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<jats:title>Axon Routing in the Olfactory System</jats:title> <jats:p> The olfactory system of mice entails a developmental program that wires neurons expressing similar olfactory receptors into glomeruli together. Although the adult olfactory system continues to produce and incorporate new neurons, it cannot withstand severe damage (see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6180" page="157" related-article-type="in-this-issue" vol="344" xlink:href="10.1126/science.1253136"> <jats:bold>Cheetham and Belluscio</jats:bold> </jats:related-article> ). <jats:bold> Ma <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6180" page="194" related-article-type="in-this-issue" vol="344" xlink:href="10.1126/science.1248805">194</jats:related-article> ) and <jats:bold>Tsai and Barnea</jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6180" page="197" related-article-type="in-this-issue" vol="344" xlink:href="10.1126/science.1248806">197</jats:related-article> ) examined the difference in responses between early development and adulthood. Manipulating the expression of an odorant receptor or the activity of the olfactory neurons altered olfactory neuron axonal pathfinding. The results suggest that the guidance systems used differ between early development and adulthood: Early axons find their own way, but later-in-life axons can only follow existing pathways. </jats:p>

<jats:title>Axon Routing in the Olfactory System</jats:title> <jats:p> The olfactory system of mice entails a developmental program that wires neurons expressing similar olfactory receptors into glomeruli together. Although the adult olfactory system continues to produce and incorporate new neurons, it cannot withstand severe damage (see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6180" page="157" related-article-type="in-this-issue" vol="344" xlink:href="10.1126/science.1253136"> <jats:bold>Cheetham and Belluscio</jats:bold> </jats:related-article> ). <jats:bold> Ma <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6180" page="194" related-article-type="in-this-issue" vol="344" xlink:href="10.1126/science.1248805">194</jats:related-article> ) and <jats:bold>Tsai and Barnea</jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6180" page="197" related-article-type="in-this-issue" vol="344" xlink:href="10.1126/science.1248806">197</jats:related-article> ) examined the difference in responses between early development and adulthood. Manipulating the expression of an odorant receptor or the activity of the olfactory neurons altered olfactory neuron axonal pathfinding. The results suggest that the guidance systems used differ between early development and adulthood: Early axons find their own way, but later-in-life axons can only follow existing pathways. </jats:p>

<jats:title>Tangling Evolutionary Trees</jats:title> <jats:p> Evolutionary rates tend to vary among taxa and may result in phylogenetic trees that do not reflect the true relationships among taxa, depending on the sequences input into the analysis. Examining vertebrate trees, <jats:bold> Evans <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6180" page="200" related-article-type="in-this-issue" vol="344" xlink:href="10.1126/science.1249325">200</jats:related-article> ) demonstrate that differences in evolutionary rates, leading to phylogenetic distortions, are correlated with the mechanisms underlying germ cell formation. Evolutionary rate is faster in cases where germ cells are established by maternal molecules (“preformed”) relative to those that are induced during embryogenesis (“epigenesis”) in slowly evolving and, presumably, ancestral lineages. For example, frogs evolve more rapidly than salamanders, and teleosts more rapidly than ascipenseriform fishes. Thus, epigenesis constrains the ability of gene regulatory networks to change, with the repeated and convergent evolution of preformation eliminating this constraint. </jats:p>

<jats:title>In the PINK1</jats:title> <jats:p> Pathogenic mutations in the kinase PINK1 are causally related to Parkinson's disease (PD). One hypothesis proposes that PINK1 regulates mitophagy—the clearance of dysfunctional mitochondria. A second hypothesis suggests that PINK1 has a direct effect on mitochondrial complex I, affecting the maintenance of the electron transport chain (ETC) resulting in decreased mitochondrial membrane potential and dysfunctional mitochondria. In support of the second hypothesis, <jats:bold> Morais <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6180" page="203" related-article-type="in-this-issue" vol="344" xlink:href="10.1126/science.1249161">203</jats:related-article> , published online 20 March) observed a complex I deficit in fibroblasts and neurons derived from induced pluripotent stem cells from PINK1 patients before any mitophagy was induced. The phosphoproteome of complex I in liver and brain from mice deficient for Pink1, compared to wild-type animals, revealed that Ser <jats:sup>250</jats:sup> in complex I subunit NdufA10 was differentially phosphorylated. Ser <jats:sup>250</jats:sup> is critically involved in the reduction of ubiquinone by complex I, explaining why <jats:italic>Pink1</jats:italic> knockout mice, flies, and patient cell lines show decreased mitochondrial membrane potential. Synaptic defects in <jats:italic>pink1</jats:italic> null mutant <jats:italic>Drosophila</jats:italic> could be rescued using phosphomimetic NdufA10. </jats:p>

<jats:title>Yeasty HIPHOP</jats:title> <jats:p> In order to identify how chemical compounds target genes and affect the physiology of the cell, tests of the perturbations that occur when treated with a range of pharmacological chemicals are required. By examining the haploinsufficiency profiling (HIP) and homozygous profiling (HOP) chemogenomic platforms, <jats:bold> Lee <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6180" page="208" related-article-type="in-this-issue" vol="344" xlink:href="10.1126/science.1250217">208</jats:related-article> ) analyzed the response of yeast to thousands of different small molecules, with genetic, proteomic, and bioinformatic analyses. Over 300 compounds were identified that targeted 121 genes within 45 cellular response signature networks. These networks were used to extrapolate the likely effects of related chemicals, their impact upon genetic pathways, and to identify putative gene functions. </jats:p>

<jats:p>"Like finding a needle in a haystack" is an overused expression, but when it comes to some biological scavenger hunts, it fits. Researchers studying rare variant biomarkers often find themselves on the lookout for faint genetic signals against an overwhelming background, sometimes as little as a single positive in 100,000 negatives or more. Such a situation cries out for polymerase chain reaction (PCR), a technique uniquely capable of capturing the proverbial needle. But standard PCR won't do—it is a qualitative technique—and neither will quantitative real-time PCR (qPCR), which often lacks the necessary accuracy and sensitivity. These days, there's a third and increasingly popular option: digital PCR (dPCR). By discretizing those 100,000 molecules in a large number of individual reactions, dPCR makes the rare positive surprisingly easy to find.</jats:p>

<jats:p>A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.</jats:p>

<jats:p>On this week's show: the mechanics of flies' evasive maneuvers and a news roundup from our daily news site.</jats:p>

<jats:p>Techniques for the study of intracellular ions are used widely in biology, including for the tracking of calcium waves or ions affecting pH within living cells. The ability to monitor changes in intracellular ion concentrations over time is vital for our understanding of signaling and functional pathways in cellular systems. These pathways are central to many fundamental processes such as muscle contraction and synaptic nerve signal transmission. Ion channels that span the outer cell membrane open or close in response to extracellular and intracellular signals, potentially altering how the cell behaves. These fluctuations can be visualized and quantified using ratiometric microscopy and special fluorescent dyes designed to bind specific ions, such as the FURA-2 indicator dye specific to calcium ions. Changes in the photophysics of the dye as it binds to its target ion allows for quantitation of the bound and unbound ratio, and thus the concentration of the ion under investigation. This webinar will introduce the viewer to the current state of technology in this important field as well as cover the latest advances in microscopy for ion signaling research.</jats:p>