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Neural network ensembling is a common and robust way to increase model efficiency. In this paper, we propose a new neural network ensemble algorithm based on Audibert's empirical star algorithm. We provide optimal theoretical minimax bound on the excess squared risk. Additionally, we empirically study this algorithm on regression and classification tasks and compare it to most popular ensembling methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Deep eutectic solvents (DESs) are eutectic mixtures of hydrogen bond acceptors and hydrogen bond donors which melt at much lower temperatures than the individual components. DESs are attracting growing interest because of a large variety of possible technological applications. Here, supercooled DESs consisting of choline chloride-urea (1 : 2) (reline) and of choline chloride-thiourea (1 : 2) (ChCl-thiourea), with introduced nitroxide spin probe tempone, were studied by electron paramagnetic resonance (EPR) spectroscopy. Conventional continuous wave (CW) EPR spectra showed the coexistence of solid and liquid microphases, with microviscosity of ∼ 10 P in the latter case. CW EPR spectra taken at different temperatures for ChCl-thiourea showed isosbestic points, which indicates that two phases are separated by sharp boundaries; for reline these points are rather diffuse, which in turn implies diffuse boundaries. Stochastic molecular librations detected by pulsed EPR possess the ability for elucidating nanoscale features of molecular packing; the data obtained showed a drastic difference for the onset of these motions for ChCl-thiourea and for reline, which was interpreted as evidence that the rigidity of molecular packing for ChCl-thiourea is stronger than that for reline. The temperature dependence of stochastic molecular librations for reline was found to be similar to that known for lipid bilayers and globular proteins, which indicates the proximity of the characteristics of molecular packing in these molecular systems.

Background: Most patients who take antihypertensive medications continue taking them on the morning of surgery and during the perioperative period. However, growing evidence suggests this practice may contribute to perioperative hypotension and a higher risk of complications. This protocol describes an acute kidney injury substudy of the Perioperative Ischemic Evaluation-3 (POISE-3) trial, which is testing the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy in patients undergoing noncardiac surgery., Objective: To conduct a substudy of POISE-3 to determine whether a perioperative hypotension-avoidance strategy reduces the risk of acute kidney injury compared with a hypertension-avoidance strategy., Design: Randomized clinical trial with 1:1 randomization to the intervention (a perioperative hypotension-avoidance strategy) or control (a hypertension-avoidance strategy)., Intervention: If the presurgery systolic blood pressure (SBP) is <130 mmHg, all antihypertensive medications are withheld on the morning of surgery. If the SBP is ≥130 mmHg, some medications (but not angiotensin receptor blockers [ACEIs], angiotensin receptor blockers [ARBs], or renin inhibitors) may be continued in a stepwise manner. During surgery, the patients' mean arterial pressure (MAP) is maintained at ≥80 mmHg. During the first 48 hours after surgery, some antihypertensive medications (but not ACEIs, ARBs, or renin inhibitors) may be restarted in a stepwise manner if the SBP is ≥130 mmHg., Control: Patients receive their usual antihypertensive medications before and after surgery. The patients' MAP is maintained at ≥60 mmHg from anesthetic induction until the end of surgery., Setting: Recruitment from 108 centers in 22 countries from 2018 to 2021., Patients: Patients (~6800) aged ≥45 years having noncardiac surgery who have or are at risk of atherosclerotic disease and who routinely take antihypertensive medications., Measurements: The primary outcome of the substudy is postoperative acute kidney injury, defined as an increase in serum creatinine concentration of either ≥26.5 μmol/L (≥0.3 mg/dL) within 48 hours of randomization or ≥50% within 7 days of randomization., Methods: The primary analysis (intention-to-treat) will examine the relative risk and 95% confidence interval of acute kidney injury in the intervention versus control group. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by preexisting chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate <60 mL/min/1.73 m 2 ., Results: Substudy results will be analyzed in 2022., Limitations: It is not possible to mask patients or providers to the intervention; however, objective measures will be used to assess acute kidney injury., Conclusions: This substudy will provide generalizable estimates of the effect of a perioperative hypotension-avoidance strategy on the risk of acute kidney injury., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) is recognized as an extremely powerful tool to study the interaction of numerous transcription factors and other chromatin-associated proteins with DNA. The core problem in the optimization of ChIP-seq protocol and the following computational data analysis is that a 'true' pattern of binding events for a given protein factor is unknown. Computer simulation of the ChIP-seq process based on 'a-priory known binding template' can contribute to a drastically reduce the number of wet lab experiments and finally help achieve radical optimization of the entire processing pipeline. We present a newly developed ChIP-sequencing simulation algorithm implemented in the novel software, in silico ChIP-seq (isChIP). We demonstrate that isChIP closely approximates real ChIP-seq protocols and is able to model data similar to those obtained from experimental sequencing. We validated isChIP using publicly available datasets generated for well-characterized transcription factors Oct4 and Sox2. Although the novel software is compatible with the Illumina protocols by default, it can also successfully perform simulations with a number of alternative sequencing platforms such as Roche454, Ion Torrent and SOLiD as well as model ChIP -Exo. The versatility of isChIP was demonstrated through modelling a wide range of binding events, including those of transcription factors and chromatin modifiers. We also performed a comparative analysis against a few existing ChIP-seq simulators and showed the fundamental superiority of our model. Due to its ability to utilize known binding templates, isChIP can potentially be employed to help investigators choose the most appropriate analytical software through benchmarking of available ChIP-seq programs and optimize the experimental parameters of ChIP-seq protocol. isChIP software is freely available at https://github.com/fnaumenko/isChIP., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Television exposure in early childhood has increased, with concerns raised regarding adverse effects on social-emotional development, and emerging self-regulation in particular. The present study addressed television exposure (i.e., amount of time watching TV) and its associations with toddler behavioral/emotional dysregulation, examining potential differences across 14 cultures. The sample consisted of an average of 60 toddlers from each of the 14 countries from the Joint Effort Toddler Temperament Consortium (JETTC; Gartstein & Putnam, 2018). Analyses were conducted relying on the multi-level modeling framework (MLM), accounting for between- and within-culture variability, and examining the extent to which TV exposure contributions were universal vs. variable across sites. Effects of time watching TV were evaluated in relation to temperament reactivity and regulation, as well as measures of emotional reactivity, attention difficulties, and aggression. Results indicated that more time spent watching TV was associated with higher ratings on Negative Emotionality, emotional reactivity, aggression, and attention problems, as well as lower levels of soothability. However, links between TV exposure and both attention problems and soothability varied significantly between cultures. Taken together, results demonstrate that increased time spent watching television was generally associated with dysregulation, although effects were not consistently uniform, but rather varied as a function of culturally-dependent contextual factors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Receptors of the leukocyte receptor cluster (LRC) play a range of important functions in the human immune system. However, the evolution of the LRC remains poorly understood, even in m\ammals not to mention nonmammalian vertebrates. We conducted a comprehensive bioinformatics analysis of the LRC-related genes in the publicly available genomes of six species that represent eutherian, marsupial, and monotreme lineages of mammals. As a result, the LRCs of African elephant and armadillo were characterized, two new genes, IGSF1 and A1BG, were attributed to the LRC of eutherian mammals, the LRC gene content was substantially extended in the short-tailed opossum and Tasmanian devil and, finally, four LRC genes were identified in the platypus genome. These findings have for the first time provided a solid basis for inference of the LRC phylogeny across mammals. Our analysis suggests that the mammalian LRC family likely derived from two ancestral genes, which evolved in a lineage-specific manner by expansion/contraction, extensive exon shuffling, and sequence divergence. The striking structural and functional diversity of eutherian LRC molecules appears largely lineage specific. The only family member retained in all the three mammalian lineages is a collagen-binding receptor OSCAR. Strong sequence conservation of a transmembrane domain known to associate with FcRγ suggests an adaptive role of this domain subtype in the LRC evolution., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

The immunoregulatory cytokine tumor necrosis factor α plays crucial roles in the pathogenesis of a broad spectrum of disorders. However, its effect may depend on the expression and co-expression of receptors on the target cell. The aim of the present study was to evaluate the expression levels of type 1 and 2 tumor necrosis factor α receptors (TNFR1/2) on individual cell subsets from peripheral blood of healthy volunteers. Flow cytometry analysis was used to study whole populations as well as subsets (T regulatory cells, T memory cells, cytotoxic T cells, T helper cells). Significant differences in the co-expression of TNFR1/2 were seen within subsets and total pools. Further studies are necessary to explore the implications of the observed differences in the modulation of tumor necrosis factor α function in health and pathology., (Copyright © 2019 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is the most widespread late-life dementia and involves the prefrontal cortex, a vulnerable brain region implicated in memory, emotion, cognition, and decision-making behavior. To understand the molecular differences between the effects of aging and AD on the prefrontal cortex, this study characterized the age-dependent changes in gene expression in Wistar rats (control) and OXYS rats (rodents that simulate key characteristics of sporadic AD) using RNA sequencing. We found that major altered biological processes during aging in Wistar rats were associated with immune processes. Gene expression changes during development of AD-like pathology as well as at the preclinical stage were related to neuronal plasticity, catalytic activity, lipid and immune processes, and mitochondria. A comparison of genes between data sets "OXYS rats" and "human AD" revealed similarity in expression alterations of genes related primarily to mitochondrial function; immune, endocrine, and circulatory systems; signal transduction; neuronal and synaptic processes; hypoxia; and apoptosis. Expression changes in mitochondrial processes identified in OXYS rats by RNA sequencing were confirmed by ultrastructural neuronal organelle alterations and low activity of respiratory chain complexes I, IV, and V in cortical mitochondria, suggesting that mitochondrial dysfunction appears to mediate or possibly even initiate the development of AD.

Objective To study the association of polymorphisms rs699947, rs2010963, rs3025039 in the VEGFA gene region and rs1870377, rs2305949, rs2071559 in the VEGFR2 gene region with the risk of primary varicose veins in ethnic Russians. Methods Genotypes were determined by real-time PCR allelic discrimination. The case group consisted of 448 patients with primary varicose veins and the control group comprised 609 individuals without a history of chronic venous disease. Association was studied by logistic regression analysis. Results Allele rs2010963 C was associated with the decreased risk of varicose veins (additive model of inheritance: odds ratio = 0.73, 95% confidence interval = 0.59-0.91, P = 0.004). Conclusions Our results provide evidence that polymorphism rs2010963 located in the 5' untranslated region of the VEGFA gene can influence genetic susceptibility to primary varicose veins in Russians. Otherwise, it can be in linkage disequilibrium with another functional single nucleotide polymorphism that can alter the level of vascular endothelial growth factor A protein.

A number of studies have shown that the presence of short (S), as opposed to long (L), allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with a higher risk for depression following exposure to stressful life events. However, many other studies failed to confirm this association. One reason for this inconsistency might be the fact that the interaction of the 5-HTTLPR polymorphism with stress may relate not to depression per se, but rather to adaptive or maladaptive emotion regulation strategies. Here we show that individuals homozygous for the long allele respond to stressful events by reappraising their emotional meaning, which may hamper the harmful effect of stress on mental health. In S genotype carriers, on the other hand, stress triggers the appearance of intrusive thoughts and vain attempts to suppress them, which in this group acts as a mediator between stress and depressive symptoms. These findings are in line with neuroimaging studies showing that 5-HTTLPR polymorphism has an effect on the connectivity among key areas involved in emotion regulation., (© 2017 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

The data and methods presented in this article are supplementing the research article "Integration of mtDNA pseudogenes into the nuclear genome coincides with speciation of the human genus. A hypothesis", DOI: 10.1016/j.mito.2016.12.001 (Gunbin et al., 2017) [1]. Mitochondrial DNA is known to get inserted into nuclear DNA to form NUMTs, i.e. nuclear DNA pseudogenes of the mtDNA. We present here the sequences of selected NUMTs, in which time of integration can be determined with sufficient precision. We report their chromosomal positions , their position within the great ape mtDNA phylogeny, and their times of integration into the nuclear genome. The methods used to generate the data and to control their quality are also presented. The dataset is made publicly available to enable critical or extended analyzes.

Fragments of mitochondrial DNA are known to get inserted into nuclear DNA to form NUMTs, i.e. nuclear pseudogenes of the mtDNA. The insertion of a NUMT is a rare event. Hundreds of pseudogenes have been cataloged in the human genome. NUMTs are, in essence, a special type of mutation with their own internal timer, which is synchronized with an established molecular clock, the mtDNA. Thus insertion of NUMTs can be timed with respect to evolution milestones such as the emergence of new species. We asked whether NUMTs were inserted uniformly over time or preferentially during certain periods of evolution, as implied by the "punctuated evolution" model. To our surprise, the NUMT insertion times do appear nonrandom with at least one cluster positioned at around 2.8 million years ago (Ma). Interestingly, 2.8Ma closely corresponds to the time of emergence of the genus Homo, and to a well-documented period of major climate change ca. 2.9-2.5Ma. It is tempting to hypothesize that the insertion of NUMTs is related to the speciation process. NUMTs could be either "riders", i.e., their insertion could be facilitated by the overall higher genome rearrangement activity during speciation, or "drivers", i.e. they may more readily get fixed in the population due to positive selection associated with speciation. If correct, the hypothesis would support the idea that evolution of our genus may have happened in a rapid, punctuated manner., (Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Here we describe a new high frequency/high field continuous wave and pulsed electrically detected magnetic resonance (CW EDMR and pEDMR) setup, operating at 263GHz and resonance fields between 0 and 12T. Spin dependent transport in illuminated hydrogenated amorphous silicon p-i-n solar cells at 5K and 90K was studied by in operando 263GHz CW and pEDMR alongside complementary X-band CW EDMR. Benefiting from the superior resolution at 263GHz, we were able to better resolve EDMR signals originating from spin dependent hopping and recombination processes. 5K EDMR spectra were found to be dominated by conduction and valence band tail states involved in spin dependent hopping, with additional contributions from triplet exciton states. 90K EDMR spectra could be assigned to spin pair recombination involving conduction band tail states and dangling bonds as the dominating spin dependent transport process, with additional contributions from valence band tail and triplet exciton states., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Lipemia modeled by injections of Triton WR-1339 (500 mg/kg) and poloxamer 407 (500 mg/kg) to mice were compared. LP fraction and subfraction compositions were compared by small-angle X-ray scattering on a diffractometer. Both compounds in the same dose caused a sharp increase in serum concentrations of total cholesterol (CH) and triglycerides (TG), the increases in response to poloxamer 407 being more pronounced. The differences in the models consisted in the levels of atherogenic fractions: CH-VLDL (subfractions CH-VLDL1-2) and CH-LDL, which were higher under the effect of poloxamer 407. Similar increases were observed for atherogenic fractions: TG-VLDL (subfractions TG-VLDL1-2) and TG-LDL (subfractions TG-LDL1-3). A specific feature of the model induced by poloxamer 407 was elevation of the concentrations of antiatherogenic CH-HDL and TG-HDL (subfractions CH-HDL2 and TG-HDL2). Both models exhibited high similarity, but changes in atherogenic fractions were more pronounced under the effect of poloxamer 407.

The characteristics of the osmotic concentration system under conditions of sodium diclofenac treatment were studied in Wistar rats with normally functioning vasopressin gene and homozygotic Brattleboro rats completely lacking endogenous vasopressin. Blockade of prostaglandin synthesis in rats with different neurohypophyseal status stimulated urinary osmolality to a different degree. Different contribution of sodium cations and urea to osmotic concentration was revealed.

A preparation of human genomic fragmented double-stranded DNA (dsDNA) was used as maturation stimulus in cultures of human dendritic cells (DCs) generated in compliance with the interferon protocol. Culturing of the DCs in medium with 5μg/ml of the DNA preparation was associated with a decrease in the relative proportion of CD14 + cells and an increase in that of CD83 + cells. These changes are markers of DC maturation. The efficiency with which the DNA preparation was able to elicit DC maturation was commensurate with that of lypopolysaccharide from bacterial cell, the standard inducer of DC maturation. Generated ex vivo, matured in the presence of the human DNA preparation, pulsed with tumor antigens mouse DCs were used as a vaccine in biological tests for its antitumor activity. The experimental results demonstrate that reinfusion of mature pulsed with tumor antigens DCs cause a statistically significant suppression of tumor graft growth., (Copyright © 2010 Elsevier Inc. All rights reserved.)

APE1 is a multifunctional enzyme that plays a central role in base excision repair (BER) of DNA. APE1 is also involved in the alternative nucleotide incision repair (NIR) pathway. We present an analysis of conformational dynamics and kinetic mechanisms of the full-length APE1 and truncated NDelta61-APE1 lacking the N-terminal 61 amino acids (REF1 domain) in BER and NIR pathways. The action of both enzyme forms were described by identical kinetic schemes, containing four stages corresponding to formation of the initial enzyme-substrate complex and isomerization of this complex; when a damaged substrate was present, these stages were followed by an irreversible catalytic stage resulting in the formation of the enzyme-product complex and the equilibrium stage of product release. For the first time we showed, that upon binding AP-containing DNA, the APE1 structure underwent conformational changes before the chemical cleavage step. Under BER conditions, the REF1 domain of APE1 influenced the stability of both the enzyme-substrate and enzyme-product complexes, as well as the isomerization rate, but did not affect the rates of initial complex formation or catalysis. Under NIR conditions, the REF1 domain affected both the rate of formation and the stability of the initial complex. In comparison with the full-length protein, NDelta61-APE1 did not display a decrease in NIR activity with a dihydrouracil-containing substrate. BER conditions decrease the rate of catalysis and strongly inhibit the rate of isomerization step for the NIR substrates. Under NIR conditions AP-endonuclease activity is still very efficient.

Administration of desmopressin for 4 days to homozygous Brattleboro rats lacking endogenous vasopressin induced an increase in osmotic concentration and was accompanied by typical changes in the morphofunctional state of interstitial cells of the renal papilla. These changes increase the permeability of extracellular matrix, which attested to the involvement of interstitial cells into hydrosmotic reaction to vasopressin.

For the first time to our knowledge we experimentally demonstrate an efficient method for the reduction of long-term radiation line drift in single-frequency cw Ti:sapphire and dye lasers that relies on a fast and precise wavelengthmeter together with a digital-analog feedback system. Generation line drift of lasers is reduced approximately by an order of magnitude down to 40 MHz/h, which corresponds to the residual drift in readings of the wavelengthmeter itself. The implemented automatic frequency control system allows us to lock the laser generation frequency to a specified absolute value. This approach may be used in single-frequency lasers of different types (solid-state, fiber, diode, dye lasers, etc.) and allows reduction by an order of magnitude or more of the long-term generation line drift in lasers that are not equipped with other systems for long-term stabilization of output radiation frequency.

Adult females of ICR strain of mice were bred, separated into different experimental groups, and treated as follows. On Days 2-4 of pregnancy, the mice received daily subcutaneous injections of either 0.05 ml sesame oil (vehicle) or same volume of 5.0mg of purified methoxychlor (MXC) suspended in the vehicle. Another group received a single subcutaneous injection of 1.0 microg of estradiol-17beta (E) on Day 2 of pregnancy only. Male offspring were tested at 3 and 6 months of age. At 3 months, E or MXC did not alter the weights of seminal vesicles, preputial glands, or testes, although after exposure for 30 min to a female in estrus behind a partition, testosterone levels were significantly reduced in treated males in comparison to control males exposed to the same partition test. At 6 months, the preputial glands and testes weight remained unchanged, while the seminal vesicles were significantly heavier in E- and MXC-treated males. Same partition tests again revealed that in E and MXC groups, testosterone levels remained significantly lower in comparison to control males. MXC or E exposures during preimplantation appear to induce long-term effects on the sexual development in 3 and 6 month-old-males by compromising their sexual arousal and altering seminal vesicles weights in the older group.

In ISIAH rat strain with stress-sensitive form of hypertension, the expression level of glucocorticoid receptor (GR) gene has been evaluated in hippocampus, hypothalamus and pituitary under basal and 2-hr restraint stress conditions. Corticosterone (CS) level in peripheral blood was also evaluated. Normotensive WAG strain was used as a control. Under basal condition, there were no interstrain differences in GR-mRNA level in any brain region under study. However, under stress condition, ISIAH rats demonstrated a significant fall of GR-mRNA in hippocampus and increase the pituitary gland as compared to basal level. On the contrary, no differences with basal level were found in stressed WAG rats. CS concentration in blood was nearly the same in nonstressed WAG and ISIAH rats. Stress influence led to a marked increase of CS in both strains. However CS level was significantly higher in stressed ISIAH rats than in stressed WAG group.

Objectives: To assess associations between mean age at death from cardiovascular disease (myocardial infarction, acute heart failure, ischemic heart disease and stroke) and sex, education, socio-professional status, marital status, region of residence at birth, month and season of birth and of death in dependence of climatic conditions., Design: A retrospective analysis of death certificates in two Siberian cities from 1971 to 1978 (Novosibirsk, south-western Siberia) and from 1968 to 1985 (Mirny, western Yakutia)., Methods: Analysis of variance, test for seasonality., Results: A remarkable effect of birthplace on longevity was observed in Novosibirsk. West Russia-born decedents were older than their cause-of-death-matched counterparts born in Siberia. In this city, men died at younger age in spring months compared to the rest of the year. In Mirny, an extreme northern town with a very harsh climate, the life span depended on the duration of living in this region prior to death., Conclusion: There was some difference among cardiovascular diagnoses and between the two cities. However, overall, the results offer some support for theories suggesting that early "imprinting" is responsible for the association between life span and region/season of birth.

The dynamics of spontaneous mutagenesis in a population of heterotrophic microorganisms during incubation in the absence of organic substrate was studied. A model of this dynamics was proposed. which is determined by the excitation by an external electromagnetic field of Langmuir proton oscillations activating the tautomeric transitions of nucleotides of DNA. It was shown that the model fits well the experimental data.

The problem is investigated whether the distributions of bending frequencies P(vbend,T) of H2O molecules in the liquid could be calculated from statistical distributions P(vOH,T) of stretching frequencies on the basis of the empirical correlation established for their mean values. It is found that correlations of different kinds fail to reproduce real spectra. They result in a bending band that is too narrow and give rise to an Evans hole in the stretching band. This provides evidence of the strong intermolecular coupling of bending modes, which makes their frequencies statistically independent from stretching frequencies.

Region 20 of the polytene X chromosome of Drosophila melanogaster was studied in salivary glands (SG) and pseudonurse cells (PNC) of otu mutants. In SG chromosomes the morphology of the region strongly depends on two modifiers of position effect variegation: temperature and amount of heterochromatin. It is banded in XYY males at 25 degrees C and beta-heterochromatic in X0 males at 14 degrees C, i.e. it shows dynamic transitions. In PNC chromosomes region 20 is not heterochromatic, but demonstrates a clear banding pattern. Some molecular markers of mitotic heterochromatin were localized by means of in situ hybridization on PNC chromosomes: DNA of the gene su(f) in section 20C, the nucleolar organizer and 359-bp satellite in 20F. The 359-bp satellite, which has been considered to be specific for heterochromatin of the mitotic X chromosome, was found at two additional sites on chromosome 3L, proximally to 80C. The right arm of the X chromosome in SG chromosomes was localized in the inversion In(ILR)pn2b: the telomeric HeT-A DNA and AAGAG satellite from the right arm are polytenized, having been relocated from heterochromatin to euchromatin.

The behavior of C57BL/6J male mice with experience of repeated victories (winners) or defeats (losers) in daily agonistic interactions, was examined in the plus-maze and partition tests. The latter procedure assesses the reactivity of mice to another conspecific in the neighboring compartment of a common cage, communicative behavior or level of sociability. The behavior of mice after 10 days (T10) and 20 days (T20) of agonistic confrontations, as well as in controls (5 days of individual housing) was analyzed. Significant differences were found between T10 and T20 losers and controls in both tests. In the partition test, a decrease in the number of approaches and total and average time spent near the partition was found in T10 and, more pronounced, in T20 losers. In the plus-maze, losers showed fewer open and total entries than controls. Moreover, rarely did they pass from one enclosed arm to another, and also showed a decreased number of 'peepings' from enclosed arms. Percentage of open time did not differ significantly in losers compared to controls. It is suggested that the level of losers' sociability, estimated as low by the partition test, can include anxiety as a component, which is confirmed, at least partly, by some parameters of the plus-maze test. There were no differences in the partition or plus-maze tests between T10 winners and controls. However, all parameters of partition behavior were significantly different between T20 winners and controls. In the plus-maze, similar to losers, T20 winners displayed fewer open arm entries, number of "peepings,' and passages than controls. It was concluded that parameters of the partition and plus-maze tests correlate in mice with the alternative experience of agonistic confrontations, positive or negative. A combination of these two tests may be used for estimation of developing anxiety in mice.

Diethyl-dithiocarbamate (DETC) chelating ferrous iron is used during EPR detection of nitric oxide (.NO) as a precursor of spin traps for the quantification of released .NO both in vitro and in vivo. This method is based on the high affinity of water insoluble iron-dithiocarbamate complexes towards .NO. The nitrosyl-iron-dithiocarbamate complex NOFe(DETC)2 is formed with characteristic triplet EPR spectrum. In the present paper we have studied the reaction of water soluble Fe(II)-proline-dithiocarbamate complex, Fe(PDTC)2, with nitric oxide using both EPR spectroscopy and laser flash photolysis. It has been found that the treatment of the Fe(PDTC)2 complex either by authentic .NO dissolved in aqua buffer solutions or by different .NO donors results in the quantitative appearance of an EPR signal of a stable mononitrosyl complex NOFe(PDTC)2 with a g-factor giso = 2.04 and a hyperfine splitting constant aN = 12.5 G. The laser flash photolysis method has been used to study the kinetics of .NO trapping by Fe(PDTC)2. Nitric oxide release from a light sensitive .NO donor, piridazinofuroxan, was induced by a short flash of UV light generated by a XeCl eximer laser. The rate constant of the reaction of .NO with Fe(PDTC)2 was found to be (1.1 +/- 0.3).10(8) M-1s-1, manifesting a high efficiency of .NO trapping by Fe(PDTC)2.

A surface NMR investigation of groundwater in the geomagnetic field is under study. To detect the surface NMR a wire loop with a diameter of about 100 m, being an antenna for both an exciting field source and the NMR signal receiver, is laid out on the ground. A sinusoidal current pulse with a rectangular envelope is passed through the loop to excite the NMR signal. The carrier frequency of the oscillating current in this pulse is equal to the Larmor frequency of protons in the Earth's magnetic field. The current amplitude is changed up to 200 amps and the pulse duration is fixed and is equal to 40 ms. The exciting pulse is followed by an induction emf signal caused by the Larmor nuclear precession in geomagnetic field. The relaxation times T1, T2, and T2* were measured by the surface NMR for both groundwater in medium to coarse-grained sand at borehole and for bulk water under the ice surface of frozen lake. To determine T1, a longitudinal interference in experiments with repeated pulses was measured. A sequence with equal period between equal excitation pulses was used. The relaxation times T1, T2, measured for bulk water under the ice of the Ob reservoir were 1.0 s and 0.7 s, respectively. To estimate an influence of dissolved oxygen T1 of the same water at the same temperature was measured by lab NMR with and without pumping of oxygen. The relaxation time T1 measured for water in the medium to coarse-grained sand is 0.65 s. The relaxation time T2 estimated by spin echo sequence is found to be equal to 0.15 s. The relaxation time T2* is found to be about 80 ms. This result contradicts published earlier phenomenological correlation between relaxation time T2* and grain size of water-bearing rock. This could be as a result of unsound approach based on grain size or influence of paramagnetic impurities.

The concept of solid-phase synthesis of oligoribonucleotides using T4 RNA ligase and T4 polynucleotide kinase has been proposed and tested with model homo-oligoribonucleotides. The method consists of the immobilization of the first oligomer block at the 3'-terminus on a solid support followed by a chain elongation in the 5'-direction with trinucleoside diphosphates using T4 RNA-ligase and phosphorylation using polynucleotide kinase. Hydrazides of Biogel P-300, Sepharose 4B and cellulose were tested as solid supports for immobilization of initial oligomers. The properties of supports were rated on reactivities of immobilized 5'-phosphorylated oligomers as phosphate donors in the solid phase reactions, hydrodynamical properties and capacity to eliminate donor molecules spontaneously during reactions. Hydrazide of Sepharose 4B appeared to be a more suitable support because of better hydrodynamic properties and highest reactivities of immobilized donors. Saturated concentrations of RNA ligase and polynucleotide kinase and optimal time of joining reaction were determined. In a model experiment ApApA was twice attached to the immobilized hydrazide of Sepharose 4B donor (pA)6pAox. The yield of (Ap)12 was 25%.

Nitric oxide (NO) has been shown to be an important mediator in vasodilation, neurotransmission and cellular cytotoxicity. We investigated a new series of nitronylnitroxyl radicals (NNR) as spin traps for NO. It was found these radicals react with NO with rate constants of about 10(4) M-1c-1 forming stable iminonitroxides with dramatic changes in EPR spectra. To overcome fast reduction of the radicals (a few seconds in rat cerebella cytosol), NNR with charged trimethylammoniophenyl group (Ib) was incorporated into the inner volume of large unilamellar phosphatidylcholine liposomes. In this case the reduction of the radical Ib in rat cerebella cytosol is slow (ca. 1% per min). The rate of NO production by NO synthase from rat cerebellum measured by NNR, Ib, is in a reasonable agreement with that obtained by spectrophotometric method.

Thirty-seven patients with seasonal affective disorder (SAD) and 25 control subjects were given a concurrent task, the verbal-manual interference paradigm, as a measure of hemispheric language lateralization. In winter, depressed patients showed a symmetrical interference pattern and control subjects experienced greater overall disruption in right-hand tapping during concurrent verbalization. Patients showed a greater left-hand tapping decrement compared with control subjects. Light treatment decreased the decrement in tapping with the left but not with the right hand in patients. After treatment, patients did not differ from controls in dual task interference effects. Patients also showed no difference from controls in summer. The difference between depressed subjects and controls in performance measures of laterality suggests that winter depression is associated with a shift of laterality from the left to the right. The winter abnormalities appear to be normalized by bright light.

The specificity of the interaction between tRNAPhe and phenylalanyl-tRNA synthetase isolated from human placenta was investigated. Using yeast tRNAPhe transcripts with different point mutations it was shown that all the five recognition points for the yeast phenylalanyl-tRNA synthetase (G20, G34, A35, A36 and A73) are also important for the reaction catalyzed by the human enzyme. A set of mutations in nucleotides involved in tertiary interactions of tRNAPhe revealed that mutations which maintained the proper folding of the molecule had almost no influence on the efficiency of aminoacylation. The most striking difference between the yeast and human phenylalanyl-tRNA synthetases involved a mutation in the lower two base pairs of the anticodon stem. This mutation did not affect aminoacylation with the yeast enzyme, but greatly reduced activity with human phenylalanyl-tRNA synthetase.