Proteomic analysis of the U1 snRNP of Schizosaccharomyces pombe reveals three essential organism-specific proteins

Characterization of spliceosomal complexes in the fission yeast Schizosaccharomyces pombe revealed particles sedimenting in the range of 30–60S, exclusively containing U1 snRNA. Here, we report the tandem affinity purification (TAP) of U1-specific protein complexes. The components of the complexes were identified using (LC-MS/MS) mass spectrometry. The fission yeast U1 snRNP contains 16 proteins, including the 7 Sm snRNP core proteins. In both fission and budding yeast, the U1 snRNP contains 9 and 10 U1 specific proteins, respectively, whereas the U1 particle found in mammalian cells contains only 3. Among the U1-specific proteins in S. pombe, three are homolog to the mammalian and six to the budding yeast Saccharomyces cerevisiae U1-specific proteins, whereas three, called U1H, U1J and U1L, are proteins specific to S. pombe. Furthermore, we demonstrate that the homolog of U1-70K and the three proteins specific to S. pombe are essential for growth. We will discuss the differences between the U1 snRNPs with respect to the organism-specific proteins found in the two yeasts and the resulting effect it has on pre-mRNA splicing

Nanoparticle Release from Thermal Decomposition of Polymer Nanocomposites and the Biological Potential of the Emissions

Adding nanoparticles to polymers improves the properties significantly, such as UV resistance or even electrical conductivity. The growing use of these composite materials leads to a higher amount in disposals eventually. Within the circular economy there are two ways of handling: the recycling by shredding and reuse and the thermal treatment by combustion in municipal waste incinerators. In both cases there is nearly no information about the behavior of the nanoparticles and possible release scenarios. In this study a laboratory burner is used as a flexible set up to incinerate the polymer nanocomposites. The flue gas containing a complex mixture of combustion gases and particles is characterized by different particle analysers, PAH analysis, VOC analysis and TEM. The biological impact is studied by using a VITROCELL Automated ALI exposure station. Hereby, cells of the adenocarcino cell line A549 as well as a reconstituted bronchial epithelium (MucilAir, Epithelix) were exposed for 4 hours to the aerosols emitted from the combustion process. Within the exposure process, cells were exposed to the native aerosol, an aerosol under conditions to increase particle deposition via high voltage as well as a filtered aerosol, and therefore the sole gaseous phase. Furthermore, each exposure included a so-called clean air control, where cells where exposed to filtered air. The exposure was followed by a 21 h post-incubation before the cytotoxic effects were determined via LDH-release. To reveal if possible adverse effects are caused by the used nano-scaled filling material, all used nanomaterials did also undergo the same combustion process as a single material. Cytotoxicity studies showed no increased cytotoxic effects after the combustion of the sole nano-scaled filling materials. However, combustion of PE containing materials resulted in an enhanced LDH-release, and therefore cytotoxicity, in both cell culture models. Since no difference between exposures of unfiltered and filtered aerosols was apparent, it suggested that the observed cytotoxicity is due to the combustion induced gaseous phase

Heidegger’s Underdeveloped Conception of the Undistinguishedness (Indifferenz) of Everyday Human Existence

This chapter provides an interpretation of the early Heidegger’s underdeveloped conception of the undistinguishedness of everyday human existence in Being and Time. After explaining why certain translation choices of some key terms in this text are interpretively and philosophically important, I first provide a concise argument for why the social constitution interpretation of the relation between ownedness and unownedness makes better overall sense of Heidegger’s ambivalent attitude toward the social constitution of the human being than the standard existentialist interpretation of this relation. I then proceed to the heart of this chapter, which develops his inchoate conception of the undistinguishedness of everydayness by arguing that it specifies the third distinctive mode of concrete human existence in addition to ownedness and unownedness. Accordingly, I show how unownedness is actually a generic phenomenon with two distinct species, namely, undistinguishedness and disownedness, which are at once closely related to, but also differ in significant respects from, each other. Consequently, instead of taking for granted a one-dimensional and mutually exclusive opposition between ‘authenticity’ and ‘inauthenticity’, I argue that we should adopt a two-dimensional and more nuanced understanding of the relations among undistinguishedness, disownedness, and ownedness that intersects with Heidegger’s underappreciated distinction between genuineness and ungenuineness. After raising and replying to some objections to this interpretation of undistinguishedness, I conclude this chapter by briefly sketching three of its philosophical consequences and pointing out its potential as an important resource for contemporary social theories

Differential modulation of immune response and cytokine profiles in the bursae and spleen of chickens infected with very virulent infectious bursal disease virus

Background: Very virulent infectious bursal disease virus (vvIBDV) induces immunosuppression and inflammation in young birds, which subsequently leads to high mortality. In addition, infectious bursal disease (IBD) is one of the leading causes of vaccine failure on farms. Therefore, understanding the immunopathogenesis of IBDV in both the spleen and the bursae could help effective vaccine development. However, previous studies only profiled the differential expression of a limited number of cytokines, in either the spleen or the bursae of Fabricius of IBDV-infected chickens. Thus, this study aims to evaluate the in vitro and in vivo immunoregulatory effects of vvIBDV infection on macrophage-like cells, spleen and bursae of Fabricius. Results: The viral load was increased during the progression of the in vitro infection in the HD11 macrophage cell line and in vivo, but no significant difference was observed between the spleen and the bursae tissue. vvIBDV infection induced the expression of pro-inflammatory and Th1 cytokines, and chemokines from HD11 cells in a time- and dosage-dependent manner. Furthermore, alterations in the lymphocyte populations, cytokine and chemokine expression, were observed in the vvIBDV-infected spleens and bursae. A drastic rise was detected in numbers of macrophages and pro-inflammatory cytokine expression in the spleen, as early as 2 days post-infection (dpi). On 4 dpi, macrophage and T lymphocyte infiltration, associated with the peak expression of pro-inflammatory cytokines in the bursae tissues of infected chickens were observed. The majority of the significantly regulated pro-inflammatory cytokines and chemokines, in vvIBDV-infected spleens and bursae, were also detected in vvIBDV-infected HD11 cells. This cellular infiltration subsequently resulted in a sharp rise in nitric oxide (NO) and lipid peroxidation levels. Conclusion: This study suggests that macrophage may play an important role in regulating the early expression of pro-inflammatory cytokines, first in the spleen and then in the bursae, the latter tissue undergoing macrophage infiltration at 4 dpi