BINA

Inactivating mutations in the Methyl-CpG Binding Protein 2 (MECP2) gene are the main cause of Rett syndrome (RTT). Despite extensive research into MECP2 function, no treatments for RTT are currently available. Here, we used an evolutionary genomics approach to construct an unbiased MECP2 gene network, using 1028 eukaryotic genomes to prioritize proteins with strong co-evolutionary signatures with MECP2. Focusing on proteins targeted by FDA-approved drugs led to three promising targets, two of which were previously linked to MECP2 function (IRAK, KEAP1) and one that was not (EPOR). The drugs targeting these three proteins (Pacritinib, DMF, and EPO) were able to rescue different phenotypes of MECP2 inactivation in cultured human neural cell types, and appeared to converge on Nuclear Factor Kappa B (NF-kB) signaling in inflammation. This study highlights the potential of comparative genomics to accelerate drug discovery, and yields potential new avenues for the treatment of RTT.

Recently, graphene and its derivatives have been extensively investigated for their interesting properties in many biomedical fields, including tissue engineering and regenerative medicine. Nonetheless, graphene oxide (GO) and reduced GO (rGO) are still under investigation for improving their dispersibility in aqueous solutions and their safety in different cell types. This work explores the interaction of GO and rGO with different polymeric dispersants, such as glycol chitosan (GC), propylene glycol alginate (PGA), and polydopamine (PDA), and their effects on human chondrocytes. GO was synthesized using Hummer’s method, followed by a sonication-assisted liquid-phase exfoliation (LPE) process, drying, and thermal reduction to obtain rGO. The flakes of GO and rGO exhibited an average lateral size of 8.8±4.6 and 18.3±8.5 µm, respectively. Their dispersibility and colloidal stability were investigated in the presence of the polymeric surfactants, resulting in an improvement in the suspension stability in terms of average size and polydispersity index over 1 h, in particular for PDA. Furthermore, cytotoxic effects induced by coated and uncoated GO and rGO on human chondrocytes at different concentrations (12.5, 25, 50 and 100 µg/mL) were assessed through LDH assay. Results showed a concentration-dependent response, and the presence of PGA contributed to statistically decreasing the difference in the LDH activity with respect to the control. These results open the way to a potentially safer use of these nanomaterials in the fields of cartilage tissue engineering and regenerative medicine. View Full-Text

Three different Terahertz quantum-cascade-laser designs supporting clean n-level systems were analyzed using nonequilibrium Green’s functions. In clean n-level systems, most of the electrons occupy the active laser levels, with thermally activated leakage channels being suppressed almost entirely up to room temperature. Simulations of the three designs, namely a resonant phonon design, a two-well design, and a split-well direct-phonon design were investigated. The results from the simulations indicated that the two-well design would perform best overall, in terms of variations in current density, interface roughness, and ionized impurity scattering. We conclude that future research aiming to improve the temperature performance of such laser designs should be based on a two-well design.

Kinetoplastids are infamous parasites that include trypanosomes and Leishmania species. Here, we developed an anti-Leishmania nano-drug using ultra-small functional maghemite (γ-Fe2O3) nanoparticles (NPs) that were surface-doped by [CeLn]3/4+ to enable effective binding of the polycationic polyethylenebyimine (PEI) polymer by coordinative chemistry. This resulting nano-drug is cytolytic in-vitro to both Trypanosoma brucei parasites, the causative agent of sleeping sickness, as well as to three Leishmania species. The nano-drug induces the rupture of the single lysosome present in these parasites attributed to the PEI, leading to cytolysis. To evaluate the efficacy of a “cream-based” version of the nano-drug, which was termed “Nano-Leish-IL” for topical treatment of cutaneous leishmaniasis (CL), we developed a rapid screening method utilizing T. brucei parasites involved in social motility and demonstrated …

Calcium-based battery systems are promising postlithium candidates; however, only a few amenable calcium materials were reported in nonaqueous electrolytes. Here, reversible storage of Ca2+ ions in aqueous and nonaqueous electrolyte solutions is shown for crystalline 3,4,9,10-perylene tetracarboxylic dianhydride. The carbonyl functional groups and the π-electrons constitute redox centers, which can reversibly interact with divalent ions. This phenomenon was clearly uncovered by combined electrochemistry, Fourier transform infrared spectroscopy, scanning electron microscopy with energy dispersive X-ray analysis, X-ray photoelectron spectroscopy, and ex situ X-ray diffraction analyses. Very promising calcium storage performances are shown with a highly reversible capacity around ∼158 mAh g–1 at a rate of 10 mA g–1 with an average voltage of ∼2.3 V band sufficient capacity retention in saturated Ca …

We study the aberrations of four-wave mixing based time lenses resulting from the cross-phase modulations of the pump wave. These temporal aberrations have no spatial equivalent and are important when imaging weak signals with strong pump waves. We show that as the pump power increases, the cross-phase modulations of the pump are responsible for shifting, defocusing, and imposing temporal coma aberrations on the image. We present experimental results of these aberrations with high agreement to analytical and numerical calculations.

Counterfactual communication protocols are analyzed using three approaches: a classical argument, the weak trace criterion, and the Fisher information criterion. It is argued that the classical analysis leads to contradiction and should therefore be abandoned. The weak trace and Fisher information criteria are shown to agree about the degree of counterfactuality of communication protocols involving postselection. It is argued that postselection is a necessary ingredient of counterfactual communication protocols. Coherent interaction experiments, as well as a recently introduced modification of counterfactual communication setups which eliminates the weak trace, are discussed.

The present work considers the production of a cheap and effective sorbent based on natural clay from the Kyzylsok deposit (Almaty region) in order to purify wastewater from heavy metal ions (Cd 2+, Pb 2+). It was found that the starting material is applicable for the extraction of Cd 2+ ions (the degree of extraction is (97.00±1.99)%), while for the extraction of Pb 2+ ions the initial clay must be modified. The modification was carried out using polyvinylpyrrolidone (PVP). The degree of extraction of Pb 2+ ions with modified clay increased from (70.00±1.77)% to (98±1.13)% The influence of PVP concentration in the composite material (modified clay) on its sorption properties was studied: the optimal concentration of PVP was 0.1% solution. The desorption of metal ions was also investigated in the work, it does not exceed 2%. It was found that the sorption process is described by the monomolecular Langmuir isotherm model and the kinetic model of the pseudo-second order.

Imaging turbid media is range limited. In contrast, sensing the medium’s optical properties is possible in larger depths using the iterative multi-plane optical properties extraction technique. It analyzes the reconstructed reemitted light phase image. The root mean square of the phase image yields two graphs with opposite behaviors that intersect at µ’s,cp. These graphs enable the extraction of a certain range of the reduced scattering coefficient, µ’s. Here, we aim to extend the range of µ’s detection by optical magnification. We use a modified diffusion theory and show how µ’s,cp shifts with the varying magnification. The theoretical results were tested experimentally, showing that the technique can be adapted to different ranges of µ’s by changing the magnification.

Three different Terahertz quantum-cascade-laser designs supporting clean n-level systems were analyzed using nonequilibrium Green’s functions. In clean n-level systems, most of the electrons occupy the active laser levels, with thermally activated leakage channels being suppressed almost entirely up to room temperature. Simulations of the three designs, namely a resonant phonon design, a two-well design, and a split-well direct-phonon design were investigated. The results from the simulations indicated that the two-well design would perform best overall, in terms of variations in current density, interface roughness, and ionized impurity scattering. We conclude that future research aiming to improve the temperature performance of such laser designs should be based on a two-well design.

The ability to direct neurons into organized neural networks has great implications for regenerative medicine, tissue engineering, and bio-interfacing. Many studies have aimed at directing neurons using chemical and topographical cues. However, reports of organizational control on a micron-scale over large areas are scarce. Here, an effective method has been described for placing neurons in preset sites and guiding neuronal outgrowth with micron-scale resolution, using magnetic platforms embedded with micro-patterned, magnetic elements. It has been demonstrated that loading neurons with magnetic nanoparticles (MNPs) converts them into sensitive magnetic units that can be influenced by magnetic gradients. Following this approach, a unique magnetic platform has been fabricated on which PC12 cells, a common neuron-like model, were plated and loaded with superparamagnetic nanoparticles. Thin films of ferromagnetic (FM) multilayers with stable perpendicular magnetization were deposited to provide effective attraction forces toward the magnetic patterns. These MNP-loaded PC12 cells, plated and differentiated atop the magnetic platforms, were preferentially attached to the magnetic patterns, and the neurite outgrowth was well aligned with the pattern shape, forming oriented networks. Quantitative characterization methods of the magnetic properties, cellular MNP uptake, cell viability, and statistical analysis of the results are presented. This approach enables the control of neural network formation and improves neuron-to-electrode interface through the manipulation of magnetic forces, which can be an effective tool for in vitro …

Metal–support interactions have been widely utilized for optimizing the catalytic reactivity of oxide-supported Au nanoparticles. Optimized reactivity was mainly detected with small (1–5 nm) oxide-supported Au nanoparticles and correlated to highly reactive sites at the oxide–metal interface. However, catalytically active sites are not necessarily restricted to the interface but reside as well on the Au surface. Uncovering the interconnection between reactive sites located at the interface and those situated at the metal surface is of crucial importance for understanding the reaction mechanism on Au nanoparticles. Herein, high-spatial-resolution IR nanospectroscopy measurements were conducted to map the localized reactivity in hydrogenation reactions on oxide-supported Au particles while using nitro-functionalized ligands as probes molecules. Comparative analysis of the reactivity pattern on single particles supported …

The spillover of animal coronaviruses (aCoVs) to humans has caused SARS, MERS, and COVID-19. While antibody responses displaying cross-reactivity between SARS-CoV-2 and seasonal/common cold human coronaviruses (hCoVs) have been reported, potential cross-reactivity with aCoVs and the diagnostic implications are incompletely understood. Here, we probed for antibody binding against all seven hCoVs and 49 aCoVs represented as 12,924 peptides within a phage-displayed antigen library. Antibody repertoires of 269 recovered COVID-19 patients showed distinct changes compared to 260 unexposed pre-pandemic controls, not limited to binding of SARS-CoV-2 antigens but including binding to antigens from hCoVs and aCoVs with shared motifs to SARS-CoV-2. We isolated broadly reactive monoclonal antibodies from recovered COVID-19 patients that bind a shared motif of SARS-CoV-2, hCoV …

Lithium-sulfur (Li-S) batteries promise high energy density for next-generation energy storage systems, yet many challenges remain. Li-S batteries follow a conversion chemistry, which radically differs from intercalation-based lithium-ion batteries. Recently, it has become clear that the chemistry of electrolyte solutions and their ability to stabilize polysulfide Li2Sx species formed by sulfur reduction have a critical effect on energy density and cycling performance. This review evaluates the key role of solution properties and polysulfide solvation. Factors that determine the solvation are discussed, including the solvent, salt, concentration, and interaction with Li-polysulfide species. Three fundamental types of electrolyte solution—moderately (conventional), sparingly, and highly solvating—are presented along with a multi-dimensional analysis of solution chemistry, polysulfide solubility, sulfur reaction pathway, Li2S …

Simple Summary Inflammatory Bowel Disease (IBD) is a complex and multifactorial systemic disease of the gastrointestinal tract, characterized by chronic inflammation, thus resulting in tissue damage and, occasionally, in cancer development. Although the precise origin is still elusive, it is widely considered a disease of modern society, caused by a complex interaction between environment, genetic, immune system, and gut microflora (microbiota). Potentially affected by all the above-mentioned variables, which interplay are highly heterogeneous, the disease appears to be patient-specific. The latter phenomenon, together with the uncertain origin, also contributes to the lack of optimal clinical treatment of these patients. Therefore, the development of appropriate models is crucial to push the research forward and to define new valuable therapeutic approaches. Although tissue biopsies and/or animal models represent the best models to study IBD onset, progression, and clinical interventions, they are both affected by limitations such as invasiveness, cost- and time-consuming, and ethical issues such as animal suffering. Here we propose a novel approach based on the cultivation of mouse tissues (colon) in an ex vivo microfluidic device (Gut-Ex-Vivo System, GEVS) to study IBD. We demonstrate that explanted mouse tissues cultivated in our GEVS can be appropriately stimulated to recapitulate the onset of the disease, in a time- and cost- effective manner. Abstract Inflammatory bowel disease (IBD) is a complex, chronic, and dysregulated inflammatory condition which etiology is still largely unknown. Its prognosis …

We examine the radiation emitted by high-energy positrons channeled into silicon crystal samples. The positrons are modeled as semiclassical vector currents coupled to an Unruh-DeWitt detector to incorporate any local change in the energy of the positron. In the subsequent accelerated QED analysis, we discover a Larmor formula and power spectrum that are both thermalized by the acceleration. Thus, these systems explicitly exhibit thermalization of the detector energy gap at the celebrated Fulling-Davies-Unruh (FDU) temperature. Our derived power spectrum, with a nonzero energy gap, is then shown to have an excellent statistical agreement with high-energy channeling experiments and also provides a method to directly measure the FDU temperature. We also investigate the Rindler horizon dynamics and confirm that the Bekenstein-Hawking area-entropy law is satisfied in these experiments. As such, we …

The study of subtle effects on transport in semiconductors requires high-quality epitaxial structures with low defect density. Using hybrid molecular beam epitaxy (MBE), SrTiO films with low-temperature mobility exceeding 42,000 cmVs at low carrier density of 3 x 10 cm were achieved. A sudden and sharp decrease in residual resistivity accompanied by an enhancement in the superconducting transition temperature were observed across the second Lifshitz transition (LT) where the third band becomes occupied, revealing dominant intra-band scattering. These films further revealed an anomalous behavior in the Hall carrier density as a consequence of the antiferrodistortive (AFD) transition and the temperature-dependence of the Hall scattering factor. Using hybrid MBE growth, phenomenological modeling, temperature-dependent transport measurements, and scanning superconducting quantum interference device imaging, we provide critical insights into the important role of inter- vs intra-band scattering and of AFD domain walls on normal-state and superconducting properties of SrTiO.

The present work considers the production of a cheap and effective sorbent based on natural clay from the Kyzylsok deposit (Almaty region) in order to purify wastewater from heavy metal ions (Cd 2+, Pb 2+). It was found that the starting material is applicable for the extraction of Cd 2+ ions (the degree of extraction is (97.00±1.99)%), while for the extraction of Pb 2+ ions the initial clay must be modified. The modification was carried out using polyvinylpyrrolidone (PVP). The degree of extraction of Pb 2+ ions with modified clay increased from (70.00±1.77)% to (98±1.13)% The influence of PVP concentration in the composite material (modified clay) on its sorption properties was studied: the optimal concentration of PVP was 0.1% solution. The desorption of metal ions was also investigated in the work, it does not exceed 2%. It was found that the sorption process is described by the monomolecular Langmuir isotherm …