Latching dynamics as a basis for short-term recall

We discuss simple models for the transient storage in short-term memory of cortical patterns of activity, all based on the notion that their recall exploits the natural tendency of the cortex to hop from state to state—latching dynamics. We show that in one such model, and in simple spatial memory tasks we have given to human subjects, short-term memory can be limited to similar low capacity by interference effects, in tasks terminated by errors, and can exhibit similar sublinear scaling, when errors are overlooked. The same mechanism can drive serial recall if combined with weak order-encoding plasticity. Finally, even when storing randomly correlated patterns of activity the network demonstrates correlation-driven latching waves, which are reflected at the outer extremes of pattern space

Новое время библиотек. Заседание Редакционного совета и Редакционной коллегии журнала «Библиотековедение»

On the Annual Meeting of the Editorial Council and the Editorial Board of the Journal «Bibliotekovedenie» («Library and Information Science Journal»), held at the Russian State Library on March 18, 2014.О ежегодном заседании Редакционного совета и Редакционной коллегии журнала «Библиотековедение», состоявшемся в Российской государственной библиотеке 18 марта 2014 года

Administration of vitamin D3 improves antimetastatic efficacy of cancer vaccine therapy of Lewis lung carcinoma

Aim: To analyze antitumor efficacy of experimental cancer vaccine therapy combined with introduction of vitamin D3 (VD3) for treatment of Lewis lung carcinoma (3LL). Materials and Methods: Cancer vaccines composed from recombinant murine beta-defensin-2 (mBD-2) and 3LL cell lysate, or DNA, coding for mBD-2-Muc1 fusion construct cloned in pcDNA3+ vector, were prepared and used for intradermal vaccination. Experimental cancer vaccines introduced i. d. at therapeutic and prophylactic regimens to 3LLbearing C57Bl mice, were applied alone or in combination with VD3 (administered per os) and/or low-dose cyclophosphamide (CP, administered intraperitoneal). Efficacy of treatments was analyzed by primary tumor growth dynamics indexes and by metastasis rate in vaccinated animals. Results: As it has been shown, administration of the protein-based vaccine composed from mBD-2 and 3LL cell lysate in combination with VD3 and CP, but not in VD3 free setting, led to significant suppression of primary tumor growth (p < 0.005) and had significant antimetastatic effect. Introduction of VD3 with or without CP in the scheme of treatment with mBD-2-Muc1-DNA vaccine at therapeutic regimen has led to significant suppression of primary tumor (p < 0.05) and metastasis volumes (p < 0.005), while in the groups of animals treated with DNA-vaccine + VD3 with or without CP at prophylactic regimen, significant antimetastatic effect (p < 0.05) and elevation of average life-span (p < 0.05) have been registered. Conclusion: The results of this pilot study have shown promising clinical effects of VD3 administration in combination with cancer vaccinotherapy in vivo

Expression of human beta-defensins-1, 2 and 4 mRNA in human lung tumor tissue: a pilot study

To analyze the patterns of human beta-defensin-1, 2, 4 (hBDs) expression in human lung tumors. Materials and Methods: Tissue samples of surgically resected human lung tumors (squamous cell carcinoma (SCC), n = 10; adenocarcinoma (AC), n = 10) paired with conditionally normal tissue samples were analized for expression of hBD-1, 2, 4 mRNA by semiquantitive RT-PCR. Results: In a number of studied lung cancer tissue samples, overexpression of defensin mRNA was registered: hBD-1 mRNA (50% of SCC and 60% AC), hBD-2 mRNA (60% of SCC and 50% of AC) or hBD-4 (40% of SCC and 20% AC). No correlation was detected between the levels of hBD-1, hBD-2 and hBD-4 mRNA and histological type, differentiation grade of the tumor, and the stage of the disease, as well as the content of hBD-2 peptide in blood serum of lung cancer patients. Conclusion: Human beta-defensins-1 and -2 are often up-regulated in human lung tumors.Цель: проанализировать особенности экспрессии мРНК бета-дефенсинов-1, 2, 4 (hBDs) в ткани опухоли легкого человека. Материалы и методы: с помощью метода полуколичественного RT-PCR-анализа изучали уровень экспрессии мРНК hBD-1, 2, 4 в образцах ткани хирургически удаленных опухолей легкого человека (плоскоклеточный рак — ПКР, n = 10; аденокарцинома — AК, n = 10) по сравнению с образцами условно-нормальной ткани легкого тех же пациентов. Результаты: в ряде исследованных образцов опухолей легкого выявлена повышенная экспрессия мРНК hBD-1 (50% ПКР и 60% AК), hBD-2 (60% ПКР и 50% АК) или hBD-4 (40% ПКР и 20% AК). Зависимости между уровнем экспрессии бета-дефенсинов и гистологическим типом опухоли, стадией заболевания и содержанием пептида hBD-2 в сыворотке крови больных не установлено. Выводы: в ткани опухоли легкого человека часто активирована экспрессия hBD-1 и hBD-2

Обеспечивая сохранение, преемственность и развитие научной мысли: взгляд из истории в будущее

The article provides an overview of the jubilee events, devoted to the 300th anniversary of the Library of the Russian Academy of Sciences, held in October-November, 2014. In the context of contemporary problems of library and information activities and continuity of knowledge development there was highlighted the research conference «Library of the Academy of Sciences: 300 years of Dedicated Service to Science». The attention is drawn to one of the major activities of the library, defining the outline of the ongoing and upcoming changes: improvement and development of the automated information-library system of the Russian Academy of Sciences, which solves the problem of openness and accessibility of the collections to the wide range of users.Статья представляет собой обзор юбилейных мероприятий в честь 300-летия Библиотеки Российской академии наук (БАН), прошедших в октябре-ноябре 2014 года. В контексте современных проблем библиотечно-информационной деятельности и преемственности развития знаний освещена научная конференция «Библиотека Академии наук: 300 лет служения науке». Обращено внимание на одно из основных направлений деятельности библиотеки, определяющее контуры происходящих и предстоящих изменений: совершенствование и развитие автоматизированной информационно-библиотечной системы РАН, решающей задачу открытости и доступности фондов для широкого круга пользователей

Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study

Aim: In the present research we analyze the mechanism of human beta-defensin-2 (hBD-2) influence on cultured malignant epithelial cell growth. Materials and Methods: The analysis of a concentration-dependent effect of recombinant hBD-2 (rec-hBD-2) on cell growth patterns and cell cycle distribution has been performed in vitro with 2 cell lines (human lung adenocarcinoma A549 cells and human epidermoid carcinoma A431 cells) using MTT test, flow cytometry and direct cell counting. To study intracellular localization of hBD-2 immunocytofluorescent and immunocytochemical analyses were applied, and effect of hBD-2 on signal cascades involved in cell cycle regulation has been studied by Western blotting. Results: According to our data, rec-hBD-2 exerts a concentration-dependent effect on the viability of cultured A549 and A431 cells. It causes proproliferative effect at concentrations below 1 nM, significant suppression of cell proliferation at concentration range from 10 nM to 1 µM (p<0.05), and cell death at higher concentrations. Using flow cytometry we have demonstrated that hBD-2 dependent growth suppression is realized via cell cycle arrest at G1/S phase (p<0.05). Also, we have registered significant activation of pRB and decreased expression of Cyclin D1 in cells treated with the defensin compared to untreated control cells, while the expression of p53 remains unaffected. The study of intracellular localization of hBD-2 in these cells has revealed that exogeneously added defensin molecules enter the cells, are distributed throughout the cytoplasm and could be detected in cell nuclei. The model study using A549 cells treated with 1,25-(OH)2D3 has shown similar cell growth suppression effect of native endogenously produced hBD-2. Conclusion: The results of our study suggest that in malignant epithelial cells hBD-2 may control cell growth via arrest of G1/S transition and activation of pRB

Fusion expression of recombinant human beta-defensin-3 and analysis of its biological activity

Human beta-defensins (hBDs) are small cationic antimicrobial peptides with multiple biologic activities. The aim of the study was cloning, expression in E.coli, purification and in vitro analysis of biological activity of recombinant human beta-defensin-3 (rec-hBD-3). hBD-3 cDNA was cloned into pGEX-2T vector, and recombinant plasmid was transformed into E.coli BL21(DE3) cells. Rec-hBD-3 was expressed in bacterial cells as GST-hBD-3 fusion protein, and purified by 3-step procedure via affine chromatography on glutathione-agarose, cleavage of fusion protein by thrombin, and reverse phase chromatography on Sep-Pack C18. Analysis of biological activity of rec-hBD-3 has shown that the peptide is active against Pseudomonas aeruginosa in micromolar concentrations in radial diffusion test. Rec-hBD-3 did not affect proliferation and viability of cultured human cancer cells of A431, A549, and TPC-1 lines, but was capable to potentiate cytotoxic effects of rec-hBD-2 and docetaxel in vitro

Involvement of human beta-defensin-2 in regulation of malignant potential of cultured human melanoma cells

Background and Aim: Human beta-defensin-2 (hBD-2) is an antimicrobial cationic peptide capable to control human carcinoma cell growth via cell cycle regulation. The present study was aimed on determination of hBD-2 influence on the growth patterns and malignant potential of cultured human melanoma cells. Methods: The study was performed on cultured human melanoma cells of mel Z and mel Is lines treated with recombinant hBD-2 (rec-hBD-2); cell viability, proliferation, cell cycle distribution, and anchorage-independent growth were analyzed using MTT test, direct cell counting, flow cytometry, and colony forming assay respectively. Expression and/or phosphorylation levels of proteins involved in cell cycle control were evaluated by Western blotting. Results: The treatment of mel Z and mel Is cells with rec-hBD-2 in a concentration range of 100–1000 nM resulted in a concentration-dependent suppression of cell proliferation, viability, and colony forming activity. It has been shown that rec-hBD-2 exerts its growth suppression effects via significant downregulation of B-Raf expression, activation of pRB and upregulation of p21WAF1 expression, downregulation of cyclin D1 and cyclin E resulting in cell cycle arrest at G1/S checkpoint. Conclusion: According to obtained results, hBD-2 exerts its growth suppression effect toward human melanoma cells via downregulation of B-Raf, cyclin D1 and cyclin E expression, upregulation of p21WAF1 expression and activation of pRB. Key Words: human beta-defensin-2, melanoma, proliferation, viability, cell cycle, B-Raf, anchorage-independent growth

Immunohistochemical analysis of beta-defensin-2 expression in human lung tumors

The aim of this paper is to present research was directed on analysis of the expression patterns of human beta-defensin-2 (hBD-2) in human lung tumors

BTK, NuTM2A, and PRPF19 are Novel KMT2A Partner Genes in Childhood Acute Leukemia

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with acute leukemias, especially in infants. KMT2A is rearranged with a big variety of partner genes and in multiple breakpoint locations. Detection of all types of KMT2A rearrangements is an essential part of acute leukemia initial diagnostics and follow-up, as it has a strong impact on the patients’ outcome. Due to their high heterogeneity, KMT2A rearrangements are most effectively uncovered by next-generation sequencing (NGS), which, however, requires a thorough prescreening by cytogenetics. Here, we aimed to characterize uncommon KMT2A rearrangements in childhood acute leukemia by conventional karyotyping, FISH, and targeted NGS on both DNA and RNA level with subse-quent validation. As a result of this comprehensive approach, three novel KMT2A rearrangements were discovered: ins(X;11)(q26;q13q25)/KMT2A-BTK, t(10;11)(q22;q23.3)/KMT2A-NUTM2A, and inv(11)(q12.2q23.3)/KMT2A-PRPF19. These novel KMT2A-chimeric genes expand our knowledge of the mechanisms of KMT2A-associated leukemogenesis and allow tracing the dynamics of minimal residual disease in the given patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Funding: KMT2A rearrangement assessment was supported by the Russian Science Foundation (grant no. 19-75-10056). Quantitative RT-PCR for MRD monitoring was supported by Russian Presidential (grant no. MK-1645.2020.7)