Feb 2013, Volume 8 Issue 1
    

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  • REVIEW
    Pippa A. THOMSON, Elise L.V. MALAVASI, Ellen GRüNEWALD, Dinesh C. SOARES, Malgorzata BORKOWSKA, J. Kirsty MILLAR

    Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points toward DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain.

  • REVIEW
    Chantal E. AYRES-SANDER, Anjelica L. GONZALEZ

    The native extracellular matrix (ECM) and the cells that comprise human tissues are together engaged in a complex relationship; cells alter the composition and structure of the ECM to regulate the material and biologic properties of the surrounding environment while the composition and structure of the ECM modulates cellular processes that maintain healthy tissue and repair diseased tissue. This reciprocal relationship occurs via cell adhesion molecules (CAMs) such as integrins, selectins, cadherins and IgSF adhesion molecules. To study these cell-ECM interactions, researchers use two-dimensional substrates or three-dimensional matrices composed of native proteins or bioactive peptide sequences to study single cell function. While two-dimensional substrates provide valuable information about cell-ECM interactions, three-dimensional matrices more closely mimic the native ECM; cells cultured in three-dimensional matrices have demonstrated greater cell movement and increased integrin expression when compared to cells cultured on two-dimensional substrates. In this article we review a number of cellular processes (adhesion, motility, phagocytosis, differentiation and survival) and examine the cell adhesion molecules and ECM proteins (or bioactive peptide sequences) that mediate cell functionality.

  • REVIEW
    Iouri CHEPELEV, Xin CHEN

    The application of stem cells to regenerative medicine depends on a thorough understanding of the molecular mechanisms underlying their pluripotency. Many studies have identified key transcription factor-regulated transcriptional networks and chromatin landscapes of embryonic and a number of adult stem cells. In addition, recent publications have revealed another interesting molecular feature of stem cells— a distinct alternative splicing pattern. Thus, it is possible that both the identity and activity of stem cells are maintained by stem cell-specific mRNA isoforms, while switching to different isoforms ensures proper differentiation. In this review, we will discuss the generality of mRNA isoform switching and its interaction with other molecular mechanisms to regulate stem cell pluripotency, as well as the reprogramming process in which differentiated cells are induced to become pluripotent stem cell-like cells (iPSCs).

  • REVIEW
    David S. SENCHINA, Justus E. HALLAM, David J. CHENEY

    This paper examines cellular and molecular mechanisms that may underpin the purported effects of five herbal supplements in the context of athlete immune function. Ginseng and echinacea are used frequently by athletes, whereas astragalus and elderberry are used infrequently and pequi is just emerging as a possible supplement. In vivo studies of these products on athlete immune function have yielded heterogeneous results, likely due to experimental design differences. Ginseng, echinacea, elderberry, and pequi are considered asterids sensu lato. Ginseng appears to exert strongest effects on components of adaptive immunity, in particular maintaining Th1/Th2 balance of CD4+ T cells and their downstream effects, via its ginsenosides, flavonoids, and polysaccharides. Echinacea alkamides, caffeic acid derivatives, and polysacchardies may target both innate and adaptive immunity, though perhaps the former more consistently. Elderberry harbors anthocyanins and lectins which may modulate innate immunity. Data on pequi is limited but suggests that carotenoids, phenols, and fatty acids may alter circulating leukocyte populations. More phylogenetically distant, astragalus is a rosid sensu lato and may influence the innate immune system through flavonoids, polysaccharides, and saponins. Supplements generally demonstrate no effects on physiologic parameters such as lactate, oxygen dynamics, or athletic performance. Bioavailability studies indicate that purported bioactive molecules of these supplements may reach circulation in low but therapeutically-relevant quantities. Difficulties in cross-comparisons due to study design differences, coupled with an overall dearth of research on the topic, currently hamper any formal conclusions regarding the efficacy of these supplements as immunoregulators for athletes.

  • REVIEW
    John-Mary VIANNEY, Monica J. MCCULLOUGH, Amy M. GYORKOS, John M. SPITSBERGEN

    The focus of this review is to highlight the importance of glial cell line-derived neurotrophic factor (GDNF) for the motor nervous system. GDNF is the most potent survival factor for motor neurons, where it enhances maintenance and survival of both developing and mature motor neurons in vivo and in vitro. GDNF aids in neuromuscular junction formation, maintenance, and plasticity, where skeletal muscle-derived GDNF may be responsible for this phenomenon. Increased levels of physical activity can increase GDNF protein levels in skeletal muscle, where alterations in acetylcholine and acetylcholine receptor activation may be involved in regulation of these changes observed. With inactivity and disuse, GDNF expression shows different patterns of regulation in the central and peripheral nervous systems. Due to its potent effects for motor neurons, GDNF is being extensively studied in neuromuscular diseases.

  • REVIEW
    Kundan KUMAR, Dhammaprakash Pandhari WANKHEDE, Alok Krishna SINHA

    Common mechanisms plants use to translate the external stimuli into cellular responses are the activation of mitogen-activated protein kinase (MAPK) cascade. These MAPK cascades are highly conserved in eukaryotes and consist of three subsequently acting protein kinases, MAP kinase kinase kinase (MAPKKK), MAP kinase kinase (MAPKK) and MAP kinase (MAPK) which are linked in various ways with upstream receptors and downstream targets. Plant MAPK cascades regulate numerous processes, including various environmental stresses, hormones, cell division and developmental processes. The number of MAPKKs in Arabidopsis and rice is almost half the number of MAPKs pointing important role of MAPKKs in integrating signals from several MAPKKKs and transducing signals to various MAPKs. The cross talks between different signal transduction pathways are concentrated at the level of MAPKK in the MAPK cascade. Here we discussed the insights into MAPKK mediated response to environmental stresses and in plant growth and development.

  • REVIEW
    Vidyalakshmi RAJAGOPALAN, Jonathan P. D’AMICO, David E. WILKES

    The dynein motor protein family is involved in a wide variety of functions in eukaryotic cells. The axonemal dynein class and cytoplasmic dynein-1 subclass have been well characterized. However, the cytoplasmic dynein-2 subclass of the family has only recently begun to be understood. We describe the entire dynein family but focus on cytoplasmic dynein-2. Dynein-2 consists of a heavy, an intermediate, a light intermediate, and a light chain. The complex appears to function primarily as the retrograde motor for intraflagellar transport. This process is important for the formation and maintenance of cilia and flagella. Additionally, dynein-2 has roles in the control of ciliary length and in non-ciliary functions. Mutations in the human dynein-2 heavy chain lead to cilia-related diseases.