Proceedings of the Natural Academy of Sciences

Proceedings of the National Academy of Sciences RSS feed -- current issue
  • Simulations of bacterial cell wall synthesis [Biophysics and Computational Biology]
    [Jul 2015]

    Bacteria are surrounded by a peptidoglycan (PG) cell wall that must be remodeled to allow cell growth. While many structural details and properties of PG and the individual enzymes involved are known, how the process is coordinated to maintain cell integrity and rod shape is not understood. We have developed...
    Categories: Journal Articles
  • Lysosome accumulations at amyloid plaques [Cell Biology]
    [Jul 2015]

    Through a comprehensive analysis of organellar markers in mouse models of Alzheimer’s disease, we document a massive accumulation of lysosome-like organelles at amyloid plaques and establish that the majority of these organelles reside within swollen axons that contact the amyloid deposits. This close spatial relationship between axonal lysosome accumulation and...
    Categories: Journal Articles
  • Molecular analysis of a conserved signaling system [Microbiology]
    [Jul 2015]

    We have functionally and structurally defined an essential protein phosphorelay that regulates expression of genes required for growth, division, and intracellular survival of the global zoonotic pathogen Brucella abortus. Our study delineates phosphoryl transfer through this molecular pathway, which initiates from the sensor kinase CckA and proceeds through the ChpT...
    Categories: Journal Articles
  • Triangulation of the reading network [Neuroscience]
    [Jul 2015]

    The goal of cognitive neuroscience is to integrate cognitive models with knowledge about underlying neural machinery. This significant challenge was explored in relation to word reading, where sophisticated computational-cognitive models exist but have made limited contact with neural data. Using distortion-corrected functional MRI and dynamic causal modeling, we investigated the...
    Categories: Journal Articles
  • Noradrenergic blockade enables fear extinction [Neuroscience]
    [Jul 2015]

    Stress-induced impairments in extinction learning are believed to sustain posttraumatic stress disorder (PTSD). Noradrenergic signaling may contribute to extinction impairments by modulating medial prefrontal cortex (mPFC) circuits involved in fear regulation. Here we demonstrate that aversive fear conditioning rapidly and persistently alters spontaneous single-unit activity in the prelimbic and infralimbic...
    Categories: Journal Articles
  • Maternal HIF2 is critical for neonatal development [Physiology]
    [Jul 2015]

    The mechanisms that are essential for the maintenance of nutrient status in breast milk are unclear. Our data demonstrate that the intestine via hypoxia-inducible factor (HIF)-2α is an essential regulatory mechanism for maintaining the quality of breast milk. During lactation, intestinal HIF-2α is highly increased, leading to an adaptive induction...
    Categories: Journal Articles
  • Nitrogen budget of China [Environmental Sciences]
    [Jul 2015]

    Reactive nitrogen (Nr) plays a central role in food production, and at the same time it can be an important pollutant with substantial effects on air and water quality, biological diversity, and human health. China now creates far more Nr than any other country. We developed a budget for Nr...
    Categories: Journal Articles
  • Genomic diversity and admixture in Brazilians [Genetics]
    [Jul 2015]

    While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed...
    Categories: Journal Articles
  • Fly circadian rhythms in seminatural environments [Genetics]
    [Jul 2015]

    Under standard laboratory conditions of rectangular light/dark cycles and constant warm temperature, Drosophila melanogaster show bursts of morning (M) and evening (E) locomotor activity and a “siesta” in the middle of the day. These M and E components have been critical for developing the neuronal dual oscillator model in which...
    Categories: Journal Articles
  • CD300f in IL-4-induced immune cell activation [Immunology and Inflammation]
    [Jul 2015]

    IL-4 receptor (R) α, the common receptor chain for IL-4 and IL-13, is a critical component in IL-4– and IL-13–mediated signaling and subsequent effector functions such as those observed in type 2 inflammatory responses. Nonetheless, the existence of intrinsic pathways capable of amplifying IL-4Rα–induced responses remains unknown. In this study,...
    Categories: Journal Articles
  • Altered metabolic landscape in young POLG mice [Medical Sciences]
    [Jul 2015]

    Mitochondria are highly adaptable organelles that can facilitate communication between tissues to meet the energetic demands of the organism. However, the mechanisms by which mitochondria can nonautonomously relay stress signals remain poorly understood. Here we report that mitochondrial mutations in the young, preprogeroid polymerase gamma mutator (POLG) mouse produce a...
    Categories: Journal Articles
  • Biodegradable nanoparticles for lung gene therapy [Medical Sciences]
    [Jul 2015]

    Gene therapy has emerged as an alternative for the treatment of diseases refractory to conventional therapeutics. Synthetic nanoparticle-based gene delivery systems offer highly tunable platforms for the delivery of therapeutic genes. However, the inability to achieve sustained, high-level transgene expression in vivo presents a significant hurdle. The respiratory system, although...
    Categories: Journal Articles
  • Notch1-STAT3-ETBR controls reactive astrogliosis [Medical Sciences]
    [Jul 2015]

    Defining the signaling network that controls reactive astrogliosis may provide novel treatment targets for patients with diverse CNS injuries and pathologies. We report that the radial glial cell antigen RC2 identifies the majority of proliferating glial fibrillary acidic protein-positive (GFAP+) reactive astrocytes after stroke. These cells highly expressed endothelin receptor...
    Categories: Journal Articles
  • Drug-eluting microarrays for cancer stem cells [Medical Sciences]
    [Jul 2015]

    A new paradigm in oncology establishes a spectrum of tumorigenic potential across the heterogeneous phenotypes within a tumor. The cancer stem cell hypothesis postulates that a minute fraction of cells within a tumor, termed cancer stem cells (CSCs), have a tumor-initiating capacity that propels tumor growth. An application of this...
    Categories: Journal Articles
  • Prophylaxis and treatment of MERS-CoV infection [Microbiology]
    [Jul 2015]

    Traditional approaches to antimicrobial drug development are poorly suited to combatting the emergence of novel pathogens. Additionally, the lack of small animal models for these infections hinders the in vivo testing of potential therapeutics. Here we demonstrate the use of the VelocImmune technology (a mouse that expresses human antibody-variable heavy...
    Categories: Journal Articles
  • Circadian control of virulence in Botrytis cinerea [Microbiology]
    [Jul 2015]

    The circadian clock of the plant model Arabidopsis thaliana modulates defense mechanisms impacting plant–pathogen interactions. Nevertheless, the effect of clock regulation on pathogenic traits has not been explored in detail. Moreover, molecular description of clocks in pathogenic fungi—or fungi in general other than the model ascomycete Neurospora crassa—has been neglected,...
    Categories: Journal Articles
  • Nurr1 as a drug target for Parkinson's disease [Neuroscience]
    [Jul 2015]

    Parkinson’s disease (PD), primarily caused by selective degeneration of midbrain dopamine (mDA) neurons, is the most prevalent movement disorder, affecting 1–2% of the global population over the age of 65. Currently available pharmacological treatments are largely symptomatic and lose their efficacy over time with accompanying severe side effects such as...
    Categories: Journal Articles
  • Tracking ongoing cognition with fMRI connectivity [Neuroscience]
    [Jul 2015]

    Functional connectivity (FC) patterns in functional MRI exhibit dynamic behavior on the scale of seconds, with rich spatiotemporal structure and limited sets of whole-brain, quasi-stable FC configurations (FC states) recurring across time and subjects. Based on previous evidence linking various aspects of cognition to group-level, minute-to-minute FC changes in localized...
    Categories: Journal Articles
  • Mitochondrial fragmentation in aging neurons [Neuroscience]
    [Jul 2015]

    Decline in mitochondrial morphology and function is a hallmark of neuronal aging. Here we report that progressive mitochondrial fragmentation is a common manifestation of aging Caenorhabditis elegans neurons and body wall muscles. We show that sensory-evoked activity was essential for maintaining neuronal mitochondrial morphology, and this activity-dependent mechanism required the...
    Categories: Journal Articles
  • CB2 receptor agonist enantiomers HU-433 and HU-308 [Pharmacology]
    [Jul 2015]

    Activation of the CB2 receptor is apparently an endogenous protective mechanism. Thus, it restrains inflammation and protects the skeleton against age-related bone loss. However, the endogenous cannabinoids, as well as Δ9-tetrahydrocannabinol, the main plant psychoactive constituent, activate both cannabinoid receptors, CB1 and CB2. HU-308 was among the first synthetic, selective...
    Categories: Journal Articles