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<jats:p>This week's show features a segment on the science of soundscapes and a roundup of shorts from our daily news site.</jats:p>

<jats:p>Acknowledges outstanding contributions to neurobiology research based on the methods of molecular and cell biology.</jats:p>

<jats:sec> <jats:title /> <jats:sec> <jats:title>Introduction</jats:title> <jats:p> Cells use multilayered regulatory systems to respond adequately to changing environments or perturbations. Failure in regulation underlies cellular malfunctioning, loss of fitness, or disease. How molecular components dynamically interact to give rise to robust and adaptive responses is not well understood. Here, we studied how the model eukaryote <jats:italic>Saccharomyces cerevisiae</jats:italic> can cope with transition to high glucose levels, a failure of which results in metabolic malfunctioning and growth arrest. </jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p> We combined experimental and modeling approaches to unravel the mechanisms used by yeast to cope with sudden glucose availability. We studied growth characteristics and metabolic state at population and single-cell levels (through flow cytometry and colony plating) of the wild type and of mutants unable to transit properly to excess glucose; such mutants are defective in trehalose synthesis, a disaccharide associated with stress resistance. Dynamic <jats:sup>13</jats:sup> C tracer enrichment was used to estimate dynamic intracellular fluxes immediately after glucose addition. Mathematical modeling was used to interpret and generalize results and to suggest subsequent experiments. </jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> The failure to cope with glucose is caused by imbalanced reactions in glycolysis, the essential pathway in energy metabolism in most organisms. In the failure mode, the first steps of glycolysis carry more flux than the downstream steps, resulting in accumulating intermediates at constant low levels of adenosine triphosphate (ATP) and inorganic phosphate. We found that cells with such an unbalanced glycolysis coexist with vital cells with normal glycolytic function. Spontaneous, nongenetic metabolic variability among individual cells determines which state is reached and consequently which cells survive. In mutants of trehalose metabolism, only 0.01% of the cells started to grow on glucose; in the wild type, the success rate was still only 93% (i.e., 7% of wild-type yeast did not properly start up glycolysis). Mathematical models predicted that the dynamics of inorganic phosphate is a key determinant in successful transition to glucose, and that phosphate release through ATP hydrolysis reduces the probability of reaching an imbalanced state. <jats:sup>13</jats:sup> C-labeling experiments confirmed the hypothesis that trehalose metabolism constitutes a futile cycle that would provide proper phosphate balance: Upon a glucose pulse, almost 30% of the glucose is transiently shuttled into trehalose metabolism. </jats:p> </jats:sec> <jats:sec> <jats:title>Discussion</jats:title> <jats:p>Our work reveals how cell fate can be determined by glycolytic dynamics combined with cell heterogeneity purely at the metabolic level. Specific regulatory mechanisms are required to initiate the glycolytic pathway; in yeast, trehalose cycling pushes glycolysis transiently into the right direction, after which cycling stops. The coexistence of two modes of glycolysis—an imbalanced state and the normal functional state—arises from the fundamental design of glycolysis. This makes the imbalanced state a generic risk for humans as well, extending our fundamental knowledge of this central pathway that is dysfunctional in diseases such as diabetes and cancer.</jats:p> </jats:sec> </jats:sec>

<jats:sec> <jats:title>Background</jats:title> <jats:p>Interest in photochemical synthesis has been motivated in part by the realization that sunlight is effectively an inexhaustible energy source.Chemists have also long recognized distinctive patterns of reactivity that are uniquely accessible via photochemical activation. However, most simple organic molecules absorb only ultraviolet (UV) light and cannot be activated by the visible wavelengths that comprise most of the solar energy that reaches Earth’s surface. Consequently, organic photochemistry has generally required the use of UV light sources.</jats:p> </jats:sec> <jats:sec> <jats:title>Advances</jats:title> <jats:p>Over the past several years, there has been a resurgence of interest in synthetic photochemistry, based on the recognition that the transition metal chromophores that have been so productively exploited in the design of technologies for solar energy conversion can also convert visible light energy into useful chemical potential for synthetic purposes. Visible light enables productive photoreactions of compounds possessing weak bonds that are sensitive toward UV photodegradation. Furthermore, visible light photoreactions can be conducted by using essentially any source of white light, including sunlight, which obviates the need for specialized UV photoreactors. This feature has expanded the accessibility of photochemical reactions to a broader range of synthetic organic chemists. A variety of reaction types have now been shown to be amenable to visible light photocatalysis via photoinduced electron transfer to or from the transition metal chromophore, as well as energy-transfer processes. The predictable reactivity of the intermediates generated and the tolerance of the reaction conditions to a wide range of functional groups have enabled the application of these reactions to the synthesis of increasingly complex target molecules.</jats:p> </jats:sec> <jats:sec> <jats:title>Outlook</jats:title> <jats:p>This general strategy for the use of visible light in organic synthesis is already being adopted by a growing community of synthetic chemists. Much of the current research in this emerging area is geared toward the discovery of photochemical solutions for increasingly ambitious synthetic goals. Visible light photocatalysis is also attracting the attention of researchers in chemical biology, materials science, and drug discovery, who recognize that these reactions offer opportunities for innovation in areas beyond traditional organic synthesis. The long-term goals of this emerging area are to continue to improve efficiency and synthetic utility and to realize the long-standing goal of performing chemical synthesis using the sun.</jats:p> </jats:sec>

<jats:title>ESCRT Your Wound Away</jats:title> <jats:p> The ESCRT (endosomal sorting complex required for transport) protein complex plays a role in budding into multivesicular bodies, in cytokinesis, and in HIV budding. Now, <jats:bold> Jimenez <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" related-article-type="in-this-issue" xlink:href="10.1126/science.1247136">10.1126/science.1247136</jats:related-article> , published online 30 January) propose a role for ESCRT proteins in wound repair at the plasma membrane. In vivo imaging, modeling, and electron microscopy were used to reveal how the ESCRTs participate in a rapid energy-independent, calcium-dependent, membrane-shedding process at the plasma membrane that reseals small wounds caused by toxins or laser treatment. </jats:p>