tail, curly tail, loop tail, shrm and numerous knockouts provide some insight into the mechanisms of NTD. Also available in the literature are a plethora of chemically induced preclosure and a few post-closure models of NTD, which highlight the fact that CNS malformations are of hetergeneitic nature. No Mendelian pattern of inheritance has been reported. Association with single gene defects, enhanced recurrence risk among siblings, and a higher frequency in twins than in singletons indicate the presence of a strong genetic contribution to the etiology of NTD. Non-availability of families with a significant number of NTD cases makes research into genetic causation of NTD difficult. Case reports and epidemiologic studies have implicated a number of chemicals, widely differing therapeutic drugs, environmental contaminants, pollutants, infectious agents, and solvents. Maternal hyperthermia, use of valproate by epileptic women during pregnancy, deficiency and excess of certain nutrients and chronic maternal diseases (e.g. diabetes mellitus) are reported to cause a manifold increase in the incidence of NTD. A host of suspected teratogens are also available in the literature. The UK and Hungarian studies showed that periconceptional supplementation of women with folate (FA) reduces significantly both the first occurrence and recurrence of NTD in the offspring. This led to mandatory periconceptional FA supplementation in a number of countries. Encouraged by the results of clinical studies, numerous laboratory investigations focused on the genes involved in the FA, vitamin B12 and homocysteine metabolism during neural tube development. As of today no clinical or experimental study has provided unequivocal evidence for a definitive role for any of these genes in the causation of NTD suggesting that a multitude of genes, growth factors and receptors interact in controlling neural tube development by yet unknown mechanisms. Future studies must address issues of gene-gene, gene-nutrient and gene,environment interactions in the pathogenesis of NTD. [source]

    Prescribing Flood Regimes to Sustain Riparian Ecosystems along Meandering Rivers

    CONSERVATION BIOLOGY, Issue 5 2000
    Brian D. Richter
    By managing river flows for water supplies and power generation, water management agencies have inadvertently caused considerable degradation of riverine ecosystems and associated biodiversity. New approaches for meeting human needs for water while conserving the ecological integrity of riverine ecosystems are greatly needed. We describe an approach for identifying the natural flooding characteristics that must be protected or restored to maintain riparian ( floodplain) ecosystems along meandering rivers. We developed a computer model to simulate flood-driven changes in the relative abundance of riparian patch types along the Yampa River in Colorado ( U.S.A.). The model is based on research suggesting that the duration of flooding at or above 209 m3 per second (125% of bankfull discharge) is particularly important in driving lateral channel migration, which is responsible for initiating ecological succession in the Yampa's riparian forest. Other hydrologic variables, such as the magnitude of annual peak flows, were not as strongly correlated with lateral channel migration rates. Model simulations enabled us to tentatively identify a threshold of alteration of flood duration that could lead to substantial changes in the abundance of forest patch types over time should river flows be regulated by future water projects. Based on this analysis, we suggest an ecologically compatible water management approach that avoids crossing flood alteration thresholds and provides opportunity to use a portion of flood waters for human purposes. Recommended improvements to the Yampa model include obtaining additional low-elevation aerial photographs of the river corridor to enable better estimation of channel migration rates and vegetation changes. These additional data should greatly improve the model's accuracy and predictive capabilities and therefore its management value. Resumen: La composición y estructura de ecosistemas ribereños están fuertemente ligadas a la variabilidad hidrológica natural. Al manejar el flujo de ríos para abastecer agua y generar energía, las agencias de manejo de agua han causado inadvertidamente una degradación considerable de los ecosistemas ribereños y la biodiversidad asociada a ellos. Se necesitan nuevas estrategias para satisfacer las necesidades humanas de agua al mismo tiempo que se conserva la integridad de los ecosistemas ribereños. Describimos una estrategia para identificar las características de inundaciones naturales que deben ser protegidas o restauradas para mantener ecosistemas riparios ( planicies de inundación) a lo largo de ríos sinuosos. Desarrollamos un modelo de computadora para simular los cambios causados por inundaciones en la abundancia relativa de tipos de parche ripario a lo largo del río Yampa, en Colorado ( Estados Unidos de Norteamérica). Este modelo se basa en investigación que sugiere que la duración de la inundación a, o mayor a, 209 m3 por segundo (125% de descarga del banco lleno a su capacidad) es particularmente importante en la conducción de la migración de canales laterales, lo cual es responsable de la iniciación de la sucesión ecológica en el bosque ripario del río Yampa. Otras variables hidrológicas, como lo es la magnitud del pico de los flujos anuales no estuvieron tan fuertemente correlacionadas con las tasas de migración lateral de canales. Las simulaciones del modelo nos permitieron identificar límites tentativos de alteración de la duración de la inundación que podrían conducir a cambios sustanciales en la abundancia de tipos de parches forestales en el tiempo si los flujos de los ríos son regulados en proyectos de agua futuros. En base a este análisis, sugerimos una estrategia de manejo de agua ecológicamente compatible que evita sobrepasar los límites de alteración de las inundaciones y provee la oportunidad de usar una porción del agua de las inundaciones para fines humanos. Las recomendaciones de mejoras al modelo del río Yampa incluyen la necesidad de obtener fotografías aéreas de baja elevación adicionales del corredor del río, que permitan una mejor estimación de las tasas de migración de los canales y los cambios en la vegetación. Estos datos adicionales deberán mejorar en gran medida la precisión del modelo y sus capacidades predictivas y, por lo tanto, su valor de manejo. [source]

    Public capital formation and labor productivity growth in Chile

    CONTEMPORARY ECONOMIC POLICY, Issue 2 2000
    MD. Ramirez
    Following the lead of the endogenous growth literature, this article analyzes the impact on labor productivity growth of public and private investment spending in Chile. Using cointegration analysis, the results of the dynamic labor productivity function for the 1960,95 period show that (lagged) public and private investment spending, as well as the rate of growth in exports, has a positive and highly significant effect on the rate of labor productivity growth. The estimates also indicate that increases in government consumption spending have a negative effect on the rate of labor productivity growth, thus suggesting that the composition of government spending may also play an important role in determining the rate of labor productivity growth. The findings call into question the politically expedient policy in many Latin American countries of disproportionately reducing public capital expenditures to meet targeted reductions in the fiscal deficit as a proportion of GDP. [source]

    DISTINCTIVE CHARACTERISTICS OF ASSAULTS MOTIVATED BY BIAS,

    CRIMINOLOGY, Issue 3 2004
    STEVEN F. MESSNER
    This research examines the ways in which assaults motivated by bias are similar to and different from other types of assault. Analyses are based on data from the National Incident Based Reporting System (NIBRS), pooled across eleven states. We find evidence suggesting that offenders motivated by racial and ethnic bias are more likely to be versatile offenders than specialists: they are more (not less) likely to be using drugs and alcohol during the crime than conventional offenders. Bias offenders are also more likely to seriously injure the victim. Finally, we find that the risks of bias crime victimization (relative to the risk of assault victimization generally) are similar for blacks and other racial minorities. [source]

    PROPOSITION 8 AND CRIME RATES IN CALIFORNIA: THE CASE OF THE DISAPPEARING DETERRENT

    CRIMINOLOGY AND PUBLIC POLICY, Issue 3 2006
    CHERYL MARIE WEBSTER
    Research Summary: In 1999, Daniel Kessler and Steven Levitt published an article that purported to provide support for the marginal deterrent effects of harsher sanctions on levels of crime. Specifically, they concluded that sentence enhancements that came into effect in California in June 1982 as a result of Proposition 8 were responsible for a subsequent drop in serious crime in this state. Our article examines the analyses and findings of this article and suggests that their conclusion of a deterrent impact fails to withstand scrutiny when more complete and more detailed crime data are used and the comparability of "control" groups is carefully examined. In particular, the addition of annual crime levels for all years (versus only the odd-numbered years that Kessler and Levitt examine) calls into question the prima facie support for a deterrent effect presented by Kessler and Levitt. Specifically, it demonstrates not only that the crime drop in California began before, rather than after, the passing into law of the sentence enhancements in 1982 but also that the downward slope did not accelerate after the change in law. Furthermore, the comparability of the two "control" groups with the "treatment" group is challenged, rendering suspect any findings based on these comparisons. Policy Implications: Case studies suggesting that crime decreased after the imposition of harsh sentencing policies are often cited as evidence of marginal general deterrence. As has been demonstrated in other contexts, the question that needs to be asked is "Compared with what?" Kessler and Levitt's (1999) article demonstrates that those interested in sentencing policy need to be sensitive not only to the appropriateness of the comparisons that are made, but also to the choice of data that are presented. [source]

    Influence of nanocrystalization on magnetoelastic Villari effect in Fe73.5Nb3Cu1Si13.5B9 alloy

    CRYSTAL RESEARCH AND TECHNOLOGY, Issue 3-5 2003
    R. Szewczyk
    Abstract The results of an investigation of the influence of thermal annealing on the magnetoelastic properties of Fe73.5Nb3Cu1Si13.5B9 soft magnetic alloy in both amorphous and nanocrystalline state are presented. A new method developed was used to apply uniform compressive stresses to the investigated ring core made of the alloy. The compressive stresses produced by external mechanical forces were applied perpendicularly to the direction of the magnetizing field. Due to the uniform distribution of stresses in the core brittle nanocrystalline alloys may be tested for stresses up to 10 MPa. The results revealed, that process of nanocrystallisation causes significant increase in the stress sensitivity of the Fe73.5Nb3Cu1Si13.5B9 alloy. Moreover the influence of stresses caused by external forces is more significant at relatively low values of the magnetizing field suggesting that these nanocrystalline soft magnetic materials are stress sensitive in the range of technical operation of inductive components based on such materials. [source]

    Synthesis and degradation of type IV collagen in rat skeletal muscle during immobilization in shortened and lengthened positions

    ACTA PHYSIOLOGICA, Issue 4 2003
    A. M. Ahtikoski
    Abstract Aim:, Type IV collagen is a major protein in basement membranes surrounding and supporting skeletal muscle cells. In the present study, we tested the hypotheses that immobilization down-regulates synthesis and up-regulates degradation of type IV collagen in skeletal muscle. Methods:, mRNA level and concentration of type IV collagen as well as mRNA levels and activities of proteins involved in its degradation were analysed from soleus (SOL), gastrocnemius (GAS) and extensor digitorum longus muscles after immobilization in shortened and lengthened positions for 1, 3 and 7 days. Results:, Following immobilization, type IV collagen mRNA level was decreased in SOL and GAS suggesting down-regulated synthesis of this protein. The mRNA level and activity of matrix metalloproteinase-2 (proMMP-2) were increased in all muscles, while the activity of tissue inhibitor of metalloproteinase-2 was decreased in SOL and GAS. These findings reflect an increased capacity for degradation of type IV collagen. Conclusions: As a consequence of decreased synthesis/degradation ratio immobilization reduced the concentration of type IV collagen in all muscles. The regulation of type IV collagen through synthesis and/or degradation seems, however, to be muscle specific. Immobilization in lengthened position seems to delay and partly decrease the net degradation of type IV collagen. [source]

    Deletion of mdmB impairs mitochondrial distribution and morphology in Aspergillus nidulans

    CYTOSKELETON, Issue 2 2003
    Katrin V. Koch
    Abstract Mitochondria form a dynamic network of interconnected tubes in the cells of Saccharomyces cerevisiae or filamentous fungi such as Aspergillus nidulans,Neurospora crassa, or Podospora anserina. The dynamics depends on the separation of mitochondrial fragments, their movement throughout the cell, and their subsequent fusion with the other parts of the organelle. Interestingly, the microtubule network is required for the distribution in N. crassa and S. pombe, while S. cerevisiae and A. nidulans appear to use the actin cytoskeleton. We studied a homologue of S. cerevisiae Mdm10 in A. nidulans, and named it MdmB. The open reading frame is disrupted by two introns, one of which is conserved in mdm10 of P. anserina. The MdmB protein consists of 428 amino acids with a predicted molecular mass of 46.5 kDa. MdmB shares 26% identical amino acids to Mdm10 from S. cerevisiae, 35% to N. crassa, and 32% to the P. anserina homologue. A MdmB-GFP fusion protein co-localized evenly distributed along mitochondria. Extraction of the protein was only possible after treatment with a non-ionic and an ionic detergent (1% Triton X-100; 0.5% SDS) suggesting that MdmB was tightly bound to the mitochondrial membrane fraction. Deletion of the gene in A. nidulans affected mitochondrial morphology and distribution at 20°C but not at 37°C. mdmB deletion cells contained two populations of mitochondria at lower temperature, the normal tubular network plus some giant, non-motile mitochondria. Cell Motil. Cytoskeleton 55:114,124, 2003. © 2003 Wiley-Liss, Inc. [source]

    Expression of WASP and Scar1/WAVE1 actin-associated proteins is differentially modulated during differentiation of HL-60 cells

    CYTOSKELETON, Issue 4 2003
    Sophie Launay
    Abstract The Wiskott-Aldrich Syndrome (WAS) is a disease associated with mutations in the WAS gene and characterised by developmental defects in haematopoietic cells such as myeloid cells. The Wiskott-Aldrich Syndrome protein (WASP)-family includes Scar1 and WASP, which are key regulators of actin reorganization in motile cells. To understand the roles of Scar1 and WASP in myeloid cells and their cytoskeletal control in haematopoietic tissues, we have explored their expression during differentiation of the promyeloid cell line HL-60. Undifferentiated HL-60 cells expressed Scar1 and WASP, and differentiation to neutrophils, induced by retinoic acid or non-retinoid agent treatments, led to a decrease in the level of expression of Scar1, whereas WASP expression was unaffected. Differentiation to monocytes/macrophages, induced by phorbol ester treatment, resulted in a decreased expression of both proteins in the adherent mature cells. Vitamin D3 treatment or cytochalasin D in combination with PMA treatment did not affect WASP expression suggesting that adhesion and cytoskeletal integrity were both essential to regulate WASP expression. Scar1 expression was regulated by differentiation, adhesion, and cytoskeletal integrity. Recently, WASP was found to colocalize with actin in the podosomes. In contrast, we show here that Scar1 did not localize with the podosomes in mature monocytes/macrophages. These observations show for the first time that modulation of Scar1 and WASP expression is a component of the differentiation program of myeloid precursors and indicate that WASP and Scar1 have different roles in mature myeloid cells. Cell Motil. Cytoskeleton 54:274,285, 2003. © 2003 Wiley-Liss, Inc. [source]

    Early adversity in chronic depression: clinical correlates and response to pharmacotherapy,,

    DEPRESSION AND ANXIETY, Issue 8 2009
    Daniel N. Klein Ph.D.
    Abstract Background: There is growing evidence suggesting that early adversity may be a marker for a distinct pathway to major depressive disorder (MDD). We examined associations between childhood adversity and a broad variety of clinical characteristics and response to pharmacotherapy in a large sample of patients with chronic forms of MDD. Methods: Subjects included 808 patients with chronic forms of MDD (chronic MDD, double depression, or recurrent MDD with incomplete recovery between episodes and a total continuous duration of >2 years) who were enrolled in a 12-week open-label trial of algorithm-guided pharmacotherapy. Baseline assessments included a semi-structured diagnostic interview, and clinician- and self-rated measures of depressive symptoms, social functioning, depressotypic cognitions, and personality traits, and childhood adversity. Patients were re-evaluated every 2 weeks. Results: A longer duration of illness; earlier onset; greater number of episodes, symptom severity, self-rated functional impairment, suicidality, and comorbid anxiety disorder; and higher levels of dysfunctional attitudes and self-criticism were each associated with multiple forms of childhood adversity. A history of maternal overcontrol, paternal abuse, paternal indifference, sexual abuse, and an index of clinically significant abuse each predicted a lower probability of remission. Among patients completing the 12-week trial, 32% with a history of clinically significant abuse, compared to 44% without such a history, achieved remission. Conclusions: These findings indicate that a history of childhood adversity is associated with an especially chronic form of MDD that is less responsive to antidepressant pharmacotherapy. Depression and Anxiety, 2009. Published 2009 Wiley-Liss, Inc. [source]

    Cardiac anxiety in people with and without coronary atherosclerosis,

    DEPRESSION AND ANXIETY, Issue 10 2008
    Craig D. Marker Ph.D.
    Abstract Many studies have shown that cardiac anxiety when occurring in the absence of coronary artery disease is common and quite costly. The Cardiac Anxiety Questionnaire (CAQ) is an 18-item self-report measure that assesses anxiety related to cardiac symptoms. To better understand the construct of cardiac anxiety, a factor analysis was conducted on CAQ data from 658 individuals who were self or physician-referred for electron beam tomographic screening to determine whether clinically significant coronary atherosclerosis was present. A four-factor solution was judged to provide the best fit with the results reflecting the following factor composition: heart-focused attention, avoidance of activities that bring on symptoms, worry or fear regarding symptoms, and reassurance-seeking. Factorial invariance across groups was also assessed to determine whether the factor structure of the CAQ was similar in individuals with and without clear evidence of coronary atherosclerosis. The factor structure of the CAQ did not differ between the two groups. However, the group without coronary atherosclerosis had significantly higher mean scores on their attention and worry/fear factors suggesting that people without a diagnosed cardiac condition pay more attention to and worry more about their cardiac-related symptoms than those people who have coronary atherosclerosis. Depression and Anxiety 2007. Published 2007 Wiley-Liss, Inc. [source]

    Childhood trauma in obsessive-compulsive disorder, trichotillomania, and controls

    DEPRESSION AND ANXIETY, Issue 2 2002
    Christine Lochner M.A.
    Abstract There is relatively little data on the link between childhood trauma and obsessive-compulsive/putative obsessive-compulsive spectrum disorders. The revised Childhood Trauma Questionnaire (CTQ), which assesses physical, emotional, and sexual abuse as well as physical and emotional neglect, was administered to female patients with obsessive-compulsive disorder (OCD; n = 74; age: 36.1 ± 16.3), TTM (n = 36; age: 31.8 ± 12.3), and a group of normal controls (n = 31; age: 21.5 ± 1.0). The findings showed a significantly greater severity of childhood trauma in general, and emotional neglect specifically, in the patient groups compared to the controls. Although various factors may play a role in the etiology of both OCD and trichotillomania (TTM), this study is consistent with some evidence from previous studies suggesting that childhood trauma may play a role in the development of these disorders. Depression and Anxiety 15:66,68, 2002. © 2002 Wiley-Liss, Inc. [source]

    Trends in Pediatric Melanoma Mortality in the United States, 1968 through 2004

    DERMATOLOGIC SURGERY, Issue 2 2008
    KEVAN G. LEWIS MD
    BACKGROUND AND OBJECTIVE Mortality from melanoma in children is a poorly understood and controversial problem in dermatology. There is paucity of research into this important public health dilemma. The purpose of this study was to characterize pediatric melanoma mortality in the United States and to evaluate trends over time. METHODS AND MATERIALS Deaths were derived from a database of more than 75 million records of the U.S. Center for National Health Statistics based on routine death certification. Information on age, race, gender, and geographic location was available for years 1968 through 2004. RESULTS During the 37-year period, there were 643 deaths attributed to melanoma in children under 20 years of age in the United States, an average of 18 per year. The overall age-adjusted mortality rate for melanoma in children was 2.25 deaths per year (per 10 million at-risk individuals). Mortality rates were strongly associated with age. In the oldest age group (age 15,19 years) the mortality rate was approximately an order of magnitude 8,18 times higher compared to younger age groups. Mortality among males was 25% higher than females. Mortality rates for white children were more than twice as high as black children. Overall mortality from melanoma in children declined steadily from 1968 to 2004. The highest mortality rates were observed in Idaho, Nevada, Arizona, and New Mexico. CONCLUSIONS Although mortality from melanoma among children in the United State is low, the magnitude of the public health burden from this preventable cause of death is substantial. In contrast to results of studies suggesting that the incidence of melanoma may be rising in children and adolescents, the data suggest that mortality in these groups may be falling. Additional study is warranted to further characterize and ultimately reduce mortality from childhood melanoma. [source]

    Inhibitory functioning across ADHD subtypes: Recent findings, clinical implications, and future directions

    DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2008
    Zachary W. Adams
    Abstract Although growing consensus supports the role of deficient behavioral inhibition as a central feature of the combined subtype of ADHD (ADHD/C; Barkley 1997 Psychol Bull 121:65,94; Nigg 2001 Psychol Bull 127:571,598), little research has focused on how this finding generalizes to the primarily inattentive subtype (ADHD/I). This question holds particular relevance in light of recent work suggesting that ADHD/I might be better characterized as a disorder separate from ADHD/C (Diamond 2005 Dev Psychopathol 17:807,825; Milich et al. 2001 Clin Psychol Sci Pract 8:463,488). This article describes major findings in the area of inhibitory performance in ADHD and highlights recent research suggesting important areas of divergence between the subtypes. In particular, preliminary findings point to potential differences between the subtypes with respect to how children process important contextual information from the environment, such as preparatory cues that precede responses and rewarding or punishing feedback following behavior. These suggestive findings are discussed in the context of treatment implications, which could involve differential intervention approaches for each subtype targeted to the specific deficit profiles that characterize each group of children. Future research avenues aimed toward building a sound theoretical model of ADHD/I and a better understanding of its relation to ADHD/C are also presented. Specifically, investigators are encouraged to continue studying the complex interplay between inhibitory and attentional processes, as this area seems particularly promising in its ability to improve our understanding of the potentially distinct pathologies underlying the ADHD subtypes. © 2008 Wiley-Liss, Inc. Dev Disabil Res Rev 2008;14:268,275. [source]

    Models of white matter injury: Comparison of infectious, hypoxic-ischemic, and excitotoxic insults

    DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 1 2002
    Henrik Hagberg
    Abstract White matter damage (WMD) in preterm neonates is strongly associated with adverse outcome. The etiology of white matter injury is not known but clinical data suggest that ischemia-reperfusion and/or infection-inflammation are important factors. Furthermore, antenatal infection seems to be an important risk factor for brain injury in term infants. In order to explore the pathophysiological mechanisms of WMD and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, numerous novel animal models have been developed over the past decade. WMD can be induced by antenatal or postnatal administration of microbes (E. coli or Gardnerella vaginalis), virus (border disease virus) or bacterial products (lipopolysaccharide, LPS). Alternatively, various hypoperfusion paradigms or administration of excitatory amino acid receptor agonists (excitotoxicity models) can be used. Irrespective of which insult is utilized, the maturational age of the CNS and choice of species seem critical. Generally, lesions with similarity to human WMD, with respect to distribution and morphological characteristics, are easier to induce in gyrencephalic species (rabbits, dogs, cats and sheep) than in rodents. Recently, however, models have been developed in rats (PND 1,7), using either bilateral carotid occlusion or combined hypoxia-ischemia, that produce predominantly white matter lesions. LPS is the infectious agent most often used to produce WMD in immature dogs, cats, or fetal sheep. The mechanism whereby LPS induces brain injury is not completely understood but involves activation of toll-like receptor 4 on immune cells with initiation of a generalized inflammatory response resulting in systemic hypoglycemia, perturbation of coagulation, cerebral hypoperfusion, and activation of inflammatory cells in the CNS. LPS and umbilical cord occlusion both produce WMD with quite similar distribution in 65% gestational sheep. The morphological appearance is different, however, with a more pronounced infiltration of inflammatory cells into the brain and focal microglia/macrophage ("inflammatory WMD") in response to LPS compared to hypoperfusion evoking a more diffuse microglial response usually devoid of cellular infiltrates ("ischemic WMD"). Furthermore, low doses of LPS that by themselves have no adverse effects in 7-day-old rats (maturation corresponding to the near term human fetus), dramatically increase brain injury to a subsequent hypoxic-ischemic challenge, implicating that bacterial products can sensitize the immature CNS. Contrary to this finding, other bacterial agents like lipoteichoic acid were recently shown to induce tolerance of the immature brain suggesting that the innate immune system may respond differently to various ligands, which needs to be further explored. MRDD Research Reviews 2002;8:30,38. © 2002 Wiley-Liss, Inc. [source]

    Mesenchymal cell remodeling during mouse secondary palate reorientation

    DEVELOPMENTAL DYNAMICS, Issue 7 2010
    Jiu-Zhen Jin
    Abstract The formation of mammalian secondary palate requires a series of developmental events such as growth, elevation, and fusion. Despite recent advances in the field of palate development, the process of palate elevation remains poorly understood. The current consensus on palate elevation is that the distal end of the vertical palatal shelf corresponds to the medial edge of the elevated horizontal palatal shelf. We provide evidence suggesting that the prospective medial edge of the vertical palate is located toward the interior side (the side adjacent to the tongue), instead of the distal end, of the vertical palatal shelf and that the horizontal palatal axis is generated through palatal outgrowth from the side of the vertical palatal shelf rather than rotating the pre-existing vertical axis orthogonally. Because palate elevation represents a classic example of embryonic tissue re-orientation, our findings here may also shed light on the process of tissue re-orientation in general. Developmental Dynamics 239:2110,2117, 2010. © 2010 Wiley-Liss, Inc. [source]

    The formation of the superior and jugular ganglia: Insights into the generation of sensory neurons by the neural crest

    DEVELOPMENTAL DYNAMICS, Issue 2 2010
    Hannah Thompson
    Abstract The superior and jugular ganglia (S/JG) are the proximal ganglia of the IXth and Xth cranial nerves and the sensory neurons of these ganglia are neural crest derived. However, it has been unclear the extent to which their differentiation resembles that of the Dorsal Root Ganglia (DRGs). In the DRGs, neural crest cells undergo neuronal differentiation just after the onset of migration and there is evidence suggesting that these cells are pre-specified towards a sensory fate. We have analysed sensory neuronal differentiation in the S/JG. We show, in keeping with previous studies, that neuronal differentiation initiates long after the cessation of neural crest migration. We also find no evidence for the existence of migratory neural crest cells pre-specified towards a sensory phenotype prior to ganglion formation. Rather our results suggest that sensory neuronal differentiation in the S/JG is the result of localised spatiotemporal cues. Developmental Dynamics 239:439,445, 2010. © 2009 Wiley-Liss, Inc. [source]

    Gli3 -deficient mice exhibit cleft palate associated with abnormal tongue development

    DEVELOPMENTAL DYNAMICS, Issue 10 2008
    Xi Huang
    Abstract Palatogenesis depends on appropriate growth, elevation, and fusion of the palatal shelves and aberration in these processes can lead to palatal clefting. We observed a high incidence of palate clefting in mice deficient in Gli3, known for its role as a repressor in the absence of Shh signaling. In contrast with several current mouse models of cleft palate, Meckel's cartilage extension, cranial neural crest migration, palatal shelf proliferation, apoptosis, and key signaling components mediated by Shh, Bmp, Fgf, and Tgf,, appeared unaffected in Gli3,/, mice. Palatal clefting in Gli3,/, mice was consistently associated with tongue abnormalities such as failure to flatten and improper positioning, implicating a critical role of Gli3 and normal tongue morphogenesis for timely palatal shelf elevation and joining. Furthermore, Gli3,/, palatal shelves grown in roller cultures without tongue can fuse suggesting that the abnormal tongue is likely an impediment for palatal shelf joining in Gli3,/, mutants. Developmental Dynamics 237:3079,3087, 2008. © 2008 Wiley-Liss, Inc. [source]

    Retinoic acid signaling is required for proper morphogenesis of mammary gland

    DEVELOPMENTAL DYNAMICS, Issue 4 2005
    Y. Alan Wang
    Abstract Retinoic acid (RA), a bioactive chemical compound synthesized from dietary derived vitamin A, has been successfully used as a chemopreventive and chemotherapeutic agent through the regulation of cell proliferation, differentiation, and apoptosis acting via the retinoic acid receptors. Despite two decades of research on the function of retinoic acid, the physiological role of RA in mammary gland development is still not well characterized. In this report, we demonstrate that RA is required for proper morphogenesis of mouse mammary gland in a novel transgenic mouse model system. It was found that inhibition of RA signaling in vivo leads to excessive mammary ductal morphogenesis through upregulation of cyclin D1 and MMP-3 expression. Furthermore, we show that the transgene-induced excessive branching morphogenesis could be reversed by treatment with RA, demonstrating the direct physiological effect of RA signaling in vivo. In addition, we demonstrate that excessive branching morphogenesis in the transgenic mammary gland are cell-autonomous and do not require stromal signals within the transgenic mammary gland. Finally, we provide evidence suggesting that retinoic acid signaling is required for appropriate mammary gland differentiation. Collectively, our data indicate for the first time that retinoic acid signaling is required to maintain the homeostasis of mammary gland morphogenesis. Developmental Dynamics 234:892,899, 2005. © 2005 Wiley-Liss, Inc. [source]

    Retinoic acid, a regeneration-inducing molecule

    DEVELOPMENTAL DYNAMICS, Issue 2 2003
    Malcolm Maden
    Abstract Retinoic acid (RA) is the biologically active metabolite of vitamin A. It is a low molecular weight, lipophilic molecule that acts on the nucleus to induce gene transcription. In amphibians and mammals, it induces the regeneration of several tissues and organs and these examples are reviewed here. RA induces the "super-regeneration" of organs that can already regenerate such as the urodele amphibian limb by respecifying positional information in the limb. In organs that cannot normally regenerate such as the adult mammalian lung, RA induces the complete regeneration of alveoli that have been destroyed by various noxious treatments. In the mammalian central nervous system (CNS), which is another tissue that cannot regenerate, RA does not induce neurite outgrowth as it does in the embryonic CNS, because one of the retinoic acid receptors, RAR,2, is not up-regulated. When RAR,2 is transfected into the adult spinal cord in vitro, then neurite outgrowth is stimulated. In all these cases, RA is required for the development of the organ, in the first place suggesting that the same gene pathways are likely to be used for both development and regeneration. This suggestion, therefore, might serve as a strategy for identifying potential tissue or organ targets that have the capacity to be stimulated to regenerate. Developmental Dynamics 226:237,244, 2003.© 2003 Wiley-Liss, Inc. [source]

    Are antidepressants safe in the treatment of bipolar depression?

    ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2008
    A critical evaluation of their potential risk to induce switch into mania or cycle acceleration
    Objective:, To address whether switch of depression into hypomania or mania or cycle acceleration in patients with bipolar disorder is caused by antidepressants or whether this phenomenon is attributable to the natural history of bipolar disorder itself. Method:, A critical review of the literature, pointing at sources of bias that have been previously overlooked. For examining the causation in question, the Bradford,Hill criteria were applied, i.e. specificity of the potential causative agent, strength of effect, consistency in findings, dose,response relation, temporal relation with exposure to agent preceding effect and biological plausibility. Results:, There is a scarcity of randomized studies addressing the question, and the available studies all suffer from various forms of bias. However, there is some evidence suggesting that antidepressants given in addition to a mood stabilizer are not associated with an increased rate of switch when compared with the rate associated with the mood stabilizer alone. Conclusion:, When combined with a mood stabilizer, antidepressants given for acute bipolar depression seemingly do not induce a switch into hypomania or mania. Whether antidepressants may accelerate episode frequency and/or may cause other forms of destabilization in patients with bipolar disorder remain to be properly studied. [source]

    Extinction in the developing rat: An examination of renewal effects

    DEVELOPMENTAL PSYCHOBIOLOGY, Issue 6 2007
    Carol S.L. Yap
    Abstract In the present series of experiments the context-specificity of extinction was examined from a developmental perspective. For postnatal day (PN) 23 rats, renewal of freezing to an aversive odor conditioned stimulus (CS) was observed when rats were conditioned in Context A, extinguished in Context B, and tested in Context A (i.e., ABA renewal). This effect was not observed in PN16 rats, which is consistent with previous studies suggesting that rats <,PN20 are impaired in encoding contextual information [i.e., Carew and Rudy [1991]. Developmental Psychobiology, 24, 191,209]. Subsequent experiments demonstrated that for rats conditioned at PN16 and tested at PN23, contextual regulation of extinction performance depended on the age at which extinction occurred. Specifically, ABA renewal was observed in rats given extinction training at PN22 but not in rats given extinction training at PN17. These latter results show that whether or not context regulates the expression of an ambiguous memory is determined by the animal's age when the memory becomes ambiguous. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 565-575, 2007. [source]

    Doesn't see, doesn't know: is anticipatory looking really related to understanding or belief?

    DEVELOPMENTAL SCIENCE, Issue 1 2001
    Wendy A. Garnham
    Clements and Perner (Cognitive Development, 9 (1994), 377,397) reported that children show understanding of a story character's belief in their anticipatory looking responses before they show this in their answers to test questions. According to Clements and Perner the anticipatory looking responses provide evidence of implicit understanding of belief. This paper examines the possibility that the anticipatory looking measure is indicative of (a) children using a seeing = knowing rule, i.e. children linking not seeing with ignorance rather than a sensitivity to belief, or (b) a tendency to associate the protagonist with the left-hand container. Thirty-two children aged between 2 years 11 months and 4 years were told a false belief story similar to that used in Clements and Perner (1994) except that three containers were used instead of two. The protagonist first looks inside the middle box but then puts the object in the left-hand box. In his absence, a second character moves the object unexpectedly to the right-hand box. If children's anticipatory looking was based on sensitivity to belief then they should have looked clearly to the left-hand box. If it was based on an association bias or sensitivity to the character not knowing then they should have looked equally to the left-hand and middle boxes. The results were consistent with the former prediction suggesting that children's anticipatory looking responses may indeed be governed by an implicit sensitivity to belief. [source]

    Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature

    DIABETES OBESITY & METABOLISM, Issue 4 2010
    L. Nalysnyk
    Aim: The objective of this review was to assess the published evidence for an association between glycaemic variability and the development of chronic micro- and macrovascular complications in patients with diabetes mellitus (DM). Methods: A systematic review of English-language literature published from January 1990 through November 2008 was performed. Interventional and observational studies in patients with type 1 or type 2 DM reporting a measure of glycaemic variability and its impact on the development or progression of micro- and macrovascular diabetic complications were assessed. Results: A total of 18 studies ,8 on type 1 DM and 10 on type 2 DM patients,meeting the inclusion criteria were identified. Studies in patients with type 1 DM revealed that glucose variability has little impact on the development of diabetic complications. Only in two of the eight type 1 DM studies did glucose variability have a significant association with microvascular complications, but not with macrovascular complications. Among type 2 DM studies, a significant positive association between glucose variability and the development or progression of diabetic retinopathy, cardiovascular events and mortality was reported in 9 of 10 studies. Only one type 2 DM study reported no association between glucose variability and progression of retinopathy. Conclusions: Based on this overview of the available evidence, there appears to be a signal suggesting that glucose variability, characterized by extreme glucose excursions, could be a predictor of diabetic complications, independent of HbA1c levels, in patients with type 2 DM. Better daily control of blood glucose excursions, especially in the postprandial period, may reduce the risk of these complications. Future prospective trials evaluating and comparing the effect of the control of glycaemic variability on the development of diabetic micro- and macrovascular complications are needed to further strengthen the evidence base. [source]

    Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathy

    DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2009
    Yumiko Yoshida
    Abstract Background Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. We investigated here whether and how PEDF could prevent the development of diabetic retinopathy. Methods Streptozotocin-induced diabetic rats were treated with or without intravenous injection of PEDF for 4 weeks. Early neuronal derangements were evaluated by electroretinogram (ERG) and immunofluorescent staining of glial fibrillary acidic protein (GFAP). Expression of PEDF and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress, was localized by immunofluorescence. Vascular endothelial growth factor (VEGF) and p22phox expression were evaluated with western blots. Breakdown of blood retinal barrier (BRB) was quantified with fluorescein isothiocynate (FITC)-conjugated dextran. NADPH oxidase activity was measured with lucigenin luminescence. Results Retinal PEDF levels were reduced, and amplitudes of a- and b-wave in the ERG were decreased in diabetic rats, which were in parallel with GFAP overexpression in the Müller cells. Further, retinal 8-OHdG, p22phox and VEGF levels and NADPH oxidase activity were increased, and BRB was broken in diabetic rats. Administration of PEDF ameliorated all of the characteristic changes in early diabetic retinopathy. Conclusions Results suggest that PEDF could prevent neuronal derangements and vascular hyperpermeability in early diabetic retinopathy via inhibition of NADPH oxidase-driven oxidative stress generation. Substitution of PEDF may offer a promising strategy for halting the development of diabetic retinopathy. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    SUMO4 and its role in type 1 diabetes pathogenesis

    DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2008
    Cong-Yi Wang
    Abstract Susceptibility to type 1 diabetes (T1D) is determined by interactions of multiple genes with unknown environmental factors. Despite the characterization of over 20 susceptibility regions for T1D, identification of specific genes in these regions is still a formidable challenge. In 2004, we first reported the cloning of a novel, small ubiquitin-like modifier (SUMO) gene, SUMO4, in the IDDM5 interval on chromosome 6q25, and presented strong genetic and functional evidence suggesting that SUMO4 is a T1D susceptibility gene. Subsequent studies have consistently confirmed this association in multiple Asian populations despite controversial observations in Caucasians. In this review, we will update the genetic evidence supporting SUMO4 as a T1D susceptibility gene and discuss the possible explanations for the discrepant associations observed in Caucasians. We will then discuss the mechanisms through which SUMO4 contributes to the pathogenesis of T1D. Copyright © 2007 John Wiley & Sons, Ltd. [source]

    Stroke in patients with diabetes mellitus

    DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2004
    Boris N. Mankovsky
    Abstract The article's objective is to review the key advances in the scientific literature related to the association of stroke with diabetes mellitus and to summarize the current approaches to stroke prevention in diabetic patients. The key findings from the literature regarding stroke incidence in patients with diabetes, specific and nonspecific risk factors of stroke in the diabetic population, such as arterial hypertension, dyslipidemia, hyperglycemia, diabetes duration, diabetic complications, insulin resistance/hyperinsulinemia, course and outcome of stroke in subjects with diabetes and/or hyperglycemia, and the peculiarities of type, site and size of stroke in diabetic patients are discussed. The results of recent clinical trials aimed at correcting hyperglycemia, hypertension, and dyslipidemia, to prevent stroke in people with diabetes, are reviewed. The medical database Medline along with original articles from peer-reviewed journals were used for analysis. There is convincing evidence suggesting that diabetes mellitus represents a strong independent risk factor of stroke. The contribution of hyperglycemia to increased stroke risk is not proven. Data suggest an association of the full cluster of the insulin resistance syndrome and stroke. Diabetes is a risk factor mainly for ischemic stroke, while its association with hemorrhagic stroke remains controversial. Hyperglycemia is common in stroke patients, but it is not known whether it independently influences the course and outcome of stroke or merely reflects stroke severity and location. Aggressive control of arterial hypertension and dyslipidemia allows to decrease the risk of stroke in diabetic patients substantially, while the importance of glucose control for stroke prevention remains unproven. Copyright © 2004 John Wiley & Sons, Ltd. [source]

    Type 2 diabetes mellitus: a disease of the innate immune system?

    DIABETIC MEDICINE, Issue 3 2004
    An update
    Abstract A few years ago a hypothesis was proposed suggesting that elements of the innate immune system, such as acute phase reactants, contribute to the development of Type 2 diabetes mellitus. Acute phase reactants such as C-reactive protein and sialic acid may thus predict risk of developing Type 2 diabetes mellitus, as well as being markers of diabetes microvascular and macrovascular complications. This article discusses these issues. [source]