Kinase Inhibitors from Marine Sponges

Protein kinases play a critical role in cell regulation and their deregulation is a contributing factor in an increasing list of diseases including cancer. Marine sponges have yielded over 70 novel compounds to date that exhibit significant inhibitory activity towards a range of protein kinases. These compounds, which belong to diverse structural classes, are reviewed herein, and ordered based upon the kinase that they inhibit. Relevant synthetic studies on the marine natural product kinase inhibitors have also been included

Molecular effects of resistance elicitors from biological origin and their potential for crop protection

Plants contain a sophisticated innate immune network to prevent pathogenic microbes from gaining access to nutrients and from colonising internal structures. The first layer of inducible response is governed by the plant following the perception of microbe- or modified plant-derived molecules. As the perception of these molecules results in a plant response that can provide efficient resistance towards non-adapted pathogens they can also be described as ‘defence elicitors’. In compatible plant/microbe interactions, adapted microorganisms have means to avoid or disable this resistance response and promote virulence. However, this requires a detailed spatial and temporal response from the invading pathogens. In agricultural practice, treating plants with isolated defence elicitors in the absence of pathogens can promote plant resistance by uncoupling defence activation from the effects of pathogen virulence determinants. The plant responses to plant, bacterial, oomycete or fungal-derived elicitors are not, in all cases, universal and need elucidating prior to the application in agriculture. This review provides an overview of currently known elicitors of biological rather than synthetic origin and places their activity into a molecular context

Noisy neighbourhoods: quorum sensing in fungal-polymicrobial infections

Quorum sensing was once considered a way in which a species was able to sense its cell density and regulate gene expression accordingly. However, it is now becoming apparent that multiple microbes can sense particular quorum-sensing molecules, enabling them to sense and respond to other microbes in their neighbourhood. Such interactions are significant within the context of polymicrobial disease, in which the competition or cooperation of microbes can alter disease progression. Fungi comprise a small but important component of the human microbiome and are in constant contact with bacteria and viruses. The discovery of quorum-sensing pathways in fungi has led to the characterization of a number of interkingdom quorum-sensing interactions. Here, we review the recent developments in quorum sensing in medically important fungi, and the implications these interactions have on the host's innate immune response

Euglena gracilis paramylon activates human lymphocytes by upregulating pro-inflammatory factors

The aim of this study was to verify the activation details and products of human lymphomonocytes, stimulated by different β-glucans, that is Euglena paramylon, MacroGard®, and lipopolysaccharide. We investigated the gene expression of inflammation-related cytokines and mediators, transactivation of relevant transcription factors, and phagocytosis role in cell-glucan interactions, by means of RT-PCR, immunocytochemistry, and colorimetric assay. Our results show that sonicated and alkalized paramylon upregulates pro-inflammatory factors (NO, TNF-α, IL-6, and COX-2) in lymphomonocytes. A clear demonstration of this upregulation is the increased transactivation of NF-kB visualized by immunofluorescence microscopy. Phagocytosis assay showed that internalization is not a mandatory step for signaling cascade to be triggered, since immune activity is not present in the lymphomonocytes that have internalized paramylon granules and particulate MacroGard®. Moreover, the response of Euglena β-glucan-activated lymphomonocytes is much greater than that induced by commercially used β-glucans such as MacroGard®. Our in vitro results indicate that linear fibrous Euglena β-glucan, obtained by sonication and alkaline treatment can act as safe and effective coadjutant of the innate immune system response

Practice makes perfect? Skillful performances in veterinary work

Is vetting a craft that must be learned owing to the limitations of scientific discipline, or simply a question of practice makes perfect? This question arose from our empirical research on veterinary surgeons (vets), who we found were often struggling with the divergence between the precise and unambiguous knowledge underlying the training and the unpredictability and imprecision of their everyday practices. These are comparatively underexplored issues insofar as the literature on vets tends to be descriptive and statistical, focusing primarily on clinical matters and associated human-animal interactions. Our cliché title has a question mark because while many vets remain embedded in the disciplined ‘certainties’ and causal regularities within their training, in practice this ordered world is rarely realized, and they are faced with indeterminacy where the ‘perfect’ solution eludes them. Vets often turn these unrealistic ideals of expertise back in on themselves, thus generating doubt and insecurity for any failure in their practices. In analysing vets’ experiences, we pay attention to the anatomical models of science, where linear causal analysis is expected to provide orderly and predictable outcomes or ‘right’ answers to problems, as well as notions of expertise that turn out to be illusory