Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning.

The NR2B subunit of the NMDA receptor interacts with several prominent proteins in the postsynaptic density, including calcium/calmodulin-dependent protein kinase II (CaMKII). To determine the function of these interactions, we derived transgenic mice expressing a ligand-activated carboxy-terminal NR2B fragment (cNR2B) by fusing this fragment to a tamoxifen (TAM)-dependent mutant of the estrogen receptor ligand-binding domain LBD(G521R). Here, we show that induction by TAM allows the transgenic cNR2B fragment to bind to endogenous CaMKII in neurons. Activation of the LBD(G521R)-cNR2B transgenic protein in mice leads to the disruption of CaMKII/NR2B interactions at synapses. The disruption decreases Thr286 phosphorylation of alphaCaMKII, lowers phosphorylation of a key CaMKII substrate in the postsynaptic membrane (AMPA receptor subunit glutamate receptor 1), and produces deficits in hippocampal long-term potentiation and spatial learning. Together our results demonstrate the importance of interactions between CaMKII and NR2B for CaMKII activity, synaptic plasticity, and learning

Teens’ social media use and collective action

This is the author's accepted manuscript, made available with the permission of the publisher.This research examined how social self-efficacy, collective self-esteem, and need to belong can be used to predict teens’ use of social media. The particular focus was on how these social psychological variables together with social media use account for variation in teens’ participation in a flash mob – an exemplar of 21st-century collective action. Empirical data come from a survey of teens in a major Midwestern city in the USA. Teens’ need to belong was positively associated with the amount of time they reported spending on social networking sites, even when controlling for gender, race, and household socio-economic status. Both teens’ social self-efficacy and time spent on YouTube were positively associated with their intention to participate in a flash mob in the future. These and other findings are discussed in the context of the role of social media in youth culture and collective action

Ariel - Volume 10 Number 1

Executive Editors Madalyn Schaefgen David Reich Business Manager David Reich News Editors Medical College Edward Zurad CAHS John Guardiani World Mark Zwanger Features Editors Meg Trexler Jim O\u27Brien Editorials Editor Jeffrey Banyas Photography and Sports Editor Stuart Singer Commons Editor Brenda Peterso

Decreased Proliferation Kinetics of Mouse Myoblasts Overexpressing FRG1

Although recent publications have linked the molecular events driving facioscapulohumeral muscular dystrophy (FSHD) to expression of the double homeobox transcription factor DUX4, overexpression of FRG1 has been proposed as one alternative causal agent as mice overexpressing FRG1 present with muscular dystrophy. Here, we characterize proliferative defects in two independent myoblast lines overexpressing FRG1. Myoblasts isolated from thigh muscle of FRG1 transgenic mice, an affected dystrophic muscle, exhibit delayed proliferation as measured by decreased clone size, whereas myoblasts isolated from the unaffected diaphragm muscle proliferated normally. To confirm the observation that overexpression of FRG1 could impair myoblast proliferation, we examined C2C12 myoblasts with inducible overexpression of FRG1, finding increased doubling time and G1-phase cells in mass culture after induction of FRG1 and decreased levels of pRb phosphorylation. We propose that depressed myoblast proliferation may contribute to the pathology of mice overexpressing FRG1 and may play a part in FSHD

Lamin A Δexon9 mutation leads to telomere and chromatin defects but not genomic instability

Over 300 mutations in the LMNA gene, encoding A-type lamins, are associated with 15 human degenerative disorders and premature aging syndromes. Although genomic instability seems to contribute to the pathophysiology of some laminopathies, there is limited information about what mutations cause genomic instability and by which molecular mechanisms. Mouse embryonic fibroblasts depleted of A-type lamins or expressing mutants lacking exons 8–11 (Lmna(Δ8–11/Δ8–11)) exhibit alterations in telomere biology and DNA repair caused by cathepsin L-mediated degradation of 53BP1 and reduced expression of BRCA1 and RAD51. Thus, a region encompassing exons 8–11 seems essential for genome integrity. Given that deletion of lamin A exon 9 in the mouse (Lmna(Δ9/Δ9)) results in a progeria phenotype, we tested if this domain is important for genome integrity. Lmna(Δ9/Δ9) MEFs exhibit telomere shortening and heterochromatin alterations but do not activate cathepsin L-mediated degradation of 53BP1 and maintain expression of BRCA1 and RAD51. Accordingly, Lmna(Δ9/Δ9) MEFs do not present genomic instability, and expression of mutant lamin A Δexon9 in lamin-depleted cells restores DNA repair factors levels and partially rescues nuclear abnormalities. These data reveal that the domain encoded by exon 9 is important to maintain telomere homeostasis and heterochromatin structure but does not play a role in DNA repair, thus pointing to other exons in the lamin A tail as responsible for the genomic instability phenotype in Lmna(Δ8–11/Δ8–11) mice. Our study also suggests that the levels of DNA repair factors 53BP1, BRCA1 and RAD51 could potentially serve as biomarkers to identify laminopathies that present with genomic instability

Architecting the Communication and Navigation Networks for NASA's Space Exploration Systems

NASA is planning a series of short and long duration human and robotic missions to explore the Moon and then Mars. A key objective of the missions is to grow, through a series of launches, a system of systems communication, navigation, and timing infrastructure at minimum cost while providing a network-centric infrastructure that maximizes the exploration capabilities and science return. There is a strong need to use architecting processes in the mission pre-formulation stage to describe the systems, interfaces, and interoperability needed to implement multiple space communication systems that are deployed over time, yet support interoperability with each deployment phase and with 20 years of legacy systems. In this paper we present a process for defining the architecture of the communications, navigation, and networks needed to support future space explorers with the best adaptable and evolable network-centric space exploration infrastructure. The process steps presented are: 1) Architecture decomposition, 2) Defining mission systems and their interfaces, 3) Developing the communication, navigation, networking architecture, and 4) Integrating systems, operational and technical views and viewpoints. We demonstrate the process through the architecture development of the communication network for upcoming NASA space exploration missions

Mechanisms and Role of Dendritic Membrane Trafficking for Long-Term Potentiation

Long-term potentiation (LTP) of excitatory synapses is a major form of plasticity for learning and memory in the central nervous system. While the molecular mechanisms of LTP have been debated for decades, there is consensus that LTP induction activates membrane trafficking pathways within dendrites that are essential for synapse growth and strengthening. Current models suggest that key molecules for synaptic potentiation are sequestered within intracellular organelles, which are mobilized by synaptic activity to fuse with the plasma membrane following LTP induction. While the identity of the factors mobilized to the plasma membrane during LTP remain obscure, the field has narrowly focused on AMPA-type glutamate receptors. Here, we review recent literature and present new experimental data from our lab investigating whether AMPA receptors trafficked from intracellular organelles directly contribute to synaptic strengthening during LTP. We propose a modified model where membrane trafficking delivers distinct factors that are required to maintain synapse growth and AMPA receptor incorporation following LTP. Finally, we pose several fundamental questions that may guide further inquiry into the role of membrane trafficking for synaptic plasticity

Equivalent roles of marine subsidies and island characteristics in shaping island bird communities

AimSpecies distributions across islands are shaped by dispersal limitations, environmental filters and biotic interactions but the relative influence of each of these processes has rarely been assessed. Here, we examine the relative contributions of island characteristics, marine subsidies, species traits, and species interactions on avian community composition.LocationCentral Coast region of British Columbia, Canada.TaxonTerrestrial breeding birds.MethodsWe observed 3610 individuals of 32 bird species on 89 islands that spanned multiple orders of magnitude in area (0.0002–3 km$^{2}$). We fit a spatially explicit joint species distribution model to estimate the relative contributions of island physical characteristics, island‐specific inputs of marine subsidies, species' traits, and biotic interactions on species distributions. Biogeographic characteristics included island area, isolation, and habitat heterogeneity, while marine influence was represented by forest‐edge soil δ$^{15}$N, wrack biomass, shoreline substrate, and distance to shore. This approach also allowed us to estimate how much variation in distributions resulted from species' biological traits (i.e. body mass, feeding guild, feeding height, and nesting height).ResultsBird species distributions were determined almost equivalently by island biogeographic characteristics (23.5% of variation explained) and marine influence (24.8%). We detected variation in species‐specific responses to both island biogeographic characteristics and marine influence, but no significant effect of any biological trait examined. Additionally, we found evidence that habitat preferences were a more important driver than competitive interactions.Main ConclusionsAlthough most island biogeographic studies focus only on islands' physical characteristics, we found evidence for an equivalent role of marine subsidy in structuring island bird communities. Our study suggests that for small islands, disentangling the effects of island biogeographic characteristics, marine inputs, and biotic interactions is a useful next step in understanding species distributions

Dose-related effects of smallpox vaccine

BACKGROUND: We conducted a double-blind, randomized trial of three dilutions of vaccinia virus vaccine in previously unimmunized adults in order to assess the clinical success rates, humoral responses, and virus-specific activity of cytotoxic T cells and interferon-gamma-producing T cells. METHODS: Sixty healthy adults were inoculated intradermally by bifurcated needle with undiluted vaccine (dose, 10(7.8) plaque-forming units [pfu] per milliliter), a 1:10 dilution (dose, 10(6.5) pfu per milliliter), or a 1:100 dilution (dose, 10(5.0) pfu per milliliter); there were 20 subjects in each group. The subjects were monitored with respect to vesicle formation (an indicator of successful vaccination), the viral titer at the time of peak lesion formation, antiviral antibodies, and cellular immune responses. RESULTS: A vaccinia vesicle developed in 19 of the 20 subjects who received undiluted vaccine (95 percent), 14 of the 20 who received the 1:10 dilution (70 percent), and 3 of the 20 who received the 1:100 dilution (15 percent). One month after vaccination, 34 of 36 subjects with vesicles had antibody responses, as compared with only 1 of 24 subjects without clinical evidence of vaccinia virus replication. Vigorous cytotoxic T-cell and interferon-gamma responses occurred in 94 percent of subjects with vesicles, and a cytotoxic T-cell response occurred in only one subject without a vesicle. CONCLUSIONS: The vaccinia virus vaccine (which was produced in 1982 or earlier) still has substantial potency when administered by a bifurcated needle to previously unvaccinated adults. Diluting the vaccine reduces the rate of successful vaccination. The development of vesicular skin lesions after vaccination correlates with the induction of the antibody and T-cell responses that are considered essential for clearing vaccinia virus infections