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Role of ATF3 in HSV latency [Microbiology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
A key property of herpes simplex viruses (HSVs) is their ability to establish latent infection in sensory or autonomic ganglia and to reactivate on physical, hormonal, or emotional stress. In latently infected ganglia, HSVs express a long noncoding RNA, a latency-associated transcript (LAT), which plays a key role in maintaining...

ALK5 is crucial for implantation and placentation [Physiology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Members of the transforming growth factor β (TGF-β) superfamily are key regulators in most developmental and physiological processes. However, the in vivo roles of TGF-β signaling in female reproduction remain uncertain. Activin receptor-like kinase 5 (ALK5) is the major type 1 receptor for the TGF-β subfamily. Absence of ALK5 leads...

Limits to wind power using two methods [Applied Physical Sciences]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Wind turbines remove kinetic energy from the atmospheric flow, which reduces wind speeds and limits generation rates of large wind farms. These interactions can be approximated using a vertical kinetic energy (VKE) flux method, which predicts that the maximum power generation potential is 26% of the instantaneous downward transport of...

Helicase assembly and phosphorylation [Biochemistry]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Dbf4-dependent kinase (DDK) phosphorylates minichromosome maintenance 2 (Mcm2) during S phase in yeast, and Sld3 recruits cell division cycle 45 (Cdc45) to minichromosome maintenance 2-7 (Mcm2-7). We show here DDK-phosphoryled Mcm2 preferentially interacts with Cdc45 in vivo, and that Sld3 stimulates DDK phosphorylation of Mcm2 by 11-fold. We identified a...

Mechanism of SPOR domain localization [Microbiology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Bacterial SPOR domains bind peptidoglycan (PG) and are thought to target proteins to the cell division site by binding to “denuded” glycan strands that lack stem peptides, but uncertainties remain, in part because septal-specific binding has yet to be studied in a purified system. Here we show that fusions of...

Oosporein biosynthesis and virulence aid in fungus [Microbiology]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Quinones are widely distributed in nature and exhibit diverse biological or pharmacological activities; however, their biosynthetic machineries are largely unknown. The bibenzoquinone oosporein was first identified from the ascomycete insect pathogen Beauveria bassiana >50 y ago. The toxin can also be produced by different plant pathogenic and endophytic fungi with...

Effects of aging on glucose and fat oxidation [Medical Sciences]

PNAS Early Edition Articles - Mon, 08/24/2015 - 13:05
Previous studies have implicated age-associated reductions in mitochondrial oxidative phosphorylation activity in skeletal muscle as a predisposing factor for intramyocellular lipid (IMCL) accumulation and muscle insulin resistance (IR) in the elderly. To further investigate potential alterations in muscle mitochondrial function associated with aging, we assessed basal and insulin-stimulated rates of...

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...
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