New HR Organizational Structures in Czech and Slovak Organizations

AbstractThe paper deals with Human Resource Organizational Structures in Czech and Slovak organizations, reflecting new trends which are related to HR Business Partner model. HR organizational structure is the framework within a human resources department that divides the decision making functions within HR into specific groups with distinct job functions. HR Business Partner model reflects modern expectations arising from new roles of human resources managers in organizations which include its strategic consequences, change support and also its abilities of HR systems development and improvement of employee engagement. The paper in its first part describes basic principles of new roles of human resource departments in organizations based on HRBP concept and also new competencies required. In the second part the paper presents situation in these aspects in organizations from different sectors of the Czech and Slovak economy (especially secondary and tertiary sector), benefits of the HR department transformation and some conclusions drawn from the analysis of data obtained from qualitative and quantitative survey. It also compares specific situations and documents specific applications of these new trends with more or less developed HR organizational structures.The contribution of the paper can be seen in practical view of theoretical concepts which constitute HR Business Partner model by Dave Ulrich and specific applications determined by human resources department transformation in Czech and Slovak organizations reflecting these concepts in different ways

THE DEVELOPMENT AND COMMITMENT OF T HELPER SUBSETS

Indiana University-Purdue University Indianapolis (IUPUI)T helper cells play a crucial role in providing protection against a wide variety of pathogens. The differentiation and effector function of T helper cell subsets is dependent on cytokine activation of Signal Transducer and Activator of Transcription (STAT) family members. The development of Th17 cells, which are important for immunity to fungi and extracellular bacteria, relies on STAT3. We show that IL-23 in combination with IL-1β promotes maintenance of the Th17 phenotype following multiple rounds of stimulation. However, IL-23 does not promote commitment of Th17 cells, and when Th17 cells are cultured with IL-12 or IL-4 they switch to a Th1 and Th2 phenotype, respectively. The maintenance of the Th17 phenotype by IL-23 also requires STAT4. STAT4-deficient memory cells cultured with IL-23 have reduced IL-17 production following stimulation with either anti-CD3 or IL-18+IL-23 stimulation compared to wild type memory cells. Furthermore, STAT4-deficient mice have impaired in vivo Th17 development following immunization with ovalbumin. This challenges a one-STAT/one-subset paradigm and suggests that multiple STAT proteins can contribute to a single phenotype. To test this further we examined whether STAT3 is required for the development of Th2 cells, a subset known to depend upon the IL-4-induced activation of STAT6 for immunity to parasites and promoting allergic inflammation. We demonstrate that in the absence of STAT3, the expression of Th2-associated cytokines and transcription factors is dramatically reduced. STAT3 is also required for in vivo development of Th2 cells. Moreover, allergic inflammation is diminished in mice that have T cells lacking expression of STAT3. STAT3 does not affect STAT6 activation, but does impact how STAT6 functions in binding target genes. Thus, multiple STAT proteins can cooperate in promoting the development of specific T helper subsets

Th17 cells demonstrate stable cytokine production in a proallergic environment

Th17 cells are critical for the clearance of extracellular bacteria and fungi, but also contribute to the pathology of autoimmune diseases and allergic inflammation. After exposure to an appropriate cytokine environment, Th17 cells can acquire a Th1-like phenotype, but less is known about their ability to adopt Th2 and Th9 effector programs. To explore this in more detail, we used an IL-17F lineage tracer mouse strain that allows tracking of cells that formerly expressed IL-17F. In vitro-derived Th17 cells adopted signature cytokine and transcription factor expression when cultured under Th1-, Th2-, or Th9-polarizing conditions. In contrast, using two models of allergic airway disease, Th17 cells from the lungs of diseased mice did not adopt Th1, Th2, or Th9 effector programs, but remained stable IL-17 secretors. Although in vitro-derived Th17 cells expressed IL-4Rα, those induced in vivo during allergic airway disease did not, possibly rendering them unresponsive to IL-4-induced signals. However, in vitro-derived, Ag-specific Th17 cells transferred in vivo to OVA and aluminum hydroxide-sensitized mice also maintained IL-17 secretion and did not produce alternative cytokines upon subsequent OVA challenge. Thus, although Th17 cells can adopt new phenotypes in response to some inflammatory environments, our data suggest that in allergic inflammation, Th17 cells are comparatively stable and retain the potential to produce IL-17. This might reflect a cytokine environment that promotes Th17 stability, and allow a broader immune response at tissue barriers that are susceptible to allergic inflammation

MARCH1 protects the lipid raft and tetraspanin web from MHCII proteotoxicity in dendritic cells

Dendritic cells (DCs) produce major histocompatibility complex II (MHCII) in large amounts to function as professional antigen presenting cells. Paradoxically, DCs also ubiquitinate and degrade MHCII in a constitutive manner. Mice deficient in the MHCII-ubiquitinating enzyme membrane-anchored RING-CH1, or the ubiquitin-acceptor lysine of MHCII, exhibit a substantial reduction in the number of regulatory T (Treg) cells, but the underlying mechanism was unclear. Here we report that ubiquitin-dependent MHCII turnover is critical to maintain homeostasis of lipid rafts and the tetraspanin web in DCs. Lack of MHCII ubiquitination results in the accumulation of excessive quantities of MHCII in the plasma membrane, and the resulting disruption to lipid rafts and the tetraspanin web leads to significant impairment in the ability of DCs to engage and activate thymocytes for Treg cell differentiation. Thus, ubiquitin-dependent MHCII turnover represents a novel quality-control mechanism by which DCs maintain homeostasis of membrane domains that support DC's Treg cell-selecting function

Stochastic descriptors to study the fate and potential of naive T cell clonotypes in the periphery

The population of naive T cells in the periphery is best described by determining both its T cell receptor diversity, or number of clonotypes, and the sizes of its clonal subsets. In this paper, we make use of a previously introduced mathematical model of naive T cell homeostasis, to study the fate and potential of naive T cell clonotypes in the periphery. This is achieved by the introduction of several new stochastic descriptors for a given naive T cell clonotype, such as its maximum clonal size, the time to reach this maximum, the number of proliferation events required to reach this maximum, the rate of contraction of the clonotype during its way to extinction, as well as the time to a given number of proliferation events. Our results show that two fates can be identified for the dynamics of the clonotype: extinction in the short-term if the clonotype experiences too hostile a peripheral environment, or establishment in the periphery in the long-term. In this second case the probability mass function for the maximum clonal size is bimodal, with one mode near one and the other mode far away from it. Our model also indicates that the fate of a recent thymic emigrant (RTE) during its journey in the periphery has a clear stochastic component, where the probability of extinction cannot be neglected, even in a friendly but competitive environment. On the other hand, a greater deterministic behaviour can be expected in the potential size of the clonotype seeded by the RTE in the long-term, once it escapes extinction

Metabolomic-Based Noninvasive Serum Test to Diagnose Nonalcoholic Steatohepatitis: Results From Discovery and Validation Cohorts

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease worldwide and includes a broad spectrum of histologic phenotypes, ranging from simple hepatic steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). While liver biopsy is the reference gold standard for NAFLD diagnosis and staging, it has limitations due to its sampling variability, invasive nature, and high cost. Thus, there is a need for noninvasive biomarkers that are robust, reliable, and cost effective. In this study, we measured 540 lipids and amino acids in serum samples from biopsy-proven subjects with normal liver (NL), NAFL, and NASH. Using logistic regression analysis, we identified two panels of triglycerides that could first discriminate between NAFLD and NL and second between NASH and NAFL. These noninvasive tests were compared to blinded histology as a reference standard. We performed these tests in an original cohort of 467 patients with NAFLD (90 NL, 246 NAFL, and 131 NASH) that was subsequently validated in a separate cohort of 192 patients (7 NL, 109 NAFL, 76 NASH). The diagnostic performances of the validated tests showed an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.88 +/- 0.05, 0.94, and 0.57, respectively, for the discrimination between NAFLD and NL and 0.79 +/- 0.04, 0.70, and 0.81, respectively, for the discrimination between NASH and NAFL. When the analysis was performed excluding patients with glucose levels >136 mg/dL, the area under the receiver operating characteristic curve for the discrimination between NASH and NAFL increased to 0.81 +/- 0.04 with sensitivity and specificity of 0.73 and 0.80, respectively. Conclusion: The assessed noninvasive lipidomic serum tests distinguish between NAFLD and NL and between NASH and NAFL with high accuracy.Supported by the National Institutes of Health Blueprint for Neuroscience Research (R01AT001576 to S.C.L., J.M.M.), Agencia Estatal de Investigacion of the Ministerio de Economia, Industria y Competitividad (SAF2014-52097R to J.M.M.), CIBER Hepatic and Digestive Diseases and Instituto de Salud Carlos III (PIE14/0003 to J.M.M.), Etorgai 2015-Gobierno Vasco (ER-2015/00015 to R.M., I.M.A., C.A., A.C.), Plan de Promocion de la Innovacion 2015-Diputacion Foral de Bizkaia (6/12/IN/2015/00131 to A.C., C.A.), National Institute of Diabetes and Digestive and Kidney Diseases (RO1DK81410 to A.J.S.), and Czech Ministry of Health (RVO VFN64165 to L.V.)

Non-Canonicaly Recruited TCRαβCD8αα IELs Recognize Microbial Antigens

In the gut, various subsets of intraepithelial T cells (IELs) respond to self or non-self-antigens derived from the body, diet, commensal and pathogenic microbiota. Dominant subset of IELs in the small intestine are TCRαβCD8αα+ cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRαβCD8αα+ IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRαβCD8αα+ IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8αα+ IELs and CD4+ T cells express identical αβTCRs and this overlap raised parallel to a surge in the diversity of microbial flora. We also found that an opportunistic pathogen (Staphylococcus aureus) isolated from mouse small intestine specifically activated CD8αα+ IELs and CD4+ derived T cell hybridomas suggesting that some of TCRαβCD8αα+ clones with microbial specificities have extrathymic origin. We also report that CD8ααCD4+ IELs and Foxp3CD4+ T cells from the small intestine shared many αβTCRs, regardless whether the later subset was isolated from Foxp3CNS1 sufficient or Foxp3CNS1 deficient mice that lacks peripherally-derived Tregs. Overall, our results imply that repertoire of TCRαβCD8αα+ in small intestine expends in situ in response to changes in microbial flora

Distinct transcriptional regulatory modules underlie STAT3's cell type-independent and cell type-specific functions

Transcription factors (TFs) regulate gene expression by binding to short DNA sequence motifs, yet their binding specificities alone cannot explain how certain TFs drive a diversity of biological processes. In order to investigate the factors that control the functions of the pleiotropic TF STAT3, we studied its genome-wide binding patterns in four different cell types: embryonic stem cells, CD4+ T cells, macrophages and AtT-20 cells. We describe for the first time two distinct modes of STAT3 binding. First, a small cell type-independent mode represented by a set of 35 evolutionarily conserved STAT3-binding sites that collectively regulate STAT3's own functions and cell growth. We show that STAT3 is recruited to sites with E2F1 already pre-bound before STAT3 activation. Second, a series of different transcriptional regulatory modules (TRMs) assemble around STAT3 to drive distinct transcriptional programs in the four cell types. These modules recognize cell type-specific binding sites and are associated with factors particular to each cell type. Our study illustrates the versatility of STAT3 to regulate both universal- and cell type-specific functions by means of distinct TRMs, a mechanism that might be common to other pleiotropic TFs. © The Author(s) 2013. Published by Oxford University Press.Link_to_subscribed_fulltex