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Nitroxide spin-labeled α-d-glycopyranosides were synthesized in good yield and in a highly stereoselective manner by reaction of per-O-benzyl-α-d-glycopyranosyl bromides with 2,2,6,6-tetramethyl-4-piperidinol under the bromide ion-catalyzed conditions devised by Lemieux etal. After hydrogenolysis, the deblocked intermidiates were oxidized to give the desired, spin-labeled α-d-glycopyranosides. Nitroxide spin-labeled α-d-glycopyranosides, as well as a β-maltoside, were synthesized by standard methods. The synthesis is also described of 2-amino-2-deoxy-d-glucose and -d-galactose derivatives having a spin label at C-2, and of the spin-labeled compound 1-[4-(β-d-galactopyranosyloxy)phenyl]-3-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-yl)-2-thiourea. 相似文献
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André R. A. Marques Jan Aten Roelof Ottenhoff Cindy P. A. A. van Roomen Daniela Herrera Moro Nike Claessen María Fernanda Vinueza Veloz Kuikui Zhou Zhanmin Lin Mina Mirzaian Rolf G. Boot Chris I. De Zeeuw Herman S. Overkleeft Yildiz Yildiz Johannes M. F. G. Aerts 《PloS one》2015,10(8)
The enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2). Given that the two β-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1
-/-) mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1
-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs), one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1
-/- mice with a brain-permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1
-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC. 相似文献
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Immunogenic HER-2/neu peptides as tumor vaccines 总被引:6,自引:0,他引:6
Baxevanis CN Sotiriadou NN Gritzapis AD Sotiropoulou PA Perez SA Cacoullos NT Papamichail M 《Cancer immunology, immunotherapy : CII》2006,55(1):85-95
During the last decade, a large number of tumor-associated antigens (TAA) have been identified, which can be recognized by
T cells. This has led to renewed interest in the use of active immunization as a modality for the treatment of cancer. HER-2/neu
is a 185-KDa receptor-like glycoprotein that is overexpressed by a variety of tumors including breast, ovarian, lung, prostate
and colorectal carcinomata. Several immunogenic HER-2/neu peptides recognized by cytotoxic T lymphocytes (CTL) or helper T
lymphocytes (TH) have been identified thus far. Patients with HER-2/neu over-expressing cancers exhibit increased frequencies
of peripheral blood T cells recognizing immunogenic HER-2/neu peptides. Various protocols for generating T cell-mediated immune
responses specific for HER-2/neu peptides have been examined in pre-clinical models or in clinical trials. Vaccination studies
in animals utilizing HER-2/neu peptides have been successful in eliminating tumor growth. In humans, however, although immunological
responses have been detected against the peptides used for vaccination, no clinical responses have been described. Because
HER-2/neu is a self-antigen, functional immune responses against it may be limited through tolerance mechanisms. Therefore,
it would be interesting to determine whether abrogation of tolerance to HER-2/neu using appropriate adjuvants and/or peptide
analogs may lead to the development of immune responses to HER-2/neu epitopes that can be of relevance to cancer immunotherapy.
Vaccine preparations containing mixtures of HER-2/neu peptides and peptide from other tumor-related antigens might also enhance
efficacy of therapeutic vaccination.
This article is a symposium paper from the conference “Progress in Vaccination against Cancer 2004 (PIVAC 4)”, held in Freudenstadt-Lauterbad,
Black Forest, Germany, on 22–25 September 2004 相似文献
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Zhang HT Zhan XB Zheng ZY Wu JR English N Yu XB Lin CC 《Applied microbiology and biotechnology》2012,93(1):367-379
A significant problem in scale-down cultures, rarely studied for metabolic characterization and curdlan-producing Agrobacterium sp. ATCC 31749, is the presence of dissolved oxygen (DO) gradients combined with pH control. Constant DO, between 5% and
75%, was maintained during batch fermentations by manipulating the agitation with PID system. Fermentation, metabolic and
kinetic characterization studies were conducted in a scale-down system. The curdlan yield, intracellular nucleotide levels
and glucose conversion efficiency into curdlan were significantly affected by DO concentrations. The optimum DO concentrations
for curdlan production were 45–60%. The average curdlan yield, curdlan productivity and glucose conversion efficiency into
curdlan were enhanced by 80%, 66% and 32%, respectively, compared to that at 15% DO. No apparent difference in the gel strength
of the resulting curdlan was detected. The comparison of curdlan biosynthesis and cellular nucleotide levels showed that curdlan
production had positive relationship with intracellular levels of UTP, ADP, AMP, NAD+, NADH and UDP-glucose. The curdlan productivity under 45% DO and 60% DO was different during 20–50 h. However, after 60 h
curdlan productivity of both conditions was similar. On that basis, a simple and reproducible two-stage DO control process
for curdlan production was developed. Curdlan production yield reached 42.8 g/l, an increase of 30% compared to that of the
single agitation speed control process. 相似文献
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NJ Krautler V Kana J Kranich Y Tian D Perera D Lemm P Schwarz A Armulik JL Browning M Tallquist T Buch JB Oliveira-Martins C Zhu M Hermann U Wagner R Brink M Heikenwalder A Aguzzi 《Cell》2012,150(1):194-206
The differentiation of follicular dendritic cells (FDC) is essential to the remarkable microanatomic plasticity of lymphoid follicles. Here we show that FDC arise from ubiquitous perivascular precursors (preFDC) expressing platelet-derived growth factor receptor β (PDGFRβ). PDGFRβ-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFRβ(+)-derived cells abolished FDC, indicating that FDC originate from PDGFRβ(+) cells. Lymphotoxin-α-overexpressing prion protein (PrP)(+) kidneys developed PrP(+) FDC after transplantation into PrP(-) mice, confirming that preFDC exist outside lymphoid organs. Adipose tissue-derived PDGFRβ(+) stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin β receptor (LTβR)(-) kidney capsules, differentiated into Mfge8(+)CD21/35(+)FcγRIIβ(+)PrP(+) FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFRβ(+) FDC precursors whose expansion required both lymphoid tissue inducer (LTi) cells and lymphotoxin. The ubiquity of preFDC and their strategic location at blood vessels may explain the de novo generation of organized lymphoid tissue at sites of lymphocytic inflammation. 相似文献
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Biomass, carbonate standing stock and production of the mediterranean coralCladocora caespitosa (L.) 总被引:1,自引:0,他引:1
Summary The Mediterranean coralCladocora caespitosa often occurs in large beds, i.e. populations of hemispherical clonies with stock densities varying between 1.9 and 4 coloneis
·m−2. Laboratory measurements of volume, skeleton weight, surface and number of corallites per colony, coupled with mean annual
growth rates evaluated through sclerochronology, allowed for the estimation of biomass, skeleton bulk density, calcimass (carbonate
standing stock) and secondary production (both organic and inorganic) of twoC. caespitosa beds at 4 and 9 m depth. The mean colony biomass varied between 0.73 and 0.99 kg dw ·m−2, corresponding to a calcimass between 2 and 5 kg CaCO3·m−2. Organic secondary production was 215.5–305.4 g dw of polyps ·m−2·y−1, while the potential (mineral) production was 1.1–1.7 kg CaCO3·m−2·y−1, for the year 1996–1997.
These values show thatC. caespitosa is one of the major carbonate producers within the Mediterranean and one of the major epibenthic species originating stable
carbonate frameworks both in recent and past times. 相似文献
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