Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives

Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of “onco-channelopathy”. Here, we review the contribution of ion channels and transporters in multiple myeloma (MM), a hematological neoplasia characterized by the expansion of tumor plasma cells (MM cells) in the bone marrow (BM). Deregulation of ion channels sustains MM progression by modulating intracellular pathways that promote MM cells’ survival, proliferation, and drug resistance. Finally, we focus on the promising role of ion channels as therapeutic targets for the treatment of MM patients in a combination strategy with currently used anti-MM drugs to improve their cytotoxic activity and reduce adverse effects.     

Tunable,Grating-Gated,Graphene-On-Polyimide Terahertz Modulators

An electrically switchable graphene terahertz (THz) modulator with a tunable-by-design optical bandwidth is presented and it is exploited to compensate the cavity dispersion of a quantum cascade laser (QCL). Electrostatic gating is achieved by a metal grating used as a gate electrode, with an HfO₂/AlO_x gate dielectric on top. This is patterned on a polyimide layer, which acts as a quarter wave resonance cavity, coupled with an Au reflector underneath. The authors achieve 90% modulation depth of the intensity, combined with a 20 kHz electrical bandwidth in the 1.9–2.7 THz range. The modulator is then integrated with a multimode THz QCL. By adjusting the modulator operational bandwidth, the authors demonstrate that the graphene modulator can partially compensate the QCL cavity dispersion, resulting in an integrated laser behaving as a stable frequency comb over 35% of the operational range, with 98 equidistant optical modes and a spectral coverage ~1.2 THz. This paves the way for applications in the terahertz, such as tunable transformation-optics devices, active photonic components, adaptive and quantum optics, and metrological tools for spectroscopy at THz frequencies.     

Morphology and surface properties of some siloxane–organic copolymers

BACKGROUND: It is well known that, due to their extremely low polarity, polysiloxanes are incompatible with almost any organic system. This incompatibility leads to phase separation in mixed siloxane–organic systems. RESULTS: Three siloxane–organic copolymers, poly[(5,5′‐methylene‐bis‐salicylaldehyde)‐imine‐(1,3‐bis(propylene)tetramethyldisiloxane)] (Paz1), poly[(2,5‐dihydroxy‐1,4‐benzoquinone)‐imine‐(1,3‐bis(propylene)tetramethyldisiloxane)] (Paz2) and poly[1,3‐bis(propylene)tetramethyldisiloxane diamide] (Pam), were prepared by the reaction of 1,3‐bis(3‐aminopropyl)tetramethyldisiloxane with appropriate organic partners (5,5′‐methylene‐bis‐salicylaldehyde, 2,5‐dihydroxy‐1,4‐benzoquinone and oxalyl chloride, respectively). The morphologies dictated by the incompatibility between siloxane and polar organic moieties were investigated using differential scanning calorimetry and scanning electron microscopy. The surface activity of the copolymers and water vapour sorption capacity were also measured. CONCLUSION: Even though the polar sequences are very short ones, the highly flexible siloxane‐containing sequence permits the self‐assembly of these into more or less polar domains. Such an organization influences the properties of the resulting materials, an important place being occupied by the surface properties. Copyright © 2009 Society of Chemical Industry     

Unconventional method used in synthesis of polyphosphoesters

Polyphosphonates, polyphosphates, polyarylazophosphonates and polyarylazophosphates were synthesized by a new alternative to the classical phase transfer catalysis, respectively, the modified inverse phase transfer catalysis (IPTC) polycondensation of various phenylphosphonic (phosphoric) dichlorides (phenylphosphonic dichloride, phenylphosphoric dichloride, p-chlorophenylphosphoric dichloride) with bisphenols: bisphenol A, tetrabromobisphenol A, bis-(4-hydroxyphenyl)methane (bisphenol F), 4,4′-dihydroxyazobenzene. The polymers were characterized by infrared spectroscopy and magnetic resonance (¹H-NMR, ³¹P-NMR, ¹³C-NMR) spectroscopy. Yields in the range of 63.5–85% and molecular weights (M _w) of ~2,000–8,200 g mol^?1 were obtained. Polyphosphonates were stable up 210–270 °C and polyphosphates up 190–220 °C in air atmosphere. For a correct estimation of the thermal behavior of similar compounds, a kinetic analysis using a modified version of Non Parametric Kinetic method for representative polyphosphonate and polyphosphate was realized. The studies made on the hydrolytic degradation of the synthesized polyphosphates show that the most stable polymer under alkali-catalyzed degradation is the polyphosphate obtained by IPTC of phenylphosphoric dichloride and bisphenol A.     

The encapsulation effect of UV molecular absorbers into biocompatible lipid nanoparticles

The efficiency of a cosmetic product depends not only on the active ingredients, but also on the carrier system devoted to improve its bioavailability. This article aims to encapsulate two couples of UV molecular absorbers, with a blocking action on both UV-A and UV-B domains, into efficient lipid nanoparticles. The effect of encapsulation on the specific properties such as sun protection factor and photostability behaviour has been demonstrated. The lipid nanoparticles with size range 30-350 nm and a polydispersity index between 0.217 and 0.244 are obtained using a modified high shear homogenisation method. The nanoparticles had spherical shapes with a single crystallisation form of lipid matrices characteristic for the least ordered crystal structure (α-form). The in vitro determination of photoprotection has led to high SPF ratings, with values of about 20, which assure a good photoprotection and filtering about 95% of UV radiation. The photoprotection effect after irradiation stage was observed to be increased more than twice compared to initial samples as a result of isomerisation phenomena. All the results have shown that good photoprotection effect and improved photostability could be obtained using such sunscreen couples, thus demonstrating that UV absorbers-solid lipid nanoparticles are promising carriers for cosmetic formulations.     

Use of chitosan complex with aminophosphonic groups and cobalt for the removal of Sr2+ ions

We briefly describe the adsorbent performance of the chitosan complex with aminophosphonic groups and cobalt in the removal process of Sr²⁺ ions from aqueous solutions. The strontium adsorption was studied as a function of pH, contact time, and initial strontium concentration. Adsorption isotherms such as Langmuir, Freundlich, Dubinin–Radushkevich, and Temkin were used to analyze the equilibrium data at different concentrations. The kinetics of the Sr²⁺ sorption was analyzed using the pseudo-first-order and pseudo-second-order kinetic models. The results clearly indicate that the chitosan complex with aminophosphonic groups and cobalt is an efficient adsorbent with respect to its capacity to absorb Sr²⁺ ions from aqueous solutions.     

Design and evaluation of an optimized W/Cu interlayer for W monoblock components

Divertor plasma-facing components of future fusion reactors should be able to withstand heat fluxes of 10-20 MW/m² in stationary operation. Tungsten blocks with an inner cooling tube made of CuCr1Zr, so-called monoblocks, are potential candidates for such water-cooled components. To increase the strength and reliability of the interface between the W and the cooling tube of a Cu-based alloy (CuCr1Zr), a novel advanced W-fibre/Cu metal matrix composite (MMC) was developed for operation temperatures up to 550 °C. Based on optimization results to enhance the adhesion between fibre and matrix, W fibres (W_f) were chemically etched, coated by physical vapour deposition with a continuously graded W/Cu_PVD interlayer and then heated to 800 °C. The W_f/Cu MMC was implemented by hot-isostatic pressing and brazing process in monoblock mock-ups reinforcing the interface between the plasma-facing material and the cooling channel. The suitability of the MMC as an efficient heat sink interface for water-cooled divertor components was tested in the high heat flux (HHF) facility GLADIS. Predictions from finite element simulations of the thermal behaviour of the component under loading conditions were confirmed by the HHF tests. The W_f/Cu MMC interlayer of the mock-ups survived cyclic heat loads above 10 MW/m² without any damage. One W block of each tested mock-up showed stable thermal behaviour at heat fluxes of up to 10.5 MW/m².     

Harmful dinoflagellate Ostreopsis cf. ovata Fukuyo: detection of ovatoxins in field samples and cell immunolocalization using antipalytoxin antibodies

Ostreopsis cf. ovata, a benthic dinoflagellate often blooming along the Mediterranean coasts, has been associated with toxic events ranging from dyspnea to mild dermatitis. In late September 2009, an Ostreopsis cf. ovata bloom occurred in the Gulf of Trieste (Northern Adriatic Sea; Italy), causing pruritus and mild dermatitis in beachgoers. An integrated study was initiated to characterize Ostreopsis cells by light and confocal microscopy, PCR techniques, immunocytochemistry, and high resolution liquid chromatography-mass spectrometry (HR LC-MS). The presence of Ostreopsis cf. ovata of the Atlantic/Mediterranean clade was unambiguously established by morphological and genetic analyses in field samples. Several palytoxin-like compounds (ovatoxin-a,-b,-c,-d,-e) were identified by HR LC-MS, ovatoxin-a being the most abundant (45-64 pg/cell). Surprisingly, no palytoxin was detected. For the first time, monoclonal and polyclonal antipalytoxin antibodies revealed the intracellular cytoplasmic localization of ovatoxins, suggesting their cross-reactivity with these antibodies. Since harmful dinoflagellates do not always produce toxins, the immunocytochemical localization of ovatoxins, although qualitative, can provide an early warning for toxic Ostreopsis cells before their massive diffusion and/or concentration in seafood.     

Determination of Sulphiting Agents in Raw and Processed Meat: Comparison Between a Modified Monier-Williams Method and the Direct Analysis by Ion Chromatography with Conductometric Detection

Sulphiting agents are a class of compounds that are used as preservatives since they release SO₂ in food. Regarding meat products, the legislation restricts the use of these food additives, due to some toxic effects that they may have in humans. The most employed analytical procedure for the determination of sulphiting agents in foodstuffs is the Monier-Williams (M-W) method, but the reliability of this method was called into question by several authors. In this work, the M-W method was modified by replacing both the distillation unit to shorten the extraction time (from hours to 5 min) and the final titration with a chromatographic separation followed by conductometric detection of sulphate ion (m-M-W/IC-CD). This method was then validated, and the performance parameters were compared with those of the method based on the direct analysis of sulphite ion by ion chromatography with conductometric detection (DIC-CD). Linearity, accuracy at 40 and 80 mg kg^?1 of SO₂ and measurement uncertainty resulted comparable. Accuracy at 10 mg kg^?1 of SO₂ resulted higher for the m-M-W/IC-CD method, but this parameter could be influenced by traces of other sulphur-containing compounds that may be present in meat. The limit of determination of the m-M-W/IC-CD method was slightly higher than that obtained by the DIC-CD method. Finally, through spiking tests, it was proved that sulphide, 2-methyl-3-furanthiol and l-methionine cause “false-positive” responses, by using M-W-based methods.