The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels

Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a similar to 10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heartderived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity

Validation and Estimation of Parameters for a General Probabilistic Model of the PCR Process

Earlier work by Saha et al. rigorously derived a general probabilistic model for the PCR process that includes as a special case the Velikanov-Kapral model where all nucleotide reaction rates are the same. In this model the probability of binding of deoxy-nucleoside triphosphate (dNTP) molecules with template strands is derived from the microscopic chemical kinetics. A recursive solution for the probability function of binding of dNTPs is developed for a single cycle and is used to calculate expected yield for a multicycle PCR. The model is able to reproduce important features of the PCR amplification process quantitatively. With a set of favorable reaction conditions, the amplification of the target sequence is fast enough to rapidly outnumber all side products. Furthermore, the final yield of the target sequence in a multicycle PCR run always approaches an asymptotic limit that is less than one. The amplification process itself is highly sensitive to initial concentrations and the reaction rates of addition to the template strand of each type of dNTP in the solution. This paper extends the earlier Saha model with a physics based model of the dependence of the reaction rates on temperature, and estimates parameters in this new model by nonlinear regression. The calibrated model is validated using RT-PCR data. Key words: Levenberg-Marquardt algorithm, multicycle PCR, nonlinear regression, polymerase chain reaction (PCR), probabilistic model, yield. 1

Magnetoelectric and magnetodielectric coupling in partially Ni-doped CoFe2O4 and 0.15(Ba0.7Ca0.3TiO3)-0.85(BaZr0.2Ti0.8O3) composites prepared via clean microwave sintering

Multiferroic composites with high magnetoelectric coupling at room temperature are considered as the most significant materials due to their potential application in many electronic devices. Furthermore, ultrafast, eco-friendly energy-efficient innovative techniques to develop multifunctional materials have attracted abundant importance. In this study, we report on ferrite–ferroelectric particulate composites prepared via clean, eco-friendly, ultrafast, hybrid-microwave sintering. Partially Ni-doped CoFe2O4 was selected as a magnetostrictive phase due to its considerable value of the magnetostriction coefficient, λ11 ≈ −118 ppm, saturation magnetization Ms ≈ 80 emu/gm, and μB ≈ 3.37 and mixed with a 0.15(Ba0·7Ca0·3TiO3)–0.85(BaZr0·2Ti0·8O3) ferroelectric phase in different content ratios of 10%, 20%, 30%, and 40%. The multiferroic properties of the sintered composite samples were investigated considering magnetoelectric and magnetodielectric couplings. The highest value of the magnetoelectric coupling coefficient, αME = 22..09 mV/Oe·cm was observed for the composite with 40% ferrite content, while similar composite exhibits the higher value of the magnetodielectric coupling coefficient which is 3.52% at 1 kHz (frequency) and 1 T (magnetic field). X-ray diffraction and Raman spectroscopy confirmed the phases of the ferrite and ferroelectric constituents without revealing any additional phases. The impedance and AC conductivity of the multiferroic compositions were analyzed under various temperatures and by applying a magnetic field at room temperature. The temperature-dependent dielectric nature confirms that the addition of Ni-doped CoFe2O4 into a ferroelectric constituent substantially influences the dielectric constant in the paraelectric region. These results may offer an alternative technique for the preparation of multiferroic composites with improved coupling properties. © 2020 Elsevier B.V.1

Correlative structural refinement-magnetic tunability, and enhanced magnetostriction in low-temperature, microwave-annealed, Ni-substituted CoFe2O4 nanoparticles

The preparation of nanomaterials by conventional methods involves multiple steps that are time-and energy-consuming; hence, it must be replaced by clean, environment-friendly processes. Nanostructured mixed spinel ferrites have wide applicability given their electrical, magnetic, and magnetostrictive properties. Herein, we present an ultrafast, eco-friendly, and thermally efficient microwave (MW)-heating technique to replace the conventional strategies for the preparation of Ni-doped CoFe2O4 ferrite nano particles. Mixed spinel ferrite nanoparticles are obtained through an MW technique carried out for 20 min at 600 degrees C. The cubic nature of the MW-processed, Ni-substituted CoFe2O4 spinel ferrite is demonstrated by Rietveld refinement. Composition-dependent tunable magnetic properties associated with cation distribution and average crystallite size variation are realized by the substitution of Ni2+ at Co2+ in the CoFe2O4 lattice. The highest values of saturation magnetization and coercivity are noted for the Co0.9Ni0.1Fe2O4 ferrite at 5 K and the average crystallite size is similar to 20 nm; the octa to tetra transition of Co2+ is observed owing to substitution by Ni2+ ions. The highest values of magnetostrictive coefficient and strain sensitivity are detected for CoFe2O4; the Ni2+-substituted Co0.9Ni0.1Fe2O4 also exhibits nearly identical behavior. Thus, Ni2+-substituted CoFe2O4 is a remarkable magnetostrictive material suitable for developing magnetoelectric composites and magneto-mechanical sensor applications. Moreover, it is observed that efficient, fast, and eco-friendly microwave processing can be adopted as an alternative approach for low-temperature processing such kinds of nanostructured materials for future electromagnetic device applications. (C) 2021 Elsevier B.V. All rights reserved