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<jats:title>Gee Fizz</jats:title> <jats:p> The next time you enjoy a carbonated beverage, you can do so with an enhanced understanding of the molecular mechanism that provides its distinctive flavor sensation. <jats:bold> Chandrashekar <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="443" related-article-type="in-this-issue" vol="326" xlink:href="10.1126/science.1174601">443</jats:related-article> ) genetically ablated specific sets of taste cells in mice and found that the sensation of CO <jats:sub>2</jats:sub> was lost in animals lacking taste cells that sense sour flavors. A screen for genes specifically expressed in these cells revealed the gene encoding carbonic anhydrase 4, which catalyzes hydration of CO <jats:sub>2</jats:sub> to form bicarbonate and free protons. Knockout animals not expressing the carbonic anhydrase 4 gene also showed diminished sensation of CO <jats:sub>2</jats:sub> . The protons produced by the enzyme appear to be the actual molecules sensed by the sour-sensitive cells. This process, combined with tactile sensations, appears to be the source of the popular fizzy sensation. </jats:p>

<jats:title>Seeing the Brain's One, Two, Three</jats:title> <jats:p> Taking advantage of the rare opportunity to record neuronal activity in the human brain using intracranial electrodes, <jats:bold> Sahin <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="445" related-article-type="in-this-issue" vol="326" xlink:href="10.1126/science.1174481">445</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="5951" page="372" related-article-type="in-this-issue" vol="326" xlink:href="10.1126/science.1181675"> <jats:bold>Hagoort and Levelt</jats:bold> </jats:related-article> </jats:bold> ) document the spatial and temporal pattern of neuronal populations within Broca's area as patients thought of a single word, changed its tense (for verbs) or number (for nouns), and articulated the word silently. For these three stages, they detected activity at 200, 320, and 450 milliseconds, moving in a caudal to rostral direction. These data fit neatly within the roughly 600 milliseconds required for the onset of speech and map the distinct neural computations within an area of the brain, known for almost a century and a half, as important for the production of language. </jats:p>

<jats:title>Subcortical Network Regulation</jats:title> <jats:p> Subcortical neuromodulatory centers dominate the motivational and emotional state–dependent control of cortical functions. Control of cortical circuits has been thought to involve a slow, diffuse neuromodulation that affects the excitability of large numbers of neurons relatively indiscriminately. <jats:bold> Varga <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="449" related-article-type="in-this-issue" vol="326" xlink:href="10.1126/science.1178307">449</jats:related-article> ) describe a form of subcortical control of cortical information processing whereby strong, spatiotemporally precise excitatory input from midbrain serotonergic neurons produces a robust activation of hippocampal interneurons. This effect is mediated by a synaptic release of both serotonin and glutamate and impacts network activity patterns. </jats:p>

<jats:p>Two years is a long time in the world of RNAi therapeutics. Since Science last covered the topic in 2007, the first Phase 3 human clinical trial of an siRNA drug has been prematurely terminated; new off-target effects have been identified; and the first miRNA-based therapeutic entered clinical trials. Yet much remains the same, especially the biggest challenge: delivery. As researchers struggle to overcome these obstacles, optimism persists undiminished.</jats:p>

<jats:p>The show includes interstellar interactions, Saudi Arabia's KAUST, the taste of carbonation, and more.</jats:p>

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