PARP1 Gene Knockout Suppresses Expression of DNA Base Excision Repair Genes.

The effect of PARP1 knockout in HEK293 cells on the gene expression of DNA base excision repair (BER) proteins was studied. It was shown that the expression of all differentially expressed genes (DEGs) of BER was reduced by knockout. The expression of the DNA glycosylase gene NEIL1, which is considered to be one of the common "hubs" for binding BER proteins, has changed the most. The expression of genes of auxiliary subunits of DNA polymerases δ and ε is also significantly reduced. The PARP1 gene knockout cell line obtained is an adequate cell model for studying the activity of the BER process in the absence of PARP1 and testing drugs aimed at inhibiting repair processes. It has been found for the first time that knockout of the PARP1 gene results in a significant change in the level of expression of proteins responsible for ribosome biogenesis and the functioning of the proteasome.

Photochemical activity in developing pea (Pisum sativum L.) cotyledons depends on the light transmittance of covering tissues and the spectral composition of light.

Many crops require not only leaf photosynthesis for their seed development but also the photochemical reactions that occur in the seeds. The purpose of this work was a comparative analysis of light transmittance and photochemical activity in the leaves of Pisum sativum L. and its pericarp, seed coat, and cotyledons at the early, middle, and late maturation stages. The spectral composition of light was measured using a spectroradiometer in the range of 390-760 nm. We assessed the light transmittance of plant tissues by placing the plant tissue between the light source and the spectroradiometer's sensor. PAM fluorometry was used to quantify the photochemical activity in plant tissues: this technique is handy for evaluating the efficiency of converting light energy into chemical energy through the analysis of the kinetics of chlorophyll fluorescence excitation and quenching. On average, a photochemically active green leaf of pea transmitted 15 % of solar radiation in the 390-760 nm, blue light was delayed entirely, and the transmitted red light never exceeded 5 %. Photochemically active radiation passing through the pericarp and coat and reaching the cotyledons at the early and middle seed maturation stages manifested a high proportion of green and far-red light; there was no blue light, and the percentage of red light was about 2 %. However, the cotyledons were photochemically active regardless of low irradiance and spectral ranges untypical of leaf photosynthesis. At the early and middle maturation stages, the maximum quantum yield of photosystem II (Fv/Fm) averaged 0.5 at the periphery of cotyledons and 0.3 at their center. Since the intensity of embryonic photochemical reactions significantly affects the efficiency of reserve nutrient accumulation, this parameter is a promising marker in pea breeding for seeds with improved nutritional qualities.

Traditional Buddhist meditations reduce mismatch negativity in experienced monk- practitioners.

Thousand-year-old Buddhist traditions have developed a wide range of methods for the subjective exploration of consciousness through meditation. Combining their subjective research with the possibilities of modern neuroscience can help us better understand the physiological mechanisms of consciousness. Therefore, we have been guided by specifically Buddhist explanations when studying the physiological mechanisms of altered states of consciousness during Buddhist meditations. In Buddhism, meditations are generally divided into two large categories: (1) one-pointed concentration and (2) analytical meditation. Maintaining both one-pointed concentration and analytical meditation on 'bodhicitta' ("the thought of awakening") and 'emptiness' is a necessary condition for transitioning into tantric practices. Tantric practices involve sophisticated visualizations of Buddhist deities, the 'energy structure' of the human body, and the visualization of the stage-by-stage process of dying accompanied with the dissolution of body elements. According to Buddhism, these meditations are characterized by the gradual withdrawal from "gross levels" of consciousness associated with the five senses. From a psychophysiological perspective, this withdrawal of sensory consciousness can be considered as the decrease of sensory stimuli recognition and attentional disengagement from the external world. We concentrated on how considered meditations affect sensory and cognitive processing of external stimuli. Auditory event-related potentials (ERPs) in the passive oddball paradigm were studied both during meditations and in a controlled state of relaxed wakefulness. It was shown with a group of 115 Buddhist monks that during meditation, mismatch negativity amplitudes, amplitudes of N1 and P2 components of ERPs to deviant stimuli, and the amplitudes of the P3a component to novel stimuli all decrease. These outcomes suggest that the considered Buddhist meditations, compared to the control state of relaxed wakefulness, are accompanied by a decrease in physiological processes responsible for maintaining attention on the outside world and recognizing changes in the stream of sensory stimuli.

Coexistence of Superconductivity and Charge Density Waves in Tantalum Disulfide: Experiment and Theory.

The coexistence of charge density wave (CDW) and superconductivity in tantalum disulfide (2H-TaS_{2}) at low temperature is boosted by applying hydrostatic pressures to study both vibrational and magnetic transport properties. Around P_{c}, we observe a superconducting dome with a maximum superconducting transition temperature T_{c}=9.1 K. First-principles calculations of the electronic structure predict that, under ambient conditions, the undistorted structure is characterized by a phonon instability at finite momentum close to the experimental CDW wave vector. Upon compression, this instability is found to disappear, indicating the suppression of CDW order. The calculations reveal an electronic topological transition (ETT), which occurs before the suppression of the phonon instability, suggesting that the ETT alone is not directly causing the structural change in the system. The temperature dependence of the first vortex penetration field has been experimentally obtained by two independent methods. While a d wave and single-gap BCS prediction cannot describe the lower critical field H_{c1} data, the temperature dependence of the H_{c1} can be well described by a single-gap anisotropic s-wave order parameter.

Generation of induced pluripotent stem cell lines ICGi021-A and ICGi022-A from peripheral blood mononuclear cells of two healthy individuals from Siberian population.

ICGi021-A and ICGi022-A iPSC lines were obtained by reprogramming PBMCs of two healthy women of the Siberian population using episomal non-integrating vectors expressing Yamanaka factors. iPSC lines expressed pluripotency markers, had a normal karyotype and demonstrated the ability to differentiate into derivatives of the three germ layers. Clinical exome sequencing data of the original biosamples of the donors are available in the NCBI SRA database. The generated cell lines are useful as "healthy" control in biomedical studies.

Complex study of air pollution in electroplating workshop.

A comprehensive analysis of the state of air inside an industrial workshop with electroplating production was carried out. The data of quantitative distribution of suspended particles by size fractions (PM0.3, PM0.5, PM1, PM3, PM5, PM10) are presented for 15 main processes of electroplating. Morphometric and chemical composition of the surface of particles were studied. We observed particles of rounded shape, various agglomerates with complex geometric shapes, acute-angular particles, which when inhaled pose a maximum threat to human health. Chemical analysis of these particles showed an absolute predominance of oxides of non-ferrous metals, the percentage of which varied depending on the type of electroplating bath. The content of highly hazardous substances of the 1st (Zn, Pb, and Cd) and the 2nd (Cu, Cr, Ni, Co, and Mo) hazard classes in each sample was recorded.

Studying ALS: Current Approaches, Effect on Potential Treatment Strategy.

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, characterized by inevitable progressive paralysis. To date, only two disease modifying therapeutic options are available for the patients with ALS, although they show very modest effect on disease course. The main reason of failure in the field of pharmacological correction of ALS is inability to untangle complex relationships taking place during ALS initiation and progression. Traditional methods of research, based on morphology or transgenic animal models studying provided lots of information about ALS throughout the years. However, translation of these results to humans was unsuccessful due to incomplete recapitulation of molecular pathology and overall inadequacy of the models used in the research.In this review we summarize current knowledge regarding ALS molecular pathology with depiction of novel methods applied recently for the studies. Furthermore we describe present and potential treatment strategies that are based on the recent findings in ALS disease mechanisms.

Generation of an induced pluripotent stem cell line, ICGi014-A, by reprogramming peripheral blood mononuclear cells from a patient with homozygous D90A mutation in SOD1 causing Amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by death of motor neurons. To date, neither etiology nor pathogenesis of ALS are known, which leads to the absence of an effective treatment strategy. ALS patient-specific induced pluripotent stem cells (iPSCs) represent an excellent tool for the disease study. We obtained iPSCs line from peripheral blood mononuclear cells of the patient with homozygous Asp90Ala mutation in the SOD1 gene using non-integrating episomal vectors. The iPSCs line retained pathological genotype and expressed pluripotency markers. It also displayed a normal karyotype and the ability to differentiate into derivatives of three germ layers.

Generation of two iPSC lines, (ICGi015-A and ICGi015-B), by reprogramming peripheral blood mononuclear cells from a patient with Parkinson's disease.

Studying Parkinson's disease (PD), one of the most common neurodegenerative disorders worldwide, requires different model systems, including patient-specific induced pluripotent stem cell lines. With the help of non-integrating episomal vectors the iPSC lines ICGi015-A and ICGi015-B were generated from blood mononuclear cells of PD patient, carrying three SNPs, associated with PD development. The obtained iPSC lines express pluripotency markers and demonstrate the ability to in vitro differentiate into the three germ layers. These cell lines may be useful for studying molecular mechanisms of PD and for drug screening.

Applying Patient-Specific Induced Pluripotent Stem Cells to Create a Model of Hypertrophic Cardiomyopathy.

Generation of patient-specific induced pluripotent stem cells (iPSCs) and their subsequent differentiation into cardiomyocytes opened new opportunities for studying pathogenesis of inherited cardiovascular diseases. One of these diseases is hypertrophic cardiomyopathy (HCM) for which no efficient therapy methods have been developed so far. In this study, the approach based on patient-specific iPSCs was applied to create a model of the disease. Genetic analysis of a hypertrophic cardiomyopathy patient revealed R326Q mutation in the MYBPC3 gene. iPSCs of the patient were generated and characterized. The cells were differentiated into cardiomyocytes together with the control iPSCs from a healthy donor. The patient's iPSC-derived cardiomyocytes exhibited early HCM features, such as abnormal calcium handling and increased intracellular calcium concentration. Therefore, cardiomyocytes obtained by directed differentiation of iPSCs from the HCM patient can be used as a model system to study HCM pathogenesis.

A Platform for Studying Neurodegeneration Mechanisms Using Genetically Encoded Biosensors.

Patient-specific induced pluripotent stem cells (iPSCs) capable of differentiation into required cell type are a promising model for studying various pathological processes and development of new therapeutic approaches. However, no conventional strategies for using iPSCs in disease research have been established yet. Genetically encoded biosensors can be used for monitoring messenger molecules, metabolites, and enzyme activity in real time with the following conversion of the registered signals in quantitative data, thus allowing evaluation of the impact of certain molecules on pathology development. In this article, we describe the development of a universal cell-based platform for studying pathological processes associated with amyotrophic lateral sclerosis. For this purpose, we have created a series of plasmid constructs for monitoring endoplasmic reticulum stress, oxidative stress, apoptosis, and Ca2+-dependent hyperexcitability and generated transgenic iPSC line carrying mutation in the superoxide dismutase 1 gene (SOD1) and healthy control cell line. Both cell lines have specific transactivator sequence required for doxycycline-controlled transcriptional activation and can be used for a single-step biosensor insertion.

Nonlinear Fourier Transform for Analysis of Coherent Structures in Dissipative Systems.

Using the cubic Ginzburg-Landau equation as an example, we demonstrate how the inverse scattering transform can be applied to characterize coherent structures in dissipative nonlinear systems. Using this approach one can reduce the number of the effective degrees of freedom in the system when the dynamic is dominated by the coherent structures, even if they are embedded in the dispersive waves and demonstrate unstable behavior.

Generation of two iPSC lines (ICGi008-A and ICGi008-B) from skin fibroblasts of a patient with early-onset Alzheimer's disease caused by London familial APP mutation (V717I).

The induced pluripotent stem cell (iPSC) lines ICGi008-A and ICGi008-B were generated from dermal fibroblasts using episomal vectors expressing pluripotency factors. Dermal fibroblasts were obtained from a 55 year old male Сaucasian familial Alzheimer's disease (AD) patient carrying heterozygous V717I mutation in the APP gene. The generated iPSC lines maintained the original APP genotype, expressed pluripotency markers, exhibited a normal karyotype and retained the ability to differentiate into cell types of the three germ layers. The iPSC lines will be useful for the study of the AD molecular and cellular mechanisms and drug screening.

Generation of two spinal muscular atrophy (SMA) type I patient-derived induced pluripotent stem cell (iPSC) lines and two SMA type II patient-derived iPSC lines.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletion or mutation in SMN1 gene. SMA human induced pluripotent stem cells (iPSCs) represent a useful and valid model for the study of the disorder, as they provide in vitro the target cells. We generated iPSCs from a SMA type I patient and SMA type II patient by using non-integrating episomal plasmid vectors. The resulting iPSCs are episomal-free, express pluripotency markers, display a normal karyotype, retain the mutation (homozygous deletion of SMN1) and are able to differentiate into the three germ layers.

Coxiella burnetii in ticks and wild birds.

The study objective was to get more information on C. burnetii prevalence in wild birds and ticks feeding on them, and the potentialities of the pathogen dissemination over Europe by both. MATERIALS: Blood, blood sera, feces of wild birds and ticks removed from those birds or from vegetation were studied at two sites in Russia: the Curonian Spit (site KK), and the vicinity of St. Petersburg (site SPb), and at two sites in Bulgaria: the Atanasovsko Lake (site AL), and the vicinity of Sofia (site SR). METHODS: C. burnetii DNA was detected in blood, feces, and ticks by PCR (polymerase chain reaction). All positive results were confirmed by Sanger's sequencing of 16SrRNA gene target fragments. The antibodies to C. burnetii in sera were detected by CFR (complement fixation reaction). RESULTS: Eleven of 55 bird species captured at KK site hosted Ixodes ricinus. C. burnetii DNA was detected in three I. ricinus nymphs removed from one bird (Erithacus rubecula), and in adult ticks flagged from vegetation: 0.7% I. persulcatus (site SPb), 0.9% I. ricinus (site KK), 1.0% D. reticulatus (AL site). C. burnetii DNA was also detected in 1.4% of bird blood samples at SPb site, and in 0.5% of those at AL site. Antibodies to C. burnetii were found in 8.1% of bird sera (site SPb). C. burnetii DNA was revealed in feces of birds: 0.6% at AL site, and 13.7% at SR site. CONCLUSIONS: Both molecular-genetic and immunological methods were applied to confirm the role of birds as a natural reservoir of C. burnetii. The places of wild bird stopover in Russia (Baltic region) and in Bulgaria (Atanasovsko Lake and Sofia region) proved to be natural foci of C. burnetii infection. Migratory birds are likely to act as efficient "vehicles" in dispersal of C. burnetii -infested ixodid ticks.

Pressure-induced metallization in layered ReSe2.

The evolution of the crystal structure and electrical transport properties of distorted layered transition metal dichalcogenide ReSe2 was studied under high pressure up to ~90 GPa by Raman spectroscopy and electrical resistivity measurements accompanied by ab initio electronic band structure calculations. Raman spectroscopy studies indicate an isostructural phase transition due to layer sliding at ~7 GPa, to the distorted 1T-phase which remains stable up to the highest pressures employed in these experiments. From a direct band gap semiconductor at ambient pressure, ReSe2 undergoes pressure-induced metallization at pressures ~35 GPa, in agreement with the ab initio calculations. Resistivity measurements performed with different loading conditions reveal the possible emergence of superconductivity, which is most likely not an intrinsic property of ReSe2, but is rather conditioned by internal stresses upon compression.

Simple geometric interpretation of signal evolution in phase-sensitive fibre optic parametric amplifier.

Visualisation of complex nonlinear equation solutions is a useful analysis tool for various scientific and engineering applications. We have re-examined the geometrical interpretation of the classical nonlinear four-wave mixing equations for the specific scheme of a phase sensitive one-pump fiber optical parametric amplification, which has recently attracted revived interest in the optical communications due to potential low noise properties of such amplifiers. Analysis of the phase portraits of the corresponding dynamical systems provide valuable additional insight into field dynamics and properties of the amplifiers. Simple geometric approach has been proposed to describe evolution of the waves, involved in phase-sensitive fiber optical parametric amplification (PS-FOPA) process, using a Hamiltonian structure of the governing equations. We have demonstrated how the proposed approach can be applied to the optimization problems arising in the design of the specific PS-FOPA scheme. The method considered here is rather general and can be used in various applications.

Atomic and electronic structures evolution of the narrow band gap semiconductor Ag2Se under high pressure.

Non-trivial electronic properties of silver telluride and other chalcogenides, such as the presence of a topological insulator state, electronic topological transitions, metallization, and the possible emergence of superconductivity under pressure have attracted attention in recent years. In this work, we studied the electronic properties of silver selenide (Ag2Se). We performed direct current electrical resistivity measurements, in situ Raman spectroscopy, and synchrotron x-ray diffraction accompanied by ab initio calculations to explore pressure-induced changes to the atomic and electronic structure of Ag2Se. The temperature dependence of the electrical resistivity was measured up to 30 GPa in the 4-300 K temperature interval. Resistivity data showed an unusual increase in the thermal energy gap of phase I, which is a semiconductor under ambient conditions. Recently, a similar effect was reported for the 3D topological insulator Bi2Se3. Raman spectroscopy studies revealed lattice instability in phase I indicated by the softening of observed vibrational modes with pressure. Our hybrid functional band structure calculations predicted that phase I of Ag2Se would be a narrow band gap semiconductor, in accordance with experimental results. At a pressure of ~7.5 GPa, Ag2Se underwent a structural transition to phase II with an orthorhombic Pnma structure. The temperature dependence of the resistivity of Ag2Se phase II demonstrated its metallic character. Ag2Se phase III, which is stable above 16.5 GPa, is also metallic according to the resistivity data. No indication of the superconducting transition is found above 4 K in the studied pressure range.

[A clinical case of combined treatment of a patient with breast cancer and metastases to the brain and meninges].

The article describes a clinical case of successful chemotherapeutic and radiation treatment of a patient with breast cancer and metastases to the brain and meninges and with a pronounced neurological deficit. The patient underwent combined treatment (whole brain radiation with TBD of 30 Gy and local radiation of a metastasis with TBD of 15 Gy associated with capecitabine therapy) with continued administration of capecitabine until improvement. A partial metastasis reduction by 50% and complete regression of the neurological deficit were observed. Disease-free period was 1 year and 10 months, and the overall survival amounted to 2 years.