Mimicking the in vivo Environment – The Effect of Crowding on RNA and Biomacromolecular Folding and Activity

In vitro studies on macromolecules, like proteins and nucleic acids, are mostly carried out in highly diluted systems where the molecules are studied under artificial conditions. These experimental conditions are optimized for both the system under investigation and the technique used. However, these conditions often do not reflect the in vivo situation and are therefore inappropriate for a reliable prediction of the native behavior of the molecules and their interactions under in vivo conditions. The intracellular environment is packed with cosolutes (macromolecules, metabolites, etc.) that create 'macromolecular crowding'. The addition of natural or synthetic macromolecules to the sample solution enables crowding to be mimicked. In this surrounding most of the studied biomolecules show a more compact structure, an increased activity, and a decrease of salt requirement for structure formation and function. Herein, we refer to a collection of examples for proteins and nucleic acids and their interactions in crowding environments and present in detail the effect of cosolutes on RNA folding and activity using a group II intron ribozyme as an example

Social inertia in collaboration networks

This work is a study of the properties of collaboration networks employing the formalism of weighted graphs to represent their one-mode projection. The weight of the edges is directly the number of times that a partnership has been repeated. This representation allows us to define the concept of "social inertia" that measures the tendency of authors to keep on collaborating with previous partners. We use a collection of empirical datasets to analyze several aspects of the social inertia: 1) its probability distribution, 2) its correlation with other properties, and 3) the correlations of the inertia between neighbors in the network. We also contrast these empirical results with the predictions of a recently proposed theoretical model for the growth of collaboration networks.Comment: 7 pages, 5 figure

Purification and Characterization of a Gamma-Like DNA-Polymerase From \u3ci\u3eChenopodium album\u3c/i\u3e L.

A DNA polymerase activity from mitochondria of the dicotyledonous angiosperm Chenopodium album L. was purified almost 9000 fold by successive column chromatography steps on DEAE cellulose, heparin agarose and ssDNA cellulose. The enzyme was characterized as a gamma-class polymerase, based on its resistance to inhibitors of the nuclear DNA polymerase alpha and its preference for poly(rA).(dT)12-18 over activated DNA in vitro. The molecular weight was estimated to be 80,000 - 90,000. A 3\u27 to 5\u27 exonuclease activity was found to be tightly associated with the DNA polymerase activity through all purification steps. This is the first report of an association between a DNA polymerase and an exonuclease activity in plant mitochondria

Complex Systems Science: Dreams of Universality, Reality of Interdisciplinarity

Using a large database (~ 215 000 records) of relevant articles, we empirically study the "complex systems" field and its claims to find universal principles applying to systems in general. The study of references shared by the papers allows us to obtain a global point of view on the structure of this highly interdisciplinary field. We show that its overall coherence does not arise from a universal theory but instead from computational techniques and fruitful adaptations of the idea of self-organization to specific systems. We also find that communication between different disciplines goes through specific "trading zones", ie sub-communities that create an interface around specific tools (a DNA microchip) or concepts (a network).Comment: Journal of the American Society for Information Science and Technology (2012) 10.1002/asi.2264

Stick, Flick, Click: DNA-guided Fluorescent Labeling of Long RNA for Single-molecule FRET

Exploring the spatiotemporal dynamics of biomolecules on a single-molecule level requires innovative ways to make them spectroscopically visible. Fluorescence resonance energy transfer (FRET) uses a pair of organic dyes as reporters to measure distances along a predefined biomolecular reaction coordinate. For this nanoscopic ruler to work, the fluorescent labels need to be coupled onto the molecule of interest in a bioorthogonal and site-selective manner. Tagging large non-coding RNAs with single-nucleotide precision is an open challenge. Here we summarize current strategies in labeling riboswitches and ribozymes for fluorescence spectroscopy and FRET in particular. A special focus lies on our recently developed, DNA-guided approach that inserts two fluorophores through a stepwise process of templated functionality transfer and click chemistry

Quantifying structure in networks

We investigate exponential families of random graph distributions as a framework for systematic quantification of structure in networks. In this paper we restrict ourselves to undirected unlabeled graphs. For these graphs, the counts of subgraphs with no more than k links are a sufficient statistics for the exponential families of graphs with interactions between at most k links. In this framework we investigate the dependencies between several observables commonly used to quantify structure in networks, such as the degree distribution, cluster and assortativity coefficients.Comment: 17 pages, 3 figure

Interfaces for science: Conceptualizing an interactive graphical interface

6,849.32 new research journal articles are published every day. The exponential growth of Scientific Knowledge Objects (SKOs) on the Web, makes searches time-consuming. Access to the right and relevant SKOs is vital for research, which calls for several topics, including the visualization of science dynamics. We present an interface model aimed to represent of the relations that emerge in the science social space dynamics, namely through the visualization and navigation of the relational structures between researchers, SKOs, knowledge domains, subdomains, and topics. This interface considers the relationship between the researcher who reads and shares the relevant articles and the researcher who wants to find the most relevant SKOs within a subject matter. This article presents the first iteration of the conceptualization process of the interface layout, its interactivity and visualization structures. It is essential to consider the hierarchical and relational structures/algorithms to represent the science social space dynamics. These structures are not being used as analysis tools, because it is not objective to show the linkage properties of these relationships. Instead, they are used as a means of representing, navigating and exploring these relationships. To sum up, this article provides a framework and fundamental guidelines for an interface layout that explores the social science space dynamics between the researcher who seeks relevant SKOs and the researchers who read and share them.This work has been supported by COMPETE: POCI-01-0145-FEDER- 007043 and FCT - Fundação para a Ciência e Tecnologia within the Project Scope: (UID/CEC/00319/2013) and the Project IViSSEM: ref: POCI-010145-FEDER-28284

Enhanced retinal image registration accuracy using expectation maximisation and variable bin-sized mutual information

While retinal images (RI) assist in the diagnosis of various eye conditions and diseases such as glaucoma and diabetic retinopathy, their innate features including low contrast homogeneous and nonuniformly illuminated regions, present a particular challenge for retinal image registration (RIR). Recently, the hybrid similarity measure, Expectation Maximization for Principal Component Analysis with Mutual Information (EMPCA-MI) has been proposed for RIR. This paper investigates incorporating various fixed and adaptive bin size selection strategies to estimate the probability distribution in the mutual information (MI) stage of EMPCA-MI, and analyses their corresponding effect upon RIR performance. Experimental results using a clinical mono-modal RI dataset confirms that adaptive bin size selection consistently provides both lower RIR errors and superior robustness compared to the empirically determined fixed bin sizes

Multimodal retinal image registration using a fast principal component analysis hybrid-based similarity measure

Multimodal retinal images (RI) are extensively used for analysing various eye diseases and conditions such as myopia and diabetic retinopathy. The incorporation of either two or more RI modalities provides complementary structure information in the presence of non-uniform illumination and low-contrast homogeneous regions. It also presents significant challenges for retinal image registration (RIR). This paper investigates how the Expectation Maximization for Principal Component Analysis with Mutual Information (EMPCA-MI) algorithm can effectively achieve multimodal RIR. This iterative hybrid-based similarity measure combines spatial features with mutual information to provide enhanced registration without recourse to either segmentation or feature extraction. Experimental results for clinical multimodal RI datasets comprising colour fundus and scanning laser ophthalmoscope images confirm EMPCA-MI is able to consistently afford superior numerical and qualitative registration performance compared with existing RIR techniques, such as the bifurcation structures method

Promoters for Pd-catalyzed methoxycarbonylation of vinyl acetate

A study on the influence of acidic and non-acidic promoters for Pd(PPh 3)-catalyzed methoxycarbonylation of vinyl acetate was conducted in order to find an efficient protocol for the synthesis of methyl O-acetyl lactate. Besides known promoters also some new catalytic systems were tested. Aluminium triflate is the most active additive