Butyrolactone: More than a Kinase Inhibitor?

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Key Words:

Butryolactone, Kinase inhibitor, cyclin-dependent kinase inhibitor, p21, p53     

Antifungal proteins: More than antimicrobials?

Antimicrobial proteins (AMPs) are widely distributed in nature. In higher eukaryotes, AMPs provide the host with an important defence mechanism against invading pathogens. AMPs of lower eukaryotes and prokaryotes may support successful competition for nutrients with other microorganisms of the same ecological niche. AMPs show a vast variety in structure, function, antimicrobial spectrum and mechanism of action. Most interestingly, there is growing evidence that AMPs also fulfil important biological functions other than antimicrobial activity. The present review focuses on the mechanistic function of small, cationic, cysteine-rich AMPs of mammals, insects, plants and fungi with antifungal activity and specifically aims at summarizing current knowledge concerning additional biological properties which opens novel aspects for their future use in medicine, agriculture and biotechnology.     

The acheulean handaxe: More like a bird's song than a beatles' tune?

The goal of this paper is to provoke debate about the nature of an iconic artifact—the Acheulean handaxe. Specifically, we want to initiate a conversation about whether or not they are cultural objects. The vast majority of archeologists assume that the behaviors involved in the production of handaxes were acquired by social learning and that handaxes are therefore cultural. We will argue that this assumption is not warranted on the basis of the available evidence and that an alternative hypothesis should be given serious consideration. This alternative hypothesis is that the form of Acheulean handaxes was at least partly under genetic control.     

Plant-endophyte-herbivore interactions: More than just alkaloids?

A recent paper by Rasmussen et al., (New Phytol 2007; 173:787–97) describes the interactions between Lolium perenne cultivars with contrasting carbohydrate content and the symbiotic fungal endophyte Neotyphodium lolii at different levels of nitrogen supply. In a subsequent study undertaken by Rasmussen et al., (Plant Physiol 2008; 146:1440–53) 66 metabolic variables were analysed in the same material, revealing widespread effects of endophyte infection, N supply and cultivar carbohydrate content on both primary and secondary metabolites. Here, we link insect numerical responses to these metabolic responses using multiple regression analysis.Key words: Neotyphodium lolii, Lolium perenne, high sugar grasses, metabolomics, insect herbivoresPasture grasses are often infected with symbiotic fungal endophytes and benefits for host plants arising out of these associations are generally ascribed to endophyte produced anti-herbivorous alkaloids. We tested the effects of (i) infection with three strains of endophytes differing in their alkaloid profiles, (ii) high vs. low nitrogen (N) supply, and (iii) ryegrass cultivars with high vs. control levels of water soluble carbohydrates (WSCs) on numerical insect responses (aphids, thrips, mites). A difference in WSC content between the cultivars had no significant effect on insect numbers, whereas high N compared to low N supply increased mites, thrips and alate Rhopalosiphum spp., but decreased apterous Rhopalosiphum spp. The effect of endophyte infection was strain dependant and differed for the different insects.A total of 66 metabolic variables of the same plants analysed prior to insect treatment were linked to insect responses using multiple regression analysis. One of the major conclusions to be drawn is that alkaloids are not always the most important factor influencing numerical insect responses which will also be determined by other metabolites, clearly indicating the importance of metabolomics type studies to point the way toward a mechanistic explanation of grass-endophyte-herbivore interactions.Grass species are often hosts of symbiotic clavicipitaceous endophytic fungi¹ residing in the apoplastic spaces of above ground plant parts and usually not causing any visible symptoms of infection.^2–4 These fungal symbionts confer protection from insect herbivory to their host plants through alkaloids,^5–8 some of which (ergovaline, lolitrem B) are also toxic to grazing mammals.^9,10 Natural endophyte strains lacking these mammalian toxins, but still retaining at least some of their insect deterring features, have been commercialized and are now widely used in ryegrass and tall fescue based pastures.^11,12     

Histone acetyltransferase 1: More than just an enzyme?

Histone acetyltransferase 1 (HAT1) is an enzyme that is likely to be responsible for the acetylation that occurs on lysines 5 and 12 of the NH(2)-terminal tail of newly synthesized histone H4. Initial studies suggested that, despite its evolutionary conservation, this modification of new histone H4 played only a minor role in chromatin assembly. However, a number of recent studies have brought into focus the important role of both this modification and HAT1 in histone dynamics. Surprisingly, the function of HAT1 in chromatin assembly may extend beyond just its catalytic activity to include its role as a major histone binding protein. These results are incorporated into a model for the function of HAT1 in histone deposition and chromatin assembly. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.     

More than a decade of developmental gene expression atlases: where are we now?

To unravel regulatory networks of genes functioning during embryonic development, information on in situ gene expression is required. Enormous amounts of such data are available in literature, where each paper reports on a limited number of genes and developmental stages. The best way to make these data accessible is via spatio-temporal gene expression atlases. Eleven atlases, describing developing vertebrates and covering at least 100 genes, were reviewed. This review focuses on: (i) the used anatomical framework, (ii) the handling of input data and (iii) the retrieval of information. Our aim is to provide insights into both the possibilities of the atlases, as well as to describe what more than a decade of developmental gene expression atlases can teach us about the requirements of the design of the ‘ideal atlas’. This review shows that most ingredients needed to develop the ideal atlas are already applied to some extent in at least one of the discussed atlases. A review of these atlases shows that the ideal atlas should be based on a spatial framework, i.e. a series of 3D reference models, which is anatomically annotated using an ontology with sufficient resolution, both for relations as well as for anatomical terms.     

Are Treatments More Effective than Placebos? A Systematic Review and Meta-Analysis

BackgroundPlacebos are widely used in clinical practice in spite of ethical restrictions. Whether such use is justified depends in part on the relative benefit of placebos compared to ‘active’ treatments. A direct test for differences between placebo and ‘active’ treatment effects has not been conducted.ObjectivesWe aimed to test for differences between treatment and placebo effects within similar trial populations.ResultsIn trials with continuous outcomes (n = 115) we found no difference between treatment and placebo effects (MD = −0.29, 95% CI −0.62 to 0.05, P = 0.10). In trials with binary outcomes (n = 37) treatments were significantly more effective than placebos (RRR = 0.72, 95%CI = 0.61 to 0.86, P = 0.0003). Treatment and placebo effects were not different in 22 out of 28 predefined subgroup analyses. Of the six subgroups with differences treatments were more effective than placebos in five. However when all criteria for reducing bias were ruled out (continuous outcomes) placebos were more effective than treatments (MD = 1.59, 95% CI = 0.40 to 2.77, P = 0.009).

Conclusions and Implications

Placebos and treatments often have similar effect sizes. Placebos with comparatively powerful effects can benefit patients either alone or as part of a therapeutic regime, and trials involving such placebos must be adequately blinded.     

The DNA-dependent protein kinase (DNA-PK): More than just a case of making ends meet?

The DNA-dependent protein kinase (DNA-PK) has a vital role in DNA double strand break repair and in mediating V(D)J recombination events. Over the years a body of data has implicated DNA-PK playing a significant role in mediating a p53-dependent apoptotic response under a range of cellular conditions including exposure to ionizing radiation (IR), environmental carcinogens, and chemotherapeutic agents or in cells that have critically shortened telomeres. These findings raise the hypothesis that DNA-PK acts as both a sensor and transmitter of DNA damage signals that directly impact cell fate. These many overlapping roles are discussed and considered in this review article.     

Slowness: An Objective for Spike-Timing–Dependent Plasticity?

Our nervous system can efficiently recognize objects in spite of changes in contextual variables such as perspective or lighting conditions. Several lines of research have proposed that this ability for invariant recognition is learned by exploiting the fact that object identities typically vary more slowly in time than contextual variables or noise. Here, we study the question of how this “temporal stability” or “slowness” approach can be implemented within the limits of biologically realistic spike-based learning rules. We first show that slow feature analysis, an algorithm that is based on slowness, can be implemented in linear continuous model neurons by means of a modified Hebbian learning rule. This approach provides a link to the trace rule, which is another implementation of slowness learning. Then, we show analytically that for linear Poisson neurons, slowness learning can be implemented by spike-timing–dependent plasticity (STDP) with a specific learning window. By studying the learning dynamics of STDP, we show that for functional interpretations of STDP, it is not the learning window alone that is relevant but rather the convolution of the learning window with the postsynaptic potential. We then derive STDP learning windows that implement slow feature analysis and the “trace rule.” The resulting learning windows are compatible with physiological data both in shape and timescale. Moreover, our analysis shows that the learning window can be split into two functionally different components that are sensitive to reversible and irreversible aspects of the input statistics, respectively. The theory indicates that irreversible input statistics are not in favor of stable weight distributions but may generate oscillatory weight dynamics. Our analysis offers a novel interpretation for the functional role of STDP in physiological neurons.