The effect of temperature and oxygen partial pressure on the concentration of iron and manganese ions in La1/3Sr2/3Fe1-xMnxO3-δ.

The oxygen content was measured in cubic perovskite-type La1/3Sr2/3Fe1-xMnxO3-δ (x = 0.1, 0.17, 0.25, and 1/3) in the range of oxygen partial pressure from 10-22 to 0.5 atm at 750-950 °C with a step of 50 °C by coulometric titration. Gradual removal of oxygen from the oxides during the measurements was carried out until the stability limit was achieved and the reductive decomposition began. An increase in manganese content was shown to lead to a decrease in the stability of La1/3Sr2/3Fe1-xMnxO3-δ under reducing conditions. The obtained data on oxygen content were used for defect chemistry modeling in the oxides. The enthalpy of the Fe3+ to Fe4+ and Mn3+ to Mn4+ oxidation reactions (ΔHox0) was determined to be -103.2 ± 0.3 and -250 ± 2 kJ mol-1, respectively, for the x = 0.1 composition, and increased slightly with increasing manganese content. The large difference in ΔHox0 determines a strong distinction between the behavior of iron and manganese in perovskite-type oxides. An increase in manganese content in La1/3Sr2/3Fe1-xMnxO3-δ was found to lead to a decrease in the concentration of Fe4+ ions, but did not affect the concentration of Fe2+ ions. The impact of La/Sr ratio was evaluated by comparison of the obtained data with that for La0.5Sr0.5Fe1-xMnxO3-δ, and found to be different for iron and manganese. An increase in lanthanum fraction causes a decrease in the concentration of Fe2+ ions and an increase in the concentration of Mn2+ under reducing conditions.

Miyoshi myopathy associated with spine rigidity and multiple contractures: a case report.

BACKGROUND: Dysferlinopathy is a phenotypically heterogeneous group of hereditary diseases caused by mutations in the DYSF gene. Early contractures are considered rare, and rigid spine syndrome in dysferlinopathy has been previously reported only once. CASE PRESENTATION: We describe a 23-year-old patient with Miyoshi myopathy with a rigid spine and multiple contractures, a rare phenotypic variant. The disease first manifested when the patient was 13 years old, with fatigue of the gastrocnemius muscles and the development of pronounced contractures of the Achilles tendons, flexors of the fingers, and extensors of the toes, followed by the involvement of large joints and the spine. Magnetic resonance imaging revealed signs of connective tissue and fatty replacement of the posterior muscles of the thighs and lower legs. Edema was noted in the anterior and medial muscle groups of the thighs, lower legs, and the multifidus muscle of the back. Whole genome sequencing revealed previously described mutations in the DYSF gene in exon 39 (c.4282 C > T) and intron 51 (c.5785-824 C > T). An immunohistochemical analysis and Western blot showed the complete absence of dysferlin protein expression in the muscle fibers. CONCLUSIONS: This case expands the range of clinical and phenotypic correlations of dysferlinopathy and complements the diagnostic search for spine rigidity.

Studying the Brain Monoaminergic Systems and Neurotrophic Factors in Minipigs with High and Low Tolerance to the Presence of Human.

Here, we present the first evidence for brain adaptation in pigs tolerant to the human presence, as a behavioral trait favoring domestication. The study was carried out on minipiglets from population bred at the Institute of Cytology and Genetics (Novosibirsk, Russia). We compared the behavior, metabolism of monoaminergic neurotransmitter systems, and functional activity of the hypothalamic-pituitary-adrenal system, as well as neurotrophic markers in the brain of minipigs differing by tolerance to human presence (HT and LT - high and low tolerance). The piglets did not differ in the levels of activity in the open field test. However, the concentration of cortisol plasma was significantly higher in minipigs with a low tolerance to the presence of humans. Moreover, LT minipigs demonstrated a decreased level of serotonin in the hypothalamus and augmented levels of serotonin and its metabolite 5-HIAA in the substantia nigra as compared to HT animals. In addition, LT minipigs showed increased content of dopamine and its metabolite DOPAC in the substantia nigra and decreased dopamine level in the striatum as well as reduced content of noradrenaline in the hippocampus. Increased mRNA levels of two markers of the serotonin system - TPH2 and HTR7 genes - in the raphe nuclei and in the prefrontal cortex, respectively, were associated in minipigs with a low tolerance to human presence. However, the expression of genes regulating a dopaminergic system (COMT, DRD1, and DRD2) in HT and LT animal groups varied depending on brain structure. In addition, a decrease in the expression of genes encoding BDNF (brain-derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) was revealed in LT minipigs. The results may contribute to our understanding of the initial stage of domestication in pigs.

Nerve ultrasound normal values in children and young adults.

BACKGROUND: The objective of the study was to determine the reference values for cross-sectional area (CSA) of the nerves in healthy subjects between the age of 2 and 30 years. METHODS: High-resolution ultrasonography (HRU) of the median, ulnar, tibial, sural, peroneal and spinal nerves C5-C7 was performed in 72 healthy subjects. RESULTS: The CSA of peripheral nerves demonstrated an age-dependent increase in size at all measurement sites in children up to around 14 years of age. This was most pronounced for large lower limb nerves and least for small nerves. Intra-nerve and inter-nerve variability of nerve CSA did not change with age. CONCLUSIONS: This study provides normative values for HRU of peripheral nerves in children and young adults. Adult reference values should not be used for children under the age of 14 years.

Comparative studies of adhesion peptides based on l- or d-amino acids.

Detailed studies comparing solid-supported l- or d-amino acid adhesion peptides based on the sequence KLHRIRA were performed. Stability towards proteases and levels of cellular adhesion to the otherwise inert surface of PEGA resin were compared by using fluorescently labelled peptides. A clear difference in the peptide stability towards cleavage by subtilisin, trypsin, or papain was observed. However, all of the on-bead peptides provided an optimal surface for cell adhesion and proliferation. In long-term experiments, these properties were still found to be similar on the resins modified either with l- or with d-amino acids and unaffected by the nature of their fluorescence labelling at either terminus. These results support that the more accessible l-amino acids can be utilized for cell adhesion experiments and confirm the nonspecific interaction mechanism of cell binding to these peptides on the bead surface. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Mild phenotype of CHAT-associated congenital myasthenic syndrome: case series.

Congenital myasthenic syndrome with episodic apnea is associated with pathogenic variants in the CHAT gene. While respiratory disorders and oculomotor findings are commonly reported in affected individuals, a subset of patients only present with muscle weakness and/or ptosis but not apneic crises. In this case series, we describe five individuals with exercise intolerance caused by single nucleotide variants in the CHAT gene. The age of onset ranged from 1 to 2.5 years, and all patients exhibited a fluctuating course of congenital myasthenic syndrome without disease progression over several years. Notably, these patients maintained a normal neurological status, except for the presence of abnormal fatigability in their leg muscles following prolonged physical activity. We conducted a modified protocol of repetitive nerve stimulation on the peroneal nerve, revealing an increased decrement in amplitude and area of compound muscle action potentials of the tibialis anterior muscle after 15-20 min of exercise. Treatment with 3,4-diaminopyridine showed clear improvement in two children, while one patient experienced severe adverse effects and is currently receiving a combination of Salbutamol Syrup and pyridostigmine with slight positive effects. Based on our findings and previous cases of early childhood onset with muscle fatigability as the sole manifestation, we propose the existence of a mild phenotype characterized by the absence of apneic episodes.

Weighted Single-Step Genomic Best Linear Unbiased Prediction Method Application for Assessing Pigs on Meat Productivity and Reproduction Traits.

Changes in the accuracy of the genomic estimates obtained by the ssGBLUP and wssGBLUP methods were evaluated using different reference groups. The weighting procedure's reasonableness of application Pwas considered to improve the accuracy of genomic predictions for meat, fattening and reproduction traits in pigs. Six reference groups were formed to assess the genomic data quantity impact on the accuracy of predicted values (groups of genotyped animals). The datasets included 62,927 records of meat and fattening productivity (fat thickness over 6-7 ribs (BF1, mm)), muscle depth (MD, mm) and precocity up to 100 kg (age, days) and 16,070 observations of reproductive qualities (the number of all born piglets (TNB) and the number of live-born piglets (NBA), according to the results of the first farrowing). The wssGBLUP method has an advantage over ssGBLUP in terms of estimation reliability. When using a small reference group, the difference in the accuracy of ssGBLUP over BLUP AM is from -1.9 to +7.3 percent points, while for wssGBLUP, the change in accuracy varies from +18.2 to +87.3 percent points. Furthermore, the superiority of the wssGBLUP is also maintained for the largest group of genotyped animals: from +4.7 to +15.9 percent points for ssGBLUP and from +21.1 to +90.5 percent points for wssGBLUP. However, for all analyzed traits, the number of markers explaining 5% of genetic variability varied from 71 to 108, and the number of such SNPs varied depending on the size of the reference group (79-88 for BF1, 72-81 for MD, 71-108 for age). The results of the genetic variation distribution have the greatest similarity between groups of about 1000 and about 1500 individuals. Thus, the size of the reference group of more than 1000 individuals gives more stable results for the estimation based on the wssGBLUP method, while using the reference group of 500 individuals can lead to distorted results of GEBV.

Ultrafast signatures of magnetic inhomogeneity in Pd1- x Fe x (x ≤ 0.08) epitaxial thin films.

A series of Pd1- x Fe x alloy epitaxial films (x = 0, 0.038, 0.062, and 0.080), a material promising for superconducting spintronics, was prepared and studied with ultrafast optical and magneto-optical laser spectroscopy in a wide temperature range of 4-300 K. It was found that the transition to the ferromagnetic state causes a qualitative change of both the reflectivity and the magneto-optical Kerr effect transients. A nanoscale magnetic inhomogeneity of the ferromagnet/paramagnet type inherent in the palladium-rich Pd1- x Fe x alloys reveals itself through the occurrence of a relatively slow, 10-25 ps, photoinduced demagnetization component following a subpicosecond one; the former vanishes at low temperatures only in the x = 0.080 sample. We argue that the 10 ps timescale demagnetization originates most probably from the diffusive transport of d electrons under the condition of nanoscale magnetic inhomogeneities. The low-temperature fraction of the residual paramagnetic phase can be deduced from the magnitude of the slow reflectivity relaxation component. It is estimated as ≈30% for x = 0.038 and ≈15% for x = 0.062 films. The minimal iron content ensuring the magnetic homogeneity of the ferromagnetic state in the Pd1- x Fe x alloy at low temperatures is about 7-8 atom %.

Structural Features and Defect Equilibrium in Cubic PrBa1-xSrxFe2O6-δ.

The structure, oxygen non-stoichiometry, and defect equilibrium in perovskite-type PrBa1-xSrxFe2O6-δ (x = 0, 0.25, 0.50) synthesized at 1350 °C were studied. For all compositions, X-ray diffraction testifies to the formation of a cubic structure (S.G. Pm3¯m), but an electron diffraction study reveals additional diffuse satellites around each Bragg spot, indicating the primary incommensurate modulation with wave vectors about ±0.43a*. The results were interpreted as a sign of the short-order in both A-cation and anion sublattices in the areas of a few nanometers in size, and of an intermediate state before the formation of an ordered superstructure. An increase in oxygen deficiency was found to promote the ordering, whereas partial substitution of barium by strontium caused the opposite effect. The oxygen content in oxides as a function of oxygen partial pressure and temperature was measured by coulometric titration, and the data were used for the modeling of defect equilibrium in oxides. The simulation results implied oxygen vacancy ordering in PrBa1-xSrxFe2O6-δ that is in agreement with the electron diffraction study. Besides oxidation and charge disproportionation reactions, the reactions of oxygen vacancy distribution between non-equivalent anion positions, and their trapping in clusters with Pr3+ ions were taken into account by the model. It was demonstrated that an increase in the strontium content in Pr0.5Ba0.5-xSrxFeO3-δ suppressed ordering of oxygen vacancies, increased the binding energy of oxygen ions in the oxides, and resulted in an increase in the concentration of p-type carriers.

Genetic and Clinical Spectrum of GNE Myopathy in Russia.

GNE myopathy (GNEM) is a rare hereditary disease, but at the same time, it is the most common distal myopathy in several countries due to a founder effect of some pathogenic variants in the GNE gene. We collected the largest cohort of patients with GNEM from Russia and analyzed their mutational spectrum and clinical data. In our cohort, 10 novel variants were found, including 2 frameshift variants and 2 large deletions. One novel missense variant c.169_170delGCinsTT (p.(Ala57Phe)) was detected in 4 families in a homozygous state and in 3 unrelated patients in a compound heterozygous state. It was the second most frequent variant in our cohort. All families with this novel frequent variant were non-consanguineous and originated from the 3 neighboring areas in the European part of Russia. The clinical picture of the patients carrying this novel variant was typical, but the severity of clinical manifestation differed significantly. In our study, we reported two atypical cases expanding the phenotypic spectrum of GNEM. One female patient had severe quadriceps atrophy, hand joint contractures, keloid scars, and non-classical pattern on leg muscle magnetic resonance imaging, which was more similar to atypical collagenopathy rather than GNEM. Another patient initially had been observed with spinal muscular atrophy due to asymmetric atrophy of hand muscles and results of electromyography. The peculiar pattern of muscle involvement on magnetic resonance imaging consisted of pronounced changes in the posterior thigh muscle group with relatively spared muscles of the lower legs, apart from the soleus muscles. Different variants in the GNE gene were found in both atypical cases. Thus, our data expand the mutational and clinical spectrum of GNEM.

Impact of oxygen content on preferred localization of p- and n-type carriers in La0.5Sr0.5Fe1-xMnxO3-δ.

The oxygen content in La0.5Sr0.5Fe1-xMnxO3-δ, measured by coulometric titration in a wide range of oxygen partial pressure at various temperatures, was used for defect chemistry analysis. The obtained data were well approximated by a model assuming defect formation in La0.5Sr0.5Fe1-xMnxO3-δvia Fe3+ and Mn3+ oxidation reactions and charge disproportionation on Fe3+ and Mn3+ ions. The partial molar enthalpy and entropy of oxygen in La0.5Sr0.5Fe1-xMnxO3-δ obtained by statistical thermodynamic calculations were found to be in satisfactory agreement with those obtained using the Gibbs-Helmholtz equations, thus further confirming the adequacy of the model. The impact of manganese substitution on defect equilibrium in La0.5Sr0.5Fe1-xMnxO3-δ was shown to be attributed to a lower enthalpy of Mn3+ oxidation reaction (vs. for the oxidation of Fe3+) and the charge disproportionation reaction on Mn3+ (vs. for that on Fe3+). The former makes Mn4+ ions more resistant to reduction than Fe4+. The latter favors the presence of Mn2+, Mn3+, and Mn4+ ions in oxides in comparable concentrations. The distribution of charge carriers over iron and manganese ions was determined as a function of oxygen content in La0.5Sr0.5Fe1-xMnxO3-δ.

Application of Genomic Data for Reliability Improvement of Pig Breeding Value Estimates.

Replacement pigs' genomic prediction for reproduction (total number and born alive piglets in the first parity), meat, fatness and growth traits (muscle depth, days to 100 kg and backfat thickness over 6-7 rib) was tested using single-step genomic best linear unbiased prediction ssGBLUP methodology. These traits were selected as the most economically significant and different in terms of heritability. The heritability for meat, fatness and growth traits varied from 0.17 to 0.39 and for reproduction traits from 0.12 to 0.14. We confirm from our data that ssGBLUP is the most appropriate method of genomic evaluation. The validation of genomic predictions was performed by calculating the correlation between preliminary GEBV (based on pedigree and genomic data only) with high reliable conventional estimates (EBV) (based on pedigree, own phenotype and offspring records) of validating animals. Validation datasets include 151 and 110 individuals for reproduction, meat and fattening traits, respectively. The level of correlation (r) between EBV and GEBV scores varied from +0.44 to +0.55 for meat and fatness traits, and from +0.75 to +0.77 for reproduction traits. Average breeding value (EBV) of group selected on genomic evaluation basis exceeded the group selected on parental average estimates by 22, 24 and 66% for muscle depth, days to 100 kg and backfat thickness over 6-7 rib, respectively. Prediction based on SNP markers data and parental estimates showed a significant increase in the reliability of low heritable reproduction traits (about 40%), which is equivalent to including information about 10 additional descendants for sows and 20 additional descendants for boars in the evaluation dataset.

Magnetic resonance imaging pattern variability in dysferlinopathy.

The widespread use of magnetic resonance imaging (MRI) in the diagnosis of myopathies has made it possible to clarify the typical MRI pattern of dysferlinopathy. However, sufficient attention has not been given to the variability of MRI patterns in dysferlinopathy. MATERIALS AND METHODS: Twenty-five patients with the clinical manifestations of dysferlinopathy were examined. For all patients, creatine phosphokinase levels were measured and molecular genetics were examined. In two patients, immunohistochemical examinations of muscle biopsies were performed. MRI scanning was included T2 multi-slice multi-echo, T1 weighted, T2 weighted and Short Tau Inversion Recovery T2 weighted sequences. Quantitative and semi-quantitative evaluations of fatty replacement and swelling of the muscles were undertaken. RESULTS: Variability in the MRI patterns was lowest in the pelvis and leg muscles and highest in the thigh muscles. Three main types of MRI patterns were distinguished: posterior-dominant (80%), anterior-dominant (16%), and diffuse (4%). Among patients with the anterior-dominant pattern, the collagen-like variant (4%), proximal variant (4%) and pseudo-myositis (8%) were separately distinguished. CONCLUSIONS: Awareness of atypical MRI patterns in dysferlinopathy is important for increasing the efficiency of routine diagnostics and optimizing the search for causative gene mutations.

Artificial two-dimensional polar metal at room temperature.

Polar metals, commonly defined by the coexistence of polar crystal structure and metallicity, are thought to be scarce because the long-range electrostatic fields favoring the polar structure are expected to be fully screened by the conduction electrons of a metal. Moreover, reducing from three to two dimensions, it remains an open question whether a polar metal can exist. Here we report on the realization of a room temperature two-dimensional polar metal of the B-site type in tri-color (tri-layer) superlattices BaTiO3/SrTiO3/LaTiO3. A combination of atomic resolution scanning transmission electron microscopy with electron energy-loss spectroscopy, optical second harmonic generation, electrical transport, and first-principles calculations have revealed the microscopic mechanisms of periodic electric polarization, charge distribution, and orbital symmetry. Our results provide a route to creating all-oxide artificial non-centrosymmetric quasi-two-dimensional metals with exotic quantum states including coexisting ferroelectric, ferromagnetic, and superconducting phases.

Picosecond laser ultrasonics for imaging of transparent polycrystalline materials compressed to megabar pressures.

Picosecond laser ultrasonics is an all-optical experimental technique based on ultrafast high repetition rate lasers applied for the generation and detection of nanometric in length coherent acoustic pulses. In optically transparent materials these pulses can be detected not only on their arrival at the sample surfaces but also all along their propagation path inside the sample providing opportunity for imaging of the sample material spatial inhomogeneities traversed by the acoustic pulse. Application of this imaging technique to polycrystalline elastically anisotropic transparent materials subject to high pressures in a diamond anvil cell reveals their significant texturing/structuring at the spatial scales exceeding dimensions of the individual crystallites.

Revealing sub-µm and µm-scale textures in H2O ice at megabar pressures by time-domain Brillouin scattering.

The time-domain Brillouin scattering technique, also known as picosecond ultrasonic interferometry, allows monitoring of the propagation of coherent acoustic pulses, having lengths ranging from nanometres to fractions of a micrometre, in samples with dimension of less than a micrometre to tens of micrometres. In this study, we applied this technique to depth-profiling of a polycrystalline aggregate of ice compressed in a diamond anvil cell to megabar pressures. The method allowed examination of the characteristic dimensions of ice texturing in the direction normal to the diamond anvil surfaces with sub-micrometre spatial resolution via time-resolved measurements of the propagation velocity of the acoustic pulses travelling in the compressed sample. The achieved imaging of ice in depth and in one of the lateral directions indicates the feasibility of three-dimensional imaging and quantitative characterisation of the acoustical, optical and acousto-optical properties of transparent polycrystalline aggregates in a diamond anvil cell with tens of nanometres in-depth resolution and a lateral spatial resolution controlled by pump laser pulses focusing, which could approach hundreds of nanometres.

Application of 3-D imaging sensor for tracking minipigs in the open field test.

BACKGROUND: The minipig is a promising model in neurobiology and psychopharmacology. However, automated tracking of minipig behavior is still unresolved problem. NEW METHOD: The study was carried out on white, agouti and black (or spotted) minipiglets (n=108) bred in the Institute of Cytology and Genetics. New method of automated tracking of minipig behavior is based on Microsoft Kinect 3-D image sensor and the 3-D image reconstruction with EthoStudio software. The algorithms of distance run and time in the center evaluation were adapted for 3-D image data and new algorithm of vertical activity quantification was developed. RESULTS: The 3-D imaging system successfully detects white, black, spotted and agouti pigs in the open field test (OFT). No effect of sex or color on horizontal (distance run), vertical activities and time in the center was shown. Agouti pigs explored the arena more intensive than white or black animals, respectively. The OFT behavioral traits were compared with the fear reaction to experimenter. Time in the center of the OFT was positively correlated with fear reaction rank (ρ=0.21, p<0.05). Black pigs were significantly more fearful compared with white or agouti animals. COMPARISON WITH EXISTING METHOD: The 3-D imaging system has three advantages over existing automated tracking systems: it avoids perspective distortion, distinguishes animals any color from any background and automatically evaluates vertical activity. CONCLUSION: The 3-D imaging system can be successfully applied for automated measurement of minipig behavior in neurobiological and psychopharmacological experiments.

Temperature dependence of the optoacoustic transformation efficiency in ex vivo tissues for application in monitoring thermal therapies.

The calibration dependencies of the optoacoustic (OA) transformation efficiency on tissue temperature are obtained for the application in OA temperature monitoring during thermal therapies. Accurate measurement of the OA signal amplitude versus temperature is performed in different ex vivo tissues in the temperature range 25°C to 80°C. The investigated tissues were selected to represent different structural components: chicken breast (skeletal muscle), porcine lard (fatty tissue), and porcine liver (richly perfused tissue). Backward mode of the OA signal detection and a narrow probe laser beam were used in the experiments to avoid the influence of changes in light scattering with tissue coagulation on the OA signal amplitude. Measurements were performed in heating and cooling regimes. Characteristic behavior of the OA signal amplitude temperature dependences in different temperature ranges were described in terms of changes in different structural components of the tissue samples. The accuracy of temperature reconstruction from the obtained calibration dependencies for the investigated tissue types is evaluated.

A very large diversity space of synthetically accessible compounds for use with drug design programs.

We have constructed a very large virtual diversity space containing more than 10(13) chemical compounds. The diversity space is built from about 400 combinatorial libraries, which have been expanded by choosing sizeable collections of suitable R-groups that can be attached to each link point of their scaffolds. These R-group collections have been created by selecting reagents that have drug-like properties from catalogs of available chemicals. As members of known combinatorial libraries, the compounds in the diversity space are in general synthetically accessible and useful as potential drug leads. Hence, the diversity space can be used as a vast source of compounds by a de novo drug design program. For example, we have used such a program to generate inhibitors of HIV integrase enzyme that exhibited activity in the micromolar range.