Recognizing a deficiency of indispensable amino acids (IAAs) for protein synthesis is vital for dietary selection in metazoans, including humans. Cells in the brain's anterior piriform cortex (APC) ...are sensitive to IAA deficiency, signaling diet rejection and foraging for complementary IAA sources, but the mechanism is unknown. Here we report that the mechanism for recognizing IAA-deficient foods follows the conserved general control (GC) system, wherein uncharged transfer RNA induces phosphorylation of eukaryotic initiation factor 2 (eIF2) via the GC nonderepressing 2 (GCN2) kinase. Thus, a basic mechanism of nutritional stress management functions in mammalian brain to guide food selection for survival.
Relationships among the incidence of tibial dyschondroplasia (TD) with 7-wk live BW, carcass component weights (CCW), and abdominal fat weight (AFW) were assessed using high and low incidence of TD ...lines developed by a seven-generation divergent selection experiment, along with a randombred control line. The incidence of TD exhibited negative genetic correlations with both BW (-.65 and -.46 estimated from sire's and dam's components of variance and covariance, respectively) and with CCW ( -.28). The incidence of TD and AFW was not correlated based on sire's components of variance and covariance. The correlation of TD incidence with AFW was not as high as with the other traits under consideration based on dam's components of variance and covariance. Correlations of AFW with CCW were negative based on sire's components of variance and covariance, but positive based on dam's components of variance and covariance. Heritabilities of TD, BW, AFW, and CCW estimated by sire's variance components were lower than those estimated by dam's variance component. Dams might have a greater influence on TD incidence than sires. Selection for decreasing TD incidence should be feasible while simultaneously increasing BW and CCW in broilers
N-methyl-D-aspartate receptors (NMDARs), ligand-gated ionotropic glutamate receptors, play key roles in normal brain development and various neurological disorders. Here we use standing variation ...data from the human population to assess which protein domains within NMDAR GluN1, GluN2A and GluN2B subunits show the strongest signal for being depleted of missense variants. We find that this includes the GluN2 pre-M1 helix and linker between the agonist-binding domain (ABD) and first transmembrane domain (M1). We then evaluate the functional changes of multiple missense mutations in the NMDAR pre-M1 helix found in children with epilepsy and developmental delay. We find mutant GluN1/GluN2A receptors exhibit prolonged glutamate response time course for channels containing 1 or 2 GluN2A-P552R subunits, and a slow rise time only for receptors with 2 mutant subunits, suggesting rearrangement of one GluN2A pre-M1 helix is sufficient for rapid activation. GluN2A-P552R and analogous mutations in other GluN subunits increased the agonist potency and slowed response time course, suggesting a functionally conserved role for this residue. Although there is no detectable change in surface expression or open probability for GluN2A-P552R, the prolonged response time course for receptors that contained GluN2A-P552R increased charge transfer for synaptic-like activation, which should promote excitotoxic damage. Transfection of cultured neurons with GluN2A-P552R prolonged EPSPs, and triggered pronounced dendritic swelling in addition to excitotoxicity, which were both attenuated by memantine. These data implicate the pre-M1 region in gating, provide insight into how different subunits contribute to gating, and suggest that mutations in the pre-M1 helix can compromise neuronal health. Evaluation of FDA-approved NMDAR inhibitors on the mutant NMDAR-mediated current response and neuronal damage provides a potential clinical path to treat individuals harboring similar mutations in NMDARs.
Photoelectron spectroscopic measurements have the potential to provide detailed mechanistic insight by resolving chemical states, electrochemically active regions and local potentials or potential ...losses in operating solid oxide electrochemical cells (SOCs), such as fuel cells. However, high-vacuum requirements have limited X-ray photoelectron spectroscopy (XPS) analysis of electrochemical cells to ex situ investigations. Using a combination of ambient-pressure XPS and CeO(2-x)/YSZ/Pt single-chamber cells, we carry out in situ spectroscopy to probe oxidation states of all exposed surfaces in operational SOCs at 750 °C in 1 mbar reactant gases H(2) and H(2)O. Kinetic energy shifts of core-level photoelectron spectra provide a direct measure of the local surface potentials and a basis for calculating local overpotentials across exposed interfaces. The mixed ionic/electronic conducting CeO(2-x) electrodes undergo Ce(3+)/Ce(4+) oxidation-reduction changes with applied bias. The simultaneous measurements of local surface Ce oxidation states and electric potentials reveal the active ceria regions during H(2) electro-oxidation and H(2)O electrolysis. The active regions extend ~150 μm from the current collectors and are not limited by the three-phase-boundary interfaces associated with other SOC materials. The persistence of the Ce(3+)/Ce(4+) shifts in the ~150 μm active region suggests that the surface reaction kinetics and lateral electron transport on the thin ceria electrodes are co-limiting processes.
The Internet of Things (IoT) redefines the way how commodity and industrial tasks are performed every day. The integration of sensors, lightweight computation, and the proliferation of different ...wireless technologies on IoT platforms enable human beings to easily interact with their surrounding physical world thoroughly. With the recent rise of IoT, several different IoT platforms have been introduced for researchers and developers to ease the management and control of various IoT devices. In general, the IoT platforms act as a bridge between core IoT functionalities and users by providing APIs. Due to their wide variety of applications, IoT platforms are mostly unique in their architectures and designs. Thus, IoT administrators, developers, and researchers (i.e., IoT users) are challenged with substantial configuration differences in the proper configuration, implementation, and protection of the IoT solutions. In this survey, we conduct an in-depth analysis of popular IoT platforms from different application domains. More specifically, we define a comprehensive evaluation framework that considers seven different technical comparison criteria: (1) topology design, (2) programming languages, (3) third-party support, (4) extended protocol support, (5) event handling, (6) security, and (7) privacy. Then, we use the framework to evaluate the different IoT platforms highlighting their distinguishing attributes on communications, security, and privacy. First, we describe the communication protocols supported by the different IoT platforms surveyed. Then, rather than uncovering novel threats affecting IoT, we aim to analyze how the different IoT platforms handle security and privacy vulnerabilities affecting the most common security services of confidentiality, integrity, availability, and access control. Further, we present possible solutions that these platforms could implement to strengthen security and privacy within the IoT solution. Finally, we discuss the advantages and disadvantages of every IoT platform, so IoT administrators, developers, and researchers (i.e., IoT users) can make an informed decision on the use of specific platforms to implement their IoT solutions. To the best of our knowledge, this is the first comprehensive survey to evaluate different IoT platforms using the criteria defined in this work.
Attentional control has been conceptualized as
executive functioning
by neuropsychologists and as
working memory capacity
by experimental psychologists. We examined the relationship between these ...constructs using a factor analytic approach in an adult life span sample. Several tests of working memory capacity and executive function were administered to more than 200 subjects between 18 and 90 years of age, along with tests of processing speed and episodic memory. The correlation between working memory capacity and executive functioning constructs was very strong (
r
= .97), but correlations between these constructs and processing speed were considerably weaker (
r
s ≈ .79). Controlling for working memory capacity and executive function eliminated age effects on episodic memory, and working memory capacity and executive function accounted for variance in episodic memory beyond that accounted for by processing speed. We conclude that tests of working memory capacity and executive function share a common underlying executive attention component that is strongly predictive of higher level cognition.
Abstract
The human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3, A3) family member proteins can deaminate cytosines in single-strand (ss) DNA, which restricts human ...immunodeficiency virus type 1 (HIV-1), retrotransposons, and other viruses such as hepatitis B virus, but can cause a mutator phenotype in many cancers. While structural information exists for several A3 proteins, the precise details regarding deamination target selection are not fully understood. Here, we report the first parallel, comparative analysis of site selection of A3 deamination using six of the seven purified A3 member enzymes, oligonucleotides having 5′TC3′ or 5′CT3′ dinucleotide target sites, and different flanking bases within diverse DNA secondary structures. A3A, A3F and A3H were observed to have strong preferences toward the TC target flanked by A or T, while all examined A3 proteins did not show a preference for a TC target flanked by a G. We observed that the TC target was strongly preferred in ssDNA regions rather than dsDNA, loop or bulge regions, with flanking bases influencing the degree of preference. CT was also shown to be a potential deamination target. Taken together, our observations provide new insights into A3 enzyme target site selection and how A3 mutagenesis impacts mutation rates.
PDF
