Gene expression during preimplantation mouse development

To develop a resource for the identification and isolation of genes expressed in the early mammalian embryo, large and representative cDNA libraries were constructed from unfertilized eggs, and two-cell, eight-cell, and blastocyst-stage mouse embryos. Using these libraries, we now report the first stages at which the cytokines interleukin (IL)-6, IL-1 beta, and interferon (IFN)-gamma are transcribed in the developing embryo and the presence of IL-7 transcripts in the unfertilized egg. Transcripts for IL-1 alpha, -2, -3, -4, or -5 were not detected at these stages. To identify novel genes expressed on activation of the embryonic genome, the egg and eight-cell stage-specific cDNA libraries were subtracted from the two-cell library, yielding a specialized cDNA library enriched for transcripts expressed at the two-cell stage. Sequence and Southern blot analysis of several of these cDNAs expressed predominantly at the two-cell stage of embryogenesis revealed them to be from novel genes, thereby providing the first molecular tools with which to approach the study of gene expression in the early mammalian embryo

Ordering our world: the quest for traces of temporal organization in autobiographical memory

An experiment examined the idea, derived from the Self Memory System model (Conway & Pleydell-Pearce, 2000), that autobiographical events are sometimes tagged in memory with labels reflecting the life era in which an event occurred. The presence of such labels should affect the ease of judgments of the order in which life events occurred. Accordingly, 39 participants judged the order of two autobiographical events. Latency data consistently showed that between-era judgments were faster than within-era judgments, when the eras were defined in terms of either: (a) college versus high school, (b) academic quarter within year, or (c) academic year within school. The accuracy data similarly supported the presence of a between-era judgment effect for the college versus high school dichotomy

Mnemic neglect : selective amnesia of one's faults

The mnemic neglect model predicts and accounts for selective memory for social feedback as a function of various feedback properties. At the heart of the model is the mnemic neglect effect (MNE), defined as inferior recall for self-threatening feedback compared to other kinds of feedback. The effect emerges both in mundane realism settings and in minimal feedback settings. The effect is presumed to occur in the service of self-protection motivation. Mnemic neglect is pronounced when the feedback poses high levels of self-threat (i.e., can detect accurately one’s weakness), but is lost when self-threat is averted via a self-affirmation manipulation. Mnemic neglect is caused by selfthreatening feedback being processed shallowly and in ways that separate it from stored (positive) self-knowledge. For example, mnemic neglect is lost when feedback processing occurs under cognitive load. The emergence of mnemic neglect is qualified by situational moderators (extent to which one considers their self-conceptions modifiable, receives feedback from a close source, or is primed with improvement-related constructs) and individual differences moderators (anxiety, dysphoria, or defensive pessimism). Finally, the MNE is present in recall, but absent in recognition. Output interference cannot explain this disparity in results, but an inhibitory repression account (e.g., experiential avoidance) can: Repressors show enhanced mnemic neglect. The findings advance research on memory, motivation, and the self

Growth and Characterization of 3C-SiC and 2H-AIN/GaN Films and Devices Produced on Step-Free 4H-SiC Mesa Substrates

While previously published experimental results have shown that the step-free (0 0 0 1) 4H-SiC mesa growth surface uniquely enables radical improvement of 3C-SiC and 2H-AlN/GaN heteroepitaxial film quality (greater than 100-fold reduction in extended defect densities), important aspects of the step-free mesa heterofilm growth processes and resulting electronic device benefits remain to be more fully elucidated. This paper reviews and updates recent ongoing studies of 3C-SiC and 2H-AlN/GaN heteroepilayers grown on top of 4H-SiC mesas. For both 3C-SiC and AlN/GaN films nucleated on 4H-SiC mesas rendered completely free of atomic-scale surface steps, TEM studies reveal that relaxation of heterofilm strain arising from in-plane film/substrate lattice constant mismatch occurs in a remarkably benign manner that avoids formation of threading dislocations in the heteroepilayer. In particular, relaxation appears to occur via nucleation and inward lateral glide of near-interfacial dislocation half-loops from the mesa sidewalls. Preliminary studies of homojunction diodes implemented in 3C-SiC and AlN/GaN heterolayers demonstrate improved electrical performance compared with much more defective heterofilms grown on neighbouring stepped 4H-SiC mesas. Recombination-enhanced dislocation motion known to degrade forward-biased 4H-SiC bipolar diodes has been completely absent from our initial studies of 3C-SiC diodes, including diodes implemented on defective 3C-SiC heterolayers grown on stepped 4H-SiC mesas

Fast Vertical Beam Instability in the CTF3 Combiner Ring

The CLIC Test Facility CTF3 is being built at CERN by an international collaboration, in order to demonstrate the main feasibility issues of the CLIC two-beam technology by 2010. The facility includes an 84 m combiner ring, which was installed and put into operation in 2007. High-current operation has shown a vertical beam break-up instability, leading to high beam losses over the four turns required for nominal operation of the CTF3 ring. Such instability is most likely due to the vertically polarized transverse mode in the RF deflectors used for beam injection and combination. In this paper we report the experimental data and compare them with simulations. Possible methods to eliminate the instability are also outlined

Achievements in CTF3 and Commissioning status

The aim of the latest CLIC test facility CTF3, built at CERN by an international collaboration, is to prove the main feasibility issues of the CLIC two-beam acceleration technology. Several of the main goals have been already achieved in the past years, like the full-loading linac operation mode and the delay loop principle. During 2008 also the combiner ring concept has been experimentally proven and the recombined beam has been used to generate the RF power. In parallel in the fall of the year also the probe beam line commissioning had started

Status of an automatic Beam Steering for the CLIC Test Facility 3

An automatic beam steering application for CTF 3 is being designed in order to automatize operation of the machine, as well as providing a test-bed for advanced steering algorithms for CLIC. Beam-based correction including dispersion free steering have been investigated. An approach based on a PLACET on-line model has been tested. This paper gives an overview of the current status and the achieved results of the CTF3 automatic steering

Substitutions near the hemagglutinin receptor-binding site determine the antigenic evolution of influenza A H3N2 viruses in U.S. swine

Swine influenza A virus is an endemic and economically important pathogen in pigs, with the potential to infect other host species. The hemagglutinin (HA) protein is the primary target of protective immune responses and the major component in swine influenza A vaccines. However, as a result of antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. Characterizing the cross-reactivity between strains in pigs and seasonal influenza virus strains in humans is also important in assessing the relative risk of interspecies transmission of viruses from one host population to the other. Hemagglutination inhibition (HI) assay data for swine and human H3N2 viruses were used with antigenic cartography to quantify the antigenic differences among H3N2 viruses isolated from pigs in the United States from 1998 to 2013 and the relative cross-reactivity between these viruses and current human seasonal influenza A virus strains. Two primary antigenic clusters were found circulating in the pig population, but with enough diversity within and between the clusters to suggest updates in vaccine strains are needed. We identified single amino acid substitutions that are likely responsible for antigenic differences between the two primary antigenic clusters and between each antigenic cluster and outliers. The antigenic distance between current seasonal influenza virus H3 strains in humans and those endemic in swine suggests that population immunity may not prevent the introduction of human viruses into pigs, and possibly vice versa, reinforcing the need to monitor and prepare for potential incursions

Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1

SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts. © 2013 Fregoso et al

Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?

© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio