Solvent Vibrations as a Proxy of the Telomere G-Quadruplex Rearrangements across Thermal Unfolding

G-quadruplexes (G4s) are noncanonical forms of DNA involved in many key genome functions. Here, we exploited UV Resonance Raman scattering to simultaneously explore the vibrational behavior of a human telomeric G4 (Tel22) and its aqueous solvent as the biomolecule underwent thermal melting. We found that the OH stretching band, related to the local hydrogen-bonded network of a water molecule, was in strict relation with the vibrational features of the G4 structure as a function of temperature. In particular, the modifications to the tetrahedral ordering of the water network were strongly coupled to the DNA rearrangements, showing changes in temperature that mirrored the multi-step melting process of Tel22. The comparison between circular dichroism and Raman results supported this view. The present findings provide novel insights into the impact of the molecular environment on G4 conformation. Improving current knowledge on the solvent structural properties will also contribute to a better understanding of the role played by water arrangement in the complexation of G4s with ligands.     

Detection of VAMP Proteolysis by Tetanus and Botulinum Neurotoxin Type B In Vivo with a Cleavage-Specific Antibody

Tetanus and Botulinum type B neurotoxins are bacterial metalloproteases that specifically cleave the vesicle-associated membrane protein VAMP at an identical peptide bond, resulting in inhibition of neuroexocytosis. The minute amounts of these neurotoxins commonly used in experimental animals are not detectable, nor is detection of their VAMP substrate sensitive enough. The immune detection of the cleaved substrate is much more sensitive, as we have previously shown for botulinum neurotoxin type A. Here, we describe the production in rabbit of a polyclonal antibody raised versus a peptide encompassing the 13 residues C-terminal with respect to the neurotoxin cleavage site. The antibody was affinity purified and found to recognize, with high specificity and selectivity, the novel N-terminus of VAMP that becomes exposed after cleavage by tetanus toxin and botulinum toxin type B. This antibody recognizes the neoepitope not only in native and denatured VAMP but also in cultured neurons and in neurons in vivo in neurotoxin-treated mice or rats, suggesting the great potential of this novel tool to elucidate tetanus and botulinum B toxin activity in vivo.     

Inactivation effect of an 18-T pulsed magnetic field combined with other technologies on Escherichia coli

The inactivation effect of 18 T pulsed magnetic fields in combination with selected non-thermal technologies was studied on Escherichia coli ATCC 11775. The bacteria were subjected to a treatment of either ultrasound (20 kHz, 70 W, 242 μm), high hydrostatic pressure (207 MPa, 5 min), pulsed electric field (6.25 kV/cm, 5.6 ms), or anti-microbials (Nisin 77.5 mg/l, lysozyme 1 mg/ml) and 50 magnetic field pulses (18 T, 30 μs). No additional inactivation or cell damage due to exposure to the pulsed magnetic field at 42°C was observed.     

Design and technical status of the EU contribution to ITER

Europe is involved in the procurement of most of the high-technology items for the ITER device (e.g. parts of the superconducting Toroidal (TF) and Poloidal Field (PF) coils, the vacuum vessel (VV), the in-vessel components, the remote handling, the additional heating systems, the tritium plant and cryoplant and finally parts of the diagnostics). In many cases the technologies required to manufacture these components are well established, in others there is still ongoing design and R&D work to select and optimise the final design solutions and to consolidate the underlying technologies as, for example, in the areas of heating and current drive, plasma diagnostics, shield blanket and first wall, remote handling, etc. A design review has recently been conducted by the ITER Organisation, with the support of the Domestic Agencies (DAs) established by the countries participating to ITER, to address the remaining outstanding technical issues and understand the associated implications for design, machine performance, schedule and cost.This paper provides an update of the design and technical status of EU contributions to ITER.     

A compact instrumentation amplifier for MEMS thermal sensor interfacing

A compact CMOS instrumentation amplifier, based on a properly modified second order G _m?CC low pass filter (LPF), is proposed as a possible readout channel for integrated thermal sensors. Low noise and low offset characteristics are obtained by applying chopper modulation to the input transconductor. The high input thermal noise density, typical of low frequency G _m?CC filters, has been significantly reduced by adopting a two-stage topology for the first transconductor. Using this approach, an input noise density adequate for thermal sensor interfacing was obtained with no need of off-chip capacitors. The intrinsic filtering property of the amplifier effectively rejects the modulated offset ripple, allowing direct connection of the amplifier output to a low sampling rate AD converter. An original switching strategy involving swapping of the input and feedback ports is used to improve the gain precision. The effectiveness of the technique is proven by means of analytical arguments and electrical simulations performed on a prototype, designed with the STMicroelectronics BCD6s process.     

Trehalose Treatment in Zebrafish Model of Lafora Disease

Mutations in the EPM2A gene encoding laforin cause Lafora disease (LD), a progressive myoclonic epilepsy characterized by drug-resistant seizures and progressive neurological impairment. To date, rodents are the only available models for studying LD; however, their use for drug screening is limited by regulatory restrictions and high breeding costs. To investigate the role of laforin loss of function in early neurodevelopment, and to screen for possible new compounds for treating the disorder, we developed a zebrafish model of LD. Our results showed the epm2a^−/− zebrafish to be a faithful model of LD, exhibiting the main disease features, namely motor impairment and neuronal hyperexcitability with spontaneous seizures. The model also showed increased inflammatory response and apoptotic death, as well as an altered autophagy pathway that occurs early in development and likely contributes to the disease progression. Early administration of trehalose was found to be effective for rescuing motor impairment and neuronal hyperexcitability associated with seizures. Our study adds a new tool for investigating LD and might help to identify new treatment opportunities.     

Waste glass as a supplementary cementitious material in concrete – Critical review of treatment methods

Concrete is the most widely used construction material and, for the most part, is produced using non-renewable natural resources and energy intensive processes which emit greenhouse gasses. There exists an opportunity to improve the sustainability of this industry by further exploring the use of alternative materials. As an aggregate, glass bottle waste has faced specific challenges including bond, ASR gel production, and strength degradation of the concrete. This paper reviews the literature pertaining to incorporating waste glass into concrete as a supplementary cementing material. Pozzolanic properties of waste glass as an SCM and ASR are related to particle size and percent addition. Lithium additives control ASR expansion; however, the mechanism of this control has yet to be defined.     

The role of weathering on fly ash charge distribution during triboelectrostatic beneficiation

Triboelectrostatic beneficiation of coal combustion fly ashes with high-unburned carbon contents can produce low-carbon ash products having value as mineral admixtures and meeting technical requirements for replacing cement in concrete. This capability is a result of establishing bipolar charge on mineral ash versus carbon particles where, typically, unburned carbon attains positive surface charge and ash attains negative surface charge under the tribocharging conditions employed in triboelectrostatic technologies. However, long-term exposure of fly ash to weathering conditions, such as moisture or high humidity, before beneficiation is known to dramatically diminish carbon-ash separation efficiencies. Although experimentation has shown that water soluble surface species can be redistributed on fly ash particles after exposure to moisture, which could affect the extent of charging and polarities, measurement of the actual amount of charge and polarity on particles after weathering exposure versus after removal of surface moisture has not been accomplished. Hence, a new experimental methodology was developed and applied to measure charge distributions on tribocharged ash and carbon particles in a fly ash that had been exposed to weathering conditions for 6 months before and after removal of the surface moisture. Weathered ash particles were found to have an average zero charge, whereas carbon particles attained an average negative charge, opposite of the normal polarity for carbon. Although the extent of uncharged particles decreased and ash particles attained an average negative charge after drying, carbon particles attained only an average zero charge. These changes were reflected in very small increases in carbon-ash separation efficiency, in contrast to previous beneficiation tests in which fly ash drying led to significant increases in carbon-ash separation efficiency. It is suggested that removal of surface moisture in the absence of other processes like surface ion redistribution would beneficially impact carbon-ash triboelectrostatic beneficiation.