Thermodynamics of micellization of oppositely charged polymers

The complexation of oppositely charged colloidal objects is considered in this paper as a thermodynamic micellization process where each kind of object needs the others to micellize. This requirement gives rise to quantitatively different behaviors than the so-called mixed-micellization where each specie can micellize separately. A simple model of the grand potential for micelles is proposed to corroborate the predictions of this general approach.Comment: 7 pages, 2 figures. Accepted for publication in Europhysics Letter

The Effects of Hg2+ on Secondary Structures Formed by T-Rich DNA

Single stranded DNA that forms secondary structures has been a popular area of research in recent years. Much research has also been done in the field of heavy metals binding to DNA. Recently, it has been discovered that mercury in the presence of thymines will form T-HgII-T bonds. It is our hypothesis that single stranded DNA rich in thymine residues will form into a structure similar to i-motifs, formed from C-rich single strands, in the presence of mercury. Based on spectral changes during a mercuric titration, it is evident that mercury induces a structural change in T-rich DNA. We then tested the thermal stability of this structure via heat-induced denaturation. Job Plots were constructed to determine the number of Hg2+ binding sites on the DNA and size-exclusion chromatography experiments were conducted to determine if T-I-motif’s are formed inter- or intra-molecularly

Slimline floor an invention by Pronk and Lichtenberg

Slimline flooring makes it possible to realize distinctive designs for both high, utility and residential construction. The floor elements can span more than 16 meters, which offers great opportunities for large open, freely arranged spaces. Because the installation space is not filled with concrete, the own weight of the total floor package is relatively low, resulting in a weight reduction of 50% compared to traditional systems. In combination with the advantage that installations at Slimline are placed in the floor and therefore not in a suspended ceiling, it is possible to design main supporting structures and lighter foundations. Slimlinefloors also offers great freedom of form. Building with Slimlinefloors means prefab, dry, fast and stamp-free construction. In this way, the client can dispose of the building earlier, but the shorter construction process also translates into an integral saving on construction costs. Due to the integration of ceiling, installation space and top floor, Slimline saves between 40 and 50 cm height per floor compared to other systems. This leads to a saving of 15% on the gross floor height. With Slimline, seven floors can therefore be realized at the same building height compared to six with other construction techniques. Slimline also offers excellent properties in terms of acoustics and comfort.Slimline prefab floor elements consist of steel IPE or HEA profiles, with a project-specific sparing pattern for the transit of installations, which have collapsed into a concrete ceiling shell. By varying the number and type of profiles, spans of more than 16 meters and high variable floor loads are possible. The package thickness depends on the profiles used. Laying the floor elements is possible on all kinds of structures, from masonry to wood and from precast concrete to steel structures. Slimline floor elements are interconnected by means of steel coupling plates to be welded in the work that connect two devices that have collapsed in the concrete shell. In this way, the floor field forms a constructive disc. Wind load is introduced through the steel profiles or indirectly through the concrete shell. On the steel profiles of the Slimline floor elements, different types of top floors with different possibilities for the accessibility of the installation space can be placed, such as a dovetail cast floor or a computer tile floor. Thanks to the two-tier construction with the acoustically decoupled floating screed on 15 mm rubber granulate, sound insulation values of Iluc and Ico > 10dB are achieved in both laboratory tests and practical measurements. The Slimline floor system is a light prefab floor construction that can be combined with all main supporting structures, allows large spans, functions as a structural disc and delivers very good performance in terms of acoustics and fire. This paper summarizes the state of the art concerning the use of this type of structure and shows an example of modelling on ABAQUS

G-Quadruplex Nucleic Acids

2 pages.-- PMID: 20814544 [PubMed].-- PMCID: PMC2931383].Peer reviewe

Using Thioflavin T as a biosensor for the detection of nucleic acid secondary structures

The purpose of this ongoing research project was to learn more about the compound Thioflavin T by developing methods using a UV/Vis spectrophotometer to study how this molecule interacts with other biomolecules. Thioflavin T (ThT), is a fluorescent dye that can bind proteins and nucleic acids and can be used to probe protein aggregation and unique nucleic acid secondary structures. It can be used as a biosensor to detect specific abnormal proteins called amyloid fibrils in biological samples. In this project, we will investigate how thioflavin T interacts with different nucleic acid secondary structures with the goal of developing a ThT-based biosensor for nucleic acid structures

Molecular recognition of poly(A) by small ligands: an alternative method of analysis reveals nanomolar, cooperative and shape-selective binding

A few drug-like molecules have recently been found to bind poly(A) and induce a stable secondary structure (T(m)approximate to 60 degrees C), even though this RNA homopolymer is single-stranded in the absence of a ligand. Here, we report results from experiments specifically designed to explore the association of small molecules with poly(A). We demonstrate that coralyne, the first small molecule discovered to bind poly(dA), binds with unexpectedly high affinity (K(a) >10(7) M(-1)), and that the crescent shape of coralyne appears necessary for poly(A) binding. We also show that the binding of similar ligands to poly(A) can be highly cooperative. For one particular ligand, at least six ligand molecules are required to stabilize the poly(A) self-structure at room temperature. This highly cooperative binding produces very sharp transitions between unstructured and structured poly(A) as a function of ligand concentration. Given the fact that junctions between Watson-Crick and A.A duplexes are tolerated, we propose that poly(A) sequence elements and appropriate ligands could be used to reversibly drive transitions in DNA and RNA-based molecular structures by simply diluting/concentrating a sample about the poly(A)-ligand 'critical concentration'. The ligands described here may also find biological or medicinal applications, owing to the 3'-polyadenylation of mRNA in living cells

Glycosyl conjugation to G-quadruplex ligands as a strategy to improve their antitumor and antiparasitic efficacy.

Congresos y Conferencias: Comunicación de Congreso - Conferencia invitada

ADN G-cuádruple: caracterización inicial de los mecanismos de formación de oligómeros por mecánica molecular

The fabrication of nanostructures based on DNA as a material to build systems capable of complex functions is a frontier in continuous exploration. In this article it is reported the detailed characterization at atomic level of G-quadruplex units in order to obtain a better comprehension on how these units can self assemble into interlocked G-quadruplexes. The method used is modeling with molecular mechanics. Previously we reported the construction of interlocked G-quadruplexes by a thermal cyclic procedure (similar in implementation as the ones used in the cycling steps in a PCR protocol) parting from the sequence 5’-TGGG-3’. Based on our experimental data reported previously, models were built for the structures, and minimization and analyses via molecular mechanics was carried out in order to understand the factors that determine the more stable structures. It was found that the identity of the 5’and 3’ ends of the oligonucleotides is of the uppermost importance in the stability of the DNA assemblies in this study. Furthermore, the presence of cations in the regions of the molecule where the degree of steric hindrance allows more room for the cations could play a significant role in the dynamics of conformation of the supramolecule at those sites and possibly limiting or capping the self assembly of the structure. In summary, the results allow a better comprehension of the system at a molecular scale with the finality of developing more efficient procedures for the controlled fabrication of nanostructures based on G-quadruplex DNA.La fabricación de nanoestructuras usando ADN como material para construir sistemas capaces de realizar funciones complejas es una frontera en continua exploración. En este artículo se reporta la caracterización detallada a nivel atómico de unidades de G-cuádruple para obtener una mejor comprensión de cómo estas unidades se pueden auto ensamblar en oligómeros tipo G-cuádruple entrelazado (interlocked G-quadruplexes). Para esto se utilizaron métodos de modelación con mecánica molecular. Previamente reportamos la construcción de G-cuádruple entrelazados por un procedimiento térmico cíclico (similar en implementación al usado para el ciclado de un protocolo de PCR) partiendo de la secuencia 5’-TGGG-3’. Basados en nuestros datos experimentales reportados anteriormente se construyeron modelos para las estructuras y se minimizaron y analizaron vía mecánica molecular para entender los factores que determinan la estructura más estable. Se encontró que la identidad de los extremos 5’y 3’de los oligonucleótidos es de importancia fundamental en la estabilidad de los ensambles de ADN en el estudio. Además, los cationes en las regiones donde el grado de impedimento estérico permite más espacio para los mismos, pueden jugar un rol significativo en la dinámica de la conformación de la supramolecula en esos sitios, posiblemente limitando el auto ensamblaje de la estructura. En resumen, los resultados permiten mejorar la comprensión de este sistema a escala molecular permitiendo desarrollar procedimientos más eficientes para el control de la fabricación de nanoestructuras basadas en DNA G-cuádruple

Involvement of G-quadruplex regions in mammalian replication origin activity.

Genome-wide studies of DNA replication origins revealed that origins preferentially associate with an Origin G-rich Repeated Element (OGRE), potentially forming G-quadruplexes (G4). Here, we functionally address their requirements for DNA replication initiation in a series of independent approaches. Deletion of the OGRE/G4 sequence strongly decreased the corresponding origin activity. Conversely, the insertion of an OGRE/G4 element created a new replication origin. This element also promoted replication of episomal EBV vectors lacking the viral origin, but not if the OGRE/G4 sequence was deleted. A potent G4 ligand, PhenDC3, stabilized G4s but did not alter the global origin activity. However, a set of new, G4-associated origins was created, whereas suppressed origins were largely G4-free. In vitro Xenopus laevis replication systems showed that OGRE/G4 sequences are involved in the activation of DNA replication, but not in the pre-replication complex formation. Altogether, these results converge to the functional importance of OGRE/G4 elements in DNA replication initiation

Distal chromosome 17q loss in Barrett's esophageal and gastric cardia adenocarcinomas: Implications for tumorigenesis

The molecular genetic mechanisms underlying esophageal cancer are poorly understood. However, a novel gene that may be involved in esophageal carcinogenesis was recently localized by others to distal 17q by linkage analysis of kindreds with palmoplantar keratoderma and squamous cell carcinoma of the esophagus. To help determine whether a distal 17q gene may also be involved in the pathogenesis of primary Barrett's esophageal and gastric cardia adenocarcinomas, we performed loss of heterozygosity (LOH) analysis of 21 Barrett's and 18 gastric cardia adenocarcinomas at loci spanning 17q: cen— BRCA1—SSTR2—D17S2058—D17S929—D17S722—D17S937—D17S802— tel. Over 50% of the Barrett's and cardia adenocarcinomas demonstrated loss of an allele at one or more informative distal 17q markers. One common overlapping region of loss involved loci mapped to distal 17q24–proximal 17q25, which tentatively defines a potential chromosomal region distal to BRCA1 involved in the pathogenesis or progression of both types of adenocarcinomas. LOH analysis of DNA from matched microdissected sections of Barrett's metaplasia suggested that loss of D17S2058 in this region may be an early event in the malignant transformation of Barrett's metaplasia. No statistically significant correlations between 17q LOH and tumor stage or patient survival were noted. In summary, LOH mapping of 17q in Barrett's and cardia adenocarcinomas suggests the existence of at least one putative distal 17q tumor suppressor gene involved in the pathogenesis of these tumors. Mol. Carcinog. 22:222–228, 1998. © 1998 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35057/1/3_ftp.pd