Underexplored Resource Research Articles

Structure elucidation and biological activities of two classes of peptides produced by the actinomycete, Kitasatospora cystarginea

Kitasatospora is a rare genus of Actinobacteria that represents an underexplored resource for the discovery of structurally diverse natural products. To highlight the production of unique metabolites produced by twelve members of this genus, the chemical screening method that combines LC-HRMS with Principal Component Analysis (PCA) was used. This approach identified the production of three novel compounds by K. cystarginea; which were determined to be a lipopeptide and two β-lactone containing peptide analogs, referred to as cystargamide and cystargolides A and B. Their structures were elucidated using NMR and MS/MS, and absolute configurations using advanced Marfey's Method. The therapeutic potential of cystargamide and cystargolides A and B were evaluated in several bioassays. Most notably, cystargolides A and B displayed inhibition of human 20S proteasome with IC50 values of 0.35 and 0.93µM respectively.

Selective isolation of Actinomycetes from mangrove sediment of Tanjung Lumpur, Kuantan, Malaysia.

Aims: Mangroves of Tanjung Lumpur, Kuantan, Pahang is considered as a relatively underexplored resource of actinomycetes. Based on the above perspective, a study was conducted on mangrove sediments of Tanjung Lumpur, Kuantan to isolate potential actinomycetes using several pretreatments and various selective media. Methodology and results: Sediments from five different sites at Tanjung Lumpur mangrove were collected and selectively pre-treated. The pretreated sediments were diluted and plated onto eight different selective media. A total of 172 potential actinomycetes were isolated from all the media. Antimicrobial activities of 61 selected strains were checked against 8 test microorganisms using cross streak method. Pretreatment of wet heat with seawater was the most effective method for the isolation of actinomycetes as it yielded a maximum of 105 actinomycete isolates and IM7 was the most suitable medium for actinomycete isolation with highest percentage of recovery (31 %). Forty three isolates (70.5 %) showed antimicrobial activities against one or more test microorganisms. Isolates IIUM B21 and IIUM B31 showed antimicrobial activity against all test microorganisms. Seven isolates showed antifungal activity as they inhibited only C. albicans. Ten isolates were randomly selected for identification based on partial sequences of 16S rRNA gene. Six isolates were found belong to the genus Streptomyces, two isolates belong to the genus Micromonospora and two isolates were identified as Rhodococcus spp. Conclusion, significance and impact of study: These findings revealed the potential of mangrove sediment of Tanjung Lumpur as an important source of actinomycetes with biosynthetic capabilities which might be beneficial to pharmaceutical industries.

‘Clearly Necessary’, ‘Wonderful’ and ‘Engrossing’? Mass Observation Correspondents Discuss Forensic Technologies

This article explores the perspectives of Mass Observation (MO) correspondents on crime investigation and application of forensic technologies in police work. Using the Panel's replies to two distinct, independently commissioned Directives (the 2006 Spring Directive, Part 1 ‘Genes, Genetics and Cloning’ and the 2011 Autumn/Winter Directive, Part 1, ‘Crime and Investigation’), the article examines the meanings and place correspondents give to genetics and forensic science in everyday life and in relation to crime and investigation, surveillance and law and order. The analysis surveys MO correspondents’ understandings of the relationship between forensic technologies and policing and identifies the ways in which correspondents interpret, engage with and discuss their writing tasks. It is argued that MO data offer significant insights into how individuals select and appropriate information on different topics and incorporate this knowledge into distinct worldviews. These accounts constitute a rich, yet under-explored resource for (1) documenting the range of resources that inform the ‘forensic imaginary’ on which correspondents draw in explaining their fascination with or disinterest in criminal investigation and (2) conceptualising the ways in which distinct publics reflect on representations of crime. While the analysis highlights the benefits and limitations of a Mass Observation approach to documenting collective views on the role of forensic technologies in crime investigation, the conclusion reflects more broadly on both the contribution such an approach could make to the literature on public understandings of science and the uses and potential of MO data for social science researchers.

Aspergillus nidulans Synthesize Insect Juvenile Hormones upon Expression of a Heterologous Regulatory Protein and in Response to Grazing by Drosophila melanogaster Larvae

Secondary metabolites are known to serve a wide range of specialized functions including communication, developmental control and defense. Genome sequencing of several fungal model species revealed that the majority of predicted secondary metabolite related genes are silent in laboratory strains, indicating that fungal secondary metabolites remain an underexplored resource of bioactive molecules. In this study, we combine heterologous expression of regulatory proteins in Aspergillus nidulans with systematic variation of growth conditions and observe induced synthesis of insect juvenile hormone-III and methyl farnesoate. Both compounds are sesquiterpenes belonging to the juvenile hormone class. Juvenile hormones regulate developmental and metabolic processes in insects and crustaceans, but have not previously been reported as fungal metabolites. We found that feeding by Drosophila melanogaster larvae induced synthesis of juvenile hormone in A. nidulans indicating a possible role of juvenile hormone biosynthesis in affecting fungal-insect antagonisms.

Diversity of endophytic fungi and screening of fungal paclitaxel producer from Anglojap yew, Taxus x media

BackgroundEndophytic fungi represent underexplored resource of novel lead compounds and have a capacity to produce diverse class of plant secondary metabolites. Here we investigated endophytic fungi diversity and screening of paclitaxel-producing fungi from Taxus x media.ResultsEighty-one endophytic fungi isolated from T. media were grouped into 8 genera based on the morphological and molecular identification. Guignardia and Colletotrichum were the dominant genera, whereas the remaining genera were infrequent groups. The genera Glomerella and Gibberella were first reported in Taxus. Three representative species of the distinct genera gave positive hits by molecular marker screening and were capable of producing taxol which were validated by HPLC-MS. Among these 3 taxol-producing fungi, the highest yield of taxol was 720 ng/l by Guignardia mangiferae HAA11 compared with those of Fusarium proliferatum HBA29 (240 ng/l) and Colletotrichum gloeosporioides TA67 (120 ng/l). This is the first report of taxol producer from Guignardia. Moreover, the lower similarities of ts and bapt between microbial and plant origin suggested that fungal taxol biosynthetic cluster might be repeatedly invented during evolution, nor horizontal gene transfer from Taxus species.ConclusionsTaxol-producing endophytic fungi could be a fascinating reservoir to generate taxol-related drug lead and to elucidate the remained 5 unknown genes or the potential regulation mechanism in the taxol biosynthesis pathway.

THE LITERAL SENSE OF SCRIPTURE ACCORDING TO HENRI DE LUBAC: INSIGHTS FROM PATRISTIC EXEGESIS OF THE TRANSFIGURATION

AbstractThis essay explicates Henri de Lubac's account of Scripture's literal sense as illumined by three patristic interpretations of the Transfiguration. Origen's exegesis highlights de Lubac's deployment of the Incarnational analogy in which history contains, veils, and discloses divine mystery. Similar to Jerome, de Lubac distinguishes the realities of biblical history (as revelatory loci) from their textual articulation. Augustine illustrates the hermeneutical influence of the interpreter's presupposed account of history, to which de Lubac, following Blondel, attributes great importance in approaching the biblical letter. De Lubac's account of the literal sense is thoroughly theological and an underexplored resource for thinking about this topic.

Snake venom: From fieldwork to the clinic

Snake venoms are recognized here as a grossly under-explored resource in pharmacological prospecting. Discoveries in snake systematics demonstrate that former taxonomic bias in research has led to the neglect of thousands of species of potential medical use. Recent discoveries reveal an unexpectedly vast degree of variation in venom composition among snakes, from different species down to litter mates. The molecular mechanisms underlying this diversity are only beginning to be understood. However, the enormous potential that this resource represents for pharmacological prospecting is clear. New high-throughput screening systems offer greatly increased speed and efficiency in identifying and extracting therapeutically useful molecules. At the same time a global biodiversity crisis is threatening the very snake populations on which hopes for new venom-derived medications depend. Biomedical researchers, pharmacologists, clinicians, herpetologists, and conservation biologists must combine their efforts if the full potential of snake venom-derived medications is to be realized.

Antibacterial metabolites from Australian macrofungi from the genus Cortinarius

Mushrooms have demonstrated significant pharmacological activity including antimicrobial, cytotoxic, anti-inflammatory, hypoglycaemic, immunomodulatory and hallucinogenic properties [1]. The fungi of Australia are diverse, largely endemic and, in contrast to their floral counterparts, have not undergone intensive taxonomic, chemical or pharmacological evaluation [2]. Furthermore, some Australian indigenous macrofungi are currently considered to be conspecific with Northern Hemisphere species, might be described as separate species once taxonomic revisions are carried out [3]. Consequently Australian mushrooms represent an under-explored resource of potentially novel metabolites. In this study, ethyl acetate and aqueous fractions from 117 collections of Australian macrofungi belonging to the genusCortinarius were screened for antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Overall, the lipophilic fractions were more active than the aqueous fractions. The ethyl acetate fractions of most or all collections of 13 described Cortinarius species and 47 collections of un-described Cortinarius species exhibited IC50 values of ≤0.09mg/mL against S. aureus. In contrast, most or all collections of only 4 described Cortinarius species and only 11 un-described Cortinarius collections exhibited similar effects against P. aeruginosa (IC50 ≤0.09mg/mL). The fungal octaketides austrocortilutein, austrocortirubin, torosachrysone, isolated from C. basirubescens, together with physcion and emodin were found to strongly inhibit the growth of S. aureus (IC50 0.7–12µg/mL) whereas only physcion and emodin exhibited potency against P. aeruginosa (IC50 1.5 and 2.0µg/mL, respectively) [4]. Australian mushrooms from the genus Cortinarius are promising sources of natural products for further drug development research, due to the high biological diversity and unique evolutionary lineages found only in the region. This is coupled with the large proportion of bioactive species and high diversity of chemical constituents.

New Innovations for an Old Infection: Antimalarial Lead Discovery from Marine Natural Products During the Period 2003–2008

Malaria remains one of the most serious global infectious diseases, with an estimated 2 billion people at risk and 1 million deaths annually. Drug resistance is hampering the effectiveness of many current antimalarial therapies and resistant strains of the parasite are now known for almost all classes of antimalarial compounds. Owing to a lack of concerted drug-discovery efforts over the last 30 years, the development pipeline is limited and the identification of new antimalarial lead compounds is a pressing concern. The development of new antimalarials that exhibit novel modes of action is of critical importance if the devastating effects of malaria are to be controlled. Natural products have traditionally played an important role in antimalarial drug development and the marine environment represents an underexplored resource in this regard. This review covers developments in the field of antimalarial drug discovery from marine sources between January 2003 and December 2008 and offers a comprehensive overview of all marine-derived compounds from this period. Marine natural products represent an emerging opportunity in the development of new antimalarial lead compounds. This review provides examples of several recent lead discovery projects that show promise in this regard and presents a perspective on areas of possible future study.

Local erotic songs and chants among rural Nigerian adolescent males

This paper investigates local erotic songs and chants circulating among adolescent males in Nigeria. The purpose is to assess the critical themes which these erotic verses evoke and their potentials in the discursive construction of adolescent sexual identities and definition of the (erotic) spaces and meanings on the basis of which young Nigerian males constitute their sexual conducts. Data indicate high level of awareness and knowledge of local erotic songs and chants among adolescent males. The songs and chants were reportedly used to learn about gender and sex roles, the body, and sexuality, and for recreation. Themes in local boys’ erotic songs and chants are primarily male privileging and penis advantaging, and celebrate male sexual activity, desire, violence, ruthlessness, and risk-taking as well as male control and subordination of women and their body. The songs and chants depict feminity and female sexuality as inferior to masculinity and male sexuality and tend to objectify women’s body as a facility for male sexual pleasure. The paper argues that while erotic verses circulating among adolescent Nigerian males help relieve them of the difficulties caused by the cultural relegation of sex and sexuality to the realm of the unspoken, they contain very disturbing and potentially dangerous images that provide little space for male responsibility and respect for women. Local erotic verses circulating among adolescents present an under-explored resource in sexuality education and a critical entry point for current efforts to understand and help young people extricate themselves from the sea of half-truths, myths, and prejudices about sex and sexuality.

A functional assay for G-protein-coupled receptors using stably transformed insect tissue culture cell lines

Insect cells are an underexplored resource for functional G-protein-coupled receptor (GPCR) assays, despite a strong record in biochemical (binding) assays. Here we describe the use of vectors capable of creating stably transformed insect cell lines to generate a cell-based functional GPCR assay. This assay employs the luminescent photoprotein aequorin and the promiscuous G-protein subunit Gα16 and is broadly applicable to human GPCRs. We demonstrate that the assay can quantitate ligand concentration–activity relationships for seven different human GPCRs, can differentiate between partial and full agonists, and can determine rank order potencies for both agonists and antagonists that match those seen with other assay systems. Human Gα16 improves signal strength but is not required for activity with some receptors. The coexpression of human and bovine βγ subunits and/or phospholipase Cβ makes no difference to agonist efficacy or potency. Two different receptors expressed in the same cell line respond to their specific agonists, and two different cell lines (Sf9 and High 5) are able to functionally detect the same expressed GPCR. Sf9 cells have the capability to produce fully functional human receptors, allied to a low background of endogenous receptors, and so are a valuable system for investigating orphan GPCRs and receptor dimerization.