Пути совершенствования управления персоналом на примере ООО "Виноград" г. Томск

Объект исследования – ООО "Виноград" г. Томска. Предметом – система управления персоналом в ООО "Виноград" г. Томска. Цель работы – анализ системы управления и направления ее совершенствования на примере ООО "Виноград" г. Томска.The object of study – "the Grapes" in the city of Tomsk. The subject is a personnel management system in OOO "Grape", Tomsk. The purpose of the work is to analyze the management system and the direction of its improvement on the example of LLC "Vinograd" Tomsk. Main design, technological and technical-operational characteristics: The degree of implementation: the presented recommendations for improving the management of personnel in the present time can be used in LLC "Vinograd" Tomsk

Loss of Cytoplasmic CDK1 Predicts Poor Survival in Human Lung Cancer and Confers Chemotherapeutic Resistance

The dismal lethality of lung cancer is due to late stage at diagnosis and inherent therapeutic resistance. The incorporation of targeted therapies has modestly improved clinical outcomes, but the identification of new targets could further improve clinical outcomes by guiding stratification of poor-risk early stage patients and individualizing therapeutic choices. We hypothesized that a sequential, combined microarray approach would be valuable to identify and validate new targets in lung cancer. We profiled gene expression signatures during lung epithelial cell immortalization and transformation, and showed that genes involved in mitosis were progressively enhanced in carcinogenesis. 28 genes were validated by immunoblotting and 4 genes were further evaluated in non-small cell lung cancer tissue microarrays. Although CDK1 was highly expressed in tumor tissues, its loss from the cytoplasm unexpectedly predicted poor survival and conferred resistance to chemotherapy in multiple cell lines, especially microtubule-directed agents. An analysis of expression of CDK1 and CDK1-associated genes in the NCI60 cell line database confirmed the broad association of these genes with chemotherapeutic responsiveness. These results have implications for personalizing lung cancer therapy and highlight the potential of combined approaches for biomarker discovery

Complex expression pattern of Wnt ligands and frizzled receptors in human placenta and its trophoblast subtypes

Canonical Wingless (Writ) signalling provoked by exogenous and endogenous Writ ligands was recently shown to play a crucial role in the invasive differentiation of human trophoblasts. To gain insights into the expression pattern of the developmental regulators, we analysed all human Writ ligands and their Frizzled (FZD) receptors in the human placenta and different trophoblast model systems using semi-quantitative PCR. Fourteen out of 19 Writ ligands and 8 out of 10 FZD receptors were detectable in placental tissues, however, expression patterns varied with gestational age and between different trophoblast subtypes suggesting cell-specific functions. Besides Writ ligands acting through the canonical pathway, non-canonical ligands such as Wnt-5a, which may also activate alternative Writ signalling pathways or inhibit canonical Writ signalling, could be identified. Western blot analyses revealed secretion of Wnt-5a from primary trophoblast cultures and trophoblastic cell lines. To evaluate the potential role of Wnt-5a, SGHPL-5 trophoblast cells were transfected with luciferase reporter plasmids harbouring eight T-cell factor (TCF) DNA-recognition sequences which are exclusively activated through the canonical Writ signalling pathway. Luciferase assays revealed that Wnt-3a-induced reporter activity was repressed by recombinant Wnt-5a indicating an antagonistic role in trophoblasts. The data suggest that a complex network of Writ ligands and FZD receptors may regulate developmental processes of the human placenta. (c) 2007 Published by IFPA and Elsevier Ltd

Tumour necrosis factor-α impairs chorionic gonadotrophin β-subunit expression and cell fusion of human villous cytotrophoblast

Growth factors expressed at the fetal-maternal interface modulate hormone expression of placental trophoblasts. The aim of this study was to investigate the effects of different cytokines on hCG subunit mRNA expression in differentiating villous cytotrophoblasts. Quantitative real-time PCR revealed a 1.8- and 6.9-fold increase of hCG-α and hCG-β mRNA levels, respectively, between 36 and 60 h of term trophoblast syncytialization. Compared with controls, neither interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, IL-13 and IL-15 nor tumour necrosis factor (TNF)-α significantly altered hCG-α mRNA expression. Similarly, the ILs did not affect hCG-β transcript levels. In contrast, TNF-α suppressed hCG-β mRNA 3.8- and 1.8-fold at 36 and 60 h of term trophoblast differentiation. Accordingly, hCG secretion was impaired by TNF-α but not by the different ILs. Moreover, TNF-α reduced luciferase expression of reporter plasmids harbouring the proximal hCG-β5 promoter to 35 and 77%, respectively, in primary term trophoblasts and trophoblastic SHGPL-5 cells. In addition, counting of nuclei in syncytialized, desmoplakin-negative areas revealed a 1.9-fold reduction of term trophoblast fusion in the presence of TNF-α. Similarly, floating explant cultures prepared from first trimester-denuded villi recovered the syncytium 2.8-fold less efficiently during 72 h of cytokine treatment. Concomitantly, TNF-α impaired induction of endogenous and secreted hCG-β protein levels in these cultures. The data suggest that TNF-α decreases hCG-β mRNA and protein expression by reducing gene transcription and trophoblast cell fusion. Suppression of these processes by TNF-α could partly explain the adverse effects of the cytokine on placental function and pregnancy outcome