Proceedings of the Natural Academy of Sciences

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Water in the kinetics of cavity-ligand binding [Biophysics and Computational Biology]

Tue, 09/29/2015 - 11:06
A key factor influencing a drug’s efficacy is its residence time in the binding pocket of the host protein. Using atomistic computer simulation to predict this residence time and the associated dissociation process is a desirable but extremely difficult task due to the long timescales involved. This gets further complicated...
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Proteomic mapping in Drosophila tissue [Cell Biology]

Tue, 09/29/2015 - 11:06
Characterization of the proteome of organelles and subcellular domains is essential for understanding cellular organization and identifying protein complexes as well as networks of protein interactions. We established a proteomic mapping platform in live Drosophila tissues using an engineered ascorbate peroxidase (APEX). Upon activation, the APEX enzyme catalyzes the biotinylation...
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Viscosity of deeply supercooled water [Chemistry]

Tue, 09/29/2015 - 11:06
The viscosity of a liquid measures its resistance to flow, with consequences for hydraulic machinery, locomotion of microorganisms, and flow of blood in vessels and sap in trees. Viscosity increases dramatically upon cooling, until dynamical arrest when a glassy state is reached. Water is a notoriously poor glassformer, and the...
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Protecting group-free selective cross-coupling [Chemistry]

Tue, 09/29/2015 - 11:06
Orthogonal reactivity modes offer substantial opportunities for rapid construction of complex small molecules. However, most strategies for imparting orthogonality to cross-coupling reactions rely on differential protection of reactive sites, greatly reducing both atom and step economies. Reported here is a strategy for orthogonal cross-coupling wherein a mechanistically distinct activation mode...
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Discovery of phosphonates by genome mining [Chemistry]

Tue, 09/29/2015 - 11:06
Although natural products have been a particularly rich source of human medicines, activity-based screening results in a very high rate of rediscovery of known molecules. Based on the large number of natural product biosynthetic genes in microbial genomes, many have proposed “genome mining” as an alternative approach for discovery efforts;...
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MYB36 regulates proliferation and differentiation [Developmental Biology]

Tue, 09/29/2015 - 11:06
Stem cells are defined by their ability to self-renew and produce daughter cells that proliferate and mature. These maturing cells transition from a proliferative state to a terminal state through the process of differentiation. In the Arabidopsis thaliana root the transcription factors SCARECROW and SHORTROOT regulate specification of the bipotent...
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Erosion in southern Tibet shut down at ~10 Ma [Earth, Atmospheric, and Planetary Sciences]

Tue, 09/29/2015 - 11:06
Exhumation of the southern Tibetan plateau margin reflects interplay between surface and lithospheric dynamics within the Himalaya–Tibet orogen. We report thermochronometric data from a 1.2-km elevation transect within granitoids of the eastern Lhasa terrane, southern Tibet, which indicate rapid exhumation exceeding 1 km/Ma from 17–16 to 12–11 Ma followed by...
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Fossil Lost City-type hydrothermal system [Earth, Atmospheric, and Planetary Sciences]

Tue, 09/29/2015 - 11:06
Subseafloor mixing of reduced hydrothermal fluids with seawater is believed to provide the energy and substrates needed to support deep chemolithoautotrophic life in the hydrated oceanic mantle (i.e., serpentinite). However, geosphere-biosphere interactions in serpentinite-hosted subseafloor mixing zones remain poorly constrained. Here we examine fossil microbial communities and fluid mixing processes...
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Iron melting at megabar pressures from XAS [Earth, Atmospheric, and Planetary Sciences]

Tue, 09/29/2015 - 11:06
Temperature, thermal history, and dynamics of Earth rely critically on the knowledge of the melting temperature of iron at the pressure conditions of the inner core boundary (ICB) where the geotherm crosses the melting curve. The literature on this subject is overwhelming, and no consensus has been reached, with a...
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Lipid pump and deep-ocean carbon sequestration [Earth, Atmospheric, and Planetary Sciences]

Tue, 09/29/2015 - 11:06
Estimates of carbon flux to the deep oceans are essential for our understanding of global carbon budgets. Sinking of detrital material (“biological pump”) is usually thought to be the main biological component of this flux. Here, we identify an additional biological mechanism, the seasonal “lipid pump,” which is highly efficient...
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Traffic noise is a source of habitat degradation [Ecology]

Tue, 09/29/2015 - 11:06
Decades of research demonstrate that roads impact wildlife and suggest traffic noise as a primary cause of population declines near roads. We created a “phantom road” using an array of speakers to apply traffic noise to a roadless landscape, directly testing the effect of noise alone on an entire songbird...
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Convergent evolution of herbivore chemical ecology [Ecology]

Tue, 09/29/2015 - 11:06
Chemical cues regulate key ecological interactions in marine and terrestrial ecosystems. They are particularly important in terrestrial plant–herbivore interactions, where they mediate both herbivore foraging and plant defense. Although well described for terrestrial interactions, the identity and ecological importance of herbivore foraging cues in marine ecosystems remain unknown. Here we...
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Climate change and disturbance impact biocrusts [Ecology]

Tue, 09/29/2015 - 11:06
Biological soil crusts (biocrusts)—communities of mosses, lichens, cyanobacteria, and heterotrophs living at the soil surface—are fundamental components of drylands worldwide, and destruction of biocrusts dramatically alters biogeochemical processes, hydrology, surface energy balance, and vegetation cover. Although there has been long-standing concern over impacts of physical disturbances on biocrusts (e.g., trampling...
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3D laser machining of biocompatible hydrogels [Engineering]

Tue, 09/29/2015 - 11:06
Light-induced material phase transitions enable the formation of shapes and patterns from the nano- to the macroscale. From lithographic techniques that enable high-density silicon circuit integration, to laser cutting and welding, light–matter interactions are pervasive in everyday materials fabrication and transformation. These noncontact patterning techniques are ideally suited to reshape...
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Seal molting alters nearshore mercury cycling [Environmental Sciences]

Tue, 09/29/2015 - 11:06
Methylmercury (MeHg) is a potent neurotoxin that is biomagnified approximately 1–10 million-fold in aquatic carnivores such as the Northern elephant seal (Mirounga angustirostris), whose excreta and molted pelage, in turn, constitute a source of environmental MeHg contamination at the base of marine food chains. The potential for this top-down contamination...
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Regional centromeres lacking heterochromatin [Genetics]

Tue, 09/29/2015 - 11:06
Point centromeres are specified by a short consensus sequence that seeds kinetochore formation, whereas regional centromeres lack a conserved sequence and instead are epigenetically inherited. Regional centromeres are generally flanked by heterochromatin that ensures high levels of cohesin and promotes faithful chromosome segregation. However, it is not known whether regional...
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BCR expression licenses B-cell mitogenic responses [Immunology and Inflammation]

Tue, 09/29/2015 - 11:06
B cells respond to antigens by engagement of their B-cell antigen receptor (BCR) and of coreceptors through which signals from helper T cells or pathogen-associated molecular patterns are delivered. We show that the proliferative response of B cells to the latter stimuli is controlled by BCR-dependent activation of phosphoinositidyl 3-kinase...
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Requirements for T-cell kinapses and synapses [Immunology and Inflammation]

Tue, 09/29/2015 - 11:06
T lymphocytes are highly motile cells that decelerate upon antigen recognition. These cells can either completely stop or maintain a low level of motility, forming contacts referred to as synapses or kinapses, respectively. Whether similar or distinct molecular mechanisms regulate T-cell deceleration during synapses or kinapses is unclear. Here, we...
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Zwitterionic nanogel protects therapeutic proteins [Medical Sciences]

Tue, 09/29/2015 - 11:06
Advances in protein therapy are hindered by the poor stability, inadequate pharmacokinetic (PK) profiles, and immunogenicity of many therapeutic proteins. Polyethylene glycol conjugation (PEGylation) is the most successful strategy to date to overcome these shortcomings, and more than 10 PEGylated proteins have been brought to market. However, anti-PEG antibodies induced...
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Skeletal anabolic effects of the myokine irisin [Medical Sciences]

Tue, 09/29/2015 - 11:06
It is unclear how physical activity stimulates new bone synthesis. We explored whether irisin, a newly discovered myokine released upon physical activity, displays anabolic actions on the skeleton. Young male mice were injected with vehicle or recombinant irisin (r-irisin) at a low cumulative weekly dose of 100 µg kg−1. We...
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