Effects of PAX3-FKHR on malignant phenotypes in alveolar rhabdomyosarcoma

The malignancy of alveolar rhabdomyosarcoma (ARMS) has been linked to expression of the PAX3-FKHR chimeric gene. To understand the effect of this gene, we used RNAi to knock down its expression (without affecting the expressions of either PAX3 or FKHR) in human ARMS cell lines. Down-regulating PAX3-FKHR caused (a) tumor cells to accumulate in the G1 phase, inhibiting the rate of cellular proliferation, (b) a reduction in the levels of the MET, reducing cell motility stimulated by HGF, and (c) induction of the myogenic differentiation gene, myogenin, and muscle differentiation (morphologic change and the expression of muscle specific proteins, desmin, and myosin heavy chain). These results suggest that PAX3-FKHR in ARMS cells promotes malignant phenotypes such as proliferation, motility, and to suppress differentiation.     

Characterising chromosome rearrangements: recent technical advances in molecular cytogenetics

Genomic rearrangements can result in losses, amplifications, translocations and inversions of DNA fragments thereby modifying genome architecture, and potentially having clinical consequences. Many genomic disorders caused by structural variation have initially been uncovered by early cytogenetic methods. The last decade has seen significant progression in molecular cytogenetic techniques, allowing rapid and precise detection of structural rearrangements on a whole-genome scale. The high resolution attainable with these recently developed techniques has also uncovered the role of structural variants in normal genetic variation alongside single-nucleotide polymorphisms (SNPs). We describe how array-based comparative genomic hybridisation, SNP arrays, array painting and next-generation sequencing analytical methods (read depth, read pair and split read) allow the extensive characterisation of chromosome rearrangements in human genomes.     

Divide and polarize: recent advances in the molecular mechanism regulating epithelial tubulogenesis

Epithelial organs are generated from groups of non-polarized cells by a combination of processes that induce the acquisition of cell polarity, lumen formation, and the subsequent steps required for tubulogenesis. The subcellular mechanisms associated to these processes are still poorly understood. The extracellular environment provides a cue for the initial polarization, while cytoskeletal rearrangements build up the three-dimensional architecture that supports the central lumen. The proper orientation of cell division in the epithelium has been found to be required for the normal formation of the central lumen in epithelial morphogenesis. Moreover, recent data in cellular models and in vivo have shed light into the underlying mechanisms that connect the spindle orientation machinery with cell polarity. In addition, recent work has clarified the core molecular components of the vesicle trafficking machinery in epithelial morphogenesis, including Rab-GTPases and the Exocyst, as well as an increasing list of microtubule-binding and actin-binding proteins and motors, most of which are conserved from yeast to humans. In this review we will focus on the discussion of novel findings that have unveiled important clues for the mechanisms that regulate epithelial tubulogenesis.     

鸟类分子系统地理学研究进展

分子系统地理学是当代生物地理学的重要分支,是以分子生物学方法重建种内和种上水平的系统发育关系,阐释进化历史,并通过分析近缘生物类群的系统发育关系与其空间和时间分布格局间的相关性构建生物区系历史的研究,是分子生物学与生物地理学结合的产物。中性进化学说和溯祖理论分析的建立,以及线粒体DNA和微卫星标记等分子遗传标记的应用,为分子系统地理学研究的开展提供了理论和实践基础。近年来,分子系统地理方法在鸟类学研究中的应用揭示了许多不同于传统认知的发现,为准确而深入的了解鸟类分子系统地理格局的差异和不同类群的起源中心提供了新颖的证据。目前的研究多从隔离分化说和扩散说的角度对鸟类分子系统地理格局的成因进行分析,而迁徙行为不同对鸟类系统地理格局的影响为成因的解释提供了新的角度。结合区域特点的比较分子系统地理研究,在更广泛的地域和更多类群中开展研究是我国鸟类分子系统地理研究的方向。此外,展望了第二代测序技术对分子生态生物地理研究具有的潜在促进作用。     

PAX genes in development and disease: the role of PAX2 in urogenital tract development

PAX genes play an important role in fetal development. Moreover, heterozygous mutations in several PAX genes cause human disease. Here we review the role of PAX2 in kidney development, focusing on the morphological effects of PAX2 mutations. We discuss the role of PAX2 in the context of an inhibitory field model of kidney branching morphogenesis and summarize recent progress in this area.     

Phytochrome structure and photochemistry: recent advances toward a complete molecular picture

Phytochromes are nature's primary photoreceptors dedicated to detecting the red and far-red regions of the visible light spectrum, a region also essential for photosynthesis and thus crucial to the survival of plants and other photosynthetic organisms. Given their roles in measuring competition and diurnal/seasonal light fluctuations, understanding how phytochromes work at the molecular level would greatly aid in engineering crop plants better suited to specific agricultural settings. Recently, scientists have determined the three-dimensional structures of prokaryotic phytochromes, which now provide clues as to how these modular photoreceptors might work at the atomic level. The models point toward a largely unifying mechanism whereby novel knot, hairpin, and dimeric interfaces transduce photoreversible bilin isomerization into protein conformational changes that alter signal output.     

Immunogenetic mechanisms leading to thyroid autoimmunity: recent advances in identifying susceptibility genes and regions

The autoimmune thyroid diseases (AITD) include Graves' disease (GD) and Hashimoto's thyroiditis (HT), which are characterised by a breakdown in immune tolerance to thyroid antigens. Unravelling the genetic architecture of AITD is vital to better understanding of AITD pathogenesis, required to advance therapeutic options in both disease management and prevention. The early whole-genome linkage and candidate gene association studies provided the first evidence that the HLA region and CTLA-4 represented AITD risk loci. Recent improvements in; high throughput genotyping technologies, collection of larger disease cohorts and cataloguing of genome-scale variation have facilitated genome-wide association studies and more thorough screening of candidate gene regions. This has allowed identification of many novel AITD risk genes and more detailed association mapping. The growing number of confirmed AITD susceptibility loci, implicates a number of putative disease mechanisms most of which are tightly linked with aspects of immune system function. The unprecedented advances in genetic study will allow future studies to identify further novel disease risk genes and to identify aetiological variants within specific gene regions, which will undoubtedly lead to a better understanding of AITD patho-physiology.