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Selected AbstractsOrgan patterning in the adult stage: The role of Wnt/,-catenin signaling in liver zonation and beyondDEVELOPMENTAL DYNAMICS, Issue 1 2010Rolf Gebhardt Abstract Wnt/,-catenin signaling has been found to play key roles in metabolic zonation of adult liver, regeneration, and hepatocellular carcinogenesis. In this review, recent progress in this field is summarized, in particular the rapidly growing knowledge about the various interactions of ,-catenin with many transcription factors involved in controlling metabolism. These interactions may provide the basis for understanding how the wide range of activities of Wnt/,-catenin signaling is differentially interpreted. Based on these results, a three-level mode for the molecular interpretation of ,-catenin activity gradients in liver is proposed favoring cell differentiation, metabolic zonation, and proliferation. While derangement of the combinatorial interplay of the various transcription factors with ,-catenin at the intermediary activity level may contribute to the development of metabolic diseases, extremely high activation of ,-catenin may eventually lead to initiation and progression of hepatocellular tumors. Developmental Dynamics 239:45,55, 2010. © 2009 Wiley-Liss, Inc. [source] Human B cells express the orphan chemokine receptor CRAM-A/B in a maturation-stage-dependent and CCL5-modulated mannerIMMUNOLOGY, Issue 2 2008Tanja N. Hartmann Summary Chemokines orchestrate the organization of leucocyte recruitment during inflammation and homeostasis. Despite growing knowledge of chemokine receptors, some orphan chemokine receptors are still not characterized. The gene CCRL2 encodes such a receptor that exists in two splice variants, CRAM-A and CRAM-B. Here, we report that CRAM is expressed by human peripheral blood and bone marrow B cells, and by different B-cell lines dependent on the B-cell maturation stage. Intriguingly, CRAM surface expression on the pre-B-cell lines Nalm6 and G2 is specifically upregulated in response to the inflammatory chemokine CCL5 (RANTES), a chemokine that is well known to play an important role in modulating immune responses. Although Nalm6 cells do not express any of the known CCL5 binding receptors, extracellular signal-regulated kinases 1 and 2 (ERK1/2) are phosphorylated upon CCL5 stimulation, suggesting a direct effect of CCL5 through the CRAM receptor. However, no calcium mobilization or migratory responses upon CCL5 stimulation are induced in B-cell lines or in transfected cells. Also, ERK1/2 phosphorylation cannot be inhibited by pertussis toxin, suggesting that CRAM does not couple to Gi proteins. Our results describe the expression of a novel, non-classical chemokine receptor on B cells that is potentially involved in immunomodulatory functions together with CCL5. [source] Comparison of Adaptive Behavior in Children With Heavy Prenatal Alcohol Exposure or Attention-Deficit/Hyperactivity DisorderALCOHOLISM, Issue 11 2009Nicole Crocker Background:, Adaptive behavior, the ability to respond successfully to everyday demands, may be especially sensitive to the effects of heavy prenatal alcohol exposure. Similar adaptive dysfunction is common in other developmental disorders including attention-deficit/hyperactivity disorder (ADHD). ADHD is frequently present in alcohol-exposed children and this overlap in clinical presentation makes identification of alcohol-exposed children difficult. Direct comparison of children with prenatal alcohol exposure and ADHD may yield distinct patterns of cognitive and behavioral performance and add to growing knowledge of the neuropsychological and behavioral profile of prenatal alcohol exposure. Therefore, the aim of the current study was to compare adaptive behavior in children with histories of heavy prenatal alcohol exposure (ALC), nonexposed children with ADHD (ADHD), and typically developing controls (CON). Methods:, Sixty-five children (ALC = 22, ADHD = 23, CON = 20) were selected from a larger ongoing study of the behavioral teratogenicity of alcohol. Alcohol-exposed and control participants were selected to match the ADHD subjects on age, sex, socioeconomic status, and race/ethnicity. Caregivers were administered the Vineland Adaptive Behavior Scales, a semi-structured interview, and were asked to rate their child's behavior on 3 domains of adaptive function. Data were analyzed using regression techniques. Results:, Relative to controls, children in both the ALC and ADHD groups showed adaptive behavior deficits on all 3 domains and children in the ALC group were significantly more impaired than the ADHD group on the daily living skills domain. Within the ALC group, socialization standard scores were lower at older ages. This negative relationship between age and standard scores in the ALC group was also observed on the communication domain, a finding not previously reported. Conclusions:, This study suggests that both children with prenatal alcohol exposure and children with ADHD show impairments in adaptive function relative to controls, but that the pattern of impairment differs between these clinical groups. Adaptive ability in children with prenatal alcohol exposure is characterized by an arrest in development, as evidenced by a lack of improvement with age in socialization and communication scores. In contrast, children with ADHD exhibit a developmental delay in adaptive ability as their scores continued to improve with age, albeit not to the level of control children. Continued research focused on elucidating the patterns of deficits that exist in alcohol-exposed children ultimately will lead to improved differential diagnosis and effective interventions. [source] PRACTICAL MANAGEMENT OF DIET AND LIFESTYLE INTERVENTIONS FOR PEOPLE WITH DIABETES OR CARDIOVASCULAR DISEASEJOURNAL OF RENAL CARE, Issue 2010Fiona Symes BSc (Hons) SUMMARY Increased collaboration between the vascular specialities is clearly leading to increased understanding of the interrelationships between the different disease states and how each impacts and influences the other. This advantage will be reflected in improved patient care if the practical outputs of this growing knowledge are carefully implemented at service level. This article outlines how the aspects of diet and lifestyle associated with vascular-related disease complement, contrast and in some cases contradict each other. It gives information and guidelines as to how the expertise of dietitians working in the different specialist areas might usefully be shared to be of maximum advantage to all patients. [source] EVALUATION OF REPLICATED PROJECTIVE MAPPING OF GRANOLA BARSJOURNAL OF SENSORY STUDIES, Issue 5 2010JESSICA KENNEDY ABSTRACT The application of projective mapping to quickly gather information on overall product differences provides a unique way to probe consumer perceptions and gather product information. A group of 15 consumers performed a projective mapping exercise three times on a set of eight "berry flavored" granola bars, including descriptors of the products. The projective mapping task was performed in replicates to evaluate the consistency of results obtained via this technique. Analysis of the replications by multifactor analysis indicated for the majority of consumers, that the three individual maps did not show a high degree of similarity (80% of RV coefficients < 0.5). However, consensus maps from the three replications indicated a similar group perception of the products over the replications, as depicted by hierarchical multifactor analysis. Terms collected from the maps were summarized and regressed into the product space for interpretation, both in terms of consumer criteria used to differentiate among products and identification of key product attributes. PRACTICAL APPLICATIONS The findings from this study add to the growing knowledge on projective mapping. The results presented here aimed to substantiate the value and reliability of projective mapping when used with consumers. Although projective mapping is not a replacement for quantitative descriptive analysis, it is an efficient tool for consumer research; as well as product or category exploration which can be utilized early in the product development process. The addition of descriptors directly onto the maps by panelists makes it possible to use projective mapping as a stand-alone method by increasing the amount and interpretability of data provided by panelists. When used with consumers, projective mapping links the consumer perception of the product space with a consumer-driven lexicon. [source] Leukotriene pathway genetics and pharmacogenetics in allergyALLERGY, Issue 6 2009N. P. Duroudier Leukotrienes (LT) are biologically active lipid mediators known to be involved in allergic inflammation. Leukotrienes have been shown to mediate diverse features of allergic conditions including inflammatory cell chemotaxis/activation and smooth muscle contraction. Cysteinyl leukotrienes (LTC4, LTD4 and, LTE4) and the dihydroxy leukotriene LTB4 are generated by a series of enzymes/proteins constituting the LT synthetic pathway or 5-lipoxygenase (5-LO) pathway. Their function is mediated by interacting with multiple receptors. Leukotriene receptor antagonists (LTRA) and LT synthesis inhibitors (LTSI) have shown clinical efficacy in asthma and more recently in allergic rhinitis. Despite growing knowledge of leukotriene biology, the molecular regulation of these inflammatory mediators remains to be fully understood. Genes encoding enzymes of the 5-LO pathway (i.e. ALOX5, LTC4S and LTA4H) and encoding for LT receptors (CYSLTR1/2 and LTB4R1/2) provide excellent candidates for disease susceptibility and severity; however, their role remains unclear. Preliminary data also suggest that 5-LO pathway/receptor gene polymorphism can predict patient responses to LTSI and LTRA; however, the exact mechanisms require elucidation. The aim of this review was to summarize the recent advances in the knowledge of these important mediators, focusing on genetic and pharmacogenetic aspects in the context of allergic phenotypes. [source] |