Structure-activity studies of a macrocyclic peptide inhibitor of histone lysine demethylase 4A

The combination of genetic code reprogramming and mRNA display is a powerful approach for the identification of macrocyclic peptides with high affinities to a target of interest. We have previously used such an approach to identify a potent inhibitor (CP2) of the human KDM4A and KDM4C lysine demethylases; important regulators of gene expression. In the present study, we have used genetic code reprogramming to synthesise very high diversity focused libraries (>10¹² compounds) based on CP2 and, through affinity screening, used these to delineate the structure activity relationship of CP2 binding to KDM4A. In the course of these experiments we identified a CP2 analogue (CP2f-7) with ～4-fold greater activity than CP2 in in vitro inhibition assays. This work will facilitate the development of more potent, selective inhibitors of lysine demethylases.     

Genetic characterization of antibiotic-resistant Staphylococcus aureus from milk in the North-West Province,South Africa

Food borne diseases are a major public health concern worldwide. Staphylococcus aureus is one of the potential food borne pathogens which causes nosocomial and community acquired infections. In the present study, 74 representative strains of S. aureus isolated and characterized in previous study from different milk samples were subjected to random amplified polymorphic DNA (RAPD) polymerase chain reaction (PCR) and enterobacterial repetitive intergenic consensus (ERIC)-PCR to generate fingerprints to determine the genetic relationships of the isolated strains. A total of 20 RAPD patterns were generated and the number of amplified fragments obtained ranged from 0 to 8 with molecular weight ranging from 250 to 2000 bp. A dendrogram based on fingerprinting pattern grouped isolates into twelve major clusters (I–XII). In the case of ERIC-PCR 9 banding patterns were obtained with amplicons ranging from 1 to 8 and band sizes ranging from 250 to 2000 bp. A total of four major clusters (I–IV) were observed in the dendrogram based on ERIC fingerprints. The discrete banding patterns obtained both from ERIC-PCR and RAPD-PCR showed remarkably the genetic diversity of S. aureus. The findings of this study indicate that raw, bulk and pasteurized milk in the North-West Province was contaminated with toxigenic and multi-drug resistant S. aureus strains. This emphasizes the need to implement appropriate control measures to reduce contamination as well as the spread of virulent S. aureus strains to reduce the burden of disease in humans.     

“Eating Hay”: The Ecology,Economy and Culture of Viliui Sakha Smallholders of Northeastern Siberia

Contemporary rural Viliui Sakha of northeastern Siberia, Russia, are a Turkicspeaking people practicing horse and cattle breeding in the subarctic. This article details their story of survival in the north as one not only of adapting a southern subsistence to an extreme climate but also to the effects of Russian colonization, Soviet collectivization, and post-Soviet decentralization. In the post-Soviet period a majority of rural Viliu Sakha adapted to the loss of a centralized agro-industrial state farm system by developing a smallholder food production system relying on cattle husbandry supplemented with other subsistence sources including fish, game, forage, other domesticates, and garden products. In the twenty-first century, this “cows-and-kin” system represents a resilient smallholder adaptation based on reviving pre-Soviet production knowledge, recalling ecological knowledge, and relying on kin. The article concludes with a discussion of the future of cows-and-kin by exploring issues of alienated youth, accessing land and the overwhelming concern of inhabitants about the local effects of global climate change.

Future societal issues in industrial biotechnology

Three international stakeholder meetings were organized by The Netherlands-based "Kluyver Center for Genomics of Industrial Fermentation" with the objective to identify the future societal issues in the field of industrial biotechnology and to develop a coordinated strategy for public dialogue. The meetings resulted in five unanimous recommendations: (i) that science, industry and the European Commission in conjunction with other stakeholders create a comprehensive roadmap towards a bio-based economy; (ii) that the European Commission initiate a series of round-table meetings to further articulate the views, interests and responsibilities of the relevant stakeholders and to define policy; (iii) that the development of new innovative communication activities is stimulated to increase public engagement and to discuss the ways that we do or do not want technologies to shape our common future; (iv) that further social studies are undertaken on public attitudes and behaviors to the bio-based economy and that novel methods are developed to assess public views of future technological developments; and (v) that the concept of sustainability is further operationalized and taken as a core value driving research and development and policy making.     

Postproduction Processing of Electrospun Fibres for Tissue Engineering

Electrospinning is a commonly used and versatile method to produce scaffolds (often biodegradable) for 3D tissue engineering.^{1, 2, 3} Many tissues in vivo undergo biaxial distension to varying extents such as skin, bladder, pelvic floor and even the hard palate as children grow. In producing scaffolds for these purposes there is a need to develop scaffolds of appropriate biomechanical properties (whether achieved without or with cells) and which are sterile for clinical use. The focus of this paper is not how to establish basic electrospinning parameters (as there is extensive literature on electrospinning) but on how to modify spun scaffolds post production to make them fit for tissue engineering purposes - here thickness, mechanical properties and sterilisation (required for clinical use) are considered and we also describe how cells can be cultured on scaffolds and subjected to biaxial strain to condition them for specific applications.Electrospinning tends to produce thin sheets; as the electrospinning collector becomes coated with insulating fibres it becomes a poor conductor such that fibres no longer deposit on it. Hence we describe approaches to produce thicker structures by heat or vapour annealing increasing the strength of scaffolds but not necessarily the elasticity. Sequential spinning of scaffolds of different polymers to achieve complex scaffolds is also described. Sterilisation methodologies can adversely affect strength and elasticity of scaffolds. We compare three methods for their effects on the biomechanical properties on electrospun scaffolds of poly lactic-co-glycolic acid (PLGA).Imaging of cells on scaffolds and assessment of production of extracellular matrix (ECM) proteins by cells on scaffolds is described. Culturing cells on scaffolds in vitro can improve scaffold strength and elasticity but the tissue engineering literature shows that cells often fail to produce appropriate ECM when cultured under static conditions. There are few commercial systems available that allow one to culture cells on scaffolds under dynamic conditioning regimes - one example is the Bose Electroforce 3100 which can be used to exert a conditioning programme on cells in scaffolds held using mechanical grips within a media filled chamber.⁴ An approach to a budget cell culture bioreactor for controlled distortion in 2 dimensions is described. We show that cells can be induced to produce elastin under these conditions. Finally assessment of the biomechanical properties of processed scaffolds cultured with or without cells is described.     

Annapurna expedition game: applying molecular biology tools to learn genetics

ABSTRACT

In this paper, we present an activity called ‘Annapurna Expedition’ through which students should apply basic concepts of genetics to solve a worldwide pandemic disease. Players take the role of scientists, involved in a research to find out which pathogen causes this pandemic and which could be the best way to solve it. Students have the opportunity to use BLAST software as a scientific bioinformatic tool to discover the main game’ enigmas. The activity uses game-based science learning methodology. This methodology incorporates multiple tools and resources, rely on learning by doing, guiding learners through a path of events and into a way of thinking. It provides students to take information from many sources and make decisions, to deduce a game’s obstacles, to understand complex systems and to collaborate with other classmates.

The activity has been developed for a range of audiences, including high school students and pre-service teachers. A case study has been carried out with a group of 80 primary pre-service teachers from the Universitat Rovira i Virgili (URV) in Tarragona (Spain) in order to verify whether this activity was well designed, engage students and it is satisfactorily implemented.     

2011年《中国科学·生命科学》回顾

Research in the field of life science is movingforward at a high pace.Science China Life Sciences istrying to reflect this trend as much as possible bypublishing research articles of notable originaldiscoveries.     

Land‐use and fire history effects on post‐fire vegetation dynamics in eastern Spain

Question: Is post‐fire, medium‐term vegetation dynamics determined by land‐use or fire history prior to fire? Location: South‐facing slope in the Gallinera valley, Alicante province, eastern Spain. Methods: After mapping the land‐use and fire history of the study site using photo‐interpretation, we sampled vegetation structure on a set of plots representing the most frequent land‐use and fire history combinations on an area burned six years before sampling. We studied the effects of land‐use history, comparing the one‐fire land‐use trajectories. We analysed the effects of fire history; comparing one‐ and two‐fire plots for both previously cropped and uncropped areas. Results: Most variables were not significantly different between the earliest abandoned plots (abandoned at least 38 years before the fire) and the uncropped plots. On the most recently abandoned plots (abandoned between one and four years before the fire), the therophyte richness and the ratio of seeder: resprouter richness were significantly greatest. Different fire recurrences did not determine different post‐fire vegetation on either the uncropped or the early abandoned plots (all dominated by fire‐recruited seeder shrubs). The most recently abandoned plots had a lower resilience to fire. Conclusions: Land‐use history and recent pre‐fire land use, in particular, determined the post‐fire vegetation in the medium term. The vegetation composition converged during secondary succession among land‐use histories. Increasing fire recurrence had a small effect on mature plant communities, due to the combination of life‐history traits determining the response to fire of the dominant species.