Щодо змін в організації виробництва і праці: трудо-правовій аспект

У статті проаналізовано зміни в організації виробництва і праці як підстави розірвання трудового договору з ініціативи роботодавця. Висловлено думку, що ліквідація та реорганізація юридичної особи-роботодавця не є видами змін в організації виробництва і праці, а скорочення чисельності або штату працівників є наслідком цих змін. Ключові слова: трудовий договір; зміни в організації виробництва і праці, скорочення штату; звільнення; ліквідація підприємства.В статье анализируются изменения в организации производства и труда как основания расторжения трудового договора по инициативе работодателя. Высказывается мнение, что ликвидация и реорганизация юридического лица-работодателя не являются видами изменений в организации производства и труда, а сокращение численности или штата работников является следствием этих изменений. Ключевые слова: трудовой договор; изменение в организации производства и труда; сокращение штата; увольнение; ликвидация предприятия.The author has analyzed variations in the organization of manufacture and work as the basis of dissolution of contract labour on the initiative of the employer. The liquidation and reorganization of the legal person-employer are not types of variations in the organization of manufacture and work, and reduction of number of workers or reduction of staff positions are results from these variations, has been offered as the opinion. Key words: contract labour; change in the organization of production and labor; staff reduction; firing; liquidation of the enterprise

Clodronate is not protective in lethal viral encephalitis despite substantially reducing inflammatory monocyte infiltration in the CNS

Bone marrow (BM)-derived monocytes induce inflammation and tissue damage in a range of pathologies. In particular, in a mouse model of West Nile virus (WNV) encephalitis (WNE), nitric oxide-producing, Ly6Chi inflammatory monocytes from the BM are recruited to the central nervous system (CNS) and contribute to lethal immune pathology. Reducing the migration of these cells into the CNS using monoclonal antibody blockade, immune-modifying particles or CSF-1R inhibitors reduces neuroinflammation, improving survival and/or clinical outcomes. Macrophages can also be targeted more broadly by administration of clodronate-encapsulated liposomes, which induce apoptosis in phagocytes. In this study, clodronate reduced the inflammatory infiltrate by 70% in WNE, however, surprisingly, this had no effect on disease outcome. More detailed analysis demonstrated a compensatory increase in neutrophils and enhanced activation status of microglia in the brain. In addition, we observed increased numbers of Ly6Chi BM monocytes with an increased proliferative capacity and expression of SCA-1 and CD16/32, potentially indicating output of immature cells from the BM. Once in the brain, these cells were more phagocytic and had a reduced expression of antigen-presenting molecules. Lastly, we show that clodronate also reduces non-myeloid cells in the spleen and BM, as well as ablating red blood cells and their proliferation. These factors likely impeded the therapeutic potential of clodronate in WNE. Thus, while clodronate provides an excellent system to deplete macrophages in the body, it has larger and broader effects on the phagocytic and non-phagocytic system, which must be considered in the interpretation of data

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL

Contribution of IFNg, NK and T cells to the immune pathology of West Nile virus encephalitis

West Nile virus (WNV) is a mosquito-borne, neurotropic virus that can cause lethal encephalitis. Pathology in West Nile virus encephalitis is mediated by infiltration of leukocytes, in particular bone marrow-derived, nitric oxide-producing Ly6Chi inflammatory monocytes. In this project, we investigated factors associated with mobilization of monocytes from the bone marrow and infiltration of these cells into the brain to reveal potential early targets for treatment. NK cells are considered unimportant in WNV encephalitis as infection up-regulates cellular expression of MHC I, which inhibits NK cell lysis; nonetheless, they constitute 10% of the leukocytes infiltrating into the WNV-infected brain, making them the second largest infiltrating population after monocytes. Detailed analysis of NK cell phenotype and function revealed that, while NK cells seem inhibited in the brain, they are the main IFN producing cells in the bone marrow. Depletion of IFN or NK cells themselves resulted in an increase in the number of Ly6Chi monocytes in the bone marrow, suggesting a role for NK cell derived IFN in inflammatory monocyte egress from the bone marrow. To explore the role of NK cells and IFN in WNV infection further we investigated disease in SJL/J mice, which have reduced NK cell and IFNγ responses. CNS infiltration of NK cells and inflammatory monocytes was substantially reduced in WNV-infected SJL/J mice, compared to C57BL/6 mice. However, disease in SJL/J mice was more severe and virus titres in the brain were higher. Intriguingly, infiltration of T cells and pDC was increased in the brain of WNV-infected SJL/J mice, raising the possibility that these cells contribute to disease severity. Further study of the role of T cells in WNV encephalitis revealed that CD4+ T cells play a pivotal role in viral clearance as CD4+ T cell depleted animals have reduced survival and higher viral loads in the brain. In contrast, depletion of CD8+ T cells seemed to improve disease signs, suggesting these cells caused damage to the brain. Our data suggest that in WNV encephalitis, NK cells in the bone marrow drive IFNγ-mediated priming and egress of pathogenic inflammatory monocytes. These findings lay the groundwork for the development of potential early treatment targets for WNV encephalitis

Effect of ATP depletion on <i>C. jejuni</i> and <i>E. coli^inv</i> invasion.

<p>Islands of polarized Caco-2 cells were treated for 1 h with 3 mM of DNP and then infected with <i>C. jejuni</i> strain 108p4 (Red) and <i>E. coli^inv</i> (Green) for 2 h after which the cells were stained with WGA-Alexa fluor633 (Blue), fixed, and visualized with confocal microscopy. As a control, islands were treated with an equivalent amount of solvent acetone (final concentration: 0.3%) and infected. Note that DNP inhibits the invasion of <i>E. coli^inv</i> but not of <i>C. jejuni</i>.</p

Microtubule and actin cytoskeleton-independent <i>C. jejuni</i> invasion of Caco-2 cells.

<p>Islands of polarized Caco-2 cells were infected (2 h) with <i>C. jejuni</i> strain 108p4 (Red) in the absence of presence of the indicated actin cytoskeleton or microtubules disrupting or stabilizing drugs. Cells were fixed and stained with WGA-alexa fluor633 (Blue). Infected cells were visualized with confocal microscopy. The following drugs were used: (A) cytochalasin D (3 µM) and jasplakinolide (1 µM) added at 1 h prior to infection; (B) colchicine (10 µM) or paclitaxel (1 µM) added at 1 h prior to infection; (C) Colchicine (10 µM) added at 1 h after start of the infection and cells fixed at 2 h post infection. As control, cells were pre-treated with an equivalent amount of solvent DMSO (Final concentration 0.2%).</p

Bacterial viability of intracellular <i>C. jejuni</i>.

<p>Islands of polarized Caco-2 cells were infected with <i>C. jejuni</i> for 5 h in Hepes buffer, washed, incubated (3 h) with gentamicin (250 ìg/ml) in DMEM, washed again, and incubated for an additional 42 h in DMEM plus 10% FCS with a low dose of gentamicin (50 ìg/ml). At the indicated times, samples were prepared for bacterial viability assay. (A) Gentamicin killing assay showing the bacterial recovery of intracellular <i>C. jejuni</i> strains 108 containing pMA5-metK-luc (white and light grey bars) and 81–176 containing pMA5-metK-luc (dark grey and black bars) from Caco-2 cells at the indicated duration of infection. CFU were enumerated after 48 h of recovery on agar plates in a 0.2% oxygen (white and dark grey bars) and 5% oxygen (light grey and black bars) environment and indicated as CFU per well. (B) Bacterial viability as measured by bacterial luciferase reporter assay at the indicated time points. Values for results presented in (A) and (B) are the mean ± SEM of at 3 independent experiments in performed in duplicate.</p

<i>C. jejuni</i> invades polarized Caco-2 islands via subvasion with high efficiency.

<p>Confocal laser microscopy on non-infected and <i>C. jejuni</i>-infected islands of polarized Caco-2 cells. (A) Uninfected island of Caco-2 cells stained with the membrane marker WGA-Alexa fluor633 (Blue) and an anti-occludin antibody (Green) showing the presence of tight junctions. (B) Caco-2 cells (Blue) at 1 h of infection in DMEM showing <i>C. jejuni</i> strain 108p4 (Red) mostly located at the basal side of cells near the edge of the island of polarized cells. (C) Caco-2 cells (Blue) at 5 h of infection in DMEM demonstrating intracellular <i>C. jejuni</i> strain 108p4 (Red) at the center of the island of cells with tight junctions (Green). (D). Polarized Caco-2 cells (Blue) infected (1 h and 5 h) with a mixture of <i>C. jejuni</i> strains 108p4 (Red) and 81–176 (Green) showing invasion of Caco-2 cells by both strains. Transversal optical sections of the cells are depicted at the bottom of each panel to show the location of the bacteria relative to the cell basis.</p