Cysteine-free peptides in scorpion venom: geographical distribution, structure-function relationship and mode of action

Scorpion venoms are well known sources of Na+-channel, K+-channel, Cl--channel, Ca2+-channel and ryanodine channel selective peptides. In 1993, the first cysteine-free peptide was isolated from scorpionvenom. Within the last six years, cysteine-free peptides with and without antimicrobial activity have been isolated from scorpion venom. The first antimicrobial peptides being parabutoporin and hadrurin, after which nine more have followed. Characteristics of these peptides include pore-formation and/or antimicrobial activity. Six peptides of similar structures without antimicrobial activity have also been isolated. Two of these peptides have bradykinin-potentiating functions. The functions of the other four are unknown. These peptides have the potential to combat cancer, a variety of skin or wound bacterial and fungal infections. This review will focus on the primary and secondary structures as well asreported functions and applications of the cysteine-free peptides identified in scorpion venom

The use of confocal microscopy in quantifying changes in membrane potential

Monitoring the plasma membrane potential and its changes can be a time consuming and challenging task especially when conventional electrophysiological techniques are used. The use of potentiometricfluorophores, namely tetramethylrhodamine methylester (TMRM), and digital imaging devices (laser scanning confocal microscopy) provides reliable and time efficient method. Two scorpion pore-forming peptides, namely PP and OP1, were used as a tool to induce depolarization of the plasma membrane potential of neuroblastoma cell line and cardiac myocytes. Alternative methods for the neuroblastoma cells and cardiac myocytes were used. Depolarization of the neuroblastoma cells was calibrated with 140 mM KCl solution with 1 ìM valinomycin, after which intensity readers were substituted in the Nernst equation for quantification. Calibration of the alternative method used of the cardiac myocytes’ plasma membrane potential changes was calibrated with the use of 5, 20, 40, and 80 mM KCl solutions with 1 ìM valinomycin. A calibration curve was then constructed from which plasma membrane potential could be calculate

Investment in sensory structures, testis size, and wing coloration in males of a diurnal moth species: trade-offs or correlated growth?

For dioecious animals, reproductive success typically involves an exchange between the sexes of signals that provide information about mate location and quality. Typically, the elaborate, secondary sexual ornaments of males signal their quality, while females may signal their location and receptivity. In theory, the receptor structures that receive the latter signals may also become elaborate or enlarged in a way that ultimately functions to enhance mating success through improved mate location. The large, elaborate antennae of many male moths are one such sensory structure, and eye size may also be important in diurnal moths. Investment in these traits may be costly, resulting in trade-offs among different traits associated with mate location. For polyandrous species, such trade-offs may also include traits associated with paternity success, such as larger testes. Conversely, we would not expect this to be the case for monandrous species, where sperm competition is unlikely. We investigated these ideas by evaluating the relationship between investment in sensory structures (antennae, eye), testis, and a putative warning signal (orange hindwing patch) in field-caught males of the monandrous diurnal painted apple moth Teia anartoides (Lepidoptera: Lymantriidae) in southeastern Australia. As predicted for a monandrous species, we found no evidence that male moths with larger sensory structures had reduced investment in testis size. However, contrary to expectation, investment in sensory structures was correlated: males with relatively larger antennae also had relatively larger eyes. Intriguingly, also, the size of male orange hindwing patches was positively correlated with testis size

Expansion of specialized epidermis induced by hormonal state and mechanical strain

In mammals, some sites of specialized skin such as the palms, soles, and lips grow proportionally with the animal. However, other types of specialized skin such as the nipple and anal/genital region are dramatically altered with changes of reproductive status. The specific cell types that mediate the growth of these sites have not been identified. In the mouse, we observed a dramatic expansion of the specialized epidermis of the nipple, coupled to changes in connective tissue and hair shaft density, which we designate as areola formation. During this process thymidine analog uptake was elevated in the epidermis and hair follicles. Although there were no changes in connective tissue cell proliferation, we did observe an altered expression of extracellular matrix genes. In addition, the fibroblasts of the virgin nipple areola and region showed increased transcript and protein levels for estrogen, progesterone, relaxin, and oxytocin relative to those of ventral skin. To determine the role of pregnancy, lactation hormonal milieu, and localized mechanical strain on areola formation, we created models that separated these stimuli and evaluated changes in gross structure, proliferation and protein expression. While modest increases of epidermal proliferation and remodeling of connective tissue occurred as a result of individual stimuli, areola formation required exposure to pregnancy hormones, as well as mechanical strain

A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network

BACKGROUND: The nuclear receptors are a large family of eukaryotic transcription factors that constitute major pharmacological targets. They exert their combinatorial control through homotypic heterodimerisation. Elucidation of this dimerisation network is vital in order to understand the complex dynamics and potential cross-talk involved. RESULTS: Phylogeny, protein-protein interactions, protein-DNA interactions and gene expression data have been integrated to provide a comprehensive and up-to-date description of the topology and properties of the nuclear receptor interaction network in humans. We discriminate between DNA-binding and non-DNA-binding dimers, and provide a comprehensive interaction map, that identifies potential cross-talk between the various pathways of nuclear receptors. CONCLUSION: We infer that the topology of this network is hub-based, and much more connected than previously thought. The hub-based topology of the network and the wide tissue expression pattern of NRs create a highly competitive environment for the common heterodimerising partners. Furthermore, a significant number of negative feedback loops is present, with the hub protein SHP [NR0B2] playing a major role. We also compare the evolution, topology and properties of the nuclear receptor network with the hub-based dimerisation network of the bHLH transcription factors in order to identify both unique themes and ubiquitous properties in gene regulation. In terms of methodology, we conclude that such a comprehensive picture can only be assembled by semi-automated text-mining, manual curation and integration of data from various sources

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants

Purifying Selection in Deeply Conserved Human Enhancers Is More Consistent than in Coding Sequences

(c) 2014 De Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Task-Specific Recognition Signals Are Located on the Legs in a Social Insect

Task allocation ensures a high level of organization within social insect colonies. Workers reveal their task assignment through cuticular hydrocarbon (CHC) signals. The source and chemical composition of these signals are largely unknown. We ask whether task recognition signals are located on particular body parts of workers of Australian meat ants (Iridomyrmex purpureus). We analyzed the CHC profile on the antennae, legs, and abdomens of workers engaged in different tasks. Discriminant analysis showed that the leg profile is the best indicator of task identification. Behavioral assays confirmed this finding: workers typically reacted differently to non-nestmates engaged in different tasks, but not if the CHCs on the legs of their opponents were removed by a solvent. Lasso and Elastic-Net Regularized Generalized Linear Model (GLMNET) revealed which CHC components show the highest correlation in task and nestmate recognition, suggesting that social insects can simultaneously convey different CHC signals on different body parts, thereby allowing efficient signaling and signal perception.a University of Melbourne Postgraduate Scholarship and a Holsworth Wildlife Research Endowment (to QW)

EGIA–evolutionary optimisation of gene regulatory networks, an integrative approach

Quantitative modelling of gene regulatory networks (GRNs) is still limited by data issues such as noise and the restricted length of available time series, creating an under-determination problem. However, large amounts of other types of biological data and knowledge are available, such as knockout experiments, annotations and so on, and it has been postulated that integration of these can improve model quality. However, integration has not been fully explored, to date. Here, we present a novel integrative framework for different types of data that aims to enhance model inference. This is based on evolutionary computation and uses different types of knowledge to introduce a novel customised initialisation and mutation operator and complex evaluation criteria, used to distinguish between candidate models. Specifically, the algorithm uses information from (i) knockout experiments, (ii) annotations of transcription factors, (iii) binding site motifs (expressed as position weight matrices) and (iv) DNA sequence of gene promoters, to drive the algorithm towards more plausible network structures. Further, the evaluation basis is also extended to include structure information included in these additional data. This framework is applied to both synthetic and real gene expression data. Models obtained by data integration display both quantitative and qualitative improvement

Observations of velocities, sand concentrations, and fluxes under velocity-asymmetric oscillatory flows

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