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Noordermeer D.,Research Frontiers
Wiley interdisciplinary reviews. Developmental biology | Year: 2013

Developmentally regulated genes are often controlled by distant enhancers, silencers and insulators, to implement their correct transcriptional programs. In recent years, the development of 3C and derived techniques (4C, 5C, HiC, ChIA-PET, etc.) has confirmed that chromatin looping is an important mechanism for the transfer of regulatory information in mammalian cells. At many developmentally regulated gene loci, transcriptional activation is indeed accompanied by the formation of chromatin loops between genes and distant enhancers. Similarly, dynamic looping between insulator elements and changes in local 3D organization may be observed upon variation in transcriptional activity. Chromatin looping also occurs at silent gene loci, where its function remains less understood. In lineage-committed cells, partial 3D configurations are detected at loci that are activated at later stages. However, these partial configurations usually lack promoter-enhancer loops that accompany transcriptional activation, suggesting they have structural functions. Definitive evidence for a repressive role of chromatin looping is still lacking. Chromatin loops have been reported at repressed loci but, alternatively, they may act as a distraction for active loops. Together, these mechanisms allow fine-tuning of regulatory programs, thus providing further diversity in the transcriptional control of developmentally regulated gene loci. Copyright © 2013 Wiley Periodicals, Inc. Source


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SIS-2010-1.3.3.1 | Award Amount: 1.81M | Year: 2011

Funding agencies and decision-makers seek to support research with a high social impact. To identify this research, they need tools. Traditional evaluation of research has used peer review (before publication) and bibliometric indicators (afterwards). However, these tools evaluate research in terms of the values and needs of the research community, rather than those of society. Against this background, the strategic goal of the SISOB is develop novel tools making it possible to measure and predict the social impact of research. More specifically, SISOB will develop tools to measure and predict the social appropriation of research knowledge, modelled as the product of complex interactions within and between multiple, intersecting communities of scientists, journalists, industrial, decision makers and consumers. In this setting, the project will use computer-supported Social Network Analysis (SNA) to analyze how the topology of these networks can measure and predict the social impact of research. The specific goals of the project are thus to: (i) create a framework modelling the actors, relationships, communities and social networks involved in the social appropriation of research knowledge; (ii) design and implement tools and indicators making it possible to automatically collect, analyze and visually represent data describing these actors and their interactions; (iii) create data-driven models of specific actors, communities and networks relevant to three case studies; (iv) use the tools and indicators developed by the project to collect and analyze data relevant to the same studies; (v) use the results from these studies to validate the methods and tools developed; (vi) Implement, and release in open source, a platform for the capture and analysis of social network data relevant to measuring the social impact of research. The case studies are: mobility of researchers, knowledge sharing and peer reviewing processes.


A display device comprising a Suspended Particle Device film or other material for controlling the amount of illumination transmitted to an object from one or more light sources to protect the object from degradation by light is described. The display is capable of being dark when the object is not being viewed and being highly transmissive when the object is to be viewed. If desired, the display device may be controlled so as to provide a substantially constant amount of illumination when the object is viewed or intended to be viewed. A method of protecting an object using the display device is also provided.


Nevalainen H.,Research Frontiers | Peterson R.,Research Frontiers
Frontiers in Microbiology | Year: 2014

Hosts used for the production of recombinant proteins are typically high-protein secreting mutant strains that have been selected for a specific purpose, such as efficient production of cellulose-degrading enzymes. Somewhat surprisingly, sequencing of the genomes of a series of mutant strains of the cellulolytic Trichoderma reesei, widely used as an expression host for recombinant gene products, has shed very little light on the nature of changes that boost high-level protein secretion. While it is generally agreed and shown that protein secretion in filamentous fungi occurs mainly through the hyphal tip, there is growing evidence that secretion of proteins also takes place in sub-apical regions. Attempts to increase correct folding and thereby the yields of heterologous proteins in fungal hosts by co-expression of cellular chaperones and foldases have resulted in variable success; underlying reasons have been explored mainly at the transcriptional level. The observed physiological changes in fungal strains experiencing increasing stress through protein overexpression under strong gene promoters also reflect the challenge the host organisms are experiencing. It is evident, that as with other eukaryotes, fungal endoplasmic reticulum is a highly dynamic structure. Considering the above, there is an emerging body of work exploring the use of weaker expression promoters to avoid undue stress. Filamentous fungi have been hailed as candidates for the production of pharmaceutically relevant proteins for therapeutic use. One of the biggest challenges in terms of fungally produced heterologous gene products is their mode of glycosylation; fungi lack the functionally important terminal sialylation of the glycans that occurs in mammalian cells. Finally, exploration of the metabolic pathways and fluxes together with the development of sophisticated fermentation protocols may result in new strategies to produce recombinant proteins in filamentous fungi. © 2014 Nevalainen and Peterson. Source


Thaysen-Andersen M.,Research Frontiers | Packer N.H.,Research Frontiers
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2014

Site-specific structural characterization of glycoproteins is important for understanding the exact functional relevance of protein glycosylation. Resulting partly from the multiple layers of structural complexity of the attached glycans, the system-wide site-specific characterization of protein glycosylation, defined as glycoproteomics, is still far from trivial leaving the N- and O-linked glycoproteomes significantly under-defined. However, recent years have seen significant advances in glycoproteomics driven, in part, by the developments of dedicated workflows and efficient sample preparation, including glycopeptide enrichment and prefractionation. In addition, glycoproteomics has benefitted from the continuous performance enhancement and more intelligent use of liquid chromatography and tandem mass spectrometry (LC-MS/MS) instrumentation and a wider selection of specialized software tackling the unique challenges of glycoproteomics data. Together these advances promise more streamlined N- and O-linked glycoproteome analysis. Tangible examples include system-wide glycoproteomics studies detecting thousands of intact glycopeptides from hundreds of glycoproteins from diverse biological samples. With a strict focus on the system-wide site-specific analysis of protein N- and O-linked glycosylation, we review the recent advances in LC-MS/MS based glycoproteomics. The review opens with a more general discussion of experimental designs in glycoproteomics and sample preparation prior to LC-MS/MS based data acquisition. Although many challenges still remain, it becomes clear that glycoproteomics, one of the last frontiers in proteomics, is gradually maturing enabling a wider spectrum of researchers to access this new emerging research discipline. The next milestone in analytical glycobiology is being reached allowing the glycoscientist to address the functional importance of protein glycosylation in a system-wide yet protein-specific manner. © 2013 Elsevier B.V. Source

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