Quantitative Distribution Research Articles

Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology.

Soluble amyloid beta (Aβ) oligomers have been suggested as initiating Aβ related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear. A total of 526 participants in early clinical stages of AD and controls from a longitudinal cohort were neurobiologically classified for amyloid and tau pathology applying the AT(N) system. Aβ and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface-based fluorescence intensity distribution analysis (sFIDA) technology. Across groups, highest Aβ oligomer levels were found in A+ with subjective cognitive decline and mild cognitive impairment. Aβ oligomers were significantly higher in A+T- compared to A-T- and A+T+. APOEε4 allele carriers showed significantly higher Aβ oligomer levels. No differences in tau oligomers were detected. The accumulation of Aβ oligomers in the CSF peaks early within the AD continuum, preceding tau pathology. Disease-modifying treatments targeting Aβ oligomers might have the highest therapeutic effect in these disease stages. Using surface-based fluorescence intensity distribution analysis (sFIDA) technology, we quantified Aβ oligomers in cerebrospinal fluid (CSF) samples of the DZNE-Longitudinal Cognitive Impairment and Dementia (DELCODE) cohortAβ oligomers were significantly elevated in mild cognitive impairment (MCI)Amyloid-positive subjects in the subjective cognitive decline (SCD) group increased compared to the amyloid-negative control groupInterestingly, levels of Aβ oligomers decrease at advanced stages of the disease (A+T+), which might be explained by altered clearing mechanisms.

Visualization of oxygen vacancies at CeO x /Y-HZO interface by spectrum imaging method and multivariate analysis

Electron energy loss spectroscopy—spectrum imaging measurements using a scanning transmission electron microscope are carried out to clarify the details of microstructure at the interface of the CeO x -capped Y-HZO film prepared by the chemical solution deposition (CSD) method. We confirmed that by the present CSD the independent capped layer of CeOx successively deposited on Y-HZO. The crystal structure of CeO x film is mainly the cubic CeO2 structure with Ce4+. Chemical state maps are also successfully obtained by the multivariate analysis. We found that Ce3+ and Ce4+ coexist in the interface layer with cubic CeO2 crystal structure containing O vacancy. The results of the quantitative elemental distribution maps of energy dispersive X-ray spectroscopy also supported that O vacancies exist at the interface.

Human head sized magnetorelaxometry imaging of magnetic nanoparticles with optically pumped magnetometers — A feasibility study

Magnetic nanoparticles (MNP) offer exciting biomedical applications, e.g. magnetic hyperthermia for tumor treatment. The knowledge of the quantitative spatial distribution of MNP in the human body is a key for treatment safety and efficiency. Here we experimentally demonstrate the reconstruction of the quantitative MNP distribution of a human head phantom by magnetorelaxometry imaging (MRXI). The MRXI setup is composed of a 50 channel optically pumped magnetometer (OPM) system and 72 excitation coils, which are operated inside a magnetically shielded room. With our setup, we were able to reconstruct a glioblastoma phantom with a clinically relevant iron amount. A simulation study reveals, that currently the main limitations in terms of reconstruction quality arise from geometrical uncertainties of the setup. Summing up, we demonstrate the feasibility of OPM-MRXI for large regions of interest, potentially advancing the monitoring of MNP in related treatments.

Geographic Information System (GIS) for ecology: a bibliometric network analysis

Introduced in 1960s to store, analyse, and manipulate data collected for the Canada Land Inventory by mapping information about soils, agriculture, recreation, wildlife, waterfowl, forestry and land use, since their origins Geographic Information Systems (GISs) have had a fundamental role in the study of the environment. As computers systems for capturing, storing, checking, and displaying data related to positions on Earth's surface, GISs have quickly become an effective and powerful tool for addressing ecological issues, analysing the relationship between living things and their habitats, assessing the environmental impact of man-made transformations of a territory. This article aims to show and discuss the results of a study concerning quantitative distribution of GIS for ecology in literature from Scopus database using bibliometric analysis. Bibliometric analysis is a scientific computer assisted review methodology to explore the major research interests in scientific literature, so to identify core research authors, as well as their relationship, by covering articles, conference papers, book chapters and reviews related to a given topic or field. The high number of scientific manuscripts published on the subject (5,204) in the analysed period (1979-2021), remarked the soundness of this topic. While China shows the greatest number of published documents, USA is the country with the most cited documents. Specifically, “remote sensing”, “spatial analysis” and “land use” are the keywords most frequently linked to GIS and ecology, so to underline respectively three aspects: the relevance of environment monitoring by satellite, airplane or drone, the utility of relating ecological questions to the geo-localization, the necessity of produce thematic maps for describing the economic and cultural activities (e.g., agricultural, residential, industrial, and recreational uses) that are practiced at a given place. Since the study shows that trend of publications focusing on the application of GIS for ecology is increasing, further growing is expected in the next future, also considering the ductility that these computer systems provide in different fields.

Reaction Thermodynamics of Zerovalent Iron and Hexavalent Chromium at the Solid-Liquid Interface and in Solution.

Zerovalent iron (Fe0) is a promising candidate for remediating hexavalent chromium (Cr(VI)) via adsorption and (or) reduction. Herein, the reaction between Fe0 and Cr(VI) at the solid-liquid interface and in solution under varying pHs was inspected using the methodology of equilibrium thermodynamics. First, species distribution functions of aqueous Cr(VI), Cr(III), Fe(III), and Fe(II) are deduced to illuminate the quantitative distribution of aqueous metal species. Second, the plausible reaction at pH = 0-14 either at the solid-liquid interface or in solution is determined according to the species distribution function. Third, the spontaneity of each reaction is evaluated via a thermodynamic calculation based on the van't Hoff equation. The results present the following. (1) At the solid-liquid interface, the redox reaction 2Cr(VI) + 3Fe0 → 2Cr(III) + 3Fe(II) is spontaneous, inducing complete Cr(VI) → Cr(III) reduction at pH = 0-14. Especially, the high spontaneity of the redox reaction is mainly ascribed to Fe0 oxidation, which serves as a highly spontaneous subreaction. (2) In solution, the redox reaction Cr(VI) + 3Fe(II) → Cr(III) + 3Fe(III) is nonspontaneous at pH = 6 and 7, whereas it is spontaneous at pH = 6-7, 0-5, and 8-14. Accordingly, no Cr(VI) → Cr(III) reduction at pH = 6-7 and complete Cr(VI) → Cr(III) reduction at pH = 0-5 and 8-14 are expected. Particularly, the nonspontaneity of the Cr(VI) reduction at pH = 6-7 is majorly attributed to water ionization, which is involved as a highly nonspontaneous subreaction. On the contrary, the spontaneity of the Cr(VI) reduction at pH = 0-5 and 8-14 is mainly owing to acid-base neutralization, which is involved as a highly spontaneous subreaction. This work may deepen our knowledge about the chemistry involved in hexavalent chromium remediation by the zerovalent iron.

Plant necrotrophic bacterial disease resistance phenotypes, QTL, and metabolites identified through integrated genetic mapping and metabolomics in Solanum species.

Most food crops are susceptible to necrotrophic bacteria that cause rotting and wilting diseases in fleshy organs and foods. All varieties of cultivated potato (Solanum tuberosum L.) are susceptible to diseases caused by Pectobacterium species, but resistance has been demonstrated in wild potato relatives including S. chacoense. Previous studies demonstrated that resistance is in part mediated by antivirulence activity of phytochemicals in stems and tubers. Little is known about the genetic basis of antivirulence traits, and the potential for inheritance and introgression into cultivated potato is unclear. Here, the metabolites and genetic loci associated with antivirulence traits in S. chacoense were elucidated by screening a sequenced S. tuberosum x S. chacoense recombinant inbred line (RIL) population for antivirulence traits of its metabolite extracts. Metabolite extracts from the RILs exhibited a quantitative distribution for two antivirulence traits that were positively correlated: quorum sensing inhibition and exo-protease inhibition, with some evidence of transgressive segregation, supporting the role of multiple loci and metabolites regulating these resistance-associated systems. Metabolomics was performed on the highly resistant and susceptible RILs that revealed 30 metabolites associated with resistance, including several alkaloids and terpenes. Specifically, several prenylated metabolites were more abundant in resistant RILs. We constructed a high-density linkage map with 795 SNPs mapped to 12 linkage groups, spanning a length of 1,507 cM and a density of 1 marker per 1.89 cM. Genetic mapping of the antivirulence and metabolite data identified five quantitative trait loci (QTLs) related to quorum sensing inhibition that explained 8-28% of the phenotypic variation and two QTLs for protease activity inhibition that explained 14-19% of the phenotypic variation. Several candidate genes including alkaloid, and secondary metabolite biosynthesis that are related to disease resistance were identified within these QTLs. Taken together, these data support that quorum sensing inhibition and exo-protease inhibition assays may serve as breeding targets to improve resistance to nectrotrophic bacterial pathogens in potato and other plants. The identified candidate genes and metabolites can be utilized in marker assisted selection and genomic selection to improve soft- rot and blackleg disease resistance.

Social structure of Ukrainian society under the influence of full-scale war: conceptual and empirical research

This research is devoted to analyzing the changes that took place in the social-group structure of Ukrainian society during a year and a half of full-scale war. In order to realize this goal, firstly, the author considers the experience and conceptual foundations of the study of the relationship between war and social structure in Western and Ukrainian science and proposes a concept of the impact of total war on the social structure of a society that resists external aggression. Secondly, several preconditions of social-group dynamics were clarified — both destructive (due to which Ukraine quickly acquired characteristic features of the social structure during the martial law), and constructive (which contributed to the reproduction of pre-war social positions of citizens and a high degree of stability of the social system in general). Thirdly, the dynamics of the distribution of social groups and classes was analyzed every six months of the war based on various open official sources and the data of sociological surveys (in particular, the project “Social Inequality: Wartime Monitoring”, which was initiated by the researchers of the Department of Social Structures of the Institute of Sociology, NAS of Ukraine). The author proves that during the year and a half of the full-scale war, significant (both objective and subjective) socio-structural changes took place among the economically active population, though not linear ones, but with certain fluctuations (a rapid and significant transformation in the first six months and a movement towards gradual recovery over the next year). In particular, a significant (three-fold) increase in two groups (members of the armed forces and the unemployed), which were outside economic activity and accounted for almost a third of the working-age population in September 2022, and a quarter — a year later. The most noticeable changes among the employed population were the reduction in the number and restructuring of the working class and the class of owners, including the oligarchs. Fourthly, the author makes a forecast of further social-group dynamics under favorable and unfavorable developments: how will the quantitative distribution and internal structure of the main classes and groups change, as well as the social structure of the country in general.

Beam-hardening correction method for quantifying moisture content in cement paste based on X-ray radiography

The X-ray spectrum changes while traveling through specimen, and this phenomenon, known as the beam-hardening effect, breaks the linear relationship between the intensity variety on radiographs and material thickness. In the detection of water transport in cement-based materials, this effect leads to inaccurate results of the quantitative moisture distribution inside the sample, and it is difficult to eliminate this effect by gravimetric calibration. To solve this problem, this paper proposed a calibration strategy for the attenuation coefficient curve of cement-water two-phase specimens, and provided a heuristic mathematical model for fitting the 2D attenuation coefficient surface of cement paste specimens. The experiments showed that for zones close to saturation, beam-hardening leads to an overestimation of moisture content, while for a zone with a low water content, the X-ray radiography results without correction tend to underestimate it. After correction, the method showed a quantitative result close to that of the gravimetric method, and maintained a good stability in samples of different thickness.

Computational studies of electromagnetic field propagation and deforming of structural elements for a thin-walled curved workpiece and an inductor

Introduction. At the present stage of industrial development, the electromagnetic field is widely used in various technological processes. The force effect of an electromagnetic field on conductive materials is used in a class of technological operations called electromagnetic forming. Problem. Under the conditions of electromagnetic forming, the main element of the technological equipment – the inductor – is simultaneously subjected to the force impact with the workpiece. At certain levels of the electromagnetic field, the deformation of the inductor becomes so significant that it can lead to a loss of its efficiency. Goal. Computational analysis of a thin-walled curved workpiece and a two-turn inductor under the conditions of electromagnetic processing of the workpiece corner zone. Determining the distribution of quantitative characteristics of the electromagnetic field and the stress-strain state and conducting assessments based on them regarding the efficiency of the technological operation. Methodology. Computational modeling using the finite element method as a method of numerical analysis. The results on the distribution of quantitative characteristics of the electromagnetic field and components of the stress-strain state for a thin-walled workpiece and an inductor are obtained. It is shown that for the specified characteristics of the technological operation, the inductor remains operational, and plastic deformations occur in the workpiece. A series of calculations were carried out, in which some parameters of the technological system were varied. Originality. For the first time, the results of the calculation analysis of the quantitative characteristics distribution of the electromagnetic field of the deformation process for the «inductor – thin-walled curved workpiece» system are presented. Practical value. The presented design scheme of a curved thin-walled workpiece and a two-turn inductor, the method of calculation analysis and some obtained results can be used in the analysis of electromagnetic processing of thin-walled structures that contain curved elements.

Spatiotemporal Visualization of Paraquat Distribution, Toxicokinetics, and Its Detoxification in Zebrafish Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging.

Paraquat is a highly toxic quaternary ammonium herbicide. It can damage the functions of multiple organs and cause irreversible pulmonary fibrosis in the human body. However, the toxicological mechanism of paraquat is not yet fully understood, and due to the lack of specific antidotes, the clinical treatment of paraquat intoxication is still a great medical challenge. In-depth research on its toxicity mechanism, toxicokinetics, and effective antidotes is urgently demanded. A new molecular imaging technique, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), can simultaneously achieve quantitative and spatial analysis and offer an alternative, distinct, and useful technique for paraquat intoxication and consequent detoxication. Here, we visualized the spatial-temporal distribution and conducted toxicokinetic research on paraquat in zebrafish by using stable isotope-labeled internal-standard-aided MALDI-MSI for the first time. The results indicated that paraquat had a fast absorption rate and was widely distributed in different organs, such as the brain, gills, kidneys, and liver in zebrafish. Its half-life was long, and the elimination rate was slow. Paraquat reached its peak at 30 min and was mainly distributed in kidneys and intestines and then showed a tendency of declining first but mildly rising later at 6 h, accompanied by a wide distribution in kidneys and intestines again. It suggested that entero-systemic recirculation might lead to the observed secondary peaks, and perhaps it extended the residence time of paraquat in the body. In addition, we validated the potential detoxification effect of sodium salicylate as a potential antidote for paraquat from both the dimensions of distribution and quantification. In conclusion, MALDI-MSI conveniently provided the distinct and quantitative spatial-temporal distribution information on paraquat in the whole body of zebrafish; it will promote the understanding of its toxicokinetic characteristics and provide more valuable information for clinical treatment.

Ocio-Economic Factors That Influence Child Labour in Nigeria

This study examined the socio-economic factors influencing child labour in Nigeria. The instruments for data collection were the questionnaire and the in-depth interview schedules. The sample size used for the study was 621 (615 for the quantitative distribution and 6 for the IDIs). The quantitative data gathered were analysed with Statistical Package for the Social Sciences using percentages (%) and Chi-square (χ2) statistics was used to test the three hypotheses, while the qualitative data gathered was analysed in themes as complement to the quantitative data. The study found that religious sex (χ2 = (615), .081; df = 1, pے =.776), education (χ2 = (N615), 2.024; df = 1, pے =.155) and marital status (χ2 = (N=615), .055; df = 1, pے =.815) had no statistically significant relationship with the effect of child labour practice while only age (χ2= (N=615), 14.577; df=1, pے =.000) had a statistical significant relationship. Furthermore, sex (χ2 = (N=615), .678; df = 1, pے =.410), marital status (χ2 = (N= 615), .012; df = 1, pے =.911), religious affiliation (χ2 = (N=615), .003; df = 1, pے =.957), education (χ2 = (N= 615), .310; df = 1, pے =.578) and occupation (χ2 = (N=615), .849; df = 1, pے =.357) showed no statistically significant relationship with the influence of child labour practices. Three hypotheses were tested and they were all accepted. Results from the regression analysis showed that only marital status had the most positive influence on child labour pratices. Results from the study has shown that child labour practices have negative effect on the child, thus, there is the need to eradicate all forms of child labour through championing sensitization and enlightenment programmes. Also, people who still choose to engage children in child labour after these sensitization and enlightenment programmes should be severely punished by the law to deter others from engaging in such acts. Finally, the study revealed that, government, youth corps members, community leaders and the general public have a role to play in putting an end to the socio-economic factors influencing child labour practices in Nigeria.

The genetic framework of primary ciliary dyskinesia assessed by soft computing analysis.

International guidelines disagree on how best to diagnose primary ciliary dyskinesia (PCD), not least because many tests rely on pattern recognition. We hypothesized that quantitative distribution of ciliary ultrastructural and motion abnormalities would detect most frequent PCD-causing groups of genes by soft computing analysis. Archived data on transmission electron microscopy and high-speed video analysis from 212 PCD patients were re-examined to quantitate distribution of ultrastructural (10 parameters) and functional ciliary features (4 beat pattern and 2 frequency parameters). The correlation between ultrastructural and motion features was evaluated by blinded clustering analysis of the first two principal components, obtained from ultrastructural variables for each patient. Soft computing was applied to ultrastructure to predict ciliary beat frequency (CBF) and motion patterns by a regression model. Another model classified the patients into the five most frequent PCD-causing gene groups, from their ultrastructure, CBF and beat patterns. The patients were subdivided into six clusters with similar values to homologous ultrastructural phenotype, motion patterns, and CBF, except for clusters 1 and 4, attributable to normal ultrastructure. The regression model confirmed the ability to predict functional ciliary features from ultrastructural parameters. The genetic classification model identified most of the different groups of genes, starting from all quantitative parameters. Applying soft computing methodologies to PCD diagnostic tests optimizes their value by moving from pattern recognition to quantification. The approach may also be useful to evaluate atypical PCD, and novel genetic abnormalities of unclear disease-producing potential in the future.

Feasibility of Customized Thermoplastic Patient-Specific Helmet Bolus for Scalp Irradiation Using Volumetric-Modulated Arc Therapy Planning.

Introduction: In this study, we sought to develop a thermoplastic patient-specific helmet bolus that could deliver a uniform therapeutic dose to the target and minimize the dose to the normal brain during whole-scalp treatment with a humanoid head phantom. Methods: The bolus material was a commercial thermoplastic used for patient immobilization, and the holes in the netting were filled with melted paraffin. We compared volumetric-modulated arc therapy treatment plans with and without the bolus for quantitative dose distribution analysis. We analyzed the dose distribution in the region of interest to compare dose differences between target and normal organs. For quantitative analysis of treatment dose, OSLD chips were attached at the vertex (VX), posterior occipital (PO), right (RT), and left temporal (LT) locations. Results: The average dose in the clinical target volume was 6553.8 cGy (99.3%) with bolus and 5874 cGy (89%) without bolus, differing by more than 10% from the prescribed dose (6600 cGy) to the scalp target. For the normal brain, it was 3747.8 cGy (56.8%) with bolus and 5484.6 cGy (83.1%) without bolus. These results show that while the dose to the treatment target decreased, the average dose to the normal brain, which is mostly inside the treatment target, increased by more than 25%. With the bolus, the OSLD measured dose was 102.5 ± 1.2% for VX and 101.5 ± 1.9%, 95.9 ± 1.9%, and 81.8 ± 2.1% for PO, RT, and LT, respectively. In addition, the average dose in the treatment plan was 102%, 101%, 93.6%, and 80.7% for VX, PO, RT, and LT. When no bolus was administered, 59.6 ± 2.4%, 112.6 ± 1.8%, 47.1 ± 1.6%, and 53.1 ± 2.3% were assessed as OSLD doses for VX, PO, RT, and LT, respectively. Conclusion: This study proposed a method to fabricate patient-specific boluses that are highly reproducible, accessible, and easy to fabricate for radiotherapy to the entire scalp and can effectively spare normal tissue while delivering sufficient surface dose.

A structural study on a specific Li-ion ordered complex in dimethyl carbonate-based dual-cation electrolytes.

Dimethyl carbonate (DMC) is a linear carbonate solvent commonly used as an electrolyte for electric double-layer capacitors (EDLCs) and Li-ion batteries. However, there are serious problems with the use of DMC as an electrolyte solvent: (1) low ionic conductivity when using Li salts (e.g. LiBF4) and (2) liquid-liquid phase separation when using spiro-type quaternary ammonium salts (e.g. SBPBF4). Dual-cation electrolytes, i.e., bi-salt (SBPBF4 and LiBF4) in DMC, are promising candidates to avoid the phase separation issue and to enhance the total and Li+ conductivities. Herein, we reported a specific Li-ion structure in DMC-based dual-cation electrolytes by combining high-energy X-ray total scattering (HEXTS) and all-atom molecular dynamics (MD) simulations. Quantitative radial distribution function analysis based on experimental and simulation results revealed that the phase-separated SBPBF4/DMC (i.e., the bottom phase of 1 M SBPBF4/DMC) forms long-range ion ordering based on the structured SBP+-BF4- ion pairs. When adding LiBF4 salt into SBPBF4/DMC (i.e., dual-cation electrolyte), the ordered SBP+-BF4- structure disappeared owing to the formation of Li-ion solvation complexes. We found that in the dual-cation electrolyte Li ions form multiple Li+-Li+ ordered complexes in spite of relatively low Li-salt concentration (1 M), being a promising Li+-conducting medium with reduced Li salt usage and low viscosity.

Application of single-molecule analysis to singularity phenomenon of cells.

Single-molecule imaging in living cells is an effective tool for elucidating the mechanisms of cellular phenomena at the molecular level. However, the analysis was not designed for throughput and requires high expertise, preventing it from reaching large scale, which is necessary when searching for rare cells that induce singularity phenomena. To overcome this limitation, we have automated the imaging procedures by combining our own focusing device, artificial intelligence, and robotics. The apparatus, called automated in-cell single-molecule imaging system (AiSIS), achieves a throughput that is a hundred-fold higher than conventional manual imaging operations, enabling the analysis of molecular events by individual cells across a large population. Here, using AiSIS, we demonstrate the single-molecule imaging of molecular behaviors and reactions related to tau protein aggregation, which is considered a singularity phenomenon in neurological disorders. Changes in the dynamics and kinetics of molecular events were observed inside and on the basal membrane of cells after the induction of aggregation. Additionally, to detect rare cells based on the molecular behavior, we developed a method to identify the state of individual cells defined by the quantitative distribution of molecular mobility and clustering. Using this method, cellular variations in receptor behavior were shown to decrease following ligand stimulation. This cell state analysis based on large-scale single-molecule imaging by AiSIS will advance the study of molecular mechanisms causing singularity phenomena.

Rational design of novel phenol ether derivatives as non-covalent proteasome inhibitors through 3D-QSAR, molecular docking and ADMET prediction

Aim: The purpose of this paper is to use different structures and ligand-based drug design methods properly to provide theoretical guidance for the design of novel non-covalent proteasome inhibitors, and conduct theoretical analysis of the binding interaction mode between receptors and ligands. At the same time, the pharmacokinetic (PK) prediction, drug-likeness, and synthesis prediction were made for the screened novel drugs. Therefore, potentially attractive non-covalent proteasome inhibitors with low toxicity could be found as anticancer drugs. Methods: In this work, computer-aided drug design methods, including quantitative structure-activity relationship (QSAR), molecular docking, absorption, distribution, metabolism, excretion, and toxicology (ADMET) prediction, and drug-likeness prediction methods were performed. Results: In this study, the structure-activity relationship (SAR) of a series of non-covalent proteasome inhibitors were studied and the optimal comparative molecular field analysis (CoMFA; Q2 = 0.574, r2 = 0.999, r2pred = 0.755) and comparative molecular similarity indices analysis (CoMSIA)-SEHA (Q2 = 0.584, r2 = 0.989, r2pred = 0.921) models were obtained. According to the results of the QSAR model, some vital clues were found that would effectively enhance the biological activity of the compound. Based on these clues, 24 novel non-covalent proteasome inhibitors (D01–D24) were finally designed and screened. While the binding models between proteasome [protein data bank (PDB) code: 3MG6] and three representative compounds (15, 20, and D24) were also analyzed by using the molecular docking method. The results suggested that hydrogen bond and hydrophobic interaction played a key role in binding interaction between the receptor and ligand. In addition, the results of ADMET prediction indicated that the new designed compounds had reasonable PK parameters and drug-like properties. Conclusions: These statistical results can provide theoretical guidance for structural optimization, design, and synthesis of more effective non-covalent proteasome inhibitors in the future.

Действие 1-метил-4-(4-фторфенил)- 1,2,3,6-тетрагидропиридина на биохимические показатели сыворотки крови и обмен моноаминов в головном мозге мышей

Changes in biochemical parameters of blood serum and monoamine metabolism in the brain were studied on male white outbred mice subjected to intraperitoneal injections of 1-methyl-4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine (MPTP-F). The levels of norepinephrine, dopamine, serotonin and their metabolites — dioxyphenylacetic, homovanilinic and 5-hydroxyindolacetic acids — were neasured by HPLC in the cerebral cortex, hippocampus, olfactory tubercle and striatum of the right and left sides of the brain. The treatement with MPTP-F did not lead to significant changes in the biochemical parameters of blood serum. An increase in the norepinephrine concentration a decrease in the dopamine level in the right striatum were found in animals treated with MPTP-F. No changes were detected in other studied brain areas. It has been suggested that the effect of the neurotoxin MPTP-F is determined by several factors, i. e. the lipophilic properties of the molecule, the quantitative distribution of dopamine neurons between right and left sides of the brain, differences in the linear velocity of blood flow through the right and left carotid arteries and the state of the blood-brain barrier. The results obtained may indicate the prospects of using MPTP-F for modeling the early stage of Parkinson’s disease.

Management practices of Cereus jamacaru DC in the Caatinga dry forest differentially affect its reproductive phenology, fruit set and nectar availability

The management of plants and landscapes can affect the reproductive cycle of species through changes in morphology, temporal distribution of resources, and productivity, with ecological implications. In this study, we investigated the influence of management practices on the reproductive phenology and nectar availability of Cereus jamacaru DC, a columnar cactus native to Brazil managed by local people in the Caatinga dry forest. Our results reveal that the traditional management practices alter the quantitative and spatiotemporal distribution of resources (flowers, fruits, and nectar) of individuals of C. jamacaru in the studied Caatinga. All populations exhibited annual patterns of flowering and fruiting. However, individuals of the ex situ managed population showed a distinct temporal distribution pattern of flowering, with flower buds and flowers more regularly distributed throughout the reproductive period, compared to individuals of the in situ and unmanaged populations. Management practices differentially affected the production of flower buds, flowers, and fruits with a positive effect on fruit set in the in situ managed population. In addition, individuals of managed populations presented anticipation in the average date of the emission peaks of flower buds and ripe fruits. Individuals from the in situ managed population had available a greater volume of nectar with a higher sugar concentration per flower (twice as high) compared to the ex situ managed population and unmanaged population. The management practices seem to provide advantageous conditions for individuals of C. jamacaru since they allow higher availability of resources (flowers, nectar, and fruits) for a longer period in the Caatinga dry forest. Thus, management practices can prolong the temporal distribution of flowers and fruits, providing more resources for specialized pollinators (Sphingids) and dispersers (birds, reptiles), which are groups vulnerable to anthropic disturbances and climate changes in the Caatinga dry forest. These practices ultimately contribute to the maintenance of key ecological interactions of other species dependent on these vectors, benefiting the whole plant and animal community in the Caatinga dry forest.

Thinking with the head, seeing with the eyes? Investigating the relationship between place of articulation (PoA) and two semantic domains in German Sign Language (DGS)

Iconicity, the (perceived) form-meaning relationship, is present on all linguistic levels insign languages. Looking at the phonological level, there is awell established relationshipbetween the (fore)head as place of articulation (PoA) and the semantic domain of cognitionfor multiple sign languages. In previous studies, this relationship has been suggestedfor German Sign Language (DGS) as well, but none of them looked at the quantitativedistribution of PoAs in signs within the semantic domain of cognition. In thisstudy, we not only investigate the quantitative distribution of PoAs in signs of the semanticdomain of cognition for DGS but also in the semantic domain of visual perception.Findings of this study are in line with previous research, suggesting a strong relationshipbetween the semantic domain of cognition and the associated PoA (fore)head. Forthe semantic domain of visual perception, signs are predominantly articulated near theupper half of the face but not always close to the expected PoA, namely the eyes in thenarrow sense.

A Study of Characters’ Speech and Thought Presentation in Sidhwa’s Work Water: A Stylistic Analysis

The present study aims at analyzing the speech modes and thought modes presentation in the novel Water (2006) by Sidhwa. The objectives of the study are to analyze the types and the quantitative distribution of the speech modes and thought modes presentation to reveal the characters in the selected novel Water (2006) by Sidhwa. The data has been collected after the close reading of the novel and then categorized according to the checklist of the Semino and Short (2004) model. The total number of 564 sentences extracted from the novel and out of which 520 are speech modes presentations and 44 are the thought modes presentations. The mixed methodology has been used in the present study. The present study carried out by using the Semino and Short (2004) model of speech modes and thought modes presentation for the analysis. The findings of the study have represented that DS and FDS have been analyzed the most occurring speech presentations in the novel which revealed that the author has given the authority to the characters. The characters speech modes presentation represented as the dominant in the novel. The IS of speech modes presentation has not been analyzed in the extracts of novel. The thought modes presentations have been analyzed as least occurred in the extracts of novel. The FIT has been analyzed as the most occurring thought modes presentations in the extracts of the novel which represented that the narrator has represented the ongoing thoughts in the minds of the characters. The future implications has been given as the comparative study of all speech modes and thoughts can be done and of male and female characters can also be carried out by using Semino and Short (2004) model.