Interferon (IFN)-induced immunoproteasomes (i-proteasomes) have been associated with improved processing of major histocompatibility complex (MHC) class I antigens. Here, we show that i-proteasomes function to protect cell viability under conditions of IFN-induced oxidative stress. IFNs trigger the production of reactive oxygen species, which induce protein oxidation and the formation of nascent, oxidant-damaged proteins. We find that the ubiquitylation machinery is concomitantly upregulated in response to IFNs, functioning to target defective ribosomal products (DRiPs) for degradation by i-proteasomes. i-proteasome-deficiency in cells and in murine inflammation models results in the formation of aggresome-like induced structures and increased sensitivity to apoptosis. Efficient clearance of these aggregates by the enhanced proteolytic activity of the i-proteasome is important for the preservation of cell viability upon IFN-induced oxidative stress. Our findings suggest that rather than having a specific role in the production of class I antigens, i-proteasomes increase the peptide supply for antigen presentation as part of a more general role in the maintenance of protein homeostasis.

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About 22,000 1-methyl-3-nitro-1-nitrosoguanidine-and UV-induced mutants of the rubber-degrading bacterium Streptomyces sp. strain K30 were characterized for the ability to produce clear zones on natural rubber latex overlay agar plates. Thirty-five mutants were defective solely in cleavage of rubber and were phenotypically complemented with the wild-type lcp (latex clearing protein) gene. Sixty-nine mutants exhibited a pleiotropic phenotype and were impaired in utilization of rubber and xylan, indicating that the enzymes responsible for the initial cleavage of these polymers are exported by the same secretion pathway (Q. In contrast, oxiB and oxiA, which are located directly downstream of lcp and putatively encode a heteromultimeric aldehyde dehydrogenase oxidizing the primary cleavage products generated by Lcp from poly(cis-1,4-isoprene), were expressed only in the presence of poly(cis-1,4-isoprene). Expression of lcp at a low level is thus required for sensing the polymer in the medium. Rubber degradation products may then induce the transcription of genes coding for enzymes catalyzing the later steps of poly(cis-1,4-isoprene) degradation and the transcription of lcp itself. lcp, oxiB, and oxiA seem to constitute an operon, as a polycistronic mRNA comprising these three genes was detected. The transcriptional start site of lcp was mapped 400 bp upstream of the lcp start codon.KThe microbial degradation of natural and synthetic poly(cis-1,4-isoprene) rubber is currently being intensively investigated (for a review, see reference 24), and two different strategies for degradation of isoprene rubber have been described (18). Members of one group of organisms form clear zones on natural rubber latex agar plates and generally belong to the mycelium-forming actinomycetes, such as Actinoplanes, Streptomyces, and Micromonospora. Members of the second group comprise nocardioform actinomycetes like Gordonia, Mycobacterium, and Nocardia and do not produce translucent halos; instead, they require direct contact with the rubber substrates (37). Xanthomonas sp. strain 35Y is the only known rubberdegrading bacterium that does not belong to the actinomycetes but is a gram-negative bacterium (34); however, in terms of its strategy for rubber degradation, it belongs to the first group and forms halos on rubber-containing agar plates.Whereas no proteins involved in rubber degradation in the nocardioform actinomycetes are known so far, the rubbercleaving dioxygenase RoxA occurring in culture supernatants of Xanthomonas sp. strain 35Y (16, 34) and the lcp gene encoding Lcp (latex clearing protein) in Streptomyces sp. strain K30 have recently been identified and characterized by Braaz et al. (6) and Rose and Steinbüchel (27), respectively. Both of these bacteria belong to the so-called clear-zone-forming group of rubber-degrading bacteria, and obviously, both RoxA and Lcp are secreted into the extracellular medium, leading to the formation of translucent halos on natural rubber latex. Sequence analysis of Lcp and characterization...

Though cognitive function is proven to be an independent predictor of survival in patients with intrinsic brain tumors, cognitive functions are still rarely considered. Aim of this study was to assess neurocognitive function and to identify risk factors for neurocognitive deficits. 103 patients with primary neuroepithelial tumors who received tumor resections or biopsies were included in this prospective study. The following data was acquired: mini-mental state examination, preoperative tumor volume, WHO grade, tumor entity and location, and the Karnofsky performance status scale. Furthermore, patients participated in extensive neuropsychological testing of attentional, memory and executive functions. General factors like age, clinical status, WHO grade, tumor volume and tumor location correlated with patients’ neurocognitive functions. Affection of the parietal lobe resulted in significant impairment of attention and memory functions. Frontal lobe involvement significantly affected patients’ abilities in planning complex actions and novel problem solving. Patients with temporal lesions were more likely to have impaired memory and executive functions. Comparing results among neuroepithelial tumor patients enables the identification of risk factors for cognitive impairment. General parameters such as age, KPS score, tumor size, and WHO grade are apart from the respective tumor location of high importance for neurocognitive function.

One third of the patients with brain abscesses showed immunosuppressive conditions, whereas brain abscesses also often occur in patients with good medical conditions. The isolation of the focus of infection is often possible. Surgical procedures showed very good outcomes. Patients over 60 years showed significantly worse clinical outcomes.

TNFα stimulates both pro- and anti-apoptotic signalling in hepatocytes. Anti-apoptotic signalling depends on a cascade of ubiquitylation steps leading to NFκB activation. Using Sharpin-deficient mice, we show that the ubiquitin binding protein Sharpin interacts with Hoip, an E3 ligase which generates linear ubiquitin chains. Sharpin-deficiency sensitized hepatocytes to induction of apoptosis by TNFα even in the absence of transcriptional inhibition. TNFα induced activation of NFκB was strongly reduced in hepatocytes from Sharpin-deficient mice, due to reduced and delayed phosphorylation and degradation of IκBα. Injection of TNFα-inducing lipopolysaccharides led to strongly exacerbated liver damage and premature death in Sharpin-deficient mice. Our findings point to an essential role of Sharpin in linear ubiquitin chain formation, NFκB activation, and protection of the liver against inflammatory damaging signals.

The heating elements we use for the viscometer cup incorporate temperature sensors, so (unlike the gellation coil heaters) they can safely be left switched on even when the apparatus is not in use. We have both cup heaters set to 95 "C, which for our modified starches is the temperature that gives the most satisfactory results.