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Exploration before exploitation
02/15/2018 06:39 PM
News at a glance
02/15/2018 06:39 PM
Science gets modest reprieve in Trump budget
02/15/2018 06:39 PM
A weight limit emerges for neutron stars
02/15/2018 06:39 PM
Artificial intelligence faces reproducibility crisis
02/15/2018 06:39 PM
U.K. moms are turning parenting into an experiment
02/15/2018 06:39 PM
'CAMERA records cell action with new CRISPR tricks
02/15/2018 06:39 PM
Isotope cloud linked to failed neutrino source
02/15/2018 06:39 PM
The data thugs
02/15/2018 06:39 PM
The carbon harvest
02/15/2018 06:39 PM
Is evolution predictable?
02/15/2018 06:39 PM
Controlling learning and epilepsy together
02/15/2018 06:39 PM
The value of pollinator species diversity
02/15/2018 06:39 PM
Capsules made from prefabricated thin films
02/15/2018 06:39 PM
The changing face of urban air pollution
02/15/2018 06:39 PM
Chromatin regulation and immune escape
02/15/2018 06:39 PM
Was there ever really a "sugar conspiracy"?
02/15/2018 06:39 PM
Electrical chaos
02/15/2018 06:39 PM
Look to the locals
02/15/2018 06:39 PM
Salton Sea: Ecosystem in transition
02/15/2018 06:39 PM
Fund the Biological Survey Unit
02/15/2018 06:39 PM
As autonomous vehicles approach
02/15/2018 06:39 PM
Investigating flu vaccine effectiveness
02/15/2018 06:39 PM
How lipopolysaccharides bridge the gap
02/15/2018 06:39 PM
SNF'ing out antitumor immunity
02/15/2018 06:39 PM
CRISPR-Cas accelerates phage evolution
02/15/2018 06:39 PM
Recognizing danger signals
02/15/2018 06:39 PM
It's a wrap
02/15/2018 06:39 PM
Forming photonic bound states
02/15/2018 06:39 PM
A way to prevent generalized seizures?
02/15/2018 06:39 PM
Air pollution evolution
02/15/2018 06:39 PM
Left- or right-handed C-H bond activation
02/15/2018 06:39 PM
Estimating the predictability of evolution
02/15/2018 06:39 PM
Protein backbone, broken and mended
02/15/2018 06:39 PM
Many, many more pollinators needed
02/15/2018 06:39 PM
A primitive role for ATF6
02/15/2018 06:39 PM
A world at war on science
02/15/2018 06:39 PM
Innate receptor sees cancer growth factor
02/15/2018 06:39 PM
Around the world in 170 million years
02/15/2018 06:39 PM
Hot mantle rushes in to fill the void
02/15/2018 06:39 PM
Checks and balances at a cellular level
02/15/2018 06:39 PM
Cities feel the heat of climate change
02/15/2018 06:39 PM
Retrotransposons acting as lightning rods
02/15/2018 06:39 PM
Volatile chemical products emerging as largest petrochemical source of urban organic emissions

A gap in emission inventories of urban volatile organic compound (VOC) sources, which contribute to regional ozone and aerosol burdens, has increased as transportation emissions in the United States and Europe have declined rapidly. A detailed mass balance demonstrates that the use of volatile chemical products (VCPs)—including pesticides, coatings, printing inks, adhesives, cleaning agents, and personal care products—now constitutes half of fossil fuel VOC emissions in industrialized cities. The high fraction of VCP emissions is consistent with observed urban outdoor and indoor air measurements. We show that human exposure to carbonaceous aerosols of fossil origin is transitioning away from transportation-related sources and toward VCPs. Existing U.S. regulations on VCPs emphasize mitigating ozone and air toxics, but they currently exempt many chemicals that lead to secondary organic aerosols.

02/15/2018 06:39 PM
Natural selection and the predictability of evolution in Timema stick insects

Predicting evolution remains difficult. We studied the evolution of cryptic body coloration and pattern in a stick insect using 25 years of field data, experiments, and genomics. We found that evolution is more difficult to predict when it involves a balance between multiple selective factors and uncertainty in environmental conditions than when it involves feedback loops that cause consistent back-and-forth fluctuations. Specifically, changes in color-morph frequencies are modestly predictable through time (r2 = 0.14) and driven by complex selective regimes and yearly fluctuations in climate. In contrast, temporal changes in pattern-morph frequencies are highly predictable due to negative frequency-dependent selection (r2 = 0.86). For both traits, however, natural selection drives evolution around a dynamic equilibrium, providing some predictability to the process.

02/15/2018 06:39 PM
A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing

Many human cancers are resistant to immunotherapy, for reasons that are poorly understood. We used a genome-scale CRISPR-Cas9 screen to identify mechanisms of tumor cell resistance to killing by cytotoxic T cells, the central effectors of antitumor immunity. Inactivation of >100 genes—including Pbrm1, Arid2, and Brd7, which encode components of the PBAF form of the SWI/SNF chromatin remodeling complex—sensitized mouse B16F10 melanoma cells to killing by T cells. Loss of PBAF function increased tumor cell sensitivity to interferon-, resulting in enhanced secretion of chemokines that recruit effector T cells. Treatment-resistant tumors became responsive to immunotherapy when Pbrm1 was inactivated. In many human cancers, expression of PBRM1 and ARID2 inversely correlated with expression of T cell cytotoxicity genes, and Pbrm1-deficient murine melanomas were more strongly infiltrated by cytotoxic T cells.

02/15/2018 06:39 PM
Wrapping with a splash: High-speed encapsulation with ultrathin sheets

Many complex fluids rely on surfactants to contain, protect, or isolate liquid drops in an immiscible continuous phase. Thin elastic sheets can wrap liquid drops in a spontaneous process driven by capillary forces. For encapsulation by sheets to be practically viable, a rapid, continuous, and scalable process is essential. We exploit the fast dynamics of droplet impact to achieve wrapping of oil droplets by ultrathin polymer films in a water phase. Despite the violence of splashing events, the process robustly yields wrappings that are optimally shaped to maximize the enclosed fluid volume and have near-perfect seams. We achieve wrappings of targeted three-dimensional (3D) shapes by tailoring the 2D boundary of the films and show the generality of the technique by producing both oil-in-water and water-in-oil wrappings.

02/15/2018 06:39 PM
Natural noncanonical protein splicing yields products with diverse {beta}-amino acid residues

Current textbook knowledge holds that the structural scope of ribosomal biosynthesis is based exclusively on α-amino acid backbone topology. Here we report the genome-guided discovery of bacterial pathways that posttranslationally create β-amino acid–containing products. The transformation is widespread in bacteria and is catalyzed by an enzyme belonging to a previously uncharacterized radical S-adenosylmethionine family. We show that the β-amino acids result from an unusual protein splicing process involving backbone carbon-carbon bond cleavage and net excision of tyramine. The reaction can be used to incorporate diverse and multiple β-amino acids into genetically encoded precursors in Escherichia coli. In addition to enlarging the set of basic amino acid components, the excision generates keto functions that are useful as orthogonal reaction sites for chemical diversification.

02/15/2018 06:39 PM
Observation of three-photon bound states in a quantum nonlinear medium

Bound states of massive particles, such as nuclei, atoms, or molecules, constitute the bulk of the visible world around us. By contrast, photons typically only interact weakly. We report the observation of traveling three-photon bound states in a quantum nonlinear medium where the interactions between photons are mediated by atomic Rydberg states. Photon correlation and conditional phase measurements reveal the distinct bunching and phase features associated with three-photon and two-photon bound states. Such photonic trimers and dimers possess shape-preserving wave functions that depend on the constituent photon number. The observed bunching and strongly nonlinear optical phase are described by an effective field theory of Rydberg-induced photon-photon interactions. These observations demonstrate the ability to realize and control strongly interacting quantum many-body states of light.

02/15/2018 06:39 PM
Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory

Temporal lobe epilepsy (TLE) is characterized by debilitating, recurring seizures and an increased risk for cognitive deficits. Mossy cells (MCs) are key neurons in the hippocampal excitatory circuit, and the partial loss of MCs is a major hallmark of TLE. We investigated how MCs contribute to spontaneous ictal activity and to spatial contextual memory in a mouse model of TLE with hippocampal sclerosis, using a combination of optogenetic, electrophysiological, and behavioral approaches. In chronically epileptic mice, real-time optogenetic modulation of MCs during spontaneous hippocampal seizures controlled the progression of activity from an electrographic to convulsive seizure. Decreased MC activity is sufficient to impede encoding of spatial context, recapitulating observed cognitive deficits in chronically epileptic mice.

02/15/2018 06:39 PM
Species turnover promotes the importance of bee diversity for crop pollination at regional scales

Ecologists have shown through hundreds of experiments that ecological communities with more species produce higher levels of essential ecosystem functions such as biomass production, nutrient cycling, and pollination, but whether this finding holds in nature (that is, in large-scale and unmanipulated systems) is controversial. This knowledge gap is troubling because ecosystem services have been widely adopted as a justification for global biodiversity conservation. Here we show that, to provide crop pollination in natural systems, the number of bee species must increase by at least one order of magnitude compared with that in field experiments. This increase is driven by species turnover and its interaction with functional dominance, mechanisms that emerge only at large scales. Our results show that maintaining ecosystem services in nature requires many species, including relatively rare ones.

02/15/2018 06:39 PM
Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement

Danger patterns on microbes or damaged host cells bind and activate C1, inducing innate immune responses and clearance through the complement cascade. How these patterns trigger complement initiation remains elusive. Here, we present cryo–electron microscopy analyses of C1 bound to monoclonal antibodies in which we observed heterogeneous structures of single and clustered C1–immunoglobulin G1 (IgG1) hexamer complexes. Distinct C1q binding sites are observed on the two Fc-CH2 domains of each IgG molecule. These are consistent with known interactions and also reveal additional interactions, which are supported by functional IgG1-mutant analysis. Upon antibody binding, the C1q arms condense, inducing rearrangements of the C1r2s2 proteases and tilting C1q’s cone-shaped stalk. The data suggest that C1r may activate C1s within single, strained C1 complexes or between neighboring C1 complexes on surfaces.

02/15/2018 06:39 PM
Lipopolysaccharide is transported to the cell surface by a membrane-to-membrane protein bridge

Gram-negative bacteria have an outer membrane that serves as a barrier to noxious agents in the environment. This protective function is dependent on lipopolysaccharide, a large glycolipid located in the outer leaflet of the outer membrane. Lipopolysaccharide is synthesized at the cytoplasmic membrane and must be transported to the cell surface. To understand this transport process, we reconstituted membrane-to-membrane movement of lipopolysaccharide by incorporating purified inner and outer membrane transport complexes into separate proteoliposomes. Transport involved stable association between the inner and outer membrane proteoliposomes. Our results support a model in which lipopolysaccharide molecules are pushed one after the other in a PEZ dispenser–like manner across a protein bridge that connects the inner and outer membranes.

02/15/2018 06:39 PM
Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma

Immune checkpoint inhibitors targeting the programmed cell death 1 receptor (PD-1) improve survival in a subset of patients with clear cell renal cell carcinoma (ccRCC). To identify genomic alterations in ccRCC that correlate with response to anti–PD-1 monotherapy, we performed whole-exome sequencing of metastatic ccRCC from 35 patients. We found that clinical benefit was associated with loss-of-function mutations in the PBRM1 gene (P = 0.012), which encodes a subunit of the PBAF switch-sucrose nonfermentable (SWI/SNF) chromatin remodeling complex. We confirmed this finding in an independent validation cohort of 63 ccRCC patients treated with PD-1 or PD-L1 (PD-1 ligand) blockade therapy alone or in combination with anti–CTLA-4 (cytotoxic T lymphocyte-associated protein 4) therapies (P = 0.0071). Gene-expression analysis of PBAF-deficient ccRCC cell lines and PBRM1-deficient tumors revealed altered transcriptional output in JAK-STAT (Janus kinase–signal transducers and activators of transcription), hypoxia, and immune signaling pathways. PBRM1 loss in ccRCC may alter global tumor-cell expression profiles to influence responsiveness to immune checkpoint therapy.

02/15/2018 06:39 PM
Gordon Research Conferences
02/15/2018 06:39 PM
New Products
02/15/2018 06:39 PM
Got milk, must conference
02/15/2018 06:39 PM
Enantioselective C(sp3)-H bond activation by chiral transition metal catalysts

Organic molecules are rich in carbon-hydrogen bonds; consequently, the transformation of C–H bonds to new functionalities (such as C–C, C–N, and C–O bonds) has garnered much attention by the synthetic chemistry community. The utility of C–H activation in organic synthesis, however, cannot be fully realized until chemists achieve stereocontrol in the modification of C–H bonds. This Review highlights recent efforts to enantioselectively functionalize C(sp3)–H bonds via transition metal catalysis, with an emphasis on key principles for both the development of chiral ligand scaffolds that can accelerate metalation of C(sp3)–H bonds and stereomodels for asymmetric metalation of prochiral C–H bonds by these catalysts.

02/15/2018 06:39 PM
Comment on "Selective anaerobic oxidation of methane enables direct synthesis of methanol"

The comment and response concerning the report of oxidation of methane to methanol by water (Reports, 5 May 2017, p. 523) do not fully capture the implications of thermodynamic limitations. A nonisothermal process in which each cycle requires a large temperature swing and permits only substoichiometric methane conversion surely could not be carried out on any practical scale.

02/15/2018 06:39 PM
Response to Comment on "Selective anaerobic oxidation of methane enables direct synthesis of methanol"

Labinger argues that stepwise reaction of methane with water to produce methanol and hydrogen will never be commercially feasible because of its substoichiometric basis with respect to the active site and the requirement of a large temperature swing. This comment is not touching any new ground, beyond describing the thermodynamic feasibility, thermal cycling, and the role of water as discussed previously. Most important, it does not have a solid numerical basis.

02/15/2018 06:39 PM