Small molecule screening identifies targetable zebrafish pigmentation pathways

Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish and investigate the effects of a few of these compounds in further detail. We identified and confirmed 57 compounds that altered pigment cell patterning, number, survival, or differentiation. Additional tissue targets and toxicity of small molecules are also discussed. Given that the majority of cell types, including pigment cells, are conserved between zebrafish and other vertebrates, we present these chemicals as molecular tools to study developmental processes of pigment cells in living animals and emphasize the value of zebrafish as an in vivo system for testing the on- and off-target activities of clinically active drugs.     

Quantitative trait loci for grain fructan concentration in wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis> L.)

Fructans (fructo-oligosaccharides) are prebiotics that are thought to selectively promote the growth of colonic bifidobacteria, thereby improving human gut health. Fructans are present in the grain of wheat, a staple food crop. In the research reported here, we aimed to detect and map loci affecting grain fructan concentration in wheat using a doubled-haploid population derived from a cross between a high-fructan breeding line, Berkut, and a low-fructan cultivar, Krichauff. Fructan concentration was measured in grain samples grown at two locations in Australia and one in Kazakhstan. Fructan concentration varied widely within the population, ranging from 0.6 to 2.6% of grain dry weight, and was quite repeatable, with broad-sense heritability estimated as 0.71. With a linkage map of 528 molecular markers, quantitative trait loci (QTLs) were detected on chromosomes 2B, 3B, 5A, 6D and 7A. Of these, the QTLs on chromosomes 6D and 7A had the largest effects, explaining 17 and 27% of the total phenotypic variance, respectively, both with the favourable (high-fructan concentration) alleles contributed from Berkut. These chromosome regions had similar effects in another mapping population, Sokoll/Krichauff, with the favourable alleles contributed from Sokoll. It is concluded that grain fructan concentration of wheat can be improved by breeding and that molecular markers could be used to select effectively for favourable alleles in two regions of the wheat genome.     

Proteolysis of proBDNF is a key regulator in the formation of memory

It is essential to understand the molecular processes underlying long-term memory to provide therapeutic targets of aberrant memory that produce pathological behaviour in humans. Under conditions of recall, fully-consolidated memories can undergo reconsolidation or extinction. These retrieval-mediated memory processes may rely on distinct molecular processes. The cellular mechanisms initiating the signature molecular events are not known. Using infusions of protein synthesis inhibitors, antisense oligonucleotide targeting brain-derived neurotrophic factor (BDNF) mRNA or tPA-STOP (an inhibitor of the proteolysis of BDNF protein) into the hippocampus of the awake rat, we show that acquisition and extinction of contextual fear memory depended on the increased and decreased proteolysis of proBDNF (precursor BDNF) in the hippocampus, respectively. Conditions of retrieval that are known to initiate the reconsolidation of contextual fear memory, a BDNF-independent memory process, were not correlated with altered proBDNF cleavage. Thus, the processing of BDNF was associated with the acquisition of new information and the updating of information about a salient stimulus. Furthermore, the differential requirement for the processing of proBDNF by tPA in distinct memory processes suggest that the molecular events actively engaged to support the storage and/or the successful retrieval of memory depends on the integration of ongoing experience with past learning.     

Is conservation triage just smart decision making?

Conservation efforts and emergency medicine face comparable problems: how to use scarce resources wisely to conserve valuable assets. In both fields, the process of prioritising actions is known as triage. Although often used implicitly by conservation managers, scientists and policymakers, triage has been misinterpreted as the process of simply deciding which assets (e.g. species, habitats) will not receive investment. As a consequence, triage is sometimes associated with a defeatist conservation ethic. However, triage is no more than the efficient allocation of conservation resources and we risk wasting scarce resources if we do not follow its basic principles.     

Biogeography of copepods in lakes and ponds of subarctic Québec,Canada

We aimed to determine whether the copepod assemblages in lakes and ponds of northern Québec, Canada, were closer in composition to those found in southern Québec, or to those reported from the subarctic and arctic. Six calanoid and five cyclopoid species were identified from 37 ponds and lakes located in the region between 55° N and 59° N. Species diversity was generally low, ranging from 0 to 4 species per lake. Dominant species were Leptodiaptomus minutus and Acanthocyclops vernalis. The species assemblages showed high affinity with those found in forested regions of southern Québec. Exceptions were Leptodiaptomus tyrrelli, previously only recorded west of Hudson Bay, and Hesperodiaptomus arcticus, hitherto recorded north of 58° N. Relationships between the lakes, species, and environmental variables were explored using multivariate analysis. Lakes situated along the coast and on two offshore islands clustered together and were characterised by higher conductivity and pH than those lakes located further inland. Leptodiaptomus tyrrelli was common in these coastal lakes. Canonical correspondence analysis revealed statistically significant relationships between copepod distributions and conductivity, dissolved organic carbon and pH. These three variables accounted for 70% of the variation in the species' distribution.     

Current Progress for the Use of miRNAs in Glioblastoma Treatment

Glioblastoma (GBM) is a highly aggressive brain cancer with the worst prognosis of any central nervous system disease despite intensive multimodal therapy. Inevitably, glioblastoma is fatal, with recurrence of treatment-resistant tumour growth at distal sites leading to an extremely low median survival rate of 12–15 months from the time of initial diagnosis. With the advent of microarray and gene profiling technology, researchers have investigated trends in genetic alterations and, in this regard, the role of dysregulated microRNAs (highly conserved endogenous small RNA molecules) in glioblastoma has been studied with a view to identifying novel mechanisms of acquired drug resistance and allow for development of microRNA (miRNA)-based therapeutics for GBM patients. Considering the development of miRNA research from initial association to GBM to commercial development of miR-based therapeutics in less than a decade, it is not beyond reasonable doubt to anticipate significant advancements in this field of study, hopefully with the ultimate conclusion of improved patient outcome. This review discusses the recent advancements in miRNA-based therapeutic development for use in glioblastoma treatment and the challenges faced with respect to in vivo and clinical application.     

Distress prevention by grooming others in crested black macaques

Allogrooming is probably one of the most common and most studied social behaviours in a variety of animals. Whereas the short-term benefits for the groomee have often been investigated, little is known about the effects for the groomer. Our study focused on the short-term effects of grooming another group member in seven adult female crested black macaques (Macaca nigra). We found reductions in self-directed behaviour, an indicator of anxiety, and aggressive tendencies soon after grooming, when compared to matched-control periods. These findings can be interpreted as evidence of distress prevention, possibly mediated by an increase in tolerance. Indeed, a former groomee was more likely to be the nearest neighbour of the former groomer in the 10 min after grooming ended. Thus, the role of grooming in short-term distress alleviation can be applicable to the groomer as well as the groomee. These short-term effects, together with the longer-term effects of large and/or strong grooming networks confirm that grooming, as well as receiving grooming, has great importance for social dynamics.     

Multifaceted Modelling of Complex Business Enterprises

We formalise and present a new generic multifaceted complex system approach for modelling complex business enterprises. Our method has a strong focus on integrating the various data types available in an enterprise which represent the diverse perspectives of various stakeholders. We explain the challenges faced and define a novel approach to converting diverse data types into usable Bayesian probability forms. The data types that can be integrated include historic data, survey data, and management planning data, expert knowledge and incomplete data. The structural complexities of the complex system modelling process, based on various decision contexts, are also explained along with a solution. This new application of complex system models as a management tool for decision making is demonstrated using a railway transport case study. The case study demonstrates how the new approach can be utilised to develop a customised decision support model for a specific enterprise. Various decision scenarios are also provided to illustrate the versatility of the decision model at different phases of enterprise operations such as planning and control.     

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Ohne Zusammenfassung     

Molecular markers for adult plant leaf rust resistance gene <Emphasis Type="Italic">Lr48</Emphasis> in wheat

Leaf rust of wheat, caused by Puccinia triticina, is an important disease throughout the world. The adult plant leaf rust resistance gene Lr48 reported in CSP44 was previously mapped in chromosome 2B, but the marker–gene association was weak. In this study, we confirmed the location of Lr48 to be in the short arm of chromosome 2B and identified closely linked markers suitable for use in breeding. The CSP44/WL711 recombinant inbred line (RIL) population (90 lines) showed monogenic segregation for Lr48. Twelve resistant and 12 susceptible RILs were used for selective genotyping using an iSelect 90K Infinium SNP assay. Closely linked SNPs were converted into Kompetitive allele-specific primers (KASP) and tested on the parental lines. KASP markers giving clear clusters for alternate genotypes were assayed on the entire RIL population. SNP markers IWB31002, IWB39832, IWB34324, IWB72894 and IWB36920 co-segregated with Lr48 and the marker IWB70147 was mapped 0.3 cM proximal to this gene. Closely linked KASP markers were tested on a set of Australian and Nordic wheat genotypes. The amplification of SNP alleles alternate to those linked with Lr48 in the majority of the Australian and Nordic wheat genotypes demonstrated the usefulness of these markers for marker-assisted pyramiding of Lr48 with other rust resistance genes.