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71.
Abstract

Due to its fully sequenced genome, high genetic homology to humans, external fertilization, fast development, transparency of embryos, low cost and active reproduction, the zebrafish (Danio rerio) has become a novel promising model organism in biomedicine. Zebrafish are a useful tool in genetic and neuroscience research, including linking various genetic mutations to brain mechanisms using forward and reverse genetics. These approaches have produced novel models of rare genetic CNS disorders and common brain illnesses, such as addiction, aggression, anxiety and depression. Genetically modified zebrafish also foster neuroanatomical studies, manipulating neural circuits and linking them to different behaviors. Here, we discuss recent advances in neurogenetics of zebrafish, and evaluate their unique strengths, inherent limitations and the rapidly growing potential for elucidating the conserved roles of genes in neuropsychiatric disorders.  相似文献   
72.
73.
74.
It is postulated a conception of immunological disbalance between carcinogenesis inhibiting and stimulating antibodies (Ab). Inhibiting Ab prevent the carcinogens and estradiol but increase the progesterone penetration into the target cells. And vise versa do stimulating Ab. Inhibiting Ab could be blocked by corresponding antiidiotypic Ab. The processes of carcinogenesis initiation and promotion are intensified when stimulating Ab prevail over inhibiting ones.  相似文献   
75.

Background

Krokodil is an informal term for a cheap injectable illicit drug domestically prepared from codeine-containing medication (CCM). The method of krokodil preparation may produce desomorphine as well as toxic reactants that cause extensive tissue necrosis. The first confirmed report of krokodil use in Russia took place in 2004. In 2012, reports of krokodil-related injection injuries began to appear beyond Russia in Western Europe and the United States.

Objective

This exploratory study had two main objectives: (1) to determine if Internet search patterns could detect regularities in behavioral responses to Russian CCM policy at the population level, and (2) to determine if complementary data sources could explain the regularities we observed.

Methods

First, we obtained krokodil-related search pattern data for each Russia subregion (oblast) between 2011 and 2012. Second, we analyzed several complementary data sources included krokodil-related court cases, and related search terms on both Google and Yandex to evaluate the characteristics of terms accompanying krokodil-related search queries.

Results

In the 6 months preceding CCM sales restrictions, 21 of Russia''s 83 oblasts had search rates higher than the national average (mean) of 16.67 searches per 100,000 population for terms associated with krokodil. In the 6 months following restrictions, mean national searches dropped to 9.65 per 100,000. Further, the number of oblasts recording a higher than average search rate dropped from 30 to 16. Second, we found krokodil-related court appearances were moderately positively correlated (Spearman correlation=.506, P≤.001) with behaviors consistent with an interest in the production and use of krokodil across Russia. Finally, Google Trends and Google and Yandex related terms suggested consistent public interest in the production and use of krokodil as well as for CCM as analgesic medication during the date range covered by this study.

Conclusions

Illicit drug use data are generally regarded as difficult to obtain through traditional survey methods. Our analysis suggests it is plausible that Yandex search behavior served as a proxy for patterns of krokodil production and use during the date range we investigated. More generally, this study demonstrates the application of novel methods recently used by policy makers to both monitor illicit drug use and influence drug policy decision making.  相似文献   
76.
To understand the nature of the bonding mechanism between poly(lactic acid) (PLA) and halloysite nanotubes (HNT), a first-principles DFT study was performed on the adsorption behavior of the PLA monomer, lactic acid (LA), on the outer, inner, and edge surfaces of the HNT. The role of LA functional groups, and its orientation behavior in the formation of bonds with HNT are systematically studied. Analysis of the adsorption energy, total and partial electron density of states (DOS), electric charge transfer between LA atoms and HNT mineral surfaces shows that van der Waals attraction governs their interaction. The calculations of the most stable adsorption configurations of LA show that the predominant number of hydrogen bonds is determined by the activity of the carboxyl functional group of LA on the hydroxylated surfaces of HNT. The important role of the –OH surface groups in the mechanism of lactic acid binding has been established; their absence on the external siloxane surface significantly reduces the LA affinity for HNT. The binding energy of lactic acid on the hydroxylated internal and edge surfaces of the HNT is much higher (by about 275%) than on the external siloxane surface. Mulliken population analysis showed that the formation of a hydrogen bond with the LA atomic groups leads to a more significant redistribution of charge on the inner and edge surfaces of the HNT in comparison with its outer surface. Van der Waals attraction between the LA and HNTs, as well as hydrogen bonds, is responsible for the formation of the bonding mechanism in halloysite nanotubes-PLA nanocomposite. Our results are in accord with available literature.

The mechanism of bond formation between PLA and outer, inner and edge surfaces of HNT was established.  相似文献   
77.
The C-methylthio derivatives of cobalt bis(dicarbollide) were synthesized by reaction of anhydrous CoCl2 with nido-carborane [7-MeS-7,8-C2B9H11] and isolated as a mixture of rac-[1,1′-(MeS)2-3,3′-Co(1,2-C2B9H10)2] and meso-[1,2′-(MeS)2-3,3′-Co(1,2-C2B9H10)2] isomers. The structures of both isomers were studied using DFT quantum chemical calculations. The most preferable geometry of rotamers and the stabilization energy of C-methylthio derivatives of cobalt bis(dicarbolide) were calculated. The (BEDT-TTF)[1,1′-(MeS)2-3,3′-Co(1,2-C2B9H10)2] salt was prepared and its structure was determined by single crystal X-ray diffraction. The cisoid conformation of the rac-[1,1′-(MeS)2-3,3′-Co(1,2-C2B9H10)2] anion is stabilized by short intramolecular CH⋯S hydrogen and BH⋯S chalcogen bonds between the dicarbollide ligands, that is in good agreement with the data of quantum chemical calculations.

The C-methylthio derivatives of cobalt bis(dicarbollide) rac-[1,1′-(MeS)2-3,3′-Co(1,2-C2B9H10)2] and meso-[1,2′-(MeS)2-3,3′-Co(1,2-C2B9H10)2] were synthesized and studied by DFT calculations and X-ray diffraction.  相似文献   
78.
Defining the structural and functional changes in the nervous system underlying learning and memory represents a major challenge for modern neuroscience. Although changes in neuronal activity following memory formation have been studied [B. F. Grewe et al., Nature 543, 670–675 (2017); M. T. Rogan, U. V. Stäubli, J. E. LeDoux, Nature 390, 604–607 (1997)], the underlying structural changes at the synapse level remain poorly understood. Here, we capture synaptic changes in the midlarval zebrafish brain that occur during associative memory formation by imaging excitatory synapses labeled with recombinant probes using selective plane illumination microscopy. Imaging the same subjects before and after classical conditioning at single-synapse resolution provides an unbiased mapping of synaptic changes accompanying memory formation. In control animals and animals that failed to learn the task, there were no significant changes in the spatial patterns of synapses in the pallium, which contains the equivalent of the mammalian amygdala and is essential for associative learning in teleost fish [M. Portavella, J. P. Vargas, B. Torres, C. Salas, Brain Res. Bull. 57, 397–399 (2002)]. In zebrafish that formed memories, we saw a dramatic increase in the number of synapses in the ventrolateral pallium, which contains neurons active during memory formation and retrieval. Concurrently, synapse loss predominated in the dorsomedial pallium. Surprisingly, we did not observe significant changes in the intensity of synaptic labeling, a proxy for synaptic strength, with memory formation in any region of the pallium. Our results suggest that memory formation due to classical conditioning is associated with reciprocal changes in synapse numbers in the pallium.

It is widely believed that memories are formed as a result of alterations in synaptic connections between axons and dendrites, an idea first proposed by Ramon y Cajal (14). Although synapse changes have been extensively studied in brain slices in the context of long-term potentiation (5, 6), less is known about how synapses in a living vertebrate are modified when a memory is formed.Memory formation has been widely studied using classical conditioning (CC), a robust and straightforward form of learning in which an animal is exposed to a neutral stimulus (conditioned stimulus, CS) paired with an appetitive or aversive stimulus (unconditioned stimulus, US) that evokes a specific behavioral response (UR, unconditioned response) (7, 8). As a result of the pairing, animals learn to associate the CS with the US, causing them to respond to the CS with a conditioned response (CR) identical to the UR, signifying memory retrieval (9, 10). Memory retrieval is also evoked by activating a cellular engram, a group of neurons active during memory formation and retrieval (1118). The central locus of CC in mammals, the amygdala (19), is located in a relatively inaccessible area beneath the cortex (20). Thus, although numerous longitudinal imaging studies have documented experience-dependent changes in the structure of spines of cortical and hippocampal neurons (21, 22), few imaging studies have directly examined synaptic changes that occur in the amygdala during associative memory formation.Instead, synaptic changes that occur in the amygdala during CC (23) have been studied primarily using indirect measures of synaptic strength, such as the ratio of α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor/N-methyl D-aspartate (AMPA/NMDA) currents in excitatory postsynaptic currents (EPSCs). Increases in AMPA/NMDA ratio in amygdalar neurons following auditory fear conditioning (FC), a type of CC (2427), indicate that associative memory formation coincides with increases in synaptic strength. In addition, imaging experiments in brain regions beyond the amygdala have shown diverse effects following CC. For example, following contextual fear conditioning, engram neurons in the CA1 region of the hippocampus that receive inputs from CA3 engram neurons displayed spines that were larger and more densely packed than nonengram cells (28). Furthermore, experiments in which neuronal morphology was directly observed before and after FC found that neurons in the frontal association (29) and primary motor cortex (30) showed a decrease in the number of spines, whereas neurons in the auditory cortex showed an increase in spine number with memory formation (31).To obtain previously unavailable insight into memory formation within the central locus of associative memory storage, we developed a paradigm combining in vivo labeling and imaging with informatics and analysis tools. We used this paradigm to map synaptic changes that occur over time in the intact brain of a living vertebrate during memory formation. We imaged the pallium of teleost fish, which contains the putative homolog of the mammalian amygdala based on anatomy (32), gene expression (33), and function (34). The pallium is on the surface of the brain (35), and zebrafish larvae are highly transparent, allowing for intact, whole-brain imaging using selective plane illumination microscopy (SPIM) without the need for invasive intervention (36). In addition, while most studies of learning in zebrafish have used adults (3740), at least one study showed that larval zebrafish can learn to associate a place with a positive valence US (41). These attributes suggest that larval zebrafish may be an ideal model organism for studying synaptic changes during memory formation due to CC. We have engaged this challenge by combining purpose-built experimental tools with data management software that enables transparent analyses of large and heterogeneous datasets. All data were characterized and stored at the time of creation in a customized data management system designed to conform to findability, accessibility, interoperability, and reusability (i.e., FAIR principles) (see Materials and Methods) (42).  相似文献   
79.
The question of the microscopic origin of the M-superstructure and additional satellite peaks in the Zr-rich lead zirconate-titanate is discussed for nearly 50 years. Clear contradiction between the selection rules of the critical scattering and the superstructure was found preventing unambiguous attributing of the observed superstructure either to the rotation of the oxygen octahedra or to the antiparallel displacements of the lead cations. Detailed analysis of the satellite pattern explained it as the result of the incommensurate phase transition rather than antiphase domains. Critical dynamics is the key point for the formulated problems. Recently, the oxygen tilt soft mode in the PbZr0.976Ti0.024O3 (PZT2.4) was found. But this does not resolve the extinction rules contradiction. The results of the inelastic X-ray scattering study of the phonon spectra of PZT2.4 around M-point are reported. Strong coupling between the lead and oxygen modes resulting in mode anticrossing and creation of the wide flat part in the lowest phonon dispersion curves is identified. This flat part corresponds to the mixture of the displacements of the lead and oxygen ions and can be an explanation of the extinction rules contradiction. Moreover, a flat dispersion surface is a typical prerequisite for the incommensurate phase transition.  相似文献   
80.
The concept of using redox-active ligands, which has become extremely widespread in organometallic chemistry, is often considered from ‘their effect on the metal center properties’ point of view and ‘how to modify the ligands’. In this paper, we present the reverse side of this effective approach – a dramatic change of redox properties of ligands under the influence of a redox-inert metal. Germanium derivatives based on 2,3-dihydroxynaphthalene (1) and N,N′-bidentate ligands, namely 2,2′-bipyridine (2) and 1,10-phenanthroline (3), were obtained and characterized by CV, UV-vis spectroscopy, DFT calculations and in the case of 3 X-ray diffraction. It was shown that the HOMO of the complexes is almost completely located on the naphthalene fragment while the LUMO is on the N,N-ligands. At the same time, there are no boundary molecular orbitals on the germanium atom, but it forms the axial part of the molecule holding two opposite motifs together. Moreover, it sharply affects the level of HOMO and LUMO. Derivatives 2 and 3 are more easily oxidized compared to 2,3-dihydroxynaphthalene by 0.31–0.34 V (7–8 kcal mol−1) and are more easily reduced compared to N,N-donors by 1.08–1.15 V (25–26.5 kcal mol−1). All this together makes it possible to form a system with a narrow HOMO/LUMO gap (∼2 eV). The crystal structure of 3 consists of alternating monomolecular easily oxidizing and easily reducing layers formed due to intermolecular interactions, in particular π-stacking. In addition, in contrast to 1 that starts to decompose noticeably at the temperatures from 200 °C, 2 and 3 have an extremely high thermal stability. They remain stable with no signs of decomposition and melting up to 400 °С. We believe that this approach to the formation of the supramolecular structure may present prospects for obtaining new functional materials.

The concept of using redox-active ligands is often considered from ‘their effect on the metal center properties’ point of view. We present the reverse side of this approach – change of redox properties of ligands under the influence of metal.  相似文献   
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