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Unconscious information changes decision accuracy [Psychological and Cognitive Sciences]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
The controversial idea that information can be processed and evaluated unconsciously to change behavior has had a particularly impactful history. Here, we extend a simple model of conscious decision-making to explain both conscious and unconscious accumulation of decisional evidence. Using a novel dichoptic suppression paradigm to titrate conscious and unconscious...

DLK1/PREF1 dosage regulates nutrient metabolism [Medical Sciences]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and obesity, as well as progressive liver dysfunction. Recent animal studies have underscored the importance of hepatic growth hormone (GH) signaling in the development of NAFLD. The imprinted Delta-like homolog 1 (Dlk1)/preadipocyte factor 1 (Pref1) gene encodes a complex protein...

FGFR inhibitors to overcome resistance [Medical Sciences]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
The human FGF receptors (FGFRs) play critical roles in various human cancers, and several FGFR inhibitors are currently under clinical investigation. Resistance usually results from selection for mutant kinases that are impervious to the action of the drug or from up-regulation of compensatory signaling pathways. Preclinical studies have demonstrated that...

NUP62 depletion and chronic stress [Neuroscience]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Genetic evidence suggests cell-type–specific functions for certain nucleoporins, and gene expression profiling has revealed that nucleoporin p62 (NUP62) transcripts are decreased in the prefrontal cortex of major depressives. Chronic stress, which can precipitate depression, induces changes in the architecture and plasticity of apical dendrites that are particularly evident in the...

Heterogeneity of drug-resistance in cancer [Applied Mathematics]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Targeted therapies provide an exciting new approach to combat human cancer. The immediate effect is a dramatic reduction in disease burden, but in most cases, the tumor returns as a consequence of resistance. Various mechanisms for the evolution of resistance have been implicated, including mutation of target genes and activation...

General mode of action of macrolide antibiotics [Biochemistry]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Macrolides are clinically important antibiotics thought to inhibit bacterial growth by impeding the passage of newly synthesized polypeptides through the nascent peptide exit tunnel of the bacterial ribosome. Recent data challenged this view by showing that macrolide antibiotics can differentially affect synthesis of individual proteins. To understand the general mechanism...

Location of PsbP and PsbQ in higher plant PS II [Plant Biology]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Protein cross-linking and radiolytic footprinting coupled with high-resolution mass spectrometry were used to examine the structure of PsbP and PsbQ when they are bound to Photosystem II. In its bound state, the N-terminal 15-amino-acid residue domain of PsbP, which is unresolved in current crystal structures, interacts with domains in the...

IP6K1 mediates CRL4-signalosome complex formation [Cell Biology]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Inositol polyphosphates containing an energetic pyrophosphate bond are formed primarily by a family of three inositol hexakisphosphate (IP6) kinases (IP6K1–3). The Cullin-RING ubiquitin ligases (CRLs) regulate diverse biological processes through substrate ubiquitylation. CRL4, comprising the scaffold Cullin 4A/B, the E2-interacting Roc1/2, and the adaptor protein damage-specific DNA-binding protein 1, is...

Macrophage lineages and cardiac injury [Developmental Biology]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
The mechanistic basis for why inflammation is simultaneously both deleterious and essential for tissue repair is not fully understood. Recently, a new paradigm has emerged: Organs are replete with resident macrophages of embryonic origin distinct from monocyte-derived macrophages. This added complexity raises the question of whether distinct immune cells drive...

Caspase-8 in age-related macular degeneration [Medical Sciences]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Geographic atrophy, an advanced form of age-related macular degeneration (AMD) characterized by death of the retinal pigmented epithelium (RPE), causes untreatable blindness in millions worldwide. The RPE of human eyes with geographic atrophy accumulates toxic Alu RNA in response to a deficit in the enzyme DICER1, which in turn leads...

aPKC activates Smo and Ci through phosphorylation [Developmental Biology]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Smoothened (Smo) is essential for transduction of the Hedgehog (Hh) signal in both insects and vertebrates. Cell surface/cilium accumulation of Smo is thought to play an important role in Hh signaling, but how the localization of Smo is controlled remains poorly understood. In this study, we demonstrate that atypical PKC...

Base excision repair by Aag promotes tissue injury [Medical Sciences]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Inflammation is accompanied by the release of highly reactive oxygen and nitrogen species (RONS) that damage DNA, among other cellular molecules. Base excision repair (BER) is initiated by DNA glycosylases and is crucial in repairing RONS-induced DNA damage; the alkyladenine DNA glycosylase (Aag/Mpg) excises several DNA base lesions induced by...

Piezo1 directs lineage choice in neural stem cells [Neuroscience]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Neural stem cells are multipotent cells with the ability to differentiate into neurons, astrocytes, and oligodendrocytes. Lineage specification is strongly sensitive to the mechanical properties of the cellular environment. However, molecular pathways transducing matrix mechanical cues to intracellular signaling pathways linked to lineage specification remain unclear. We found that the...

Multiple patterns of polymer gels in microspheres [Applied Physical Sciences]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
We report the spontaneous patterning of polymer microgels by confining a polymer blend within microspheres. A poly(ethylene glycol) (PEG) and gelatin solution was confined inside water-in-oil (W/O) microdroplets coated with a layer of zwitterionic lipids: dioleoylphosphatidylethanolamine (PE) and dioleoylphosphatidylcholine (PC). The droplet confinement affected the kinetics of the phase separation,...

Dimerization of an intrinsically disordered domain [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Intrinsically disordered protein regions are widely distributed in the cytoplasmic domains of many transmembrane receptors. The cytoplasmic domain of a disintegrin and metalloprotease (ADAM)10, a transmembrane metalloprotease mediating ectodomain shedding of diverse membrane proteins, was recently suggested to mediate the homodimerization of ADAM10. Here we show that a recombinant cytoplasmic...

Rainfall sensitivity of the Amazon [Environmental Sciences]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
We show that the vegetation canopy of the Amazon rainforest is highly sensitive to changes in precipitation patterns and that reduction in rainfall since 2000 has diminished vegetation greenness across large parts of Amazonia. Large-scale directional declines in vegetation greenness may indicate decreases in carbon uptake and substantial changes in...

Mating-type switching in methylotrophs [Evolution]

PNAS Early Edition Articles - Mon, 10/27/2014 - 13:06
Saccharomyces cerevisiae has a complex system for switching the mating type of haploid cells, requiring the genome to have three mating-type (MAT)–like loci and a mechanism for silencing two of them. How this system originated is unknown, because the three-locus system is present throughout the family Saccharomycetaceae, whereas species in...
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