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<jats:p> <jats:italic>Mycobacterium tuberculosis</jats:italic> has a penetrance of its host population that would be the envy of most human pathogens. About one-third of the human population would have a positive skin test for the infection and is thus thought to harbor the bacterium. Globally, 22 “high-burden” countries account for more than 80% of the active tuberculosis cases in the world, which shows the inequitable distribution of the disease. There is no effective vaccine against infection, and current drug therapies are fraught with problems, predominantly because of the protracted nature of the treatment and the increasing occurrence of drug resistance. Here we focus on the biology of the host-pathogen interaction and discuss new and evolving strategies for intervention. </jats:p>

<jats:p> More than 36 million patients have been successfully treated via the World Health Organization’s strategy for tuberculosis (TB) control since 1995. Despite predictions of a decline in global incidence, the number of new cases continues to grow, approaching 10 million in 2010. Here we review the changing relationship between the causative agent, <jats:italic>Mycobacterium tuberculosis</jats:italic> , and its human host and examine a range of factors that could explain the persistence of TB. Although there are ways to reduce susceptibility to infection and disease, and a high-efficacy vaccine would boost TB prevention, early diagnosis and drug treatment to interrupt transmission remain the top priorities for control. Whatever the technology used, success depends critically on the social, institutional, and epidemiological context in which it is applied. </jats:p>

<jats:p> The global research community must take up the challenge to work toward the eradication of malaria. In the past, malaria research has focused on drugs and vaccines that target the blood stage of infection, and mainly on the most deadly species, <jats:italic>Plasmodium falciparum</jats:italic> , all of which is justified by the need to prevent and treat the disease. This work remains critically important today. However, an increased research focus is now being placed on potential interventions that aim to kill the parasite stages transmitted to and by the mosquito vector because they may represent more vulnerable targets to stop the spread of malaria. Here, we highlight some of the research into malaria parasite biology that has the potential to provide new intervention targets for antimalarial drugs and vaccines. </jats:p>

<jats:p> Malaria parasites have to survive and transmit within a highly selective and ever-changing host environment. Because immunity to malaria is nonsterilizing and builds up slowly through repeated infections, commonly the parasite invades a host that is immunologically and physiologically different from its previous host. During the course of infection, the parasite must also keep pace with changes in host immune responses and red-blood-cell physiology. Here, we describe the “selection landscape” of the most virulent of the human malaria parasites, <jats:italic>Plasmodium falciparum</jats:italic> , and the adaptive mechanisms it uses to navigate through that landscape. Taking a cost-benefit view of parasite fitness, we consider the evolutionary outcomes of the most important forces of selection operating on the parasite, namely immunity, host death, drugs, mosquito availability, and coinfection. Given the huge potential for malaria parasite evolution in the context of the recently renewed effort to eradicate malaria, a deeper understanding of <jats:italic>P. falciparum</jats:italic> adaptation is essential. </jats:p>

<jats:title>siRNA Movement in Plant Tissues</jats:title> <jats:p> Long-distance movement of RNA interference (RNAi)–derived signals in plants plays an important role in development and in defense against viral attack. The nature of the signals that spread from cell to cell is not known, although evidence suggests that they are nucleic acids of some sort (see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="5980" page="834" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1190510">Martienssen</jats:related-article> </jats:bold> ). <jats:bold> Molnar <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="872" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1187959">872</jats:related-article> , published online 22 April) and <jats:bold> Dunoyer <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="912" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1185880">912</jats:related-article> , published online 22 April) now show that in <jats:italic>Arabidopsis</jats:italic> , both exogenous and endogenous small interfering RNAs (siRNAs), rather than their long double-stranded precursor RNAs, are the molecules that transfer information between plant cells. A viral protein that counters RNAi though sequestering siRNAs blocked spreading of a transgene RNAi silencing signal. Furthermore, siRNA-processing enzymes were required in the source, and not the recipient, cells for spreading, and bombardment of plants with double-stranded siRNAs directly showed siRNA spread between cells. Endogenous siRNAs also spread between tissues and were capable of directing DNA methylation of target sequences in distant tissues. </jats:p>

<jats:title>Network Notation</jats:title> <jats:p> Networks are often characterized by clusters of constituents that interact more closely with each other and have more connections to one another than they do with the rest of the components of the network. However, systematically identifying and studying such community structure in complicated networks is not easy, especially when the network interactions change over time or contain multiple types of connections, as seen in many biological regulatory networks or social networks. <jats:bold> Mucha <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="876" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1184819">876</jats:related-article> ) developed a mathematical method to allow detection of communities that may be critical functional units of such networks. Application to real-world tasks—like making sense of the voting record in the U.S. Senate—demonstrated the promise of the method. </jats:p>

<jats:title>All and Nothing</jats:title> <jats:p> Entanglement, where a system can be in a superposition of a number of distinct states simultaneously, is a principle at the foundation of quantum mechanics (recall Schrödinger's cat, which is both dead and alive). It can also be used in many applications—imaging, communication, patterning, and metrology—with the effect being amplified by entangling larger systems. However, the systematic generation of “large” entangled systems is challenging. <jats:bold> Afek <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="879" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1188172">879</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="5980" page="835" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1190491">Wildfeuer</jats:related-article> </jats:bold> ) present a technique for generating many-photon entanglement in so-called NOON states, where there are two possible paths and <jats:italic>N</jats:italic> photons in one path and 0 in the other—the system being a superposition of “all and nothing” states. Mixing of entangled pairs with classical light at a beam splitter formed up to five photon-entangled states. The technique should be generally applicable to generate higher-order entangled states. </jats:p>

<jats:title>Stop or Go on Oxide Surfaces</jats:title> <jats:p> Direct studies of surface diffusion with instruments such as the scanning tunneling microscope (STM) have often focused on species on metal surfaces, but surface diffusion can play an important role for reactions on metal oxide surfaces. <jats:bold> Li <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="882" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1188328">882</jats:related-article> ) used STM and density functional theory calculations to study how catechol (a benzene ring bearing two −OH groups) diffuses on the surface of the rutile phase of titanium dioxide. Both mobile and immobile species were observed on the time scale of minutes while making repeated STM scans. Hydrogen atom transfers between surface OH groups and the molecule changed the interaction energy between the molecule and the surface, and hence the barrier for diffusion. </jats:p>

<jats:title>Earth's Silver Lining</jats:title> <jats:p> The age of the oldest rocks on Earth's surface is controversial, but, even if they are at their oldest estimate, hundreds of millions of years in our planet's earliest history are still missing. However, in some rocks that until relatively recently resided in the mantle, the isotopic signature from the time of Earth's formation is still preserved. <jats:bold> Schönbächler <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="884" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1186239">884</jats:related-article> ) exploited this preservation to constrain models that describe the early material that assembled together to form Earth. Because the isotopic profile of silver in these rocks is nearly identical to that measured in a class of primitive meteorites, the earliest material probably had high volatile content. However, the fractionation of other isotopes suggests that the volatile content probably decreased over time in subsequent accretion events. With these isotopic model constraints, it is possible that one of the last major collisions—the Moon-forming giant impact—added considerable amounts of water and other volatile elements to Earth. </jats:p>

<jats:title>Poor Flight of the Ancients</jats:title> <jats:p> In order to fly, the feathers of birds must be strong enough to support the bird's weight without breaking or bending. The main part of a feather providing structural support is its central shaft, which stiffens the feather along its length. In modern birds, this is hollow to reduce weight. <jats:bold>Nudds and Dyke</jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="887" related-article-type="in-this-issue" vol="328" xlink:href="10.1126/science.1188895">887</jats:related-article> ) show that the cross-section of the shaft of the Mesozoic birds <jats:italic>Archaeopteryx</jats:italic> and <jats:italic>Confuciusornis</jats:italic> was much smaller than that of modern birds. Calculations imply that even if it was solid, it would have been too weak to support powered flight and barely strong enough to allow gliding. Thus, powered flight probably arose later in the evolution of birds and these early birds were poor fliers. </jats:p>