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STE affects telomere sequence and Pot1 binding [Genetics]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
The stem terminus element (STE), which was discovered 13 y ago in human telomerase RNA, is required for telomerase activity, yet its mode of action is unknown. We report that the Schizosaccharomyces pombe telomerase RNA, TER1 (telomerase RNA 1), also contains a STE, which is essential for telomere maintenance. Cells...

Conformational activation of Mad2 [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
The spindle checkpoint senses unattached kinetochores during prometaphase and inhibits the anaphase-promoting complex or cyclosome (APC/C), thus ensuring accurate chromosome segregation. The checkpoint protein mitotic arrest deficient 2 (Mad2) is an unusual protein with multiple folded states. Mad2 adopts the closed conformation (C-Mad2) in a Mad1–Mad2 core complex. In mitosis,...

Hybrid approach to solar-to-chemical conversion [Chemistry]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Natural photosynthesis harnesses solar energy to convert CO2 and water to value-added chemical products for sustaining life. We present a hybrid bioinorganic approach to solar-to-chemical conversion in which sustainable electrical and/or solar input drives production of hydrogen from water splitting using biocompatible inorganic catalysts. The hydrogen is then used by...

RGS9-2 modulates antidepressant drug actions [Pharmacology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
The striatal protein Regulator of G-protein signaling 9-2 (RGS9-2) plays a key modulatory role in opioid, monoamine, and other G-protein–coupled receptor responses. Here, we use the murine spared-nerve injury model of neuropathic pain to investigate the mechanism by which RGS9-2 in the nucleus accumbens (NAc), a brain region involved in...

COUP-TFII/Nrp2 regulates caudal migration from POa [Developmental Biology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
The preoptic area (POa) of the rostral diencephalon supplies the neocortex and the amygdala with GABAergic neurons in the developing mouse brain. However, the molecular mechanisms that determine the pathway and destinations of POa-derived neurons have not yet been identified. Here we show that Chicken ovalbumin upstream promoter transcription factor...

Formation of the mitochondrial nucleoid [Cell Biology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Mammalian mitochondrial DNA (mtDNA) is packaged by mitochondrial transcription factor A (TFAM) into mitochondrial nucleoids that are of key importance in controlling the transmission and expression of mtDNA. Nucleoid ultrastructure is poorly defined, and therefore we used a combination of biochemistry, superresolution microscopy, and electron microscopy to show that mitochondrial...

Protective role of IFN-{gamma} in the CNS during EAE [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Evidence has suggested both a pathogenic and a protective role for the proinflammatory cytokine IFN-γ in experimental autoimmune encephalomyelitis (EAE). However, the mechanisms underlying the protective role of IFN-γ in EAE have not been fully resolved, particularly in the context of CNS antigen-presenting cells (APCs). In this study we examined...

Structures of ODC-Az and AzIN-Az complexes [Biochemistry]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Polyamines are organic polycations essential for cell growth and differentiation; their aberrant accumulation is often associated with diseases, including many types of cancer. To maintain polyamine homeostasis, the catalytic activity and protein abundance of ornithine decarboxylase (ODC), the committed enzyme for polyamine biosynthesis, are reciprocally controlled by the regulatory proteins...

Bacteria induce farming in amoebae [Evolution]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Symbiotic associations can allow an organism to acquire novel traits by accessing the genetic repertoire of its partner. In the Dictyostelium discoideum farming symbiosis, certain amoebas (termed “farmers”) stably associate with bacterial partners. Farmers can suffer a reproductive cost but also gain beneficial capabilities, such as carriage of bacterial food...

Structured meaning in superior temporal cortex [Psychological and Cognitive Sciences]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Human brains flexibly combine the meanings of words to compose structured thoughts. For example, by combining the meanings of “bite,” “dog,” and “man,” we can think about a dog biting a man, or a man biting a dog. Here, in two functional magnetic resonance imaging (fMRI) experiments using multivoxel pattern...

Viral battle vestiges in algal genome [Microbiology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Virophages are recently discovered double-stranded DNA virus satellites that prey on giant viruses (nucleocytoplasmic large DNA viruses; NCLDVs), which are themselves parasites of unicellular eukaryotes. This coupled parasitism can result in the indirect control of eukaryotic cell mortality by virophages. However, the details of such tripartite relationships remain largely unexplored....

Whole-genome siRNA screening for AAV permissivity [Cell Biology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Viral vectors based on the adeno-associated virus (AAV) hold great promise for in vivo gene transfer; several unknowns, however, still limit the vectors’ broader and more efficient application. Here, we report the results of a high-throughput, whole-genome siRNA screening aimed at identifying cellular factors regulating AAV transduction. We identified 1,483...

EBV LMP2A evasion of GC B-cell affinity selection [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Epstein–Barr virus (EBV) infects germinal center (GC) B cells and establishes persistent infection in memory B cells. EBV-infected B cells can cause B-cell malignancies in humans with T- or natural killer-cell deficiency. We now find that EBV-encoded latent membrane protein 2A (LMP2A) mimics B-cell antigen receptor (BCR) signaling in murine...

Oligoribonuclease degrades pGpG [Microbiology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
The bacterial second messenger cyclic di-GMP (c-di-GMP) controls biofilm formation and other phenotypes relevant to pathogenesis. Cyclic-di-GMP is synthesized by diguanylate cyclases (DGCs). Phosphodiesterases (PDE-As) end signaling by linearizing c-di-GMP to 5ʹ-phosphoguanylyl-(3ʹ,5ʹ)-guanosine (pGpG), which is then hydrolyzed to two GMP molecules by yet unidentified enzymes termed PDE-Bs. We show that...

Synaptic IL-1{beta} sensitivity in the aged brain [Neuroscience]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
In the aged brain, synaptic plasticity and memory show increased vulnerability to impairment by the inflammatory cytokine interleukin 1β (IL-1β). In this study, we evaluated the possibility that synapses may directly undergo maladaptive changes with age that augment sensitivity to IL-1β impairment. In hippocampal neuronal cultures, IL-1β increased the expression...

Encoding celestial cue preference [Physiology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Diurnal and nocturnal African dung beetles use celestial cues, such as the sun, the moon, and the polarization pattern, to roll dung balls along straight paths across the savanna. Although nocturnal beetles move in the same manner through the same environment as their diurnal relatives, they do so when light...

Paleointensity and thermoremanence instability [Earth, Atmospheric, and Planetary Sciences]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Data on the past intensity of Earth’s magnetic field (paleointensity) are essential for understanding Earth’s deep interior, climatic modeling, and geochronology applications, among other items. Here we demonstrate the possibility that much of available paleointensity data could be biased by instability of thermoremanent magnetization (TRM) associated with non-single-domain (SD) particles....
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