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Structural basis for specific ligation of the peroxisome proliferator-activated receptor {delta} [Chemistry]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
The peroxisome proliferator-activated receptor (PPAR) family comprises three subtypes: PPARα, PPARγ, and PPARδ. PPARδ transcriptionally modulates lipid metabolism and the control of energy homeostasis; therefore, PPARδ agonists are promising agents for treating a variety of metabolic disorders. In the present study, we develop a panel of rationally designed PPARδ agonists....

Glass transition imminent, resistance is futile [Commentaries]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
The immense variety of glassy materials around us makes it is easy to get caught up in excessive detail when thinking about the structural glass transition. For decades, there have been only a few attempts to describe covalently bonded, molecular, and metallic glasses on the same footing, so different do...

Structure of a headful DNA-packaging bacterial virus at 2.9 A resolution by electron cryo-microscopy [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
The enormous prevalence of tailed DNA bacteriophages on this planet is enabled by highly efficient self-assembly of hundreds of protein subunits into highly stable capsids. These capsids can stand with an internal pressure as high as ∼50 atmospheres as a result of the phage DNA-packaging process. Here we report the...

Correction to Supporting Information for Rascon et al., Geometry-induced capillary emptying [SI Correction]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
APPLIED PHYSICAL SCIENCES Correction to Supporting Information for “Geometry-induced capillary emptying,” by Carlos Rascón, Andrew O. Parry, and Dirk G. A. L. Aarts, which appeared in issue 45, November 8, 2016, of Proc Natl Acad Sci USA (113:12633–12636; first published October 24, 2016; 10.1073/pnas.1606217113). The authors note that on page...

Recurrent rewiring and emergence of RNA regulatory networks [Biochemistry]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
Alterations in regulatory networks contribute to evolutionary change. Transcriptional networks are reconfigured by changes in the binding specificity of transcription factors and their cognate sites. The evolution of RNA–protein regulatory networks is far less understood. The PUF (Pumilio and FBF) family of RNA regulatory proteins controls the translation, stability, and...

Identification of a putative binding site critical for general anesthetic activation of TRPA1 [Pharmacology]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
General anesthetics suppress CNS activity by modulating the function of membrane ion channels, in particular, by enhancing activity of GABAA receptors. In contrast, several volatile (isoflurane, desflurane) and i.v. (propofol) general anesthetics excite peripheral sensory nerves to cause pain and irritation upon administration. These noxious anesthetics activate transient receptor potential...

Species richness alone does not predict cultural ecosystem service value [Sustainability Science]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
Many biodiversity-ecosystem services studies omit cultural ecosystem services (CES) or use species richness as a proxy and assume that more species confer greater CES value. We studied wildflower viewing, a key biodiversity-based CES in amenity-based landscapes, in Southern Appalachian Mountain forests and asked (i) How do aesthetic preferences for wildflower...

Cerberus-Nodal-Lefty-Pitx signaling cascade controls left-right asymmetry in amphioxus [Evolution]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
Many bilaterally symmetrical animals develop genetically programmed left–right asymmetries. In vertebrates, this process is under the control of Nodal signaling, which is restricted to the left side by Nodal antagonists Cerberus and Lefty. Amphioxus, the earliest diverging chordate lineage, has profound left–right asymmetry as a larva. We show that Cerberus,...

Collaboration, conflict, and disconnect between psychologists and economists [Commentaries]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
In PNAS, Bruine de Bruin and Fischhoff (1) describe two collaborations of psychologists and economists in which they made the central contributions by psychologists. In both cases, the objective was to design survey questions that measure in probabilistic terms the expectations that individuals hold for future events. They judged both...

Rationally designed PPAR{delta}-specific agonists and their therapeutic potential for metabolic syndrome [Commentaries]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
The peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors regulates a wide variety of lipid-related genes, including those responsible for adipose differentiation, cholesterol metabolism, and lipid metabolism and transport. There are three different PPAR nuclear receptors, with different localizations and specializations. PPARα is primarily expressed in the liver, heart, kidney,...

Highly oriented photosynthetic reaction centers generate a proton gradient in synthetic protocells [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
Photosynthesis is responsible for the photochemical conversion of light into the chemical energy that fuels the planet Earth. The photochemical core of this process in all photosynthetic organisms is a transmembrane protein called the reaction center. In purple photosynthetic bacteria a simple version of this photoenzyme catalyzes the reduction of...

Discovery of scmR as a global regulator of secondary metabolism and virulence in Burkholderia thailandensis E264 [Microbiology]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
Bacteria produce a diverse array of secondary metabolites that have been invaluable in the clinic and in research. These metabolites are synthesized by dedicated biosynthetic gene clusters (BGCs), which assemble architecturally complex molecules from simple building blocks. The majority of BGCs in a given bacterium are not expressed under normal...

Ultrathin dendrimer-graphene oxide composite film for stable cycling lithium-sulfur batteries [Chemistry]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
Lithium–sulfur batteries (Li–S batteries) have attracted intense interest because of their high specific capacity and low cost, although they are still hindered by severe capacity loss upon cycling caused by the soluble lithium polysulfide intermediates. Although many structure innovations at the material and device levels have been explored for the...

Correction for Sterky et al., Carbonic anhydrase-related protein CA10 is an evolutionarily conserved pan-neurexin ligand [Corrections]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
NEUROSCIENCE Correction for “Carbonic anhydrase-related protein CA10 is an evolutionarily conserved pan-neurexin ligand,” by Fredrik H. Sterky, Justin H. Trotter, Sung-Jin Lee, Christian V. Recktenwald, Xiao Du, Bo Zhou, Peng Zhou, Jochen Schwenk, Bernd Fakler, and Thomas C. Südhof, which appeared in issue 7, February 14, 2017, of Proc Natl...

Negative allosteric regulation of Enterococcus faecalis small alarmone synthetase RelQ by single-stranded RNA [Microbiology]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
The alarmone nucleotides guanosine pentaphosphate (pppGpp) and tetraphosphate (ppGpp), collectively referred to as (p)ppGpp, are key regulators of bacterial growth, stress adaptation, pathogenicity, and antibiotic tolerance. We show that the tetrameric small alarmone synthetase (SAS) RelQ from the Gram-positive pathogen Enterococcus faecalis is a sequence-specific RNA-binding protein. RelQ’s enzymatic and...

Three-dimensional culture system identifies a new mode of cetuximab resistance and disease-relevant genes in colorectal cancer [Cell Biology]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
We previously reported that single cells from a human colorectal cancer (CRC) cell line (HCA-7) formed either hollow single-layered polarized cysts or solid spiky masses when plated in 3D in type-I collagen. To begin in-depth analyses into whether clonal cysts and spiky masses possessed divergent properties, individual colonies of each...

Experimental evidence that parasites drive eco-evolutionary feedbacks [Ecology]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
Host resistance to parasites is a rapidly evolving trait that can influence how hosts modify ecosystems. Eco-evolutionary feedbacks may develop if the ecosystem effects of host resistance influence selection on subsequent host generations. In a mesocosm experiment, using a recently diverged (<100 generations) pair of lake and stream three-spined sticklebacks,...

Potent neuroprotection after stroke afforded by a double-knot spider-venom peptide that inhibits acid-sensing ion channel 1a [Pharmacology]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
Stroke is the second-leading cause of death worldwide, yet there are no drugs available to protect the brain from stroke-induced neuronal injury. Acid-sensing ion channel 1a (ASIC1a) is the primary acid sensor in mammalian brain and a key mediator of acidosis-induced neuronal damage following cerebral ischemia. Genetic ablation and selective...

EGF and NRG induce phosphorylation of HER3/ERBB3 by EGFR using distinct oligomeric mechanisms [Biochemistry]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
Heteromeric interactions between the catalytically impaired human epidermal growth factor receptor (HER3/ERBB3) and its catalytically active homologs EGFR and HER2 are essential for their signaling. Different ligands can activate these receptor pairs but lead to divergent signaling outcomes through mechanisms that remain largely unknown. We used stochastic optical reconstruction microscopy...

Prion protein dynamics before aggregation [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 03/20/2017 - 13:07
Prion diseases, like Alzheimer’s disease and Parkinson disease, are rapidly progressive neurodegenerative disorders caused by misfolding followed by aggregation and accumulation of protein deposits in neuronal cells. Here we measure intramolecular polypeptide backbone reconfiguration as a way to understand the molecular basis of prion aggregation. Our hypothesis is that when...
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