13,305 research outputs found
Design and application of single-cell RNA sequencing to study kidney immune cells in lupus nephritis
The opposites task: Using general rules to test cognitive flexibility in preschoolers
A brief narrative description of the journal article, document, or resource. Executive functions play an important role in cognitive development, and during the preschool years especially, children's performance is limited in tasks that demand flexibility in their behavior. We asked whether preschoolers would exhibit limitations when they are required to apply a general rule in the context of novel stimuli on every trial (the "opposites" task). Two types of inhibitory processing were measured: response interference (resistance to interference from a competing response) and proactive interference (resistance to interference from a previously relevant rule). Group data show 3-year-olds have difficulty inhibiting prepotent tendencies under these conditions, whereas 5-year-olds' accuracy is near ceiling in the task. (Contains 4 footnotes and 1 table.
The interferon-induced exonuclease ISG20 exerts antiviral activity through upregulation of type I interferon response proteins
The host immune responses to infection lead to the production of type I interferon (IFN), and the upregulation of interferon-stimulated genes (ISGs) reduces virus replication and virus dissemination within a host. Ectopic expression of the interferon-induced 20-kDa exonuclease ISG20 suppressed replication of chikungunya virus and Venezuelan equine encephalitis virus, two mosquito-vectored RNA alphaviruses. Since the replication of alphavirus genomes occurs exclusively in the cytoplasm, the mechanism of nucleus-localized ISG20 inhibition of replication is unclear. In this study, we determined that ISG20 acts as a master regulator of over 100 genes, many of which are ISGs. Specifically, ISG20 upregulated IFIT1 genes and inhibited translation of the alphavirus genome. Furthermore, IFIT1-sensitive alphavirus replication was increased in Isg20â/â mice compared to the replication of wild-type viruses but not in cells ectopically expressing ISG20. We propose that ISG20 acts as an indirect regulator of RNA virus replication in the cytoplasm through the upregulation of many other ISGs.Type I interferon (IFN)-stimulated genes (ISGs) have critical roles in inhibiting virus replication and dissemination. Despite advances in understanding the molecular basis of ISG restriction, the antiviral mechanisms of many remain unclear. The 20-kDa ISG ISG20 is a nuclear 3â˛â5Ⲡexonuclease with preference for single-stranded RNA (ssRNA) and has been implicated in the IFN-mediated restriction of several RNA viruses. Although the exonuclease activity of ISG20 has been shown to degrade viral RNA in vitro, evidence has yet to be presented that virus inhibition in cells requires this activity. Here, we utilized a combination of an inducible, ectopic expression system and newly generated Isg20â/â mice to investigate mechanisms and consequences of ISG20-mediated restriction. Ectopically expressed ISG20 localized primarily to Cajal bodies in the nucleus and restricted replication of chikungunya and Venezuelan equine encephalitis viruses. Although restriction by ISG20 was associated with inhibition of translation of infecting genomic RNA, degradation of viral RNAs was not observed. Instead, translation inhibition of viral RNA was associated with ISG20-induced upregulation of over 100 other genes, many of which encode known antiviral effectors. ISG20 modulated the production of IFIT1, an ISG that suppresses translation of alphavirus RNAs. Consistent with this observation, the pathogenicity of IFIT1-sensitive alphaviruses was increased in Isg20â/â mice compared to that of wild-type viruses but not in cells ectopically expressing ISG20. Our findings establish an indirect role for ISG20 in the early restriction of RNA virus replication by regulating expression of other ISGs that inhibit translation and possibly other activities in the replication cycle
Self-Organized States in Cellular Automata: Exact Solution
The spatial structure, fluctuations as well as all state probabilities of
self-organized (steady) states of cellular automata can be found (almost)
exactly and {\em explicitly} from their Markovian dynamics. The method is shown
on an example of a natural sand pile model with a gradient threshold.Comment: 4 pages (REVTeX), incl. 2 figures (PostScript
Edge Shear Flows and Particle Transport near the Density Limit in the HL-2A Tokamak
Edge shear flow and its effect on regulating turbulent transport have long
been suspected to play an important role in plasmas operating near the
Greenwald density limit . In this study, equilibrium profiles as well as
the turbulent particle flux and Reynolds stress across the separatrix in the
HL-2A tokamak are examined as is approached in ohmic L-mode discharges.
As the normalized line-averaged density is raised, the
shearing rate of the mean poloidal flow drops, and the
turbulent drive for the low-frequency zonal flow (the Reynolds power ) collapses. Correspondingly, the turbulent particle
transport increases drastically with increasing collision rates. The geodesic
acoustic modes (GAMs) gain more energy from the ambient turbulence at higher
densities, but have smaller shearing rate than low-frequency zonal flows. The
increased density also introduces decreased adiabaticity which not only
enhances the particle transport but is also related to a reduction in the
eddy-tilting and the Reynolds power. Both effects may lead to the cooling of
edge plasmas and therefore the onset of MHD instabilities that limit the plasma
density
Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval
We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24âh later. Rat brains were extracted 30âmin after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30âmin prior to training (Pre-Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group exhibited excellent 24âh memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval
Notch/Delta signaling constrains reengineering of pro-T cells by PU.1
PU.1 is essential for early stages of mouse T cell development but antagonizes it if expressed constitutively. Two separable mechanisms are involved: attenuation and diversion. Dysregulated PU.1 expression inhibits pro-T cell survival, proliferation, and passage through β-selection by blocking essential T cell transcription factors, signaling molecules, and Rag gene expression, which expression of a rearranged T cell antigen receptor transgene cannot rescue. However, Bcl2 transgenic cells are protected from this attenuation and may even undergo β-selection, as shown by PU.1 transduction of defined subsets of Bcl2 transgenic fetal thymocytes with differentiation in OP9-DL1 and OP9 control cultures. The outcome of PU.1 expression in these cells depends on Notch/Delta signaling. PU.1 can efficiently divert thymocytes toward a myeloid-like state with multigene regulatory changes, but Notch/Delta signaling vetoes diversion. Gene expression analysis distinguishes sets of critical T lineage regulatory genes with different combinatorial responses to PU.1 and Notch/Delta signals, suggesting particular importance for inhibition of E proteins, Myb, and/or Gfi1 (growth factor independence 1) in diversion. However, Notch signaling only protects against diversion of cells that have undergone T lineage specification after Thy-1 and CD25 up-regulation. The results imply that in T cell precursors, Notch/Delta signaling normally acts to modulate and channel PU.1 transcriptional activities during the stages from T lineage specification until commitment
Consumer credit information systems: A critical review of the literature. Too little attention paid by lawyers?
This paper reviews the existing literature on consumer credit reporting, the most extensively used instrument to overcome information asymmetry and adverse selection problems in credit markets. Despite the copious literature in economics and some research in regulatory policy, the legal community has paid almost no attention to the legal framework of consumer credit information systems, especially within the context of the European Union. Studies on the topic, however, seem particularly relevant in view of the establishment of a single market for consumer credit. This article ultimately calls for further legal research to address consumer protection concerns and inform future legislation
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