Highly Improved Electrospray Ionization-Mass Spectrometry Detection of G-Quadruplex-Folded Oligonucleotides and Their Complexes with Small Molecules

G-quadruplexes are nucleic acids structures stabilized by physiological concentration of potassium ions. Because low stability G-quadruplexes are hardly detectable by mass spectrometry, we optimized solvent conditions: isopropanol in a triethylamine/hexafluoroisopropanol mixture highly increased G-quadruplex sensitivity with no modification of the physiological G-quadruplex conformation. G-quadruplexes/G-quadruplex-ligand complexes were also correctly detected at concentration as low as 40 nM. Detection of the physiological conformation of G4s and their complexes opens up the possibility to perform high-throughput screening of G-quadruplex ligands for the development of drug molecules effective against critical human diseases

Chern-Simons theory and atypical Hall conductivity in the Varma phase

In this letter, we analyze the topological response of a fermionic model defined on the Lieb lattice in presence of an electromagnetic field. The tight-binding model is built in terms of three species of spinless fermions and supports a topological Varma phase due to the spontaneous breaking of time-reversal symmetry. In the low-energy regime, the emergent effective Hamiltonian coincides with the so-called Duffin-Kemmer-Petiau (DKP) Hamiltonian, which describes relativistic pseudospin-0 quasiparticles. By considering a minimal coupling between the DKP quasiparticles and an external Abelian gauge field, we calculate both the Landau-level spectrum and the emergent Chern-Simons theory. The corresponding Hall conductivity reveals an atypical quantum Hall effect, which can be simulated in an artificial Lieb lattice.Comment: 5 pages, 3 figures; New version with an improved discussion about our finding

Conformal QED in two-dimensional topological insulators

It has been shown recently that local four-fermion interactions on the edges of two-dimensional time-reversal-invariant topological insulators give rise to a new non-Fermi-liquid phase, called helical Luttinger liquid (HLL). In this work, we provide a first-principle derivation of this non-Fermi-liquid phase based on the gauge-theory approach. Firstly, we derive a gauge theory for the edge states by simply assuming that the interactions between the Dirac fermions at the edge are mediated by a quantum dynamical electromagnetic field. Here, the massless Dirac fermions are confined to live on the one-dimensional boundary, while the (virtual) photons of the U(1) gauge field are free to propagate in all the three spatial dimensions that represent the physical space where the topological insulator is embedded. We then determine the effective 1+1-dimensional conformal field theory (CFT) given by the conformal quantum electrodynamics (CQED). By integrating out the gauge field in the corresponding partition function, we show that the CQED gives rise to a 1+1-dimensional Thirring model. The bosonized Thirring Hamiltonian describes exactly a HLL with a parameter K and a renormalized Fermi velocity that depend on the value of the fine-structure constant $\alpha$.Comment: (5+4) pages, 2 figure

The cellular protein nucleolin preferentially binds long-looped G-quadruplex nucleic acids

open5noBACKGROUND: G-quadruplexes (G4s) are four-stranded nucleic acid structures that form in G-rich sequences. Nucleolin (NCL) is a cellular protein reported for its functions upon G4 recognition, such as induction of neurodegenerative diseases, tumor and virus mechanisms activation. We here aimed at defining NCL/G4 binding determinants. METHODS: Electrophoresis mobility shift assay was used to detect NCL/G4 binding; circular dichroism to assess G4 folding, topology and stability; dimethylsulfate footprinting to detect G bases involved in G4 folding. RESULTS: The purified full-length human NCL was initially tested on telomeric G4 target sequences to allow for modulation of loop, conformation, length, G-tract number, stability. G4s in promoter regions with more complex sequences were next employed. We found that NCL binding to G4s heavily relies on G4 loop length, independently of the conformation and oligonucleotide/loop sequence. Low stability G4s are preferred. When alternative G4 conformations are possible, those with longer loops are preferred upon binding to NCL, even if G-tracts need to be spared from G4 folding. CONCLUSIONS: Our data provide insight into how G4s and the associated proteins may control the ON/OFF molecular switch to several pathological processes, including neurodegeneration, tumor and virus activation. Understanding these regulatory determinants is the first step towards the development of targeted therapies. GENERAL SIGNIFICANCE: The indication that NCL binding preferentially stimulates and induces folding of G4s containing long loops suggests NCL ability to modify the overall structure and steric hindrance of the involved nucleic acid regions. This protein-induced modification of the G4 structure may represent a cellular mechanosensor mechanism to molecular signaling and disease pathogenesis.openLago, Sara; Tosoni, Elena; Nadai, Matteo; Palumbo, Manlio; Richter, Sara NLago, Sara; Tosoni, Elena; Nadai, Matteo; Palumbo, Manlio; Richter, Sar

Two Studies on the Effect of Audio-tape Structure on the Immediate Recall of Factual Information

The last decade of educational research has witnessed an expansion of interest in the technology of education (Gage, 1963; Travers, 1973). This proliferation of research, however, was bothered by a continued confusion between the mechanics of the technology and the design rules for the process of education. The needed distinction between the instruments of instruction and the application of instructional processes was made clear recently by Armsey and Dahl (1974). Nevertheless, the confusion continues, particularly in the kind of research that is being conducted

The Role of the New Technologies in the Italian Primary School: Historical and Educational Outlines

Education is a process which helps the growth of the students. Thanks to it students can grow, develop and become adult and qualified persons in different fields of the humans ’ activity. Hence, the school educates only when it supports the students in getting and developing their own skills and when it helps them to get new attitudes towards themselves as well as the human, natural and artificial world. In this perspective, the school cannot continue to be a mere teaching-learning environment, just making frontal lessons, even if with the support of advanced multimedia technologies, but it should, indeed, focus the attention on the learning processes. This is the deepest change that the school needs. The possibilities offered by the computers in the educational field are many, especially as support in special didactics. In this sense, the access to multimedia and telematics has caused the activation of an autonomous process to build knowledge. The interpersonal exchanges mediated by the computer can break the isolation of a disabled person. The introduction of multimedia in school can then enhance both the teacher and the student to help the cooperative dimension of the teaching / learning process. The school has to open itself to new technologies and help the students to select the necessary information for the construction of th

Hydrogen absorption properties of amorphous (Ni0.6Nb0.4−yTay)100−xZrx membranes

Ni based amorphous materials have great potential as hydrogen purification membranes. In the present work the melt spun (Ni0.6Nb0.4−yTay)100−xZrx with y=0, 0.1 and x=20, 30 was studied. The result of X-ray diffraction spectra of the ribbons showed an amorphous nature of the alloys. Heating these ribbons below T < 400 °C, even in a hydrogen atmosphere (1−10 bar), the amorphous structure was retained. The crystallization process was characterized by differential thermal analysis and the activation energy of such process was obtained. The hydrogen absorption properties of the samples in their amorphous state were studied by the volumetric method, and the results showed that the addition of Ta did not significantly influence the absorption properties, a clear change of the hydrogen solubility was observed with the variation of the Zr content. The values of the hydrogenation enthalpy changed from ~37 kJ/mol for x=30 to ~9 kJ/mol for x=20. The analysis of the volumetric data provides the indications about the hydrogen occupation sites during hydrogenation, suggesting that at the beginning of the absorption process the deepest energy levels are occupied, while only shallower energy levels are available at higher hydrogen content, with the available interstitial sites forming a continuum of energy levels