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July 2nd

  • Stirred, Not Shaken: Bio-inspired Cilia Mix Medical Reagents At Small Scales: research groups have tried to develop structures that mimic cilia, which do the small-scale moving and shaking inside the human body. The problem is that each cilium finger must be very flexible in order to vibrate -- so delicate, in fact, that manufactured cilia of this size collapse as they are placed in water. The UW team solved the problem by manufacturing the cilia underwater, Chung said. The resulting prototype is a flexible rubber structure with fingers 400 micrometers long (about 1/100 of an inch)

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  • Animal models of human disease: zebrafish swim into view: Despite the pre-eminence of the mouse in modelling human disease, several aspects of murine biology limit its routine use in large-scale genetic and therapeutic screening. Many researchers who are interested in an embryologicall y and genetically tractable disease model have now turned to zebrafish. Zebrafish biology allows ready access to all developmental stages, and the optical clarity of embryos and larvae allow real-time imaging of developing pathologies. Sophisticated mutagenesis and screening strategies on a large scale, and with an economy that is not possible in other vertebrate systems, have generated zebrafish models of a wide variety of human diseases. This Review surveys the achievements and potential of zebrafish for modelling human diseases and for drug discovery and development(Ma y 2007)
  • The cell biological basis of ciliary disease: Defects in cilia cause a broad spectrum of human diseases known collectively as the ciliopathies. Although all ciliopathies arise from defective cilia, the range of symptoms can vary significantly, and only a small subset of the possible ciliary disease symptoms may be present in any given syndrome. This complexity is puzzling until one realizes that the cilia are themselves exceedingly complex machines that perform multiple functions simultaneously , such that breaking one piece of the machine can leave some functions intact while destroying others. The clinical complexity of the ciliopathies can therefore only be understood in light of the basic cell biology of the cilia themselves, which I will discuss from the viewpoint of cell biological studies in model organisms (January 2008)
  • Finding function in novel targets: C. elegans as a model organism: Despite its apparent simplicity, the nematode worm Caenorhabditis elegans has developed into an important model for biomedical research, particularly in the functional characterizati on of novel drug targets that have been identified using genomics technologies (2006)
  • Cilia and disease: Although the function of primary cilia in some organs is being elucidated, in many other organs they have not been studied at all. It is probable that many more cilia-related disorders remain to be discovered (2006)
  • Two rights make a wrong: human left-right malformations: Like all vertebrates, humans establish anatomical left?right asymmetry during embryogenesis. Variation from this normal arrangement (situs solitus) results in heterotaxy, expressed either as randomization (situs ambiguus) or complete reversal (situs inversus) of normal organ position. Familial heterotaxy occurs with autosomal dominant, recessive and X-linked inheritance. All possible situs variants, solitus, mbiguus and inversus, can appear among some heterotaxy families. Positional cloning has led to the identification of a gene on the X chromosome responsible for some cases of human heterotaxy. Additional candidate genes have emerged from recent studies of left?right axis development in chick, frog and mouse, which have begun to elucidate a tightly regulated genetic cascade that differentiates the left and right sides prior to the appearance of morphological asymmetry (1998)
  • Caenorhabditis elegans as a Model to Study Renal Development and Disease: Sexy Cilia: The nematode Caenorhabditis elegans has no kidney per se, yet ?the worm? has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases (2005)
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