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<jats:title>Translating Polyproline</jats:title> <jats:p> Translation of messenger RNA into protein is carried out by the ribosome, together with a variety of accessory factors, which offer the potential for regulation of this critical step in gene expression (see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6115" page="38" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1233338"> <jats:bold>Buskirk and Green</jats:bold> </jats:related-article> ). <jats:bold> Ude <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="82" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1228985">82</jats:related-article> , published online 13 December), using bacterial genetics and an in vitro reconstituted translation system, and <jats:bold> Doerfel <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="85" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1229017">85</jats:related-article> , published online 13 December), using a model assay for peptide bond formation, find that the universally conserved bacterial elongation factor P (EF-P) (which is orthologous to the archaeal and eukaryotic initiation factor 5A) is required for the efficient translation of polyproline-containing polypeptides. Such short polyproline stretches (with runs of two, three, or more proline residues) would otherwise cause ribosomal stalling. </jats:p>

<jats:title>Poisoned Pathways</jats:title> <jats:p> Fifty years ago, <jats:italic>para</jats:italic> -aminosalicyclic acid (PAS) was developed as an antituberculosis drug. Since then, it has been assumed that PAS acts to competitively inhibit <jats:italic>para</jats:italic> -aminobenzoate (PABA) from entering the folate pathway at the enzyme dihydropteroate synthase (DHPS). Strangely, the well-known inhibitors of DHPS—the sulfonamide drugs—are useless in tuberculosis treatment, although they are effective against other microbial pathogens. <jats:bold> Chakraborty <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="88" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1228980">88</jats:related-article> , published online 1 November) addressed this conundrum by comparing the effect of several sulfonamides, as well as PAS and PABA, on the folate pathway of live <jats:italic>Mycobacterium tuberculosis.</jats:italic> It seems the bacterium is better at inactivating sulfonamides than PAS and that PAS does not really compete with PABA. Instead, PAS cascades through the folate pathway generating a series of poisonous intermediates. </jats:p>

<jats:title>All About Noise</jats:title> <jats:p> How individual cells behave within a larger “average” population can be surprising. <jats:bold> Wakamoto <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="91" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1229858">91</jats:related-article> ) developed a method for investigating the consequences of phenotypic variability in single mycobacterial cells exposed to the pro-drug, isoniazid. Isoniazid needs to be activated by bacterial catalase. In the isoniazid–mycobacterium system, random fluctuations in catalase activity were important for cell survival. Because catalase is essential, it cannot be ablated; however, catalase activity pulsed randomly in the mycobacteria. Thus, a subpopulation of individual cells manage to avoid being killed by the activated antibiotic. </jats:p>

<jats:title>Older and Wiser</jats:title> <jats:p> Do we ever stop growing up? <jats:bold> Quoidbach <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="96" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1229294">96</jats:related-article> ) elicited estimates of people's personality, values, and choices and compared how much, for instance, 33-year-olds believed that they would change in the next 10 years with how much 43-year-olds reported that they had changed in the past 10 years. For groups spanning 18 to 68 years of age, people of all ages described more change in the past 10 years than they would have predicted 10 years ago. </jats:p>

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