Комплексні одиниці словотвору

У статті розглянуті комплексні одиниці словотвору, починаючи зі словотвірної категорії, похідного слова, яке входить в словотвірну пару, словотвірний ланцюжок, словотвірну парадигму, словотвірне гніздо, словотвірний тип, словотвірний ряд. Основну увагу приділено розмежуванню цих складних одиниць словотвору та встановлення різниці між ними. А також автор в статті має на меті з’ясувати, яка ж комплексна одиниця є основною в словотворі і доходить до висновку, що кожна з них може бути розглянутою як основна в залежності від того, яка мета і які аналітичні завдання стоять перед дослідником. (This article deals with the complex entities of word building beginning with the word building category, derivative word that forms word building pair, word building chain, word building paradigm, word building nest, word building type, word building family. Main attention was given to the distinction of these word building’s complex entities and to the establishment of their differences. Also in this article the author wants to clear up what complex entity is the main in the word building and come to the conclusion that every entity can be examined as the main. It depends on the goal and on the analytical questions of the researcher. Every complex entity has own structure, semantic characteristics, and can be divided into smaller units. Identifying similarities in the organization of complex units, first of all we pay attention to their formal semantic component. In our view, it is enough to reveal and describe the structure of the less structurally unit to understand the organization of bigger one.

Functional Networks Involved in Cell Wall Biosynthesis and the Isoprenoid Pathway in the Yeast Saccharomyces cerevisiae

Ce travail porte sur la réponse de la levure à des composés chimiques, qui de manière similaire aux antifongiques, altèrent la structure pariétale et/ou la biosynthèse de l'ergostérol. Ces deux voies sont essentielles pour la survie des champignons, la paroi les protège de leur environnement, alors que l'ergostérol garantit un fonctionnement correct de la membrane plasmique. Pour comprendre ces mécanismes et leurs interactions, nous avons choisi un organisme modèle, la levure Saccharomyces cerevisiae, et étudié sa réponse à des agents perturbant la synthèse de la paroi (populacandine B, rouge Congo, caféine et Calcofluor White), ainsi qu'à des inhibiteurs de la biosynthèse de l'ergostérol (lovastatine et acide zaragozic). Nous avons découvert que la caféine inhibe Tor1p et provoque une baisse rapide et transitoire du niveau intracellulaire en AMPc. Nous avons ainsi montré que Rom2p, un élément de la voie du maintien de l’intégrité pariétale, agit sous l'effet de la caféine comme une protéine "pivot" en transmettant le signal à la kinase Mpk1, mais également à la voie de signalisation de l'AMPc. La caféine a induit un "renforcement" de la paroi mais, contrairement aux autres drogues testées, cet effet ne s'exerce pas à travers une interaction directe. En effet, ce remodelage ne se produit pas à travers la voie habituelle Rlm1p, mais nécessite d'autres facteurs de transcription comme Crz1p, Swi4p et Msn2/4p. Ces résultats nous ont permis d'identifier de nouvelles relations entre les voies de maintien de l'intégrité pariétale, TOR, et la cascade de signalisation de l'AMPc, qui exercent un contrôle synergique sur la croissance des champignons en réponse aux stress.\ud ___________________________________________________________________This work is focused on the fungal response to the chemical compounds, which similarly to antifungal drugs, impair the cell wall or ergosterol biosynthesis. Both examined pathways are essential for survival of fungi. The cell wall protects them from the harmful environment whereas ergosterol ensures correct functioning of the plasma membrane. For investigation of those pathways, we chose the genetically tractable fungus, the yeast Saccharomyces cerevisiae, and studied its response to the cell wall damaging agents, i.e. Papulacandin B, Congo red, Calcofluor white and caffeine, and to the inhibitors of the ergosterol biosynthesis like lovastatin and zaragozic acid. A novel function of caffeine was discovered to inhibit Tor1p and to cause a rapid but transient decrease in the intracellular level of cAMP. We have identified Rom2p, a component of the cell wall integrity pathway, as a pivotal protein mediating caffeine-derived signaling to Mpk1 kinase as well as to the cAMP signaling pathway. Caffeine induced strengthening of the cell wall but, in contrast to other tested drugs, this effect was not exerted through a direct interaction with the cell wall structure. Moreover, the caffeine-induced remodeling of the cell wall did not occur through the usual Rlm1p-mediated way but it required some other transcription factors like Crz1p, Swi4p and Msn2/4p. Altogether, we report here a number of results that bear on the relationship between the cell wall integrity, the TOR pathway and the cAMP signaling cascade that together control the growth of the fungal cell in response to stressing conditions

In acute myeloid leukemia, B7-H1 (PD-L1) protection of blasts from cytotoxic T cells is induced by TLR ligands and interferon-gamma and can be reversed using MEK inhibitors

B7-H1 (PD-L1) is a B7-related protein that inhibits T-cell responses. B7-H1 participates in the immunoescape of cancer cells and is also involved in the long-term persistence of leukemic cells in a mouse model of leukemia. B7-H1 can be constitutively expressed by cancer cells, but is also induced by various stimuli. Therefore, we examined the constitutive and inducible expression of B7-H1 and the consequences of this expression in human acute myeloid leukemia (AML). We analyzed B7-H1 expression in a cohort of 79 patients with AML. In addition, we studied blast cells after incubation with interferon-gamma or toll-like receptors (TLR) ligands. Finally, we evaluated functionality of cytotoxic T-cell activity against blast cells. Expression of B7-H1 upon diagnosis was high in 18% of patients. Expression of TLR2, 4 and 9 was detected in one-third of AML samples. Expression of TLR2 and TLR4 ligands or IFN-γ induced by B7-H1 was found to protect AML cells from CTL-mediated lysis. Spontaneous B7-H1 expression was also found to be enhanced upon relapse in some patients. MEK inhibitors, including UO126 and AZD6244, reduced B7-H1 expression and restored CTL-mediated lysis of blast cells. In AML, B7-H1 expression by blasts represents a possible immune escape mechanism. The inducibility of B7-H1 expression by IFN-γ or TLR ligands suggests that various stimuli, either produced during the immune response against leukemia cells or released by infectious microorganisms, could protect leukemic cells from T cells. The efficacy of MEK inhibitors against B7-H1-mediated inhibition of CTLs suggests a possible cancer immunotherapy strategy using targeted drugs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-010-0909-y) contains supplementary material, which is available to authorized users

Finding undetected protein associations in cell signaling by belief propagation

External information propagates in the cell mainly through signaling cascades and transcriptional activation, allowing it to react to a wide spectrum of environmental changes. High throughput experiments identify numerous molecular components of such cascades that may, however, interact through unknown partners. Some of them may be detected using data coming from the integration of a protein-protein interaction network and mRNA expression profiles. This inference problem can be mapped onto the problem of finding appropriate optimal connected subgraphs of a network defined by these datasets. The optimization procedure turns out to be computationally intractable in general. Here we present a new distributed algorithm for this task, inspired from statistical physics, and apply this scheme to alpha factor and drug perturbations data in yeast. We identify the role of the COS8 protein, a member of a gene family of previously unknown function, and validate the results by genetic experiments. The algorithm we present is specially suited for very large datasets, can run in parallel, and can be adapted to other problems in systems biology. On renowned benchmarks it outperforms other algorithms in the field.Comment: 6 pages, 3 figures, 1 table, Supporting Informatio

Small-Sized Holographic Devices With Polymer based Reversible Recording Medium

The principle of the photothermoplastic method of hologram recording as well as the general requirements for photothermoplastic holographic recording media based on photoconductive polymer films are considered. The holographic recording media obtained by authors based on carbazolyl- and ferrocenyl-containing oligomers doped with organic dyes are discussed Some examples of practical application of such media in holographic interferometry are demonstrated

On the origin of biological construction, with a focus on multicellularity

Biology is marked by a hierarchical organization: all life consists of cells; in some cases, these cells assemble into groups, such as endosymbionts or multicellular organisms; in turn, multicellular organisms sometimes assemble into yet other groups, such as primate societies or ant colonies. The construction of new organizational layers results from hierarchical evolutionary transitions, in which biological units (e.g., cells) form groups that evolve into new units of biological organization (e.g., multicellular organisms). Despite considerable advances, there is no bottom-up, dynamical account of how, starting from the solitary ancestor, the first groups originate and subsequently evolve the organizing principles that qualify them as new units. Guided by six central questions, we propose an integrative bottom-up approach for studying the dynamics underlying hierarchical evolutionary transitions, which builds on and synthesizes existing knowledge. This approach highlights the crucial role of the ecology and development of the solitary ancestor in the emergence and subsequent evolution of groups, and it stresses the paramount importance of the life cycle: only by evaluating groups in the context of their life cycle can we unravel the evolutionary trajectory of hierarchical transitions. These insights also provide a starting point for understanding the types of subsequent organizational complexity. The central research questions outlined here naturally link existing research programs on biological construction (e.g., on cooperation, multilevel selection, self-organization, and development) and thereby help integrate knowledge stemming from diverse fields of biology

Impact of paracoccin gene silencing on Paracoccidioides brasiliensis Virulence

Among the endemic deep mycoses in Latin America, paracoccidioidomycosis (PCM), caused by thermodimorphic fungi of the Paracoccidioides genus, is a major cause of morbidity. Disease development and its manifestations are associated with both host and fungal factors. Concerning the latter, several recent studies have employed the methodology of gene modulation in P. brasiliensis using antisense RNA (AsRNA) and Agrobacterium tumefaciens-mediated transformation (ATMT) to identify proteins that influence fungus virulence. Our previous observations suggested that paracoccin (PCN), a multidomain fungal protein with both lectin and enzymatic activities, may be a potential P. brasiliensis virulence factor. To explore this, we used AsRNA and ATMT methodology to obtain three independent PCN-silenced P. brasiliensis yeast strains (AsPCN1, AsPCN2, and AsPCN3) and characterized them with regard to P. brasiliensis biology and pathogenicity. AsPCN1, AsPCN2, and AsPCN3 showed relative PCN expression levels that were 60%, 40%, and 60% of that of the wild-type (WT) strain, respectively. PCN silencing led to the aggregation of fungal cells, blocked the morphological yeast-to-mycelium transition, and rendered the yeast less resistant to macrophage fungicidal activity. In addition, mice infected with AsPCN1, AsPCN2, and AsPCN3 showed a reduction in fungal burden of approximately 96% compared with those inoculated with the WT strain, which displayed a more extensive destruction of lung tissue. Finally, mice infected with the PCN-silenced yeast strains had lower mortality than those infected with the WT strain. These data demonstrate that PCN acts as a P. brasiliensis contributory virulence factor directly affecting fungal pathogenesis. IMPORTANCE The nonexistence of efficient genetic transformation systems has hampered studies in the dimorphic fungus Paracoccidioides brasiliensis, the etiological agent of the most frequent systemic mycosis in Latin America. The recent development of a method for gene expression knockdown by antisense RNA technology, associated with an Agrobacterium tumefaciens-mediated transformation system, provides new strategies for studying P. brasiliensis. Through this technology, we generated yeasts that were silenced for paracoccin (PCN), a P. brasiliensis component that has lectin and enzymatic properties. By comparing the phenotypes of PCN-silenced and wild-type strains of P. brasiliensis, we identified PCN as a virulence factor whose absence renders the yeasts unable to undergo the transition to mycelium and causes a milder pulmonary disease in mice, with a lower mortality rate. Our report highlights the importance of the technology used for P. brasiliensis transformation and demonstrates that paracoccin is a virulence factor acting on fungal biology and pathogenesis.This work had financial support from the following agencies: Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP (2016/00629-4, 2014/05359-0, 2012/08552-0, 2014/22561-7, 2012/09611-0, 2016/04877-2, 2016/60642-2, and 2013/04088-0); Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (150036/2014-0, 477161/2008-1, and 475357/2013-2); Financiadora de Estudos e Projetos – FINEP (0110045900); Ministry of Education and Science – Fundação para a Ciência e a Tecnologia – FCT (SFRH/BPD/96176/2013 and IF/00735/2014)info:eu-repo/semantics/publishedVersio

The antifungal protein PAF interferes with PKC/MPK and cAMP/PKA signalling of Aspergillus nidulans

The Penicillium chrysogenum antifungal protein PAF inhibits polar growth and induces apoptosis in Aspergillus nidulans. We report here that two signalling cascades are implicated in its antifungal activity. PAF activates the cAMP/protein kinase A (Pka) signalling cascade. A pkaA deletion mutant exhibited reduced sensitivity towards PAF. This was substantiated by the use of pharmacological modulators: PAF aggravated the effect of the activator 8-Br-cAMP and partially relieved the repressive activity of caffeine. Furthermore, the Pkc/mitogen-activated protein kinase (Mpk) signalling cascade mediated basal resistance to PAF, which was independent of the small GTPase RhoA. Non-functional mutations of both genes resulted in hypersensitivity towards PAF. PAF did not increase MpkA phosphorylation or induce enzymes involved in the remodelling of the cell wall, which normally occurs in response to activators of the cell wall integrity pathway. Notably, PAF exposure resulted in actin gene repression and a deregulation of the chitin deposition at hyphal tips of A. nidulans, which offers an explanation for the morphological effects evoked by PAF and which could be attributed to the interconnection of the two signalling pathways. Thus, PAF represents an excellent tool to study signalling pathways in this model organism and to define potential fungal targets to develop new antifungals