Modeling the influence of DNA lesion on the regulation of gene expression

Nucleic acids are organic macromolecules that result from the polymerization of nucleotides. These molecules are generally considered as the support of the genetic information. Two families of nucleic acids are currently known: DNA and RNA. From a structural point of view, the most popular form is the double helix of DNA. However, other forms exist and among them are the G-quadruplex. This is a folding of the DNA, or RNA, in an area rich in guanines. These form quadruplex of guanines, which are stacked on top of each other and are stabilized by a central cation. G-quadruplex structures are increasingly studied. This is not surprising since their biological role involves the regulation of genetic mechanisms. They are notably involved in the regulation of the cell cycle, but they also play a role in cancer, certain neurological or viral diseases. The aim of this PhD thesis is to study G-quadruplex using theoretical chemistry tools. The three years of work raise very important points for the research on G-quadruplex. First, the modeling of a theoretical G-quadruplex structure can be achieved by sequence homology and validated by calculations of a theoretical circular dichroism spectrum. Consequently, it is possible to use these tools to propose and use a G-quadruplex structure if it is not yet experimentally solved. Then, the work done shows that G-quadruplex form a very stable folding since they are globally conserved even when 8-oxo-guanine or strand breaks lesions are introduced at the quartets. Then, the paper focuses on the interaction between G-quadruplex and proteins. It highlights the important role of G-quadruplex RNA in the infection of the viral pathogen SARS-CoV-2. This RNA promotes the dimerization of the SUD protein of the virus, which in turn is responsible for the disruption of the immune system. Finally, this thesis provides a structural explanation for the specific interaction between the DARPin 2E4 protein and the G-quadruplex of the c-Myc promoter

Phytochrome genes in higher plants: Structure,expression, and evolution

© 2006 Springer. All Rights Reserved. Phytochromes play critical roles in monitoring light quantity, quality, and periodicity in plants and they relay this photosensory information to a large number of signaling pathways that regulate plant growth and development. Given these complex functions, it is not surprising that the phytochrome apoproteins are encoded by small multigene families and that different forms of phytochrome regulate different aspects of photomorphogenesis. Over the course of the last decade, progress has been made in defining the number, molecular properties, and biological activities of the photoreceptors that constitute a plant R/FR sensing system. This chapter summarizes our current understanding of the structure of the genes that encode the phytochrome apoproteins (the PHY genes), the expression patterns of those genes, the nature of the phytochrome apoprotein family, and PHY gene evolution in seed plants. Phytochrome was discovered and its basic photochemical properties were first described through physiological studies of light-sensitive seed germination and photoperiodic effects on flowering (Borthwick, et al., 1948, Borthwick, et al., 1952). The pigment itself was initially isolated from extracts of dark-grown (etiolated) plant tissue in 1959 (Butler, et al., 1959), but it was not until much later that phytochrome was purified to homogeneity in an undegraded form (Vierstra and Quail, 1983). DNA sequences of gene and cDNA clones for oat etiolated-tissue spectroscopically in planta and purified in its native form, this dark-tissue phytochrome (now called phyA) remains the most completely biochemically and spectroscopically characterized form of the receptor. At various times throughout the first 40 years of the study of the abundant etiolated-tissue phytochrome, evidence for the presence and activity of additional forms of phytochrome, often referred to as green-tissue or light-stable phytochromes, was obtained. Initially, in physiological experiments, it was sometimes not possible to correlate specific in vivo phytochrome activities with the phytochrome provided the first complete descriptions of the apoprotein (Hershey et al., 1985). Because it accumulates to levels that permit it to be assayed known spectroscopic properties of the molecule. Later, direct evidence for multiple species of phytochrome in plants and in plant extracts was obtained using both spectroscopic and immunochemical methods (reviewed in Pratt, 1995). The molecular identities of these additional phytochrome forms were ultimately deduced from cDNA clones that were isolated by nucleic acid similarity to etiolated-tissue phytochrome sequences (Sharrock and Quail, 1989). More recently, analysis of a large number of complete and partial PHY gene or cDNA sequences from a broad sampling of plant phylogenetic groups and sequencing of several plant genomes have resulted in a much clearer and more general picture of what constitutes a higher plant R/FR photoreceptor family. It is likely that the major types of long-wavelength photosensing pigments have now been identified and the challenge that lies ahead is to understand how the signalling mechanisms, expression patterns, and interactions of these molecules contribute to plant responses to the R/FR environment. Extending the investigation of phytochrome gene families and their functions to additional angiosperm and gymnosperm genera will be an integral component of this effort and of our ability to utilize this growing understanding of phytochrome function to modify the agricultural properties of plants and to better understand the history of land plants

25th Annual Computational Neuroscience Meeting: CNS-2016

Abstracts of the 25th Annual Computational Neuroscience Meeting: CNS-2016 Seogwipo City, Jeju-do, South Korea. 2–7 July 201

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Laboratory-directed research and development: FY 1996 progress report

This report summarizes the FY 1996 goals and accomplishments of Laboratory-Directed Research and Development (LDRD) projects. It gives an overview of the LDRD program, summarizes work done on individual research projects, and provides an index to the projects` principal investigators. Projects are grouped by their LDRD component: Individual Projects, Competency Development, and Program Development. Within each component, they are further divided into nine technical disciplines: (1) materials science, (2) engineering and base technologies, (3) plasmas, fluids, and particle beams, (4) chemistry, (5) mathematics and computational sciences, (6) atomic and molecular physics, (7) geoscience, space science, and astrophysics, (8) nuclear and particle physics, and (9) biosciences

Ab initio computational applications to complex biomolecular systems

Title from PDF of title page, viewed on January 17, 2012Dissertation advisor: Wai-Yim ChingVitaIncludes bibliographic references (p. 119-129)Thesis (Ph.D.)--Dept. of Physics and Dept. of Mathematics and Statistics. University of Missouri--Kansas City, 2011A series of biomaterial related systems ― including water and DNA molecules ― have been studied using ab initio (first-principles) methods. By investigating the properties of water as the preliminary step, the hydrogen bond (HB) interactions, which play important roles in biomolecules, were better understood from the quantum mechanical viewpoint. The calculated K-edge x-ray absorption near edge structure (XANES) spectra of all 340 oxygen atoms in the model have been accumulated to reproduce the experimental one. The spectra were shown to be very sensitive to the HB configurations of O atoms, which could be used to elucidate the subtle structural variations in complex biomolecules. The simulation of singlemolecule DNA overstretching experiments under torsionally constrained condition has been carried out afterwards. The initial DNA models were stretched stepwisely and eventually gained an extension of 1.5-fold (150% × the original length). The variation of total energy, atomic configuration, and the electronic structure during this process were analyzed in details. At the extension of ~1.3-fold, the ring opening reactions occurred in the backbones. The backbone nicks appeared at elongations of ~1.40-fold. The whole process was accompanied by HB breaking and charge transfers. We have proposed an overstretched structure named O-DNA (Opened-DNA) to clarify the confusion in understanding the behavior of DNA under high force load. With more experiences gained, a comprehensive methodology revealing the underlying principles of bioprocesses from the quantum mechanical viewpoint eventually come up. For the purpose of better computational accuracy, the scheme of implementing the generalized gradient approximation (GGA) exchangecorrelation functionals into the Orthogonalized Linear Combination of Atomic Orbitals (OLCAO) program suite has been discussed, and the computational efficiency has been analyzed correspondingly. Moreover, the parallel strategy for performing evaluation on a regular mesh and relevant updates to the file system were also presented. All the fundamental works above paved the way for more sophisticated study on wet DNA model and interfaces between biomolecules and bioceramic materials in the future.Introduction -- Theoretical methods -- Case studies -- Future work -- Appendix A. VASP relaxation running time comparison -- Appendix B. Typical initial datasets of oxygen atomic orbitals -- Appendix D. Abbreviaiton

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Abstracts of manuscripts submitted in 1990 for publication

This volume contans the abstracts of manuscripts submitted for publication during calendar year 1990 by the staff and students of the Woods Hole Oceanographic Institution. We identify the journal of those manuscripts which are in press or have been published. The volume is intended to be informative, but not a bibliography. The abstracts are listed by title in the Table of Contents and are grouped into one of our five deparments, Marine Policy Center, Coastal Research Center, or the student category. An author index is presented in the back to facilitate locating specific papers