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991.
Astrid Tschan-Plessl Christian P. Kalberer Ronja Wieboldt Martin Stern Uwe Siegler Aleksandra Wodnar-Filipowicz Sabine Gerull Jörg Halter Dominik Heim André Tichelli Dimitrios A. Tsakiris Karl-Johan Malmberg Jakob R. Passweg Alessia Bottos 《Cytotherapy》2021,23(4):329-338
Background aimsTo investigate the feasibility and safety of haploidentical natural killer (NK) cell infusions as consolidation immunotherapy after autologous stem cell transplant (ASCT) in patients with plasma cell myeloma.MethodsTen patients (median age, 59 years) received induction treatment followed by high-dose melphalan (200 mg/m2) at day –1, ASCT at day 0 and increasing NK cell doses (1.5 × 106, 1.5 × 107 and multiple doses of 1.0 × 108 cells/kg body weight) from day +1 to day +30 after ASCT. NK cells were harvested and purified from peripheral blood of haploidentical donors and expanded for 19 days with interleukin (IL)-2 and IL-15 under Good Manufacturing Practice conditions.ResultsNK cell numbers increased 56.0-fold (37.4- to 75.5-fold). Patients received a median of 3.8 × 108 (0.9–5.7 × 108) NK cells/kg body weight in six (three to eight) infusions. Multiparametric mass cytometry analysis demonstrated an altered surface receptor repertoire of expanded NK cells with increased degranulation and cytokine production activities but diminished expression of perforin. Donor NK cells were detectable in the peripheral blood, peaking 1 h after each dose (up to 90% donor NK cells). The treatment was safe and well tolerated, without evidence of graft-versus-host disease. Comparison with a control patient population receiving ASCT without NK cell infusions showed no significant difference in relapse, progression-free survival and overall survival.ConclusionsThis study demonstrates reliable manufacturing of high numbers of activated NK cells for multiple-dose infusions and safe administration of these cellular products. The trial was registered at ClinicalTrials.gov (identifier no. NCT01040026). 相似文献
992.
Modes of branching of appressoria on conidial germ tubes of 36 Erysiphe spp. were studied. Only unlobed appressoria, termed alobatus pattern, were seen in E. lonicerae, E. magnifica and E. symphoricarpi. Viewed from above with light or scanning electron microscopes, other species had ± irregular lobing, but from below in the
plane of contact with the substrate successive dichotomous branchings at 120° were seen to produce a five-lobed appressorium
within 6 h. Each division produced a temporarily dormant outward-facing lobe and an inward limb that continued growth and
division to form the axis of curved, hooked, single- or double-headed symmetrical or asymmetrical structures in a helicoid
cyme-like pattern. Outlines of extracellular material after removal of germinated conidia confirmed this manner of branching.
After 36 h some lobes re-divided forming botryose or jigsaw patterns even extending with extra appressoria to form candelabra-like
structures. Conidia developed only one true germ tube; rarely secondary unswollen tubes emerged from spare shoulders or ends.
The same true germ tubes developed initially on host surfaces, where secondary tubes and/or extensions from appressorial lobes
grew into colony-forming hyphae. Lobed appressoria of Neoerysphe and Phyllactinia also branched at 120°. Podosphaera xanthii exhibited a simpler branching pattern. 相似文献
993.
Frequent gene movement and pseudogene evolution is common to the large and complex genomes of wheat, barley, and their relatives 总被引:1,自引:0,他引:1
Wicker T Mayer KF Gundlach H Martis M Steuernagel B Scholz U Simková H Kubaláková M Choulet F Taudien S Platzer M Feuillet C Fahima T Budak H Dolezel J Keller B Stein N 《The Plant cell》2011,23(5):1706-1718
All six arms of the group 1 chromosomes of hexaploid wheat (Triticum aestivum) were sequenced with Roche/454 to 1.3- to 2.2-fold coverage and compared with similar data sets from the homoeologous chromosome 1H of barley (Hordeum vulgare). Six to ten thousand gene sequences were sampled per chromosome. These were classified into genes that have their closest homologs in the Triticeae group 1 syntenic region in Brachypodium, rice (Oryza sativa), and/or sorghum (Sorghum bicolor) and genes that have their homologs elsewhere in these model grass genomes. Although the number of syntenic genes was similar between the homologous groups, the amount of nonsyntenic genes was found to be extremely diverse between wheat and barley and even between wheat subgenomes. Besides a small core group of genes that are nonsyntenic in other grasses but conserved among Triticeae, we found thousands of genic sequences that are specific to chromosomes of one single species or subgenome. By examining in detail 50 genes from chromosome 1H for which BAC sequences were available, we found that many represent pseudogenes that resulted from transposable element activity and double-strand break repair. Thus, Triticeae seem to accumulate nonsyntenic genes frequently. Since many of them are likely to be pseudogenes, total gene numbers in Triticeae are prone to pronounced overestimates. 相似文献
994.
995.
Advances in reporters for gene expression have made it possible to document and quantify expression patterns in 2D-4D. In contrast to microarrays, which provide data for many genes but averaged and/or at low resolution, images reveal the high spatial dynamics of gene expression. Developing computational methods to compare, annotate, and model gene expression based on images is imperative, considering that available data are rapidly increasing. We have developed a sparse Bayesian factor analysis model in which the observed expression diversity of among a large set of high-dimensional images is modeled by a small number of hidden common factors. We apply this approach on embryonic expression patterns from a Drosophila RNA in situ image database, and show that the automatically inferred factors provide for a meaningful decomposition and represent common co-regulation or biological functions. The low-dimensional set of factor mixing weights is further used as features by a classifier to annotate expression patterns with functional categories. On human-curated annotations, our sparse approach reaches similar or better classification of expression patterns at different developmental stages, when compared to other automatic image annotation methods using thousands of hard-to-interpret features. Our study therefore outlines a general framework for large microscopy data sets, in which both the generative model itself, as well as its application for analysis tasks such as automated annotation, can provide insight into biological questions. 相似文献
996.
Opitz E Koch A Klingel K Schmidt F Prokop S Rahnefeld A Sauter M Heppner FL Völker U Kandolf R Kuckelkorn U Stangl K Krüger E Kloetzel PM Voigt A 《PLoS pathogens》2011,7(9):e1002233
Proteasomes recognize and degrade poly-ubiquitinylated proteins. In infectious disease, cells activated by interferons (IFNs) express three unique catalytic subunits β1i/LMP2, β2i/MECL-1 and β5i/LMP7 forming an alternative proteasome isoform, the immunoproteasome (IP). The in vivo function of IPs in pathogen-induced inflammation is still a matter of controversy. IPs were mainly associated with MHC class I antigen processing. However, recent findings pointed to a more general function of IPs in response to cytokine stress. Here, we report on the role of IPs in acute coxsackievirus B3 (CVB3) myocarditis reflecting one of the most common viral disease entities among young people. Despite identical viral load in both control and IP-deficient mice, IP-deficiency was associated with severe acute heart muscle injury reflected by large foci of inflammatory lesions and severe myocardial tissue damage. Exacerbation of acute heart muscle injury in this host was ascribed to disequilibrium in protein homeostasis in viral heart disease as indicated by the detection of increased proteotoxic stress in cytokine-challenged cardiomyocytes and inflammatory cells from IP-deficient mice. In fact, due to IP-dependent removal of poly-ubiquitinylated protein aggregates in the injured myocardium IPs protected CVB3-challenged mice from oxidant-protein damage. Impaired NFκB activation in IP-deficient cardiomyocytes and inflammatory cells and proteotoxic stress in combination with severe inflammation in CVB3-challenged hearts from IP-deficient mice potentiated apoptotic cell death in this host, thus exacerbating acute tissue damage. Adoptive T cell transfer studies in IP-deficient mice are in agreement with data pointing towards an effective CD8 T cell immune. This study therefore demonstrates that IP formation primarily protects the target organ of CVB3 infection from excessive inflammatory tissue damage in a virus-induced proinflammatory cytokine milieu. 相似文献
997.
Rafael Salas Urban Tillmann Uwe John Jane Kilcoyne Amanda Burson Caoimhe Cantwell Philipp Hess Thierry Jauffrais Joe Silke 《Harmful algae》2011,10(6):774-783
Azaspiracids (AZAs) are a group of lipophilic polyether compounds first detected in Ireland which have been implicated in shellfish poisoning incidents around Europe. These toxins regularly effect shellfish mariculture operations including protracted closures of shellfish harvesting areas for human consumption. The armoured dinoflagellate Azadinium spinosum Elbrächter et Tillmann gen. et sp. nov. (Dinophyceae) has been described as the de novo azaspiracid toxin producer; nonetheless the link between this organism and AZA toxin accumulation in shellfish has not yet been established. In August 2009, shellfish samples of blue mussel (Mytilus edulis) from the Southwest of Ireland were analysed using liquid chromatography–tandem-mass spectrometry (LC–MS/MS) and were found to be above the regulatory limit (0.16 μg g−1 AZA-equiv.) for AZAs. Water samples from this area were collected and one algal isolate was identified as A. spinosum and was shown to produce azaspiracid toxins. This is the first strain of A. spinosum isolated from Irish waters. The Irish A. spinosum is identical with the other two available A. spinosum strains from Scotland (3D9) and from Denmark (UTHE2) in its sequence of the D1–D2 regions of the LSU rDNA.A 24 h feeding trial of blue mussels (M. edulis) using an algal suspension of the Irish A. spinosum culture at different cell densities demonstrated that A. spinosum is filtered, consumed and digested directly by mussels. Also, LC–MS/MS analysis had shown that AZAs were accumulating in the shellfish hepatopancreas. The toxins AZA1 and -2 were detected in the shellfish together with the AZA analogues AZA3, AZA6, AZA17 and -19 suggesting that AZA1 and -2 are metabolised in the shellfish within the first 24 h after ingestion of the algae. The levels of AZA17 detected in the shellfish hepatopancreas (HP) were equivalent to the levels of AZA1 but in the remainder tissues the levels of AZA17 were four to five times higher than that of AZA1, only small quantities of AZA3 and -19 were present with negligible amounts of AZA6 detected after the 24 h period. This could have implications in the future monitoring of these toxins given that at present according to EU legislation only AZA1–AZA3 is regulated for. This is the first report of blue mussels’ (M. edulis) feeding on the azaspiracid producing algae A. spinosum from Irish waters. 相似文献
998.
999.
Protein MM0632 from the methanogenic archaeon Methanosarcina mazei showed strong superoxide reductase activity and rapidly decomposed superoxide radicals to peroxides. The superoxide reductase activity of the heterologously produced enzyme was determined by a cytochrome c assay and in a test system with NADPH, ferredoxin:NADP(+) reductase, and rubredoxin. Furthermore, EPR spectroscopy showed that MM0632 is the first superoxide reductase that possesses an iron-sulfur cluster instead of a second mononuclear iron center. We propose the name methanoferrodoxin for this new class of superoxide reductase with an [Fe(NHis)(4)(SCys)] site as the catalytic center and a [4Fe-4S] cluster as second prosthetic group that is probably involved in electron transfer to the catalytic center. Methanosarcina mazei grows only under anaerobic conditions, but is one of the most aerotolerant methanogens. It is tempting to speculate that methanoferrodoxin contributes to the protection of cells from oxygen radicals formed by flavoproteins during periodic exposure to oxygen in natural environments. 相似文献
1000.
Mayada M Gwida Adel H El-Gohary Falk Melzer Herbert Tomaso Uwe Rösler Ulrich Wernery Renate Wernery Mandy C Elschner Iahtasham Khan Meike Eickhoff Daniel Schöner Heinrich Neubauer 《BMC research notes》2011,4(1):525