Putative Circulating MicroRNAs Are Able to Identify Patients with Mitral Valve Prolapse and Severe Regurgitation

Mitral valve prolapse (MVP) associated with severe mitral regurgitation is a debilitating disease with no pharmacological therapies available. MicroRNAs (miRNA) represent an emerging class of circulating biomarkers that have never been evaluated in MVP human plasma. Our aim was to identify a possible miRNA signature that is able to discriminate MVP patients from healthy subjects (CTRL) and to shed light on the putative altered molecular pathways in MVP. We evaluated a plasma miRNA profile using Human MicroRNA Card A followed by real-time PCR validations. In addition, to assess the discriminative power of selected miRNAs, we implemented a machine learning analysis. MiRNA profiling and validations revealed that miR-140-3p, 150-5p, 210-3p, 451a, and 487a-3p were significantly upregulated in MVP, while miR-223-3p, 323a-3p, 340-5p, and 361-5p were significantly downregulated in MVP compared to CTRL (p ≤ 0.01). Functional analysis identified several biological processes possible linked to MVP. In addition, machine learning analysis correctly classified MVP patients from CTRL with high accuracy (0.93) and an area under the receiving operator characteristic curve (AUC) of 0.97. To the best of our knowledge, this is the first study performed on human plasma, showing a strong association between miRNAs and MVP. Thus, a circulating molecular signature could be used as a first-line, fast, and cheap screening tool for MVP identification.     

Gap Junctional Communication via Connexin43 between Purkinje Fibers and Working Myocytes Explains the Epicardial Activation Pattern in the Postnatal Mouse Left Ventricle

The mammalian ventricular myocardium forms a functional syncytium due to flow of electrical current mediated in part by gap junctions localized within intercalated disks. The connexin (Cx) subunit of gap junctions have direct and indirect roles in conduction of electrical impulse from the cardiac pacemaker via the cardiac conduction system (CCS) to working myocytes. Cx43 is the dominant isoform in these channels. We have studied the distribution of Cx43 junctions between the CCS and working myocytes in a transgenic mouse model, which had the His-Purkinje portion of the CCS labeled with green fluorescence protein. The highest number of such connections was found in a region about one-third of ventricular length above the apex, and it correlated with the peak proportion of Purkinje fibers (PFs) to the ventricular myocardium. At this location, on the septal surface of the left ventricle, the insulated left bundle branch split into the uninsulated network of PFs that continued to the free wall anteriorly and posteriorly. The second peak of PF abundance was present in the ventricular apex. Epicardial activation maps correspondingly placed the site of the first activation in the apical region, while some hearts presented more highly located breakthrough sites. Taken together, these results increase our understanding of the physiological pattern of ventricular activation and its morphological underpinning through detailed CCS anatomy and distribution of its gap junctional coupling to the working myocardium.     

Influence of addition of nanosize barium cerate on the microstructure and properties of top-seeded melt growth YBCO bulk superconductors

Barium cerate (BaCeO₃) is one of the possible additions to bulk YBa₂Cu₃O₇ single-grain superconductors to suppress the growth of Y₂BaCuO₅ (Y211) particles. This paper investigates the synthesis of barium cerate powder and its use in YBa₂Cu₃O₇ bulk superconductors. Crystalline barium cerate was synthesized by solid-state reaction, by co-precipitation of oxalates and by sol-gel method. Final calcination was held in air or in vacuum. It is shown that the most efficient in refining Y211 is nanocrystalline barium cerate prepared by sol-gel method calcined in vacuum. The effective refinement of Y211 particles occurred over the entire interval of nanocrystalline BaCeO₃ addition from 0.38 to 1.90 wt%. The optimal concentration of nanosize barium cerate was determined, microstructure and superconducting properties were characterized. The effect of Y211 content on trapped field in YBCO bulks with addition of nanocrystalline barium cerate is shown.     

Restoration of stormwater retention capacity at the allotment-scale through a novel economic instrument

Urbanisation results in changes to runoff behaviour which, if not addressed, inevitably degrade receiving waters. To date, most stormwater management has focussed on the streetscape and public open space. Given that much of the catchment imperviousness is located on private land, we developed and tested a novel economic instrument (a uniform price auction) for encouraging allotment-scale stormwater retention. We evaluated bids using an integrated environmental benefit index (EBI), based on the ability of the proposed works to reduce runoff frequency, pollutant loads and to reduce potable water demand. The uniform price auction resulted in 1.4 ha of impervious areas being effectively 'disconnected' from the stormwater system. The EBI provided an objective and transparent method of comparing bids, which varied in the type of works proposed (e.g. rainwater tank, rain-garden), the cost and the resulting environmental benefit. Whilst the pilot auction was a success, the public subsidy of works undertaken was around 85%, meaning that property owners a relatively small private benefit in the works. Future auction rounds will be revised to (i) test an EBI which is more focussed on the protection of streams (assessing changes to runoff frequency, baseflow volumes and water quality) and (ii) provide an auction process which is simpler to understand, and provides greater practical support for landholders who wish to undertake works.     

High performance liquid chromatographic detection of a strongly retained pigment fraction in Capsicum annuum

A new colour pigment fraction was detected in Capsicum annuum by high performance liquid chromatography. Surprisingly the pigment was strongly bound both to silica and octadecylsilica surfaces indicating that its molecular mass is probably high. Peak purity tests proved that the fraction is not homogeneous and the degree of inhomogeneity depends on the wavelength used for the peak purity test. The spectra taken at one minute intervals of the peak were strikingly different supporting the above conclusions. It is possible that this highly lipophilic pigment is a secondary product of the ripening and processing procedures and is a mixture of individual pigments covalently bound to each other.     

Multifunctional Gadolinium‐Doped Mesoporous TiO2 Nanobeads: Photoluminescence,Enhanced Spin Relaxation,and Reactive Oxygen Species Photogeneration,Beneficial for Cancer Diagnosis and Treatment

Materials with controllable multifunctional abilities for optical imaging (OI) and magnetic resonant imaging (MRI) that also can be used in photodynamic therapy are very interesting for future applications. Mesoporous TiO₂ sub‐micrometer particles are doped with gadolinium to improve photoluminescence functionality and spin relaxation for MRI, with the added benefit of enhanced generation of reactive oxygen species (ROS). The Gd‐doped TiO₂ exhibits red emission at 637 nm that is beneficial for OI and significantly improves MRI relaxation times, with a beneficial decrease in spin–lattice and spin–spin relaxation times. Density functional theory calculations show that Gd³⁺ ions introduce impurity energy levels inside the bandgap of anatase TiO₂, and also create dipoles that are beneficial for charge separation and decreased electron–hole recombination in the doped lattice. The Gd‐doped TiO₂ nanobeads (NBs) show enhanced ability for ROS monitored via ^?OH radical photogeneration, in comparison with undoped TiO₂ nanobeads and TiO₂ P25, for Gd‐doping up to 10%. Cellular internalization and biocompatibility of TiO₂@x Gd NBs are tested in vitro on MG‐63 human osteosarcoma cells, showing full biocompatibility. After photoactivation of the particles, anticancer trace by means of ROS photogeneration is observed just after 3 min irradiation.     

Structure and morphology of linear polyethylene extrudates induced by elongational flow

This study focuses on the structure, morphology, and properties of linear polyethylene (PE) profiles manufactured by continuous extrusion. High level of chain orientation was achieved using specific flow and processing conditions. An extrusion die with semihyperbolic convergency was used to generate high percentage of elongational flow and chain extension. Simultaneously, high extrusion pressure and relatively low melt temperature led to flow‐induced crystallization of PE extended chains. The structure of PE tapes consists of crystal aggregates with different level of orientation and crystallinity. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Novel Furin Inhibitors with Potent Anti‐infectious Activity

New peptidomimetic furin inhibitors with unnatural amino acid residues in the P3 position were synthesized. The most potent compound 4‐guanidinomethyl‐phenylacteyl‐Arg‐Tle‐Arg‐4‐amidinobenzylamide (MI‐1148) inhibits furin with a K_i value of 5.5 pM . The derivatives also strongly inhibit PC1/3, whereas PC2 is less affected. Selected inhibitors were tested in cell culture for antibacterial and antiviral activity against infectious agents known to be dependent on furin activity. A significant protective effect against anthrax and diphtheria toxin was observed in the presence of the furin inhibitors. Furthermore, the spread of the highly pathogenic H5N1 and H7N1 avian influenza viruses and propagation of canine distemper virus was strongly inhibited. Inhibitor MI‐1148 was crystallized in complex with human furin. Its N‐terminal guanidinomethyl group in the para position of the P5 phenyl ring occupies the same position as that found previously for a structurally related inhibitor containing this substitution in the meta position, thereby maintaining all of the important P5 interactions. Our results confirm that the inhibition of furin is a promising strategy for a short‐term treatment of acute infectious diseases.     

Formulating Pantone colors by unused base inks,formulation software,and a spectrophotometer

Unused base inks that are not going to be used for printing production are considered to be hazardous materials. Their disposal is expensive, and strict environmental regulations should be followed for their disposal. As an alternative, this article describes how spectral data of unused base inks can be gathered and mixed to generate new colors to incorporate them back to print production for small‐volume jobs. In this study, 30 different Pantone colors were selected as target colors. The CIE L*a*b* spectral data of Pantone colors and unused base inks were gathered via a spectrophotometer. A commercial formulation software, based on multiflux theory and CIE L*a*b* color space, was used to formulate ink recipes that contained the base inks. To quantify the performance of ink recipes, they were mixed and printed using an offset printability tester. The CIELAB ΔE*_ab metric, developed by CIE, was used to detect the visual differences between the target Pantone Color and printed colors.