Nature 453, xii (2008). doi:10.1038/7192xiia

Enzymes made from scratch to speed up a common chemical reaction.

Nature 453, xii (2008). doi:10.1038/7192xiib

First authorIn 2000, researchers predicted that warming equatorial oceans would cause permanent El Niño conditions, which would shift tropical rainfall patterns away from the Amazon rainforest. In 2005, the rainforest did experience severe drought, but El Niño was not to blame. On page 212

Nature 453, xii (2008). doi:10.1038/7192xiic

According to a recent online survey, most biologists don't read science blogs or participate in social networking sites (see discussion at Gobbledygook blog http://tinyurl.com/5psqp3). Biologists prefer to read the literature; Web 2.0 sites for scientists haven't yet built up a reputation for accuracy; and

Nature 453, 133 (2008). doi:10.1038/453133a

The French scientific research system is ripe for reform.

Nature 453, 133 (2008). doi:10.1038/453133b

Two years on, a National Academies report on US competitiveness struggles to make an impact.

Nature 453, 134 (2008). doi:10.1038/453134a

Whether in music or in nature, noise can be full of riches. The trick is to recognize the treasures.

Nature 453, 136 (2008). doi:10.1038/453136a

Geophys. Res. Lett. doi:10.1029/2008GL033510 (2008)The Vatnajökull ice cap in Iceland lost about a tenth of its mass during the twentieth century. As a result, the crust around its edges has risen and this, according to new research, has led

Nature 453, 136 (2008). doi:10.1038/453136b

Nano Lett. doi:10.1021/nl080649i (2008)Lumps of graphite are sooty; its constituent layers of graphene, however, are transparent, a property that researchers have used in a liquid-crystal device. Kostya Novoselov at the University of Manchester, UK, and his co-workers have shown

Nature 453, 136 (2008). doi:10.1038/453136c

Science320, 649–65210.1126/science.1154690(2008)The possibility of adding prostratin to antiretroviral therapies has been held back because it is scarce in nature, an impediment that the chemical's laboratory synthesis has just removed. Prostratin activates latent HIV viruses even in

Nature 453, 136 (2008). doi:10.1038/453136d

PLoS One3, e206410.1371/journal.pone.0002064(2008)Hans Rolf of the University of Göttingen in Germany and his colleagues report that they have found evidence of stem cells in the antler 'growth zones' of fallow deer (Dama dama; pictured). They hunted

Nature 453, 136 (2008). doi:10.1038/453136e

Science320, 630–63410.1126/science.1155140 (2008)The babbling calls of baby songbirds involve separate brain circuitry from that used to generate more complex adult song, report neuroscientists at the Massachusetts Institute of Technology in Cambridge.Michale Fee and his team

Nature 453, 136 (2008). doi:10.1038/453136f

Proc. Natl Acad. Sci. USA105, 6730–673410.1073/pnas.0707522105(2008)A gargantuan bacterium carries tens of thousands of copies of its genome, researchers have found.One species of the cigar-shaped bacterium Epulopiscium lives in the intestines of the unicornfish Naso

Nature 453, 137 (2008). doi:10.1038/453137a

Nature Nanotech. doi:10.1038/nnano.2008.98 (2008)Micromechanical devices are most commonly made from silicon; now it is time to welcome carbon-based wafers to the party. Kenji Hata at the Nanotube Research Center in Tsukuba, Japan, and his co-workers say wafers such as

Nature 453, 137 (2008). doi:10.1038/453137b

Plasmodium falciparum

Nature 453, 137 (2008). doi:10.1038/453137c

Astrophys. J.678, 144–15310.1086/529127(2008)Astronomers measure distance to galaxies in terms of 'redshift' — the far-off reddening of a galaxy's light as it zooms away from us. Current spectroscopic techniques measure at most a few hundred redshifts at

Nature 453, 137 (2008). doi:10.1038/453137d

Environ. Sci. Technol. doi:10.1021/es800312v (2008)Hydrogen is a useful and clean energy source, and it can be obtained from bacteria such as Rhodopseudomonas palustris. Bruce Logan of Pennsylvania State University, University Park, and his collaborators have found that this

Nature 453, 137 (2008). doi:10.1038/453137e

Author: François Balloux

A population geneticist looks back in time in search of human origins.When and where anatomically modern humans evolved is arguably one of the most fundamental scientific questions. The issue also has philosophical and possibly even moral implications because it influences our definition of humanity.

Nature 453, 154 (2008). doi:10.1038/453154a

Author: Vaclav Smil

SirI largely agree with the overall conclusion of Pielke et al. in their Commentary ‘Dangerous assumptions’ (Nature452, 531–532; 2008) that the Intergovernmental Panel on Climate Change (IPCC) assessment is overly optimistic, but I fear that the

Nature 453, 154 (2008). doi:10.1038/453154b

Author: Christopher B. Field

SirPielke et al. correctly point out in their Commentary ‘Dangerous assumptions’ (Nature452, 531–532; 2008) that almost all of the Intergovernmental Panel on Climate Change (IPCC) emissions scenarios assume continuing improvements in the energy intensity of the

Nature 453, 155 (2008). doi:10.1038/453155a

Authors: Richard G. Richels, Richard S. J. Tol & Gary W. Yohe

SirIn their Commentary ‘Dangerous assumptions’ (Nature452, 531–531; 2008), Pielke et al. show that the 2000 Special Report on Emissions Scenarios (SRES) reflects unrealistic progress on both the supply and demand sides of the energy sector. These

Nature 453, 155 (2008). doi:10.1038/453155b

Authors: Ottmar Edenhofer, Bill Hare, Brigitte Knopf & Gunnar Luderer

SirIn their Commentary ‘Dangerous assumptions’ (Nature452, 531–532; 2008), Roger Pielke and colleagues argue that the Intergovernmental Panel on Climate Change (IPCC) “seriously” underestimates the scale of the technological changes required to stabilize greenhouse-gas concentrations, and hence conveyed

Nature 453, 155 (2008). doi:10.1038/453155c

Author: Joseph Romm

SirIn the Commentary ‘Dangerous assumptions’ (Nature452, 531–532; 2008), Pielke et al. suggest that the Intergovernmental Panel on Climate Change (IPCC) underestimates the challenge of global warming. I find their analysis misleading.They criticize the IPCC for

Nature 453, 156 (2008). doi:10.1038/453156a

Author: Owen Gingerich

Volunteer star-gazers tracking satellites at the start of the space age often surpassed the professionals.

Nature 453, 157 (2008). doi:10.1038/453157a

Author: Bruce M. Hood

At some point in their career, every scientist considers writing a book. But what type of book? A textbook may be most familiar, but increasingly, researchers are trying their hand at and gaining credit for penning books aimed at the popular market. An additional challenge

Nature 453, 158 (2008). doi:10.1038/453158a

Author: Chris Turney

As we are alerted to the perils of climate change, we need a long-term perspective to understand the capabilities of Earth's climate. Looking to the past can help us evaluate the risks and judge the best way to manage them.Fixing Climate gives a

Nature 453, 158 (2008). doi:10.1038/453158b

Author: Emma Marris

Coal provides half of the United States' electricity. Increasing demand and eased regulation are fuelling coal-mining operations such as mountain-top removal, in which miners access coal seams, without digging below the surface, by dynamiting the summits of mountains and dumping the blasted rock in adjoining

Nature 453, 159 (2008). doi:10.1038/453159a

Author: Giacomo Chiari

A conservation scientist explains how borrowing gadgets from Mars rovers helps preserve culture on Earth.

Nature 453, 160 (2008). doi:10.1038/453160a

Author: Philip Ball

At the heart of any scientific explanation of music is an understanding of how and why it affects us. In the first of a nine-part essay series, Philip Ball explores just how far we can hope to achieve a full scientific theory of music.

Nature 453, 163 (2008). doi:10.1038/453163a

Authors: Timothy E. Dowling

Fifteen-year oscillations in Saturn's equatorial stratosphere bear a striking resemblance to the shorter-term oscillations seen on Earth and Jupiter — akin to notes played on a cello, a violin and a viola.

Nature 453, 164 (2008). doi:10.1038/453164a

Authors: Giovanna Ghirlanda

Although enzymes are superb catalysts, their range of reactions is limited to those that support life. Their repertoire could be expanded by a method that allows artificial enzymes to be made from scratch.

Nature 453, 165 (2008). doi:10.1038/453165a

50 years agoA Hundred Years of Evolution. By Dr. G. S. Carter — It is fundamental to the neo-Darwinian theory that Weismann's concept of the inviolability of germ plasm by soma is correct, and that mutational changes in the gene complex arise solely

Nature 453, 166 (2008). doi:10.1038/453166a

Authors: Robert M. Westervelt

A clever device uses the quantum statistics of electron tunnelling to match image patterns. The circuit is low-power, works at room temperature — and could point to a way forward for silicon electronics.

Nature 453, 167 (2008). doi:10.1038/453167a

Authors: Philip C. E. Stamp

Uncontrollable outside influences undermine the whole enterprise of quantum computing. Nailing down the sources of this 'decoherence' in a solid-state system is a step towards solving the problem.

Nature 453, 169 (2008). doi:10.1038/453169a

Author: Sadaf Shadan

In the American sitcom Friends, Monica bakes mouth-watering cookies for her housemates, but — having been overweight as a teenager (pictured) — she is reluctant to eat them herself. Kirsty Spalding and colleagues now provide scientific evidence for why Monica has every reason to

Nature 453, 169 (2008). doi:10.1038/453169b

Authors: Eddy Arnold & Stefan G. Sarafianos

With two catalytic activities and many substrates, how does HIV's reverse transcriptase enzyme know what to do to which substrate? Zooming in on the enzyme's molecular interactions provides tantalizing clues.

Nature 453, 171 (2008). doi:10.1038/453171a

Authors: Tom F. A. de Greef & E. W. Meijer

Most polymers consist of long molecular chains made up of many units connected by covalent bonds — but supramolecular polymers are different. The strikingly dynamic properties of these materials arise from the reversible bonds that hold their chains together, and open up the prospect of many new applications.

Nature 453, 175 (2008). doi:10.1038/nature06936

Authors:

We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are

Nature 453, 184 (2008). doi:10.1038/nature06941

Authors: Elio A. Abbondanzieri, Gregory Bokinsky, Jason W. Rausch, Jennifer X. Zhang, Stuart F. J. Le Grice & Xiaowei Zhuang

The reverse transcriptase of human immunodeficiency virus (HIV) catalyses a series of reactions to convert the single-stranded RNA genome of HIV into double-stranded DNA for host-cell integration. This task requires the reverse transcriptase to discriminate a variety of nucleic-acid substrates such that active sites of

Nature 453, 190 (2008). doi:10.1038/nature06879

Authors: Daniela Röthlisberger, Olga Khersonsky, Andrew M. Wollacott, Lin Jiang, Jason DeChancie, Jamie Betker, Jasmine L. Gallaher, Eric A. Althoff, Alexandre Zanghellini, Orly Dym, Shira Albeck, Kendall N. Houk, Dan S. Tawfik & David Baker

The design of new enzymes for reactions not catalysed by naturally occurring biocatalysts is a challenge for protein engineering and is a critical test of our understanding of enzyme catalysis. Here we describe the computational design of eight enzymes that use two different catalytic motifs

Nature 453, 196 (2008). doi:10.1038/nature06897

Authors: Glenn S. Orton, Padma A. Yanamandra-Fisher, Brendan M. Fisher, A. James Friedson, Paul D. Parrish, Jesse F. Nelson, Amber Swenson Bauermeister, Leigh Fletcher, Daniel Y. Gezari, Frank Varosi, Alan T. Tokunaga, John Caldwell, Kevin H. Baines, Joseph L. Hora, Michael E. Ressler, Takuya Fujiyoshi, Tetsuharu Fuse, Hagop Hagopian, Terry Z. Martin, Jay T. Bergstralh, Carly Howett, William F. Hoffmann, Lynne K. Deutsch, Jeffrey E. Van Cleve, Eldar Noe, Joseph D. Adams, Marc Kassis & Eric Tollestrup

Observations of oscillations of temperature and wind in planetary atmospheres provide a means of generalizing models for atmospheric dynamics in a diverse set of planets in the Solar System and elsewhere. An equatorial oscillation similar to one in the Earth’s atmosphere has been discovered in Jupiter. Here we report the existence of similar oscillations in Saturn’s atmosphere, from an analysis of over two decades of spatially resolved observations of its 7.8-μm methane and 12.2-μm ethane stratospheric emissions, where we compare zonal-mean stratospheric brightness temperatures at planetographic latitudes of 3.6° and 15.5° in both the northern and the southern hemispheres. These results support the interpretation of vertical and meridional variability of temperatures in Saturn’s stratosphere as a manifestation of a wave phenomenon similar to that on the Earth and in Jupiter. The period of this oscillation is 14.8 ± 1.2 terrestrial years, roughly half of Saturn’s year, suggesting the influence of seasonal forcing, as is the case with the Earth’s semi-annual oscillation.

Nature 453, 200 (2008). doi:10.1038/nature06912

Authors: T. Fouchet, S. Guerlet, D. F. Strobel, A. A. Simon-Miller, B. Bézard & F. M. Flasar

The middle atmospheres of planets are driven by a combination of radiative heating and cooling, mean meridional motions, and vertically propagating waves (which originate in the deep troposphere). It is very difficult to model these effects and, therefore, observations are essential to advancing our understanding of atmospheres. The equatorial stratospheres of Earth and Jupiter oscillate quasi-periodically on timescales of about two and four years, respectively, driven by wave-induced momentum transport. On Venus and Titan, waves originating from surface–atmosphere interaction and inertial instability are thought to drive the atmosphere to rotate more rapidly than the surface (superrotation). However, the relevant wave modes have not yet been precisely identified. Here we report infrared observations showing that Saturn has an equatorial oscillation like those found on Earth and Jupiter, as well as a mid-latitude subsidence that may be associated with the equatorial motion. The latitudinal extent of Saturn’s oscillation shows that it obeys the same basic physics as do those on Earth and Jupiter. Future highly resolved observations of the temperature profile together with modelling of these three different atmospheres will allow us determine the wave mode, the wavelength and the wave amplitude that lead to middle atmosphere oscillation.

Nature 453, 203 (2008). doi:10.1038/nature06962

Authors: S. Bertaina, S. Gambarelli, T. Mitra, B. Tsukerblat, A. Müller & B. Barbara

The term ‘molecular magnet’ generally refers to a molecular entity containing several magnetic ions whose coupled spins generate a collective spin, S (ref. 1). Such complex multi-spin systems provide attractive targets for the study of quantum effects at the mesoscopic scale. In these molecules, the large energy barriers between collective spin states can be crossed by thermal activation or quantum tunnelling, depending on the temperature or an applied magnetic field. There is the hope that these mesoscopic spin states can be harnessed for the realization of quantum bits—‘qubits’, the basic building blocks of a quantum computer—based on molecular magnets. But strong decoherence must be overcome if the envisaged applications are to become practical. Here we report the observation and analysis of Rabi oscillations (quantum oscillations resulting from the coherent absorption and emission of photons driven by an electromagnetic wave) of a molecular magnet in a hybrid system, in which discrete and well-separated magnetic nature06962-m6jpg7453022 clusters are embedded in a self-organized non-magnetic environment. Each cluster contains 15 antiferromagnetically coupled S = 1/2 spins, leading to an S = 1/2 collective ground state. When this system is placed into a resonant cavity, the microwave field induces oscillatory transitions between the ground and excited collective spin states, indicative of long-lived quantum coherence. The present observation of quantum oscillations suggests that low-dimension self-organized qubit networks having coherence times of the order of 100 μs (at liquid helium temperatures) are a realistic prospect.

Nature 453, 207 (2008). doi:10.1038/nature06900

Authors: Bo Wang, Adrien P. Côté, Hiroyasu Furukawa, Michael O’Keeffe & Omar M. Yaghi

Zeolitic imidazolate frameworks (ZIFs) are porous crystalline materials with tetrahedral networks that resemble those of zeolites: transition metals (Zn, Co) replace tetrahedrally coordinated atoms (for example, Si), and imidazolate links replace oxygen bridges. A striking feature of these materials is that the structure adopted by a given ZIF is determined by link–link interactions, rather than by the structure directing agents used in zeolite synthesis. As a result, systematic variations of linker substituents have yielded many different ZIFs that exhibit known or predicted zeolite topologies. The materials are chemically and thermally stable, yet have the long-sought-after design flexibility offered by functionalized organic links and a high density of transition metal ions. Here we report the synthesis and characterization of two porous ZIFs—ZIF-95 and ZIF-100—with structures of a scale and complexity previously unknown in zeolites. The materials have complex cages that contain up to 264 vertices, and are constructed from as many as 7,524 atoms. As expected from the adsorption selectivity recently documented for other members of this materials family, both ZIFs selectively capture carbon dioxide from several different gas mixtures at room temperature, with ZIF-100 capable of storing 28 litres per litre of material at standard temperature and pressure. These characteristics, combined with their high thermal and chemical stability and ease of fabrication, make ZIFs promising candidate materials for strategies aimed at ameliorating increasing atmospheric carbon dioxide levels.

Nature 453, 212 (2008). doi:10.1038/nature06960

Authors: Peter M. Cox, Phil P. Harris, Chris Huntingford, Richard A. Betts, Matthew Collins, Chris D. Jones, Tim E. Jupp, José A. Marengo & Carlos A. Nobre

The Amazon rainforest plays a crucial role in the climate system, helping to drive atmospheric circulations in the tropics by absorbing energy and recycling about half of the rainfall that falls on it. This region (Amazonia) is also estimated to contain about one-tenth of the total carbon stored in land ecosystems, and to account for one-tenth of global, net primary productivity. The resilience of the forest to the combined pressures of deforestation and global warming is therefore of great concern, especially as some general circulation models (GCMs) predict a severe drying of Amazonia in the twenty-first century. Here we analyse these climate projections with reference to the 2005 drought in western Amazonia, which was associated with unusually warm North Atlantic sea surface temperatures (SSTs). We show that reduction of dry-season (July–October) rainfall in western Amazonia correlates well with an index of the north–south SST gradient across the equatorial Atlantic (the ‘Atlantic N–S gradient’). Our climate model is unusual among current GCMs in that it is able to reproduce this relationship and also the observed twentieth-century multidecadal variability in the Atlantic N–S gradient, provided that the effects of aerosols are included in the model. Simulations for the twenty-first century using the same model show a strong tendency for the SST conditions associated with the 2005 drought to become much more common, owing to continuing reductions in reflective aerosol pollution in the Northern Hemisphere.

Nature 453, 216 (2008). doi:10.1038/nature06812

Authors: D. Nogués-Bravo, M. B. Araújo, T. Romdal & C. Rahbek

Despite two centuries of effort in characterizing environmental gradients of species richness in search of universal patterns, surprisingly few of these patterns have been widely acknowledged. Species richness along altitudinal gradients was previously assumed to increase universally from cool highlands to warm lowlands, mirroring the latitudinal increase in species richness from cool to warm latitudes. However, since the more recent general acceptance of altitudinal gradients as model templates for testing hypotheses behind large-scale patterns of diversity, these gradients have been used in support of all the main diversity hypotheses, although little consensus has been achieved. Here we show that when resampling a data set comprising 400,000 records for 3,046 Pyrenean floristic species at different scales of analysis (achieved by varying grain size and the extent of the gradients sampled), the derived species richness pattern changed progressively from hump-shaped to a monotonic pattern as the scale of extent diminished. Scale effects alone gave rise to as many conflicting patterns of species richness as had previously been reported in the literature, and scale effects lent significantly different statistical support to competing diversity hypotheses. Effects of scale on current studies may be affected by human activities, because montane ecosystems and human activities are intimately connected. This interdependence has led to a global reduction in natural lowland habitats, hampering our ability to detect universal patterns and impeding the search for universal diversity gradients to discover the mechanisms determining the distribution of biological diversity on Earth.

Nature 453, 220 (2008). doi:10.1038/nature06813

Authors: Rachata Muneepeerakul, Enrico Bertuzzo, Heather J. Lynch, William F. Fagan, Andrea Rinaldo & Ignacio Rodriguez-Iturbe

River networks, seen as ecological corridors featuring connected and hierarchical dendritic landscapes for animals and plants, present unique challenges and opportunities for testing biogeographical theories and macroecological laws. Although local and basin-scale differences in riverine fish diversity have been analysed as functions of energy availability and habitat heterogeneity, scale-dependent environmental conditions and river discharge, a model that predicts a comprehensive set of system-wide diversity patterns has been hard to find. Here we show that fish diversity patterns throughout the Mississippi–Missouri River System are well described by a neutral metacommunity model coupled with an appropriate habitat capacity distribution and dispersal kernel. River network structure acts as an effective template for characterizing spatial attributes of fish biodiversity. We show that estimates of average dispersal behaviour and habitat capacities, objectively calculated from average runoff production, yield reliable predictions of large-scale spatial biodiversity patterns in riverine systems. The success of the neutral theory in two-dimensional forest ecosystems and here in dendritic riverine ecosystems suggests the possible application of neutral metacommunity models in a diverse suite of ecosystems. This framework offers direct linkage from large-scale forcing, such as global climate change, to biodiversity patterns.

Nature 453, 223 (2008). doi:10.1038/nature06863

Authors: Sanjay K. Singh, Mohamedi N. Kagalwala, Jan Parker-Thornburg, Henry Adams & Sadhan Majumder

The neuronal repressor REST (RE1-silencing transcription factor; also called NRSF) is expressed at high levels in mouse embryonic stem (ES) cells, but its role in these cells is unclear. Here we show that REST maintains self-renewal and pluripotency in mouse ES cells through suppression of the microRNA miR-21. We found that, as with known self-renewal markers, the level of REST expression is much higher in self-renewing mouse ES cells than in differentiating mouse ES (embryoid body, EB) cells. Heterozygous deletion of Rest (Rest+/-) and its short-interfering-RNA-mediated knockdown in mouse ES cells cause a loss of self-renewal—even when these cells are grown under self-renewal conditions—and lead to the expression of markers specific for multiple lineages. Conversely, exogenously added REST maintains self-renewal in mouse EB cells. Furthermore, Rest+/- mouse ES cells cultured under self-renewal conditions express substantially reduced levels of several self-renewal regulators, including Oct4 (also called Pou5f1), Nanog, Sox2 and c-Myc, and exogenously added REST in mouse EB cells maintains the self-renewal phenotypes and expression of these self-renewal regulators. We also show that in mouse ES cells, REST is bound to the gene chromatin of a set of miRNAs that potentially target self-renewal genes. Whereas mouse ES cells and mouse EB cells containing exogenously added REST express lower levels of these miRNAs, EB cells, Rest+/- ES cells and ES cells treated with short interfering RNA targeting Rest express higher levels of these miRNAs. At least one of these REST-regulated miRNAs, miR-21, specifically suppresses the self-renewal of mouse ES cells, corresponding to the decreased expression of Oct4, Nanog, Sox2 and c-Myc. Thus, REST is a newly discovered element of the interconnected regulatory network that maintains the self-renewal and pluripotency of mouse ES cells.

Nature 453, 228 (2008). doi:10.1038/nature06869

Authors: Omobolaji O. Akala, In-Kyung Park, Dalong Qian, Michael Pihalja, Michael W. Becker & Michael F. Clarke

Haematopoiesis is maintained by a hierarchical system where haematopoietic stem cells (HSCs) give rise to multipotent progenitors, which in turn differentiate into all types of mature blood cells. HSCs maintain themselves for the lifetime of the organism because of their ability to self-renew. However, multipotent progenitors lack the ability to self-renew, therefore their mitotic capacity and expansion potential are limited and they are destined to eventually stop proliferating after a finite number of cell divisions. The molecular mechanisms that limit the proliferation capacity of multipotent progenitors and other more mature progenitors are not fully understood. Here we show that bone marrow cells from mice deficient in three genes genetically downstream of Bmi1—p16Ink4a, p19Arf and Trp53 (triple mutant mice; p16Ink4a and p19Arf are alternative reading frames of the same gene (also called Cdkn2a) that encode different proteins)—have an approximately 10-fold increase in cells able to reconstitute the blood long term. This increase is associated with the acquisition of long-term reconstitution capacity by cells of the phenotype c-kit+Sca-1+Flt3+CD150-CD48-Lin-, which defines multipotent progenitors in wild-type mice. The pattern of triple mutant multipotent progenitor response to growth factors resembles that of wild-type multipotent progenitors but not wild-type HSCs. These results demonstrate that p16Ink4a/p19Arf and Trp53 have a central role in limiting the expansion potential of multipotent progenitors. These pathways are commonly repressed in cancer, suggesting a mechanism by which early progenitor cells could gain the ability to self-renew and become malignant with further oncogenic mutations.

Nature 453, 233 (2008). doi:10.1038/nature06860

Authors: Weiwei Zhang & Steven J. Luck

Limits on the storage capacity of working memory significantly affect cognitive abilities in a wide range of domains, but the nature of these capacity limits has been elusive. Some researchers have proposed that working memory stores a limited set of discrete, fixed-resolution representations, whereas others have proposed that working memory consists of a pool of resources that can be allocated flexibly to provide either a small number of high-resolution representations or a large number of low-resolution representations. Here we resolve this controversy by providing independent measures of capacity and resolution. We show that, when presented with more than a few simple objects, human observers store a high-resolution representation of a subset of the objects and retain no information about the others. Memory resolution varied over a narrow range that cannot be explained in terms of a general resource pool but can be well explained by a small set of discrete, fixed-resolution representations.

Nature 453, 236 (2008). doi:10.1038/nature06878

Authors: Liang Zhou, Jared E. Lopes, Mark M. W. Chong, Ivaylo I. Ivanov, Roy Min, Gabriel D. Victora, Yuelei Shen, Jianguang Du, Yuri P. Rubtsov, Alexander Y. Rudensky, Steven F. Ziegler & Dan R. Littman

T helper cells that produce IL-17 (TH17 cells) promote autoimmunity in mice and have been implicated in the pathogenesis of human inflammatory diseases. At mucosal surfaces, TH17 cells are thought to protect the host from infection, whereas regulatory T (Treg) cells control immune responses and inflammation triggered by the resident microflora. Differentiation of both cell types requires transforming growth factor-β (TGF-β), but depends on distinct transcription factors: RORγt (encoded by Rorc(γt)) for TH17 cells and Foxp3 for Treg cells. How TGF-β regulates the differentiation of T cells with opposing activities has been perplexing. Here we demonstrate that, together with pro-inflammatory cytokines, TGF-β orchestrates TH17 cell differentiation in a concentration-dependent manner. At low concentrations, TGF-β synergizes with interleukin (IL)-6 and IL-21 (refs 9–11) to promote IL-23 receptor (Il23r) expression, favouring TH17 cell differentiation. High concentrations of TGF-β repress IL23r expression and favour Foxp3+ Treg cells. RORγt and Foxp3 are co-expressed in naive CD4+ T cells exposed to TGF-β and in a subset of T cells in the small intestinal lamina propria of the mouse. In vitro, TGF-β-induced Foxp3 inhibits RORγt function, at least in part through their interaction. Accordingly, lamina propria T cells that co-express both transcription factors produce less IL-17 (also known as IL-17a) than those that express RORγt alone. IL-6, IL-21 and IL-23 relieve Foxp3-mediated inhibition of RORγt, thereby promoting TH17 cell differentiation. Therefore, the decision of antigen-stimulated cells to differentiate into either TH17 or Treg cells depends on the cytokine-regulated balance of RORγt and Foxp3.

Nature 453, 241 (2008). doi:10.1038/nature06857

Authors: Masahiro Kitano, Michio Nakaya, Takeshi Nakamura, Shigekazu Nagata & Michiyuki Matsuda

Efficient phagocytosis of apoptotic cells is crucial for tissue homeostasis and the immune response. Rab5 is known as a key regulator of the early endocytic pathway and we have recently shown that Rab5 is also implicated in apoptotic cell engulfment; however, the precise spatio-temporal dynamics of Rab5 activity remain unknown. Here, using a newly developed fluorescence resonance energy transfer biosensor, we describe a change in Rab5 activity during the engulfment of apoptotic thymocytes. Rab5 activity on phagosome membranes began to increase on disassembly of the actin coat encapsulating phagosomes. Rab5 activation was either continuous or repetitive for up to 10 min, but it ended before the collapse of engulfed apoptotic cells. Expression of a dominant-negative mutant of Rab5 delayed this collapse of apoptotic thymocytes, showing a role for Rab5 in phagosome maturation. Disruption of microtubules with nocodazole inhibited Rab5 activation on the phagosome membrane without perturbing the engulfment of apoptotic cells. Furthermore, we found that Gapex-5 is the guanine nucleotide exchange factor essential for Rab5 activation during the engulfment of apoptotic cells. Gapex-5 was bound to a microtubule-tip-associating protein, EB1, whose depletion inhibited Rab5 activation during phagocytosis. We therefore propose a mechanistic model in which the recruitment of Gapex-5 to phagosomes through the microtubule network induces the transient Rab5 activation.

Nature 453, 246 (2008). doi:10.1038/nature06867

Authors: Felix H. Lam, David J. Steger & Erin K. O’Shea

Chromatin influences gene expression by restricting access of DNA binding proteins to their cognate sites in the genome. Large-scale characterization of nucleosome positioning in Saccharomyces cerevisiae has revealed a stereotyped promoter organization in which a nucleosome-free region (NFR) is present within several hundred base pairs upstream of the translation start site. Many transcription factors bind within NFRs and nucleate chromatin remodelling events which then expose other cis-regulatory elements. However, it is not clear how transcription-factor binding and chromatin influence quantitative attributes of gene expression. Here we show that nucleosomes function largely to decouple the threshold of induction from dynamic range. With a series of variants of one promoter, we establish that the affinity of exposed binding sites is a primary determinant of the level of physiological stimulus necessary for substantial gene activation, and sites located within nucleosomal regions serve to scale expression once chromatin is remodelled. Furthermore, we find that the S. cerevisiae phosphate response (PHO) pathway exploits these promoter designs to tailor gene expression to different environmental phosphate levels. Our results suggest that the interplay of chromatin and binding-site affinity provides a mechanism for fine-tuning responses to the same cellular state. Moreover, these findings may be a starting point for more detailed models of eukaryotic transcriptional control.

Nature 453, 256 (2008). doi:10.1038/453256a

Author: John P. Boyd

A slight detour?