Proceedings of the Natural Academy of Sciences

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Viral tRNA mimicry of an IRES [Biochemistry]

Tue, 11/24/2015 - 13:04
The dicistrovirus intergenic region internal ribosome entry site (IRES) adopts a triple-pseudoknotted RNA structure and occupies the core ribosomal E, P, and A sites to directly recruit the ribosome and initiate translation at a non-AUG codon. A subset of dicistrovirus IRESs directs translation in the 0 and +1 frames to...
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Extrusion predicts 3D genome engineering results [Biophysics and Computational Biology]

Tue, 11/24/2015 - 13:04
We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state...
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HAX-1 impedes mitochondrial permeability transition [Cell Biology]

Tue, 11/24/2015 - 13:04
The major underpinning of massive cell death associated with myocardial infarction involves opening of the mitochondrial permeability transition pore (mPTP), resulting in disruption of mitochondria membrane integrity and programmed necrosis. Studies in human lymphocytes suggested that the hematopoietic-substrate-1 associated protein X-1 (HAX-1) is linked to regulation of mitochondrial membrane function,...
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EphA2 is a KRasG12D cooperative tumor suppressor [Cell Biology]

Tue, 11/24/2015 - 13:04
Lung adenocarcinoma, a major form of non-small cell lung cancer, is the leading cause of cancer deaths. The Cancer Genome Atlas analysis of lung adenocarcinoma has identified a large number of previously unknown copy number alterations and mutations, requiring experimental validation before use in therapeutics. Here, we describe an shRNA-mediated...
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TRPC6 and phagosomal function [Cell Biology]

Tue, 11/24/2015 - 13:04
Defects in the innate immune system in the lung with attendant bacterial infections contribute to lung tissue damage, respiratory insufficiency, and ultimately death in the pathogenesis of cystic fibrosis (CF). Professional phagocytes, including alveolar macrophages (AMs), have specialized pathways that ensure efficient killing of pathogens in phagosomes. Phagosomal acidification facilitates...
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Quest for isolated tsetse populations [Applied Biological Sciences]

Tue, 11/24/2015 - 13:04
Tsetse flies are the cyclical vectors of deadly human and animal trypanosomes in sub-Saharan Africa. Tsetse control is a key component for the integrated management of both plagues, but local eradication successes have been limited to less than 2% of the infested area. This is attributed to either resurgence of...
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Accelerating collective discovery [Applied Mathematics]

Tue, 11/24/2015 - 13:04
A scientist’s choice of research problem affects his or her personal career trajectory. Scientists’ combined choices affect the direction and efficiency of scientific discovery as a whole. In this paper, we infer preferences that shape problem selection from patterns of published findings and then quantify their efficiency. We represent research...
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Intrinsic excitability measures [Applied Mathematics]

Tue, 11/24/2015 - 13:04
Pathological changes in excitability of cortical tissue commonly underlie the initiation and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring excitability and controlling its degree using antiepileptic drugs (AEDs) is of prime importance for clinical care and treatment. To date, adequate measures of excitability and action of...
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G-quadruplexes responsive to guanine derivatives [Biochemistry]

Tue, 11/24/2015 - 13:04
G-quadruplex structures formed by guanine-rich nucleic acids are implicated in essential physiological and pathological processes and nanodevices. G-quadruplexes are normally composed of four Gn (n ≥ 3) tracts assembled into a core of multiple stacked G-quartet layers. By dimethyl sulfate footprinting, circular dichroism spectroscopy, thermal melting, and photo-cross-linking, here we...
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dFOXO regulates RNA interference [Biochemistry]

Tue, 11/24/2015 - 13:04
Small RNA pathways are important players in posttranscriptional regulation of gene expression. These pathways play important roles in all aspects of cellular physiology from development to fertility to innate immunity. However, almost nothing is known about the regulation of the central genes in these pathways. The forkhead box O (FOXO)...
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Kinetic mechanism of lever arm movement in myosin [Biochemistry]

Tue, 11/24/2015 - 13:04
Myosins use a conserved structural mechanism to convert the energy from ATP hydrolysis into a large swing of the force-generating lever arm. The precise timing of the lever arm movement with respect to the steps in the actomyosin ATPase cycle has not been determined. We have developed a FRET system...
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Directed evolution of tryptophan synthase [Biochemistry]

Tue, 11/24/2015 - 13:04
Enzymes in heteromeric, allosterically regulated complexes catalyze a rich array of chemical reactions. Separating the subunits of such complexes, however, often severely attenuates their catalytic activities, because they can no longer be activated by their protein partners. We used directed evolution to explore allosteric regulation as a source of latent...
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Designing proteins with extreme kinetic stability [Biophysics and Computational Biology]

Tue, 11/24/2015 - 13:04
The design of stable, functional proteins is difficult. Improved design requires a deeper knowledge of the molecular basis for design outcomes and properties. We previously used a bioinformatics and energy function method to design a symmetric superfold protein composed of repeating structural elements with multivalent carbohydrate-binding function, called ThreeFoil. This...
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Structure of CAP-Gly on microtubules by MAS NMR [Biophysics and Computational Biology]

Tue, 11/24/2015 - 13:04
Microtubules and their associated proteins perform a broad array of essential physiological functions, including mitosis, polarization and differentiation, cell migration, and vesicle and organelle transport. As such, they have been extensively studied at multiple levels of resolution (e.g., from structural biology to cell biology). Despite these efforts, there remain significant...
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Dynamic allostery in CypA-HIV capsid interplay [Biophysics and Computational Biology]

Tue, 11/24/2015 - 13:04
Host factor protein Cyclophilin A (CypA) regulates HIV-1 viral infectivity through direct interactions with the viral capsid, by an unknown mechanism. CypA can either promote or inhibit viral infection, depending on host cell type and HIV-1 capsid (CA) protein sequence. We have examined the role of conformational dynamics on the...
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Modulation of shedding by O-glycosylation [Cell Biology]

Tue, 11/24/2015 - 13:04
Regulated shedding of the ectodomain of cell membrane proteins by proteases is a common process that releases the extracellular domain from the cell and activates cell signaling. Ectodomain shedding occurs in the immediate extracellular juxtamembrane region, which is also where O-glycosylation is often found and examples of crosstalk between shedding...
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Human round spermatid injection [Developmental Biology]

Tue, 11/24/2015 - 13:04
During the human in vitro fertilization procedure in the assisted reproductive technology, intracytoplasmic sperm injection is routinely used to inject a spermatozoon or a less mature elongating spermatid into the oocyte. In some infertile men, round spermatids (haploid male germ cells that have completed meiosis) are the most mature cells...
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Epigenetic landscape of meiotic chromosomes [Developmental Biology]

Tue, 11/24/2015 - 13:04
During meiosis, homologous chromosomes associate to form the synaptonemal complex (SC), a structure essential for fertility. Information about the epigenetic features of chromatin within this structure at the level of superresolution microscopy is largely lacking. We combined single-molecule localization microscopy (SMLM) with quantitative analytical methods to describe the epigenetic landscape...
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Retrotransposon silencing in mouse embryos [Developmental Biology]

Tue, 11/24/2015 - 13:04
Substantial proportions of mammalian genomes comprise repetitive elements including endogenous retrotransposons. Although these play diverse roles during development, their appropriate silencing is critically important in maintaining genomic integrity in the host cells. The major mechanism for retrotransposon silencing is DNA methylation, but the wave of global DNA demethylation that occurs...
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Potentially biogenic 4.1 billion-year-old carbon [Earth, Atmospheric, and Planetary Sciences]

Tue, 11/24/2015 - 13:04
Evidence of life on Earth is manifestly preserved in the rock record. However, the microfossil record only extends to ∼3.5 billion years (Ga), the chemofossil record arguably to ∼3.8 Ga, and the rock record to 4.0 Ga. Detrital zircons from Jack Hills, Western Australia range in age up to nearly...
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