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iFGF regulation of Nav channels [Commentaries]

PNAS Early Edition Articles - Tue, 04/26/2016 - 09:55
Neuronal communication requires the propagation of precisely regulated action potentials. Although a myriad of ion channels and modulatory proteins contribute to the action potential waveform and firing properties of each neuron, voltage-gated sodium (Nav) channels typically generate the crucial depolarizing event. Early Nav channel biochemistry identified two beta subunits (1),...

Programmable RNA binding protein [Cell Biology]

PNAS Early Edition Articles - Tue, 04/26/2016 - 09:55
The ability to monitor and perturb RNAs in living cells would benefit greatly from a modular protein architecture that targets unmodified RNA sequences in a programmable way. We report that the RNA-binding protein PumHD (Pumilio homology domain), which has been widely used in native and modified form for targeting RNA,...

Allometry of oxygen diffusion [Ecology]

PNAS Early Edition Articles - Tue, 04/26/2016 - 09:55
The area and thickness of respiratory surfaces, and the constraints they impose on passive oxygen diffusion, have been linked to differences in oxygen consumption rates and/or aerobic activity levels in vertebrates. However, it remains unclear how respiratory surfaces and associated diffusion rates vary with body mass across vertebrates, particularly in...

Trophoblast cell differentiation [Commentaries]

PNAS Early Edition Articles - Tue, 04/26/2016 - 09:55
Understanding the development of the human trophoblast lineage and placentation is a challenge. Ethical issues prevent the most direct experimentation. Animal models have provided considerable insight, but species differences exist and knowledge of key regulatory events in human development is missing, which precludes an appreciation of conserved processes. In the...

Big data stratification of gliomas [Medical Sciences]

PNAS Early Edition Articles - Tue, 04/26/2016 - 09:55
We show that visualizing large molecular and clinical datasets enables discovery of molecularly defined categories of highly similar patients. We generated a series of linked 2D sample similarity plots using genome-wide single nucleotide alterations (SNAs), copy number alterations (CNAs), DNA methylation, and RNA expression data. Applying this approach to the...

Russian proposal for nuclear fuel leasing and recycling

World Nuclear News - Tue, 04/26/2016 - 09:34
At the recent World Nuclear Fuel Cycle conference in Abu Dhabi, a new concept of nuclear fuel leasing was publicly proposed, writes Ian Hore-Lacy.

Toshiba expects $2.3 billion write-down on Westinghouse

World Nuclear News - Tue, 04/26/2016 - 09:29
Japan's Toshiba Corporation announced today it expects to take an impairment charge of JPY260 billion ($2.3 billion) for part of the goodwill of its US-based nuclear power subsidiary Westinghouse Electric Company.

French and Russian nuclear utilities extend collaboration

World Nuclear News - Tue, 04/26/2016 - 07:59
French utility EDF has signed an agreement to extend its cooperation with Rosenergoatom, the operator of Russia's civil nuclear power plants. The companies will cooperate in reactor operations, decommissioning and waste management.

Antibody sequence and structural insights [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 04/25/2016 - 13:49
Elucidating how antigen exposure and selection shape the human antibody repertoire is fundamental to our understanding of B-cell immunity. We sequenced the paired heavy- and light-chain variable regions (VH and VL, respectively) from large populations of single B cells combined with computational modeling of antibody structures to evaluate sequence and...

EPO targeted to red blood cell precursors [Applied Biological Sciences]

PNAS Early Edition Articles - Mon, 04/25/2016 - 13:49
The design of cell-targeted protein therapeutics can be informed by natural protein–protein interactions that use cooperative physical contacts to achieve cell type specificity. Here we applied this approach in vivo to the anemia drug erythropoietin (EPO), to direct its activity to EPO receptors (EPO-Rs) on red blood cell (RBC) precursors...

Mechanism of APC/CCDC20 activation [Biochemistry]

PNAS Early Edition Articles - Mon, 04/25/2016 - 13:49
Chromosome segregation and mitotic exit are initiated by the 1.2-MDa ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) and its coactivator CDC20 (cell division cycle 20). To avoid chromosome missegregation, APC/CCDC20 activation is tightly controlled. CDC20 only associates with APC/C in mitosis when APC/C has become phosphorylated and is further inhibited by a...

Capture and cleavage of IgG by mycoplasmas [Microbiology]

PNAS Early Edition Articles - Mon, 04/25/2016 - 13:49
Mycoplasmas are “minimal” bacteria able to infect humans, wildlife, and a large number of economically important livestock species. Mycoplasma infections include a spectrum of clinical manifestations ranging from simple fever to fulminant inflammatory diseases with high mortality rates. These infections are mostly chronic, suggesting that mycoplasmas have developed means to...

Reassortment is favored in influenza host switches [Ecology]

PNAS Early Edition Articles - Mon, 04/25/2016 - 13:49
Reticulate evolution is thought to accelerate the process of evolution beyond simple genetic drift and selection, helping to rapidly generate novel hybrids with combinations of adaptive traits. However, the long-standing dogma that reticulate evolutionary processes are likewise advantageous for switching ecological niches, as in microbial pathogen host switch events, has...

Remarkably low affinity of CD4 for pMHC II [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 04/25/2016 - 13:49
The αβ T-cell coreceptor CD4 enhances immune responses more than 1 million-fold in some assays, and yet the affinity of CD4 for its ligand, peptide-major histocompatibility class II (pMHC II) on antigen-presenting cells, is so weak that it was previously unquantifiable. Here, we report that a soluble form of CD4...

biGBac DNA assembly for protein complex expression [Biochemistry]

PNAS Early Edition Articles - Mon, 04/25/2016 - 13:49
Analyses of protein complexes are facilitated by methods that enable the generation of recombinant complexes via coexpression of their subunits from multigene DNA constructs. However, low experimental throughput limits the generation of such constructs in parallel. Here we describe a method that allows up to 25 cDNAs to be assembled...

Recruitment of NTC to spliceosome requires AtPRMT5 [Plant Biology]

PNAS Early Edition Articles - Mon, 04/25/2016 - 13:49
Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is involved in a multitude of biological processes in eukaryotes. Symmetric arginine dimethylation mediated by PRMT5 modulates constitutive and alternative pre-mRNA splicing of diverse genes to regulate normal growth and development in multiple species; however, the underlying molecular mechanism remains largely...

PSI-U1 snRNP regulates fly male courtship behavior [Biochemistry]

PNAS Early Edition Articles - Mon, 04/25/2016 - 13:49
Alternative pre-mRNA splicing (AS) is a critical regulatory mechanism that operates extensively in the nervous system to produce diverse protein isoforms. Fruitless AS isoforms have been shown to influence male courtship behavior, but the underlying mechanisms are unknown. Using genome-wide approaches and quantitative behavioral assays, we show that the P-element...

Importin 8 mediates nuclear import of eIF4E [Biochemistry]

PNAS Early Edition Articles - Mon, 04/25/2016 - 13:49
Regulation of nuclear-cytoplasmic trafficking of oncoproteins is critical for growth homeostasis. Dysregulated trafficking contributes to malignancy, whereas understanding the process can reveal unique therapeutic opportunities. Here, we focus on eukaryotic translation initiation factor 4E (eIF4E), a prooncogenic protein highly elevated in many cancers, including acute myeloid leukemia (AML). Typically, eIF4E...

KLF2 controls mature NK cell homeostasis [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 04/25/2016 - 13:49
Natural killer (NK) cells are innate lymphocytes that recognize and lyse virally infected or transformed cells. This latter property is being pursued in clinics to treat leukemia with the hope that further breakthroughs in NK cell biology can extend treatments to other cancers. At issue is the ability to expand...
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