Presence Of Analogues Research Articles

8010 Potent MSB-61 as Type 1 Diabetes (T1D) therapy: mechanism of action in insulin secretion

Abstract Disclosure: N. Ajmal: None. M. Bogart: None. K. Corbin: None. P. Khan: None. M. Shafqat: None. S. Bergmeier: None. G. Gu: None. X. Tong: None. C.S. Nunemaker: None. Type 1 diabetes (T1D) is a chronic autoimmune disorder caused by proinflammatory cytokines (Interleukin 1-beta; IL1-β, Tumor Necrosis Factor-alpha; TNF-α, and Interferon-gamma; IFN-ϒ) from immune cells that destroy insulin-producing beta cells in pancreatic islets and lead to hyperglycemia. The development of possible treatments to cure T1D is needed besides intensive insulin therapy that does not halt disease progression. We have identified a small molecule called MSB-61 that can protect islet cells from endoplasmic reticulum stressors (66% protection) and cytokines (33% protection) as measured by propidium iodide in islets isolated from mice using 50uM MSB-61. Importantly, we observed large increases in insulin secretion during overnight exposure to 50uM MSB-61. Insulin secretion began to increase in response to MSB-61 at ∼4h, reaching a plateau at ∼8h of greater than 4-fold insulin release compared to controls. The Kegg pathway analysis of RNA-seq data on MSB-61 suggested that multiple genes upregulated by MSB-61 are involved in insulin secretion through an amplifying pathway that includes cAMP/PKA and Pi3k/Akt signaling cascades. Based on RNA sequencing data, this study aimed to test MSB-61 for identifying pathway by which it potentiates insulin secretion. Islets from CD-1 mice and mouse insulinoma Min-6 cell lines were used to test amplifying pathways by using cAMP/PKA and Pi3k/Akt analogs and antagonists with and without MSB-61, and overnight insulin secretion and insulin content will be measured by enzyme-linked immunosorbent assay (ELISA). MSB-61 showed no potential effects on insulin secretion when tested for Pi3k/Akt pathway in the presence of analogs and antagonists such as 740-Y-P and wortmannin. It further suggests MSB-61 might potentiate insulin secretion through the cAMP/PKA pathway, which is still under investigation. RNA sequencing analysis of mouse islets showed several genes that belong to Ras family member-2 and have GTPase activity. Genes with GTPase activity will be further investigated to help identify if MSB-61 stimulates insulin secretion through an amplifying pathway involving the cAMP/PKA downstream signaling cascade. Identifying the mechanism of action and signaling pathway by which MSB-61 potentiates insulin secretion will open new ways of identifying T1D therapeutic interventions that would help replace standard insulin therapy. Presentation: 6/3/2024

Многоликий жанр в концепции филолога В. С. Вахрушева

This article presents an interdisciplinary conception of genre proposed by the Russian philologist from Balashov, Professor Vladimir Serafimovich Vakhrushev. The feasibility of this task can be mainly seen in two aspects. First of all, Vakhrushev conceives genre as an ideal model generating versatile phenomena not only of discursive, but also of social, cultural, and historical processes. His broad understanding of genre can contribute to the comprehension of the specific speech genres, studied within the specific disciplines isolated so far by their primary tasks, as the elements of a coherent macro system “Genre – Text – Man – Society – Culture – Nature”. Within this macro system, the genres of verbal texts appear to be the structures similar to those of other types, existing elsewhere beyond the realm of art or everyday speech, namely, in nature, history and society. According to V. Vakhrushev, verbal genres and the genres of natural and sociohistorical phenomena share a number of intrinsic properties which are determined by the global ecological law of their adaptation to the ever-changing environment. Secondly, this publication is timed to coincide with Professor Vakhrushev’s 90th anniversary, which falls on September 2022, thus providing a motive for presenting his theoretical legacy to a wider community of linguists, literary scholars, cultural studies scholars, perhaps sociologists, historians, and natural scientists to engage them in a critical discussion. Researchers of speech genres and literary studies may be particularly interested in Vakhrushev’s phenomenological definition of genre and in the ways he is reasoning the isomorphism and the presence of analogies between text genres and the genres of other life forms, such as biology, daily social life and history.

ECOSYSTEM OF SCHOOL EDUCATION QUALITY: FORMATION AND DEVELOPMENT

The article analyzes the concepts of "ecosystem" and "ecosystem approach", their evolution in the field of business, economics, the possibility of using the potential of the ecosystem approach in relation to solving management issues and assessing the quality of education at school. Attention is focused on the presence of analogies, common trends and approaches in the business environment and the field of general education. The signs and manifestations of the ecosystem approach in relation to the ecosystem of the quality of school education are considered (cooperation and competition; formation of new values of activity and usefulness of the school; the focus on integrated solutions; the effect of saving on diversity). A special place in the article is given to the interpretation of the quality of school education as a multidimensional and interdisciplinary phenomenon. The characteristic of the subjects of activity that ensure the quality of education within the school ecosystem and the value creation process is given. The article also presents and discusses the results of a survey of teaching staff of secondary schools in St. Petersburg and the Leningrad region on the formation and development of the ecosystem of the quality of school education. On the basis of theoretical and experimental studies generalizing conclusions are formulated, prospects for further study of the phenomenon of "ecosystem of school education quality" are determined.

Catalytic Substrate-Selective Silylation of Primary Alcohols via Remote Functional-Group Discrimination.

Silylation of alcohols has generally been known to take place at the sterically most accessible less-hindered hydroxy group. Herein, the catalyst-controlled substrate-selective silylation of primary alcohols, in which the selectivity was controlled independently of the innate reactivity of the hydroxy group, based on the steric environment, is reported. The chain-length-selective silylation of 1,n-amino alcohol derivatives was achieved and 1,5-amino alcohol derivatives showed outstandingly high reactivity in the presence of analogues with a shorter or longer chain length under catalyst-controlled conditions. A highly substrate-selective catalytic silylation of pentanol analogues was also developed, in which the remote functionality at C(5) from the reacting hydroxy groups was effectively discriminated on silylation.

Catalytic Substrate‐Selective Silylation of Primary Alcohols via Remote Functional‐Group Discrimination

AbstractSilylation of alcohols has generally been known to take place at the sterically most accessible less‐hindered hydroxy group. Herein, the catalyst‐controlled substrate‐selective silylation of primary alcohols, in which the selectivity was controlled independently of the innate reactivity of the hydroxy group, based on the steric environment, is reported. The chain‐length‐selective silylation of 1,n‐amino alcohol derivatives was achieved and 1,5‐amino alcohol derivatives showed outstandingly high reactivity in the presence of analogues with a shorter or longer chain length under catalyst‐controlled conditions. A highly substrate‐selective catalytic silylation of pentanol analogues was also developed, in which the remote functionality at C(5) from the reacting hydroxy groups was effectively discriminated on silylation.

Strigolactones and Auxin Cooperate to Regulate Maize Root Development and Response to Nitrate.

In maize, nitrate regulates root development thanks to the coordinated action of many players. In this study, the involvement of strigolactones (SLs) and auxin as putative components of the nitrate regulation of lateral root (LR) was investigated. To this aim, the endogenous SL content of maize root in response to nitrate was assessed by liquid chromatography with tandem mass Spectrometry (LC-MS/MS) and measurements of LR density in the presence of analogues or inhibitors of auxin and SLs were performed. Furthermore, an untargeted RNA-sequencing (RNA-seq)-based approach was used to better characterize the participation of auxin and SLs to the transcriptional signature of maize root response to nitrate. Our results suggested that N deprivation induces zealactone and carlactonoic acid biosynthesis in root, to a higher extent if compared to P-deprived roots. Moreover, data on LR density led to hypothesize that the induction of LR development early occurring upon nitrate supply involves the inhibition of SL biosynthesis, but that the downstream target of SL shutdown, besides auxin, also includes additional unknown players. Furthermore, RNA-seq results provided a set of putative markers for the auxin- or SL-dependent action of nitrate, meanwhile also allowing to identify novel components of the molecular regulation of maize root response to nitrate. Globally, the existence of at least four different pathways was hypothesized: one dependent on auxin, a second one mediated by SLs, a third deriving from the SL-auxin interplay, and a last one attributable to nitrate itself through further downstream signals. Further work will be necessary to better assess the reliability of the model proposed.

A nitrile-mediated SERS aptasensor coupled with magnetic separation for optical interference-free detection of atrazine

A novel aptasensor based on the combination of surface-enhanced Raman scattering (SERS) and magnetic separation is presented for sensitive and selective determination of atrazine. 4-(Mercaptomethyl) benzonitrile (MMBN), providing a prominent peak (2227 cm−1) in the Raman-silent spectral window (1800–2800 cm−1), is selected as Raman tag to eliminate optical interference from biomolecules in sensing system. The MMBN and atrazine-binding aptamer are assembled on silver nanoparticles (AgNPs) to serve as Raman probe (MMBN-AgNPs-aptamer). Meanwhile, Fe3O4@Au core/shell nanoparticles conjugated with the complementary DNA (Fe3O4@Au-cDNA) are prepared as Raman substrate to extract the Raman probe with magnetic separation. Atrazine specifically binds to aptamer, and hinders the formation of Fe3O4@Au-cDNA-aptamer-AgNPs-MMBN (expressed as “Fe3O4@Au-AgNPs”) complex. Therefore, the Raman intensity of MMBN on substrate decreases with the increment of atrazine concentration. Under optimal SERS conditions, the proposed aptasensor is used to detect atrazine in the laboratory and real samples. The as-prepared atrazine sensor demonstrates a broad dynamic range of 1–50 nM, as well as a low detection limit of 0.67 nM (S/N = 3). For real sample test, the recovery rate ranges from 98.7%–106.6%. The fabricated aptasensor shows superior interference-free performance for atrazine determination in the presence of analogs at high levels.

A signal on-off ratiometric electrochemical sensor coupled with a molecular imprinted polymer for selective and stable determination of imidacloprid

This work presents a signal on-off ratiometric electrochemical sensor coupled with a molecular imprinted polymer (MIP) for imidacloprid (IMI) determination. The ratiometric strategy corrects the detection results by setting 6-(Ferrocenyl)hexanethiol (FcHT) as an internal reference. The MIP membrane, as a molecular recognition receptor, has a three-dimensional structure and is complementary in the shape and chemical functionality to the template. The combination of a ratiometric strategy and MIP improves the sensitivity and selectivity of the sensors. The experimental parameters, such as monomer/template ratio, electropolymerization cycle and adsorption time, are optimized to improve the IMI sensing performance of the as-fabricated electrode. Under optimal electrochemical conditions, the proposed sensor is used to detect IMI in laboratory and real samples. In a range as wide as 5 × 10−7−1 × 10−4 mol L−1, a linear relationship is well established, and the value of the correlation coefficient is 0.9984. The limit of detection (LOD, S/N = 3) is well defined as 4.7 × 10−8 mol L−1. The recovery rates range from 97.4% to 103.5% while testing real samples. The fabricated electrode shows superior anti-interference ability for IMI determination in the presence of analogs at a higher level.

ФАКТОРЫ ЗАБЫВАЕМОСТИ ИЕРОГЛИФОВ ПРИ ОБУЧЕНИИ КИТАЙСКОМУ ЯЗЫКУ КАК ИНОСТРАННОМУ

The study focuses on the problem of forgetting Chinese hieroglyphs that arises in the process of learning the Chinese language. The problem is relevant with regard to the modern methods in teaching Chinese as a foreign language. The author sets the following tasks: 1) by the example of students specializing in linguistics at Perm State University, to analyze experimentally the process of forgetting the lexical minimum; 2) to study the cognitive characteristics and patterns of forgetting hieroglyphics. The experiment results were analyzed based on the reactions ‘Reading’ and ‘Translation’. It was found that for students it is easier to remember translation rather than reading of a hieroglyph: the coefficient of correct answers for the ‘Translation’ reaction is on average higher than that for the ‘Reading’ reaction. Comparative tables were compiled showing the average value of the forgetting coefficient among students learning vocabulary HSK 1 and HSK 2 at three control time points. The experiment showed that at all levels and for both reactions one tendency is observed: the degree of forgetting hieroglyphics increases by the beginning of the academic period following the previously completed period but decreases by the end of the educational period to the initial or lower level. There were identified factors that can increase recognition of hieroglyphs, for example, the presence of analogues in the Russian language (terms of kinship, numerals, pronouns). The process of forgetting was analyzed; analysis showed that hieroglyphs are forgotten only at the initial stage of training, with subsequent increase in the memorizing degree exceeding the initial indicators. The data obtained can serve as an important empirical basis in developing approaches to the methodology of teaching the Chinese language, and can also be useful for research concerning the problems of forgetting lexical units when studying foreign languages and, in particular, the memorization of hieroglyphs.

The art of metaphore in the poems of baderkhan sindi’s divan (hozanet min) as a model

The metaphor is the main focus of this research and metaphor in terms of language taking something from me something else, while in terms of the conversion of meaning from one word to another in the presence of analogy in its hidden structure and the importance of metaphor in the approximation qualities of the subject to be stronger impact on the self and the performance of rhetorical expression and create a new image. The metaphor is one of the main rhetoric arts which fall within the framework of rhetorical arts. This art is used extensively for the construction of the poetic language, where poetry schools of various kinds rely on metaphors in order to build their literary language. The poet Badrakhan Sindi belongs to any modern poetical school, a great echo in the literary circles, especially in the province of Dohuk, is a poet who adopted the arts of rhetoric to the systems of their logo, especially the art of metaphor. This study is devoted to the identification and analysis of the art of metaphor in his poetry, and this is to show how the use of this graphic art of various kinds in his poetry. The study was based on its identified debt (hozanit min) of Badrakhan Sindi. Through the study was identified metaphors and hidden metaphor in various types of poetry. This study is described as "the art of borrowing in the poems of Badrakhan Sindi Diwan, (Hozanit Min) as a model, an attempt to determine the art of borrowing in his poet's.

Principles and Legal Forms of Cooperation in Science, Technology and Innovation between Russia and the EU Countries

The article is devoted to the analysis of mutual relations between Russia and the EU countries in the sphere of science, technology and innovation. It focuses on the analysis of principles and forms of cooperation taking into account their evolution and assimilation of the previous experience of the Soviet Union in the implementation of international scientific and technical cooperation (STC) with States of different levels of economic development. The presence of analogues or the same forms that were previously known in interstate relations in the affected area is now revealed. Thus, the combination of contractual and institutional instruments for the implementation of international relations concerning scientific and technical cooperation remains important. At the same time, there are also new means generated by the need to improve the registration of contractual relations in the field of STC and adjustment of the legal regulation in this part to the realities of life.

When analogies harm: The effects of analogies on metacomprehension

The main goal of the present research was to test whether the presence of analogies would affect the relative accuracy of metacognitive judgments about learning from expository science texts, and whether any effect would depend on the type of cues that readers used as the basis for their judgments of comprehension. In a series of experiments, students read texts that either contained or did not contain analogies; were asked to judge how well they understood each text; took comprehension tests for each topic; and were asked to self-report the basis for their judgments. Relative metacomprehension accuracy was computed as the intra-individual correlation between judgments and test performance. Results showed that the presence of analogies can lead to poor relative metacomprehension accuracy for students who fail to use situation-model-based cues to judge their understanding of text.

Increased yield of β-glucosidase-catalyzed hydrolysis reactions in the presence of betaine-type metabolite analog.

β-Glucosidases (EC 3.2.1.21), abundant enzymes distributed in animals, plants and microorganism, has been generating lots of attentions for bioethanol production from cellulosic biomass. In this study, using three different origins of β-glucosidases, glucose productivity of β-glucosidase-catalyzed hydrolysis reactions in the presence of synthetic betaine-type metabolite analog (2-N,N,N-tri-n-butylammonium) acetate, was investigated. By the addition of the analog, the hydrolysis yields for all β-glucosidases was highly improved from 4-13 to 64-100%. To understand the factors affecting on the yield enhancements, the kinetic parameters, inhibition constants of end-product and temporal stability of β-glucosidases were compared. As a result, enhancement of the yields is mainly related to the increase in the temporal stability of β-glucosidases in the presence of the analog. The present findings lead to not only improve the glucose productivity of β-glucosidase-catalyzed hydrolysis reaction toward bioethanol production but also apply to a new stabilization method for various unstable enzymes.

Electrochemical Determination of Dopamine by a Reduced Graphene Oxide–Gold Nanoparticle-Modified Glassy Carbon Electrode

ABSTRACTA novel electrochemical aptasensor is reported for the label-free determination of dopamine by electrochemically reduced graphene oxide and a gold nanocomposite with a ribonucleic acid (RNA) aptamer. The nanocomposite was fabricated by layer-to-layer electrochemical deposition. The aptamer was immobilized on the surface of the gold nanoparticles through the formation of thiol–gold bonds. Dopamine was determined through specific interaction with the immobilized aptamer. The redox activity of the analyte enabled direct electrochemical analysis. The conductivity and structure of the nanocomposite were characterized by cyclic voltammetry and scanning electron microscopy. In contrast to bare or reduced graphene oxide-modified electrodes, the nanocomposite-modified electrode significantly enhanced the current response. The electrochemical aptasensor provided a detection limit of 0.13 µM with a linear dynamic range from 0.5 to 20 µM. In addition, the sensor was shown to provide high selectivity and satisfactory stability for the determination of dopamine in the presence of analogs and in human serum.

The Scope of Application of Analogical Reasoning in Precedential Law

This article describes the scope of application of an analogical argument in the province of precedential law. Inter alia, it revolves around such issues of the doctrine of precedent as: distinguishing, ascertaining and crystallizing the meaning of ratio decidendi or expanding its coverage onto the cases of first impression. Allowance has also been made for the presence of analogy in searching for the law-maker’s intention, the determining of the obsolescence of precedents and quoting precedents out-of-jurisdiction. The place analogical reasoning has in legal education has also been touched upon. On top of that, the article highlights the usage of analogy in precedential law which enables the replacement of the conception of rationes decidendi for the proposition of applying judicial precedents directly upon the relationship of similarity that obtains between cases decided previously and the instant case.

Study of the interaction between bovine hemoglobin and analogs of biphenyldicarboxylate by spectrofluorimetry

The interaction between bovine hemoglobin and analogs of Biphenyldicarboxylate was investigated by fluorescence, synchronous fluorescence, ultraviolet–vis absorbance, resonance light-scattering spectra and three-dimensional fluorescence spectra at pH 7.40. The quenching mechanism and binding constants were determined by the quenching of bovine hemoglobin fluorescence in presence of analogs. Results showed that the nature of the quenching was of static type. Both the van der Waals and hydrogen bonding played a major role in stabilizing the complex. The distance between donor and acceptors was obtained to be 2.11–2.25nm according to Förster's theory. The influence of analogs on the conformation of bovine hemoglobin was investigated.

Vitamin B12 and homocysteine levels in blood of dairy cows during subacute ruminal acidosis

Abstract. The aim of this study was to investigate the variations of vitamin B12 and homocysteine in blood of dairy cows during subacute ruminal acidosis (SARA). On 228 subjects ruminal liquid was collected through rumenocentesis technique and rumen pH was immediately measured by a portable pH-meter. On the basis of pH values all cows were classified (bovine class) in Group A (animals with rumen pH>5.7), Group B (animals with rumen pH between 5.6 and 5.7) and Group C (animals with rumen pH<5.6). In relation to the acidosis risk depending on the rumen pH (herd class), the herds were classified in Group 1 (normal herds: less than 33 % cows with rumen pH<5.8), Group 2 (critical herds: more than 33 % cows with rumen pH between 5.5 and 5.8) and Group 3 (acidosis herds: more than 33 % cows with rumen pH<5.5). On blood samples, collected by jugular venipuncture, vitamin B12 and homocysteine were measured by chemiluminescent immunological tests. One-way analysis of variance (ANOVA), followed by Bonferroni test, showed significant differences (P<0.05) for vitamin B12 in bovine class and significant differences (P<0.05) for homocysteine in herd class. The influence of rumen pH values resulted in adequate vitamin B12 and homocysteine levels to meet microbial and cow requirements and fatty acids modifications in dairy cows affected by SARA. Moreover, the increase of vitamin B12 could be due to the presence of analogues which interfere with the transport of the vitamin. These findings provide more information on blood modifications during SARA.

Lipid Channels: Positive and Negative Cooperativity and Regulation by Proteins

The sphingolipid, ceramide, self-assembles in phospholipid membranes, forming large channels capable of translocating proteins across said membranes. These channels are believed responsible for protein release from mitochondria, a key, decision-making step in apoptosis. Rather unexpectedly for lipids, ceramide channels reveal a high degree of order and display properties similar to those of protein channels. They contain amide linkages believed to be responsible for organizing individual lipids into columns, a kind of secondary structure. The columns self-assemble into a barrel-stave, essentially quaternary structure, that is so highly-organized that it shows both negative and positive cooperativity in the presence of chemical analogs. Depending on the location of the chemical change, the presence of the analog could favor channel formation or inhibit the formation. Thus the analogs must intercalate into the structure, altering its stability. Furthermore, ceramide channels can be destabilized or stabilized by proteins that regulate apoptosis and these act in a very specific manner. These proteins do not act as catalysts but rather as modulators or allosteric modifiers. They act to shift the stability constants that determine the equilibrium between channels, monomers, and non-channel aggregates. Bcl-xL destabilizes the channels by forming what appears to be a 1:1 complex with the ceramide channel. The stoichiometry of the interaction with oligomeric Bax, the protein that stabilizes the channel, appears to be larger than 1:1 but the variable oligomeric nature of the protein complicates the interpretation. The affinity between oligomeric Bax and the ceramide channel seems to increase with channel size indicating the possibility of a conformation-driven enlargement of the channel. (supported by NSF grant: MCB-0641208 and a Nano-Biotechnology DBED award)

Os contratos entre enunciador e enunciatário no discurso de Luís Inácio Lula da Silva

No presente artigo, analisamos o discurso do Presidente Lula, buscando articular a semiótica greimasiana com a retórica moderna (Perelman e outros), a fim de verificar os procedimentos argumentativos utilizados pelo enunciador para fazer com que os enunciatários creiam nele (nos seus esforços, nas suas boas intenções) e no seu governo. Nesse sentido, duas estratégias básicas podem ser observadas, dada a sua recorrência no referido discurso: o uso da 1ª pessoa (eu ou nós), por meio do qual se confere ao dizer um "tom" de compromisso pessoal, e a presença de analogias e metáforas, que procuram tornar o discurso mais acessível para o cidadão comum.
 
 Palavras-chave: Retórica Moderna. Procedimentos Argumentativos. Enunciador. Enunciatário.

The Effects of Retinoic Acid on the Insulin‐like Growth Factor Axis in Primary Tissue Culture from Hyperparathyroidism

The importance of the IGF system in HPT has been previously demonstrated. Additionally, the role of vitamin A in HPT has been reported. Retinoic acid (RA), a derivative of vitamin A, is a ligand for the IGF II receptor (IGF2R). We have evaluated the interactions of RA with the IGF system in a primary parathyroid cell culture model. Primary cell cultures were prepared from nine patients. Following adhesion, the cells were transferred to serum-free medium and dosed once with growth factors +/- RA for 96 hours. Proliferation was assessed by measuring tritiated thymidine incorporation. Compared with the control group (100%), both IGF I and II increased DNA synthesis significantly. Retinoic acid significantly reduced the basal DNA synthesis to 82.2% +/- 4.2% compared with control (P < 0.05). Retinoic acid x10(-5) M completely abrogated the proliferative actions of IGF II (70.2% +/- 9.7%, P < 0.05) but had no significant effect on the IGF I response (P > 0.05). To evaluate the role of IGF2R or IGFBPs in mediating the actions of RA, the IGF II analogs [Leu27]IGF II (10-20-fold reduced IGF I receptor affinity) and des(1-6) IGF II (lower IGFBP binding affinity) were used. The IGF II inhibitory effect of RA was enhanced in the presence of analogs [Leu27]IGF II (P = 0.052) but not with des(1-6)IGF II (P > 0.05), compared with wild-type IGF II. These data implicate a novel antiproliferative role for RA in enhancing the pericellular clearance of IGF II via the IGF2R preventing ligand activation of the IGF I receptor. This may have broader implications for RA effects in other tumors.