The mode of action of the plant antimicrobial peptide MiAMP1 differs from that of its structural homologue, the yeast killer toxin WmKT

The plant antimicrobial peptide MiAMP1 from Macadamia integrifolia and the yeast killer toxin peptide WmKT from Williopsis mrakii are structural homologues. Comparative studies of yeast mutants were performed to test their sensitivity to these two antimicrobial peptides. No differences in susceptibility to MiAMP1 were detected between wild-type and several WmKT-resistant mutant yeast strains. A yeast mutant MT1, resistant to MiAMP1 but unaffected in its susceptibility to plant defensins and hydrogen peroxide, also did not show enhanced tolerance towards WmKT. It is therefore probable that the Greek key beta-barrel structure shared by MiAMP1 and WmKT provides a robust structural framework ensuring stability for the two proteins but that the specific action of the peptides depends on other motifs. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

Modulation of proliferation-specific and differentiation-specific markers in human keratinocytes by SMAD7

We examined the potential role of SMAD7 in human epidermal keratinocyte differentiation. Overexpression of SMAD7 inhibited the activity of the proliferation-specific promoters for the keratin 14 and cdc2 genes and reduced the expression of the mRNA for the proliferation-specific genes cdc2 and E2F1. The ability of SMAD7 to suppress cdc2 promoter activity was lost in transformed keratinocyte cell lines and was mediated by a domain(s) located between aa 195-395 of SMAD7. This domain lies outside the domain required to inhibit TGFbeta1 signaling, suggesting that this activity is mediated by a novel functional domain(s). Examination of AP1, NFkappaB, serum response element, Gli, wnt, and E2F responsive reporters indicated that SMAD7 significantly suppressed the E2F responsive reporter and modestly increased AP1 activity in proliferating keratinocytes. These data Suggest that SMAD7 may have a role in TGFbeta-independent signaling events in proliferating/undifferentiated keratinocytes. The effects of SMAD7 in differentiated keratinocytes indicated a more traditional role for SMAD7 as an inhibitor of TGFbeta action. SMAD7 was unable to initiate the expression of differentiation markers but was able to superinduce/derepress differentiation-specific markers and genes in differentiated keratinocytes. This latter role is consistent with the ability of SMAD7 to inhibit TGFbeta-mediated suppression of keratinocyte differentiation and suggest that the opposing actions of SMAD7 and TGFbeta may serve to modulate squamous differentiation. (C) 2004 Elsevier Inc. All rights reserved.

LPS regulates a set of genes in primary murine macrophages by antagonising CSF-1 action

We previously reported that bacterial products such as LPS and CpG DNA down-modulated cell surface levels of the Colony Stimulating Factor (CSF)-1 receptor (CSF-1R) on primary murine macrophages in an all-or-nothing manner. Here we show that the ability of bacterial products to down-modulate the CSF-IR rendered bone marrow-derived macrophages (BMM) unresponsive to CSF-1 as assessed by Akt and ERK 1/2 phosphorylation. Using toll-like receptor (th-)9 as a model CSF-1-repressed gene, we show that LPS induced tlr9 expression in BMM only when CSF-1 was present, suggesting that LPS relieves CSF-1-mediated inhibition to induce gene expression. Using cDNA microarrays, we identified a cluster of similarly CSF-1 repressed genes in BMM. By real time PCR we confirmed that the expression of a selection of these genes, including integral membrane protein 2B (itm2b), receptor activity-modifying protein 2 (ramp2) and macrophage-specific gene 1 (mpg-1), were repressed by CSF-1 and were induced by LPS only in the presence of CSF-1. This pattern of gene regulation was also apparent in thioglycollate-elicited peritoneal macrophages (TEPM). LPS also counteracted CSF-1 action to induce mRNA expression of a number of transcription factors including interferon consensus sequence binding protein 1 (Icsbp1), suggesting that this mechanism leads to transcriptional reprogramming in macrophages. Since the majority of in vitro studies on macrophage biology do not include CSF-1, these genes represent a set of previously uncharacterised LPS-inducible genes. This study identifies a new mechanism of macrophage activation, in which LPS (and other toll-like receptor agonists) regulate gene expression by switching off the CSF-1R signal. This finding also provides a biological relevance to the well-documented ability of macrophage activators to down-modulate surface expression of the CSF-1R. (C) 2005 Elsevier GmbH. All rights reserved.

An archaeology of the instant? Action and narrative in microscopic archaeological residue analyses

The discovery and interpretation of microscopic residues on stone artefacts is an expanding front within archaeological science, allowing reconstructions of the past use of specific tools. With notable exceptions, however, the field has seen little theoretical development, relying largely on a rationale in which either individual findings are widely generalized or the age of the site determines the importance of the results. Here an approach to residue interpretation is proposed that draws on notions of narrative, scale, action and agency as one means of expanding the theoretical scope and application of residue studies. It is suggested that the individual resonance of the findings of residue analyses with people in the present day can be used to provide a more nuanced understanding of past actions, which in turn allows both better integration and communication of those findings within and outside the archaeological comm unity, and begins to overcome the problems associated with the typically small sample sizes analysed in stone-tool residue studies.

Effects of acoustic startle stimuli on interceptive action

In reaction time (RT) tasks, presentation of a startling acoustic stimulus (SAS) together with a visual imperative stimulus can dramatically reduce RT while leaving response execution unchanged. It has been suggested that a prepared motor response program is triggered early by the SAS but is not otherwise affected. Movements aimed at intercepting moving targets are usually considered to be similarly governed by a prepared program. This program is triggered when visual stimulus information about the time to arrival of the moving target reaches a specific criterion. We investigated whether a SAS could also trigger such a movement. Human experimental participants were trained to hit moving targets with movements of a specific duration. This permitted an estimate of when movement would begin (expected onset time). Startling and sub-startle threshold acoustic probe stimuli were delivered unexpectedly among control trials: 65, 85, 115 and 135 ms prior to expected onset (10:1 ratio of control to probe trials). Results showed that startling probe stimuli at 85 and 115 ms produced early response onsets but not those at 65 or 135 ms. Sub-threshold stimuli at 115 and 135 ms also produced early onsets. Startle probes led to an increased vigor in the response, but sub-threshold probes had no detectable effects. These data can be explained by a simple model in which preparatory, response-related activation builds up in the circuits responsible for generating motor commands in anticipation of the GO command. If early triggering by the acoustic probes is the mechanism underlying the findings, then the data support the hypothesis that rapid interceptions are governed by a motor program. © 2006 Published by Elsevier Ltd on behalf of IBRO.