Current Issue

In This Issue [This Week in PNAS]

2013-05-21T10:03:27-07:00

How a wildebeest herpesvirus threatens cattle Blue wildebeest (Connochaetes taurinus) in the Maasai Mara National Reserve. Annual wildebeest migrations through the Serengeti and Maasai Mara national reserves pose challenges for African livestock herders because the ocular and nasal excretions of young wildebeest transmit a virus known as Alcelaphine herpesvirus 1...

The oceanic cadmium cycle [Physical Sciences]

Morel, F. M. M. — 2013-05-21T10:03:29-07:00

Based on isotope-fractionation experiments with a transformed Escherichia coli strain expressing the cambialistic carbonic anhydrase (CDCA), which can use Cd or Zn as a metal center, Horner et al. conclude recently in PNAS that Cd is “mistakenly” taken up by marine phytoplankton and that its nutrient-like behavior in the oceans...

Cd as a micronutrient and macrotoxin in the oceans [Physical Sciences]

Horner, T. J., Lee, R. B. Y., Henderson, G. M., Rickaby, R. E. M. — 2013-05-21T10:03:29-07:00

We thank François Morel for his interest in our study. Morel states that our conclusions are based on the approximate match between the Cd-isotope composition of cultured bacteria and the fractionation of Cd isotopes seen in seawater (1). This match is only a minor component of our argument, and we...

QnAs with Randolph Blake [QnAs]

Azar, B. — 2013-05-21T10:03:27-07:00

Psychologist Randolph Blake has been fascinated for most of his career by a form of perceptual magic called binocular rivalry: Dissimilar images presented simultaneously one to each eye take turns perceptually disappearing and reappearing unpredictably. Furthermore, it is impossible to hold just one of those images in conscious awareness indefinitely....

Sinuous rivers [Earth, Atmospheric, and Planetary Sciences]

Baker, V. R. — 2013-05-21T10:03:27-07:00

The windings of rivers have long fascinated their human observers. For example, Aboriginal legend explains the sinuous pattern of the modern Finke River (Fig. 1) as the creation of the immense and powerful Rainbow Serpent as he emerged during the Dreamtime from deep waterholes. Recently in PNAS (1), a new...

More mixotrophy in the marine microbial mix [Ecology]

Moore, L. R. — 2013-05-21T10:03:27-07:00

Since the turn of the century, the paradigm of the marine microbial assemblage being composed primarily of photoautotrophs and chemoheterotrophs is shifting and challenging our understanding of how the microbial diversity contributes to the flow of energy, carbon, and other nutrients in the oceans. In PNAS, Muñoz-Marín et al. (1)...

Single-agent combinatorial cancer therapy [Medical Sciences]

Stritzker, J., Szalay, A. A. — 2013-05-21T10:03:27-07:00

Laboratories all over the world conduct research aimed at developing novel strategies to treat cancer. The approaches include innovative chemotherapy and prodrug agents, therapeutic antibodies, immunotherapies, nanoparticle-based approaches, targeted ultrasound, photodynamic therapy, radiation therapy, biological therapies, and combinations thereof. Recently, live vectors for the treatment and delivery of anticancer agents...

HIV integrase inhibitors disrupt virion maturation [Microbiology]

Potempa, M., Swanstrom, R. — 2013-05-21T10:03:27-07:00

In PNAS, Jurado et al. (1) describe an unexpected mechanism of action of a new class of HIV type 1 (HIV-1) integrase (IN) inhibitors. Several years ago it was discovered that the HIV-1 IN was targeted to sites in chromatin by the host protein lens epithelium-derived growth factor (LEDGF)/p75 (2)....

Structural analysis of Stc1 [Cell Biology]

2013-05-21T10:03:29-07:00

Noncoding RNAs can modulate gene expression by directing modifications to histones that alter chromatin structure. In fission yeast, siRNAs produced via the RNAi pathway direct modifications associated with heterochromatin formation. siRNAs associate with the RNAi effector protein Argonaute 1 (Ago1), targeting the Ago1-containing RNA-induced transcriptional silencing (RITS) complex to homologous...

Intermediate filament cytoskeleton in polar growth [Cell Biology]

2013-05-21T10:03:29-07:00

Intermediate filament (IF)-like cytoskeleton emerges as a versatile tool for cellular organization in all kingdoms of life, underscoring the importance of mechanistically understanding its diverse manifestations. We showed previously that, in Streptomyces (a bacterium with a mycelial lifestyle similar to that of filamentous fungi, including extreme cell and growth polarity),...

Kif7 is required for normal diaphragm development [Developmental Biology]

Coles, G. L., Ackerman, K. G. — 2013-05-21T10:03:29-07:00

Congenital diaphragmatic hernia (CDH) is a common birth defect that results in a high degree of neonatal morbidity and mortality, but its pathological mechanisms are largely unknown. Therefore, we performed a forward genetic screen in mice to identify unique genes, models, and mechanisms of abnormal diaphragm development. We identified a...

Telomere length analysis for single cells [Genetics]

2013-05-21T10:03:29-07:00

Measurement of telomere length currently requires a large population of cells, which masks telomere length heterogeneity in single cells, or requires FISH in metaphase arrested cells, posing technical challenges. A practical method for measuring telomere length in single cells has been lacking. We established a simple and robust approach for...

Spread of T. gondii infection by gut neutrophils [Immunology]

2013-05-21T10:03:29-07:00

Toxoplasma gondii infection occurs through the oral route, but we lack important information about how the parasite interacts with the host immune system in the intestine. We used two-photon laser-scanning microscopy in conjunction with a mouse model of oral T. gondii infection to address this issue. T. gondii established discrete...

Importance of lamin B farnesylation [Medical Sciences]

2013-05-21T10:03:29-07:00

The role of protein farnesylation in lamin A biogenesis and the pathogenesis of progeria has been studied in considerable detail, but the importance of farnesylation for the B-type lamins, lamin B1 and lamin B2, has received little attention. Lamins B1 and B2 are expressed in nearly every cell type from...

{gamma}-Herpesvirus latency in malignant catarrhal fever [Microbiology]

2013-05-21T10:03:29-07:00

Wildebeests carry asymptomatically alcelaphine herpesvirus 1 (AlHV-1), a γ-herpesvirus inducing malignant catarrhal fever (MCF) to several ruminant species (including cattle). This acute and lethal lymphoproliferative disease occurs after a prolonged asymptomatic incubation period after transmission. Our recent findings with the rabbit model indicated that AlHV-1 infection is not productive during...

Nogo-A is a negative regulator of CNS angiogenesis [Neuroscience]

2013-05-21T10:03:29-07:00

Nogo-A is an important axonal growth inhibitor in the adult and developing CNS. In vitro, Nogo-A has been shown to inhibit migration and cell spreading of neuronal and nonneuronal cell types. Here, we studied in vivo and in vitro effects of Nogo-A on vascular endothelial cells during angiogenesis of the...

Neuropsychology and neurohistology for E.P. [Neuroscience]

Insausti, R., Annese, J., Amaral, D. G., Squire, L. R. — 2013-05-21T10:03:29-07:00

We present neurohistological information for a case of bilateral, symmetrical damage to the medial temporal lobe and well-documented memory impairment. E.P. developed profound memory impairment at age 70 y and then was studied for 14 y He had no capacity for learning facts and events and had retrograde amnesia covering...

WRKY8 in TMV-cg defense by ABA and ethylene signal [Plant Biology]

Chen, L., Zhang, L., Li, D., Wang, F., Yu, D. — 2013-05-21T10:03:29-07:00

WRKY transcription factors are key players in the plant immune response, but less is known about their involvement in antiviral defense than about their roles in defense against bacterial or fungi pathogens. Here, we report that Arabidopsis thaliana WRKY DNA-binding protein 8 (WRKY8) has a role in mediating the long-distance...

Agricultural innovation to protect environment [Introductions]

Sayer, J., Cassman, K. G. — 2013-05-21T10:03:27-07:00

In a world of 9.5 billion people, global demand for food, fiber, and biofuels has to be met with minimal possible increases in land, water, fossil fuels, and the minerals used to produce fertilizers (1–4). The problem is debated at three levels: first, that agriculture will not be able to...

Landscape approach [Social Sciences]

2013-05-21T10:03:27-07:00

“Landscape approaches” seek to provide tools and concepts for allocating and managing land to achieve social, economic, and environmental objectives in areas where agriculture, mining, and other productive land uses compete with environmental and biodiversity goals. Here we synthesize the current consensus on landscape approaches. This is based on published...

Eco-efficiency in diverse cropping systems [Research Article]

2013-05-21T10:03:27-07:00

Global food security requires eco-efficient agriculture to produce the required food and fiber products concomitant with ecologically efficient use of resources. This eco-efficiency concept is used to diagnose the state of agricultural production in China (irrigated wheat–maize double-cropping systems), Zimbabwe (rainfed maize systems), and Australia (rainfed wheat systems). More than...

Retargeting of Bt toxins against insect pests [Agricultural Sciences]

2013-05-21T10:03:27-07:00

Although transgenic crops expressing Bacillus thuringiensis (Bt) toxins have been used successfully for management of lepidopteran and coleopteran pest species, the sap-sucking insects (Hemiptera) are not particularly susceptible to Bt toxins. To overcome this limitation, we demonstrate that addition of a short peptide sequence selected for binding to the gut...

Ultraconserved words [Anthropology]

Pagel, M., Atkinson, Q. D., S. Calude, A., Meade, A. — 2013-05-21T10:03:27-07:00

The search for ever deeper relationships among the World’s languages is bedeviled by the fact that most words evolve too rapidly to preserve evidence of their ancestry beyond 5,000 to 9,000 y. On the other hand, quantitative modeling indicates that some “ultraconserved” words exist that might be used to find...

Matrix recovery phase transition [Applied Mathematics]

Donoho, D. L., Gavish, M., Montanari, A. — 2013-05-21T10:03:27-07:00

Let be an unknown M by N matrix. In matrix recovery, one takes linear measurements of , where and each is an M by N matrix. A popular approach for matrix recovery is nuclear norm minimization (NNM): solving the convex optimization problem for all , where denotes the nuclear norm,...

Huygens principle for superdiffusion [Applied Mathematics]

Gottwald, G. A., Melbourne, I. — 2013-05-21T10:03:27-07:00

We present a universal view on diffusive behavior in chaotic spatially extended systems for anisotropic and isotropic media. For anisotropic systems, strong chaos leads to diffusive behavior (Brownian motion with drift) and weak chaos leads to superdiffusive behavior (Lévy processes with drift). For isotropic systems, the drift term vanishes and...

Single spin fluorescence thermometry [Applied Physical Sciences]

2013-05-21T10:03:27-07:00

We demonstrate fluorescence thermometry techniques with sensitivities approaching 10 mK⋅Hz−1/2 based on the spin-dependent photoluminescence of nitrogen vacancy (NV) centers in diamond. These techniques use dynamical decoupling protocols to convert thermally induced shifts in the NV center's spin resonance frequencies into large changes in its fluorescence. By mitigating interactions with...

Control of slippage with tunable bubble mattresses [Applied Physical Sciences]

2013-05-21T10:03:27-07:00

Tailoring the hydrodynamic boundary condition is essential for both applied and fundamental aspects of drag reduction. Hydrodynamic friction on superhydrophobic substrates providing gas–liquid interfaces can potentially be optimized by controlling the interface geometry. Therefore, establishing stable and optimal interfaces is crucial but rather challenging. Here we present unique superhydrophobic microfluidic...

Procaspase-3 and procaspase-7 structure and activation [Biochemistry]

Thomsen, N. D., Koerber, J. T., Wells, J. A. — 2013-05-21T10:03:27-07:00

Procaspase-3 (P3) and procaspase-7 (P7) are activated through proteolytic maturation to form caspase-3 (C3) and caspase-7 (C7), respectively, which serve overlapping but nonredundant roles as the executioners of apoptosis in humans. However, it is unclear if differences in P3 and P7 maturation mechanisms underlie their unique biological functions, as the...

Berninamycin posttranslational cascade [Biochemistry]

Malcolmson, S. J., Young, T. S., Ruby, J. G., Skewes-Cox, P., Walsh, C. T. — 2013-05-21T10:03:27-07:00

Berninamycin is a member of the pyridine-containing thiopeptide class of antibiotics that undergoes massive posttranslational modifications from ribosomally generated preproteins. Berninamycin has a 2-oxazolyl-3-thiazolyl-pyridine core embedded in a 35-atom macrocycle rather than typical trithiazolylpyridine cores embedded in 26-atom and 29-atom peptide macrocycles. We describe the cloning of an 11-gene berninamycin...

NSS chloride site [Biochemistry]

2013-05-21T10:03:27-07:00

Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs have a serine. The LeuT-E290S mutant displays chloride-dependent activity. We show...

Induced histone-DNA contacts [Biochemistry]

Wang, F., Li, G., Altaf, M., Lu, C., Currie, M. A., Johnson, A., Moazed, D. — 2013-05-21T10:03:27-07:00

The regulated binding of effector proteins to the nucleosome plays a central role in the activation and silencing of eukaryotic genes. How this binding changes the properties of chromatin to mediate gene activation or silencing is not fully understood. Here we provide evidence that association of the budding yeast silent...

23S rRNA cleavage by a mycobacterial MazF toxin [Biochemistry]

2013-05-21T10:03:27-07:00

The Mycobacterium tuberculosis genome contains an unusually high number of toxin–antitoxin modules, some of which have been suggested to play a role in the establishment and maintenance of latent tuberculosis. Nine of these toxin–antitoxin loci belong to the mazEF family, encoding the intracellular toxin MazF and its antitoxin inhibitor MazE....

Structure of CaBP1 bound to InsP3R1 [Biochemistry]

2013-05-21T10:03:27-07:00

Calcium-binding protein 1 (CaBP1) is a neuron-specific member of the calmodulin superfamily that regulates several Ca2+ channels, including inositol 1,4,5-trisphosphate receptors (InsP3Rs). CaBP1 alone does not affect InsP3R activity, but it inhibits InsP3-evoked Ca2+ release by slowing the rate of InsP3R opening. The inhibition is enhanced by Ca2+ binding to...

Hsp70 is an activator of the Hsp104 motor [Biochemistry]

Lee, J., Kim, J.-H., Biter, A. B., Sielaff, B., Lee, S., Tsai, F. T. F. — 2013-05-21T10:03:27-07:00

Heat shock protein (Hsp) 104 is a ring-forming, protein-remodeling machine that harnesses the energy of ATP binding and hydrolysis to drive protein disaggregation. Although Hsp104 is an active ATPase, the recovery of functional protein requires the species-specific cooperation of the Hsp70 system. However, like Hsp104, Hsp70 is an active ATPase,...

Structure of anaerobic sulfatase maturating enzyme [Biochemistry]

2013-05-21T10:03:27-07:00

Arylsulfatases require a maturating enzyme to perform a co- or posttranslational modification to form a catalytically essential formylglycine (FGly) residue. In organisms that live aerobically, molecular oxygen is used enzymatically to oxidize cysteine to FGly. Under anaerobic conditions, S-adenosylmethionine (AdoMet) radical chemistry is used. Here we present the structures of...

Conformational changes in VraR activation [Biochemistry]

Leonard, P. G., Golemi-Kotra, D., Stock, A. M. — 2013-05-21T10:03:27-07:00

Staphylococcus aureus VraR, a vancomycin-resistance-associated response regulator, activates a cell-wall–stress stimulon in response to antibiotics that inhibit cell wall formation. X-ray crystal structures of VraR in both unphosphorylated and beryllofluoride-activated states have been determined, revealing a mechanism of phosphorylation-induced dimerization that features a deep hydrophobic pocket at the center of...

PKA enhances Rac-PAK signaling to Erk1/2 [Biochemistry]

2013-05-21T10:03:28-07:00

Activated G protein-coupled receptors (GPCRs) and receptor tyrosine kinases relay extracellular signals through spatial and temporal controlled kinase and GTPase entities. These enzymes are coordinated by multifunctional scaffolding proteins for precise intracellular signal processing. The cAMP-dependent protein kinase A (PKA) is the prime example for compartmentalized signal transmission downstream of...

Multilayered upright peptide assembly on mica [Biophysics and Computational Biology]

2013-05-21T10:03:28-07:00

Surface-assisted self-assembly of amyloid-like peptides has received considerable interest in both amyloidosis research and nanotechnology in recent years. Despite extensive studies, some controlling factors, such as salts, are still not well understood, even though it is known that some salts can promote peptide self-assemblies through the so-called “salting-out” effect. However,...

Structural plasticity of cellular prion protein [Biophysics and Computational Biology]

Christen, B., Damberger, F. F., Perez, D. R., Hornemann, S., Wuthrich, K. — 2013-05-21T10:03:28-07:00

Two lines of transgenic mice expressing mouse/elk and mouse/horse prion protein (PrP) hybrids, which both form a well-structured β2–α2 loop in the NMR structures at 20 °C termed rigid-loop cellular prion proteins (RL-PrPC), presented with accumulation of the aggregated scrapie form of PrP in brain tissue, and the mouse/elk hybrid...

TR4 in Cushing disease [Cell Biology]

2013-05-21T10:03:28-07:00

Cushing disease (CD) is a life-threatening disorder attributed to excess pituitary tumor-derived adrenocorticotrophic hormone (ACTH) and adrenal steroid secretion caused by pituitary tumors. Whereas CD was first described in 1932, the underlying genetic basis driving tumor growth and ACTH secretion remains unsolved. Here, we show that testicular orphan nuclear receptor...

Structure of a Ca2+-regulated myosin filament [Cell Biology]

Woodhead, J. L., Zhao, F.-Q., Craig, R. — 2013-05-21T10:03:28-07:00

Myosin filaments of muscle are regulated either by phosphorylation of their regulatory light chains or Ca2+ binding to the essential light chains, contributing to on–off switching or modulation of contraction. Phosphorylation-regulated filaments in the relaxed state are characterized by an asymmetric interaction between the two myosin heads, inhibiting their actin...

Cell-cell proximity reporter [Cell Biology]

2013-05-21T10:03:28-07:00

Interactions among neighboring cells underpin many physiological processes ranging from early development to immune responses. When these interactions do not function properly, numerous pathologies, including infection and cancer, can result. Molecular imaging technologies, especially optical imaging, are uniquely suited to illuminate complex cellular interactions within the context of living tissues...

MET and EGFR cross-talk in NSCLC involves miR-27a [Cell Biology]

2013-05-21T10:03:28-07:00

In the past decade, we have observed exciting advances in lung cancer therapy, including the development of targeted therapies. However, additional strategies for early detection and tumor-based therapy are still essential in improving patient outcomes. EGF receptor (EGFR) and MET (the receptor tyrosine kinase for hepatocyte growth factors) are cell-surface...

CENP-A phosphorylation is required in mitosis [Cell Biology]

2013-05-21T10:03:28-07:00

The role of the mitotic phosphorylation of the amino (NH2) terminus of Centromere Protein A (CENP-A), the histone variant epigenetic centromeric marker, remains elusive. Here, we show that the NH2 terminus of human CENP-A is essential for mitotic progression and that localization of CENP-C, another key centromeric protein, requires only...

Question of the bridged fluoronium ion [Chemistry]

Olah, G. A., Prakash, G. K. S., Rasul, G. — 2013-05-21T10:03:27-07:00

A comparative study of the 2,3-dimethyl-3-fluoro-2-butyl cation and its chloro analog was carried out by the ab initio/GIAO-CCSD(T) (gauge invariant atomic orbital-coupled cluster with single, double, and perturbative triple excitation) method. The structures and 13C NMR chemical shifts of the cations were calculated at the GIAO-CCSD(T)/tzp/dz//MP2/cc-pVTZ level. Bridged fluoronium ion...

Intermediates in electrocatalytic O2 reduction [Chemistry]

Sengupta, K., Chatterjee, S., Samanta, S., Dey, A. — 2013-05-21T10:03:27-07:00

Heme/porphyrin-based electrocatalysts (both synthetic and natural) have been known to catalyze electrochemical O2, H+, and CO2 reduction for more than five decades. So far, no direct spectroscopic investigations of intermediates formed on the electrodes during these processes have been reported; and this has limited detailed understanding of the mechanism of...

Methanol incorporation in clathrate hydrates [Chemistry]

2013-05-21T10:03:27-07:00

One of the best-known uses of methanol is as antifreeze. Methanol is used in large quantities in industrial applications to prevent methane clathrate hydrate blockages from forming in oil and gas pipelines. Methanol is also assigned a major role as antifreeze in giving icy planetary bodies (e.g., Titan) a liquid...

Optimal fold symmetry of LH2 rings [Chemistry]

Cleary, L., Chen, H., Chuang, C., Silbey, R. J., Cao, J. — 2013-05-21T10:03:28-07:00

An intriguing observation of photosynthetic light-harvesting systems is the N-fold symmetry of light-harvesting complex 2 (LH2) of purple bacteria. We calculate the optimal rotational configuration of N-fold rings on a hexagonal lattice and establish two related mechanisms for the promotion of maximum excitation energy transfer (EET). (i) For certain fold...

Female mice lack active adult germ-line stem cells [Developmental Biology]

Lei, L., Spradling, A. C. — 2013-05-21T10:03:28-07:00

Whether or not mammalian females generate new oocytes during adulthood from germ-line stem cells to sustain the ovarian follicle pool has recently generated controversy. We used a sensitive lineage-labeling system to determine whether stem cells are needed in female adult mice to compensate for follicular losses and to directly identify...

GRN for neurogenesis in a sea star embryo [Developmental Biology]

Yankura, K. A., Koechlein, C. S., Cryan, A. F., Cheatle, A., Hinman, V. F. — 2013-05-21T10:03:28-07:00

A great challenge in development biology is to understand how interacting networks of regulatory genes can direct the often highly complex patterning of cells in a 3D embryo. Here, we detail the gene regulatory network that describes the distribution of ciliary band-associated neurons in the bipinnaria larva of the sea...

Evolution of the Phanerozoic sulfur cycle [Earth, Atmospheric, and Planetary Sciences]

Canfield, D. E. — 2013-05-21T10:03:27-07:00

Sulfate is the second most abundant anion (behind chloride) in modern seawater, and its cycling is intimately coupled to the cycling of organic matter and oxygen at the Earth’s surface. For example, the reduction of sulfide by microbes oxidizes vast amounts of organic carbon and the subsequent reaction of sulfide...

Channel sinuosity [Earth, Atmospheric, and Planetary Sciences]

Lazarus, E. D., Constantine, J. A. — 2013-05-21T10:03:27-07:00

Sinuous patterns traced by fluid flows are a ubiquitous feature of physical landscapes on Earth, Mars, the volcanic floodplains of the Moon and Venus, and other planetary bodies. Typically discussed as a consequence of migration processes in meandering rivers, sinuosity is also expressed in channel types that show little or...

Persistence and origin of the lunar core dynamo [Earth, Atmospheric, and Planetary Sciences]

2013-05-21T10:03:27-07:00

The lifetime of the ancient lunar core dynamo has implications for its power source and the mechanism of field generation. Here, we report analyses of two 3.56-Gy-old mare basalts demonstrating that they were magnetized in a stable and surprisingly intense dynamo magnetic field of at least ∼13 μT. These data...

Glucose uptake by Prochlorococcus in the ocean [Ecology]

2013-05-21T10:03:28-07:00

Prochlorococcus is responsible for a significant part of CO2 fixation in the ocean. Although it was long considered an autotrophic cyanobacterium, the uptake of organic compounds has been reported, assuming they were sources of limited biogenic elements. We have shown in laboratory experiments that Prochlorococcus can take up glucose. However,...

Consumer-mediated effects of climate change [Ecology]

Alsterberg, C., Eklof, J. S., Gamfeldt, L., Havenhand, J. N., Sundback, K. — 2013-05-21T10:03:28-07:00

It is well known that ocean acidification can have profound impacts on marine organisms. However, we know little about the direct and indirect effects of ocean acidification and also how these effects interact with other features of environmental change such as warming and declining consumer pressure. In this study, we...

Green Revolution research saved 18-27 M ha land [Research Articles]

Stevenson, J. R., Villoria, N., Byerlee, D., Kelley, T., Maredia, M. — 2013-05-21T10:03:27-07:00

New estimates of the impacts of germplasm improvement in the major staple crops between 1965 and 2004 on global land-cover change are presented, based on simulations carried out using a global economic model (Global Trade Analysis Project Agro-Ecological Zone), a multicommodity, multiregional computable general equilibrium model linked to a global...

Affordable water purification using nanomaterials [Engineering]

2013-05-21T10:03:27-07:00

Creation of affordable materials for constant release of silver ions in water is one of the most promising ways to provide microbially safe drinking water for all. Combining the capacity of diverse nanocomposites to scavenge toxic species such as arsenic, lead, and other contaminants along with the above capability can...

Phenotyping RASA1 with NIRF lymphatic imaging [Engineering]

2013-05-21T10:03:28-07:00

Mutations in gene RASA1 have been historically associated with capillary malformation–arteriovenous malformation, but sporadic reports of lymphatic involvement have yet to be investigated in detail. To investigate the impact of RASA1 mutations in the lymphatic system, we performed investigational near-infrared fluorescence lymphatic imaging and confirmatory radiographic lymphangiography in a Parkes–Weber...

The Black Sea's plankton paleome [Environmental Sciences]

2013-05-21T10:03:28-07:00

The complex interplay of climate shifts over Eurasia and global sea level changes modulates freshwater and saltwater inputs to the Black Sea. The dynamics of the hydrologic changes from the Late Glacial into the Holocene remain a matter of debate, and information on how these changes affected the ecology of...

Uncertainty adaptation agriculture [Research Article]

2013-05-21T10:03:27-07:00

We present a framework for prioritizing adaptation approaches at a range of timeframes. The framework is illustrated by four case studies from developing countries, each with associated characterization of uncertainty. Two cases on near-term adaptation planning in Sri Lanka and on stakeholder scenario exercises in East Africa show how the...

Frequent adaptation and the McDonald-Kreitman test [Evolution]

Messer, P. W., Petrov, D. A. — 2013-05-21T10:03:28-07:00

Population genomic studies have shown that genetic draft and background selection can profoundly affect the genome-wide patterns of molecular variation. We performed forward simulations under realistic gene-structure and selection scenarios to investigate whether such linkage effects impinge on the ability of the McDonald–Kreitman (MK) test to infer the rate of...

Dnmt2 methylomes lack DNA methylation [Genetics]

2013-05-21T10:03:28-07:00

Several organisms have retained methyltransferase 2 (Dnmt2) as their only candidate DNA methyltransferase gene. However, information about Dnmt2-dependent methylation patterns has been limited to a few isolated loci and the results have been discussed controversially. In addition, recent studies have shown that Dnmt2 functions as a tRNA methyltransferase, which raised...

PALB2 suppresses breast cancer in a mouse model [Genetics]

2013-05-21T10:03:28-07:00

Germ-line mutations in PALB2 lead to a familial predisposition to breast and pancreatic cancer or to Fanconi Anemia subtype N. PALB2 performs its tumor suppressor role, at least in part, by supporting homologous recombination-type double strand break repair (HR-DSBR) through physical interactions with BRCA1, BRCA2, and RAD51. To further understand...

Antiaging activity of Parkin in Drosophila [Genetics]

Rana, A., Rera, M., Walker, D. W. — 2013-05-21T10:03:28-07:00

Aberrant protein aggregation and mitochondrial dysfunction have each been linked to aging and a number of age-onset neurodegenerative disorders, including Parkinson disease. Loss-of-function mutations in parkin, an E3 ubiquitin ligase that functions to promote the ubiquitin–proteasome system of protein degradation and also in mitochondrial quality control, have been implicated in...

ALDH1A3 in mesenchymal glioma stem cells [Genetics]

2013-05-21T10:03:28-07:00

Tumor heterogeneity of high-grade glioma (HGG) is recognized by four clinically relevant subtypes based on core gene signatures. However, molecular signaling in glioma stem cells (GSCs) in individual HGG subtypes is poorly characterized. Here we identified and characterized two mutually exclusive GSC subtypes with distinct dysregulated signaling pathways. Analysis of...

Identification of the C1r/C1s-binding sites of C1q [Immunology]

2013-05-21T10:03:28-07:00

Complement C1q is a hexameric molecule assembled from 18 polypeptide chains of three different types encoded by three genes. This versatile recognition protein senses a wide variety of immune and nonimmune ligands, including pathogens and altered self components, and triggers the classical complement pathway through activation of its associated proteases...

Stat2 and LPS-induced sepsis [Immunology]

2013-05-21T10:03:28-07:00

Deregulated Toll-like receptor (TLR)-triggered inflammatory responses that depend on NF-κB are detrimental to the host via excessive production of proinflammatory cytokines, including TNF-α. Stat2 is a critical component of type I IFN signaling, but it is not thought to participate in TLR signaling. Our study shows that LPS-induced lethality in...

Zoonosis emergence and agroecological change [Research Article]

2013-05-21T10:03:27-07:00

A systematic review was conducted by a multidisciplinary team to analyze qualitatively best available scientific evidence on the effect of agricultural intensification and environmental changes on the risk of zoonoses for which there are epidemiological interactions between wildlife and livestock. The study found several examples in which agricultural intensification and/or...

Avidity-tuned nanoparticles reach the brain [Medical Sciences]

Wiley, D. T., Webster, P., Gale, A., Davis, M. E. — 2013-05-21T10:03:28-07:00

Receptor-mediated transcytosis across the blood–brain barrier (BBB) may be a useful way to transport therapeutics into the brain. Here we report that transferrin (Tf)-containing gold nanoparticles can reach the brain parenchyma from systemic administration in mice through a receptor-mediated transcytosis pathway. This transport is aided by tuning the nanoparticle avidity...

Radioactive Listeria against pancreatic cancer [Medical Sciences]

2013-05-21T10:03:28-07:00

No significant improvement in therapy of pancreatic cancer has been reported over the last 25 y, underscoring the urgent need for new alternative therapies. Here, we coupled a radioisotope, 188Rhenium, to an attenuated (at) live Listeria monocytogenes (Listeriaat) using Listeria-binding antibodies, thus creating a unique radioactive Listeriaat (RL). We then...

PAD4 is crucial for deep vein thrombosis [Medical Sciences]

2013-05-21T10:03:28-07:00

Deep vein thrombosis and pulmonary embolism are major health problems associated with high mortality. Recently, DNA-based neutrophil extracellular traps (NETs) resulting from the release of decondensed chromatin, were found to be part of the thrombus scaffold and to promote coagulation. However, the significance of nuclear decondensation and NET generation in...

Engineering bone tissue substitutes from hiPSCs [Medical Sciences]

2013-05-21T10:03:28-07:00

Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate...

Peptide-morpholino oligo as an antibiotic [Microbiology]

Wesolowski, D., Alonso, D., Altman, S. — 2013-05-21T10:03:28-07:00

A cell-penetrating peptide (CPP)–morpholino oligonucleotide (MO) conjugate (PMO) that has an antibiotic effect in culture had some contaminating CPPs in earlier preparations. The mixed conjugate had gene-specific and gene-nonspecific effects. An improved purification procedure separates the PMO from the free CPP and MO. The gene-specific effects are a result of...

IN inhibitors that block HIV-1 core formation [Microbiology]

2013-05-21T10:03:28-07:00

Integration is essential for HIV-1 replication, and the viral integrase (IN) protein is an important therapeutic target. Allosteric IN inhibitors (ALLINIs) that engage the IN dimer interface at the binding site for the host protein lens epithelium-derived growth factor (LEDGF)/transcriptional coactivator p75 are an emerging class of small molecule antagonists....

Nitrogen isotope discrimination in E. coli [Microbiology]

Vo, J., Inwood, W., Hayes, J. M., Kustu, S. — 2013-05-21T10:03:28-07:00

Organisms that use ammonium as the sole nitrogen source discriminate between [15N] and [14N] ammonium. This selectivity leaves an isotopic signature in their biomass that depends on the external concentration of ammonium. To dissect how differences in discrimination arise molecularly, we examined a wild-type (WT) strain of Escherichia coli K12...

Monocular contribution to stimulus rivalry [Neuroscience]

Brascamp, J., Sohn, H., Lee, S.-H., Blake, R. — 2013-05-21T10:03:27-07:00

When corresponding areas of the two eyes view dissimilar images, stable perception gives way to visual competition wherein perceptual awareness alternates between those images. Moreover, a given image can remain visually dominant for several seconds at a time even when the competing images are swapped between the eyes multiple times...

Global view of neuropeptide evolution [Neuroscience]

Jekely, G. — 2013-05-21T10:03:28-07:00

Neuropeptides are signaling molecules that commonly act via G protein-coupled receptors (GPCRs) and are generated in neurons by proneuropeptide (pNP) cleavage. Present in both cnidarians and bilaterians, neuropeptides represent an ancient and widespread mode of neuronal communication. Due to the inherent difficulties of analyzing highly diverse and repetitive pNPs, the...

Role of SGK1 in depression and neurogenesis [Neuroscience]

2013-05-21T10:03:28-07:00

Stress and glucocorticoid hormones regulate hippocampal neurogenesis, but the molecular mechanisms mediating these effects are poorly understood. Here we identify the glucocorticoid receptor (GR) target gene, serum- and glucocorticoid-inducible kinase 1 (SGK1), as one such mechanism. Using a human hippocampal progenitor cell line, we found that a small molecule inhibitor...

Activated microglia enhance neurogenesis [Neuroscience]

Nikolakopoulou, A. M., Dutta, R., Chen, Z., Miller, R. H., Trapp, B. D. — 2013-05-21T10:03:28-07:00

White matter neurons in multiple sclerosis brains are destroyed during demyelination and then replaced in some chronic multiple sclerosis lesions that exhibit a morphologically distinct population of activated microglia [Chang A, et al. (2008) Brain 131(Pt 9):2366–2375]. Here we investigated whether activated microglia secrete factors that promote the generation of...

Spiking activity regulates IHC synaptic maturation [Neuroscience]

2013-05-21T10:03:28-07:00

The development of neural circuits relies on spontaneous electrical activity that occurs during immature stages of development. In the developing mammalian auditory system, spontaneous calcium action potentials are generated by inner hair cells (IHCs), which form the primary sensory synapse. It remains unknown whether this electrical activity is required for...

PIP2 switches drug selectivity [Pharmacology]

Zhou, P., Yu, H., Gu, M., Nan, F.-j., Gao, Z., Li, M. — 2013-05-21T10:03:28-07:00

Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1–KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M...

Stoichiometry-specified drug sensitivity [Pharmacology]

2013-05-21T10:03:28-07:00

Voltage-gated KCNQ1 (Kv7.1) potassium channels are expressed abundantly in heart but they are also found in multiple other tissues. Differential coassembly with single transmembrane KCNE beta subunits in different cell types gives rise to a variety of biophysical properties, hence endowing distinct physiological roles for KCNQ1–KCNEx complexes. Mutations in either...

Muscle PGC-1{alpha} controls lactate metabolism [Physiology]

Summermatter, S., Santos, G., Perez–Schindler, J., Handschin, C. — 2013-05-21T10:03:28-07:00

The peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) controls metabolic adaptations. We now show that PGC-1α in skeletal muscle drives the expression of lactate dehydrogenase (LDH) B in an estrogen-related receptor-α–dependent manner. Concomitantly, PGC-1α reduces the expression of LDH A and one of its regulators, the transcription factor myelocytomatosis oncogene. PGC-1α...

Plant CDPK/NADPH-oxidase activation circuit [Plant Biology]

2013-05-21T10:03:28-07:00

In animals and plants, pathogen recognition triggers the local activation of intracellular signaling that is prerequisite for mounting systemic defenses in the whole organism. We identified that Arabidopsis thaliana isoform CPK5 of the plant calcium-dependent protein kinase family becomes rapidly biochemically activated in response to pathogen-associated molecular pattern (PAMP) stimulation....

GHG reduction from N fertilizer in China [Research Articles]

2013-05-21T10:03:27-07:00

Synthetic nitrogen (N) fertilizer has played a key role in enhancing food production and keeping half of the world’s population adequately fed. However, decades of N fertilizer overuse in many parts of the world have contributed to soil, water, and air pollution; reducing excessive N losses and emissions is a...

Innovations in capture fisheries [Research Article]

Hall, S. J., Hilborn, R., Andrew, N. L., Allison, E. H. — 2013-05-21T10:03:27-07:00

This article examines two strands of discourse on wild capture fisheries; one that focuses on resource sustainability and environmental impacts, another related to food and nutrition security and human well-being. Available data and research show that, for countries most dependent on fish to meet the nutritional requirements of their population,...

Improving degraded grasslands [Research Articles]

2013-05-21T10:03:27-07:00

Grasslands occupy 40% of the world’s land surface (excluding Antarctica and Greenland) and support diverse groups, from traditional extensive nomadic to intense livestock-production systems. Population pressures mean that many of these grasslands are in a degraded state, particularly in less-productive areas of developing countries, affecting not only productivity but also...

Ecosystem service and farm management interactions [Research Articles]

Boreux, V., Kushalappa, C. G., Vaast, P., Ghazoul, J. — 2013-05-21T10:03:27-07:00

Crop productivity is improved by ecosystem services, including pollination, but this should be set in the context of trade-offs among multiple management practices. We investigated the impact of pollination services on coffee production, considering variation in fertilization, irrigation, shade cover, and environmental variables such as rainfall (which stimulates coffee flowering...

Correction for Schulten et al., Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals [Correction]

2013-05-21T10:03:29-07:00

IMMUNOLOGY Correction for “Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals,” by Véronique Schulten, Jason A. Greenbaum, Michael Hauser, Denise M. McKinney, John Sidney, Ravi Kolla, Cecilia S. Lindestam Arlehamn, Carla Oseroff, Rapheul Alam, David H. Broide, Fatima Ferreira,...

Correction for Ndeffo Mbah et al., Cost-effectiveness of a community-based intervention for reducing the transmission of Schistosoma haematobium and HIV in Africa [Correction]

2013-05-21T10:03:29-07:00

POPULATION BIOLOGY, ECONOMIC SCIENCES Correction for “Cost-effectiveness of a community-based intervention for reducing the transmission of Schistosoma haematobium and HIV in Africa,” by Martial L. Ndeffo Mbah, Eyrun F. Kjetland, Katherine E. Atkins, Eric M. Poolman, Evan W. Orenstein, Lauren Ancel Meyers, Jeffrey P. Townsend, and Alison P. Galvani, which...

Correction for Sievert et al., Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas [Correction]

2013-05-21T10:03:29-07:00

CELL BIOLOGY Correction for “Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas,” by Angela J. Sievert, Shih-Shan Lang, Katie L. Boucher, Peter J. Madsen, Erin Slaunwhite, Namrata Choudhari, Meghan Kellet, Phillip B. Storm, and Adam C. Resnick, which appeared in issue 15, April 9,...

Radiated relics [Science and Culture]

Horne, R. — 2013-05-21T10:03:27-07:00

“Little Bottle” cyanotype of Atomic-bombed bottle from the Peace Memorial Museum’s archive, 2008, 8′′ x 10′′, by Elin O’Hara Slavick. “The history of the atomic age is intertwined with that of photography. Uranium’s radioactivity was discovered through a photograph,” says Elin O’Hara Slavick. She is the first American to photograph...

3D viewing in the deep sea [Inner Workings]

Schrope, M. — 2013-05-21T10:03:27-07:00

A team from WHOI uses a new super high-resolution panoramic camera system affixed to a small remotely operated vehicle to explore a coral reef in Palau. Image courtesy of Bill Lange. A new multicamera system enables unprecedented panoramic video feeds from remotely operated vehicles (ROVs) used to explore the deep...

Metamaterials [Core Concepts]

Ornes, S. — 2013-05-21T10:03:27-07:00

These metamaterial cloaks can hide objects from bands of microwave radiation. Image courtesy of David Schurig. In the June 2006 issue of Science, two independent teams of physicists simultaneously presented blueprints for an invisibility cloak. One team included David Smith from Duke University and John Pendry from Imperial College London...