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11.
Blaney Davidson EN Scharstuhl A Vitters EL van der Kraan PM van den Berg WB 《Arthritis research & therapy》2005,7(6):R1338-R1347
Osteoarthritis (OA) is a common joint disease, mainly effecting the elderly population. The cause of OA seems to be an imbalance
in catabolic and anabolic factors that develops with age. IL-1 is a catabolic factor known to induce cartilage damage, and
transforming growth factor (TGF)-beta is an anabolic factor that can counteract many IL-1-induced effects. In old mice, we
observed reduced responsiveness to TGF-beta-induced IL-1 counteraction. We investigated whether expression of TGF-beta and
its signaling molecules altered with age. To mimic the TGF-beta deprived conditions in aged mice, we assessed the functional
consequence of TGF-beta blocking. We isolated knee joints of mice aged 5 months or 2 years, half of which were exposed to
IL-1 by intra-articular injection 24 h prior to knee joint isolation. Immunohistochemistry was performed, staining for TGF-beta1,
-2 or -3, TGF-betaRI or -RII, Smad2, -3, -4, -6 and -7 and Smad-2P. The percentage of cells staining positive was determined
in tibial cartilage. To mimic the lack of TGF-beta signaling in old mice, young mice were injected with IL-1 and after 2 days
Ad-LAP (TGF-beta inhibitor) or a control virus were injected. Proteoglycan (PG) synthesis (35S-sulfate incorporation) and PG content of the cartilage were determined. Our experiments revealed that TGF-beta2 and -3 expression
decreased with age, as did the TGF-beta receptors. Although the number of cells positive for the Smad proteins was not altered,
the number of cells expressing Smad2P strongly dropped in old mice. IL-1 did not alter the expression patterns. We mimicked
the lack of TGF-beta signaling in old mice by TGF-beta inhibition with LAP. This resulted in a reduced level of PG synthesis
and aggravation of PG depletion. The limited response of old mice to TGF-beta induced-IL-1 counteraction is not due to a diminished
level of intracellular signaling molecules or an upregulation of intracellular inhibitors, but is likely due to an intrinsic
absence of sufficient TGF-beta receptor expression. Blocking TGF-beta distorted the natural repair response after IL-1 injection.
In conclusion, TGF-beta appears to play an important role in repair of cartilage and a lack of TGF-beta responsiveness in
old mice might be at the root of OA development. 相似文献
12.
MARC PHILIPPE HONG‐EN JIANG KYUNGSIK KIM CHANGHWAN OH DMITRY GROMYKO MELISE HARLAND IN‐SUNG PAIK FREDERIC THÉVENARD 《Lethaia: An International Journal of Palaeontology and Stratigraphy》2009,42(4):393-406
Although the faunal elements of Far East Asian Mesozoic terrestrial biota have attracted much attention in recent years, their palaeoecology remains poorly known. In particular, features of the palaeoclimate are highly controversial. To address this point we used the Mesozoic fossil wood Xenoxylon , a genus recognized as an indicator of wet temperate biotopes and which is common in the area during the Carnian–Maastrichtian interval. We re-appraised bibliographic data and gathered new data for Xenoxylon in the Mesozoic of Far East Asia. This demonstrated that previous taxonomic approaches to the genus have been so far idiosyncratic. We examined the anatomical diversity of morphogenus Xenoxylon in Far East Asia and compared it to that of samples from Europe. This indicates that in an area centred on north-eastern China, Xenoxylon reached a level of anatomical diversity unmatched elsewhere in the world. We hypothesize that this diversity witnesses the persistence of palaeoecological conditions particularly suitable for Xenoxylon and that a wet temperate climate prevailed over most of the area throughout the Carnian–Maastrichtian interval. It is in this setting that the famous Jehol Biota probably evolved. 相似文献
13.
14.
用抗性筛选法选育γ—亚麻酸(GLA)高产菌株 总被引:13,自引:0,他引:13
以深黄被孢霉(Mortierella isabellina)为出发菌株,经紫外线诱变处理,采用抗性筛选法,直接在梯度平板上挑选取抗脂肪酸脱氢酶抑制物抑芽丹(maleic hydrazide)的菌株进行初筛,然后经摇瓶发酵法测定相关性能指标进行得筛,获得一株生产性能比出发菌株显提高的突变株M80,其菌体收率达25.10g/L、油脂产率达12.35g/L、γ-亚麻酸(GLA)产率达771.88mg/L。 相似文献
15.
O'Neill E Martinez I Villinger F Rivera M Gascot S Colon C Arana T Sidhu M Stout R Montefiori DC Martinez M Ansari AA Israel ZR Kraiselburd E 《Journal of medical primatology》2002,31(4-5):217-227
The ever increasing number of people infected by human immunodeficiency virus (HIV) throughout the world renders the development of effective vaccines an urgent priority. Herein, we report on an attempt to induce and enhance antiviral responses using a deoxyribonucleic acid (DNA) prime/virus-like particles (VLP) protein boost strategy adjuvanted with interleukin (IL)-12/GM-CSF in rhesus macaques challenged with simian immunodeficiency virus (SIV). Thus, groups of monkeys were administered three consecutive doses of pVecB7 a plasmid expressing VLP with or without plasmids expressing IL-12 and GM-CSF at weeks 0, 13 and 26. The VLP boost was administered at week 39 with or without IL-12. All monkeys were challenged intrarectally with SIVsmE660 2 months following the protein boost. All except one immunized monkey became infected. While all immunized monkeys showed a marked reduction of acute viral peaks, reduction of viral load set points was only achieved in groups whose prime-boost immunizations were supplemented with IL-12/GM-CSF (prime) and/or with IL-12 (boost). Control of viremia correlated with lack of disease progression and survival. Detection of virus in rectal washes at 1 year post-challenge was only successful in monkeys whose immunizations did not include cytokine adjuvant, but these loads did not correlate with plasma viral loads. In summary, use of IL-12 and/or GM-CSF was shown to provide significant differences in the outcome of SIV challenge of prime/boost immunized monkeys. 相似文献
16.
Intraspecific nuclear DNA variation in Drosophila 总被引:12,自引:6,他引:12
We have summarized and analyzed all available nuclear DNA sequence
polymorphism studies for three species of Drosophila, D. melanogaster (24
loci), D. simulans (12 loci), and D. pseudoobscura (5 loci). Our major
findings are: (1) The average nucleotide heterozygosity ranges from about
0.4% to 2% depending upon species and function of the region, i.e., coding
or noncoding. (2) Compared to D. simulans and D. pseudoobscura (which are
about equally variable), D. melanogaster displays a low degree of DNA
polymorphism. (3) Noncoding introns and 3' and 5' flanking DNA shows less
polymorphism than silent sites within coding DNA. (4) X-linked genes are
less variable than autosomal genes. (5) Transition (Ts) and transversion
(Tv) polymorphisms are about equally frequent in non-coding DNA and at
fourfold degenerate sites in coding DNA while Ts polymorphisms outnumber Tv
polymorphisms by about 2:1 in total coding DNA. The increased Ts
polymorphism in coding regions is likely due to the structure of the
genetic code: silent changes are more often Ts's than are replacement
substitutions. (6) The proportion of replacement polymorphisms is
significantly higher in D. melanogaster than in D. simulans. (7) The level
of variation in coding DNA and the adjacent noncoding DNA is significantly
correlated indicating regional effects, most notably recombination. (8)
Surprisingly, the level of polymorphism at silent coding sites in D.
melanogaster is positively correlated with degree of codon usage bias. (9)
Three proposed tests of the neutral theory of DNA polymorphisms have been
performed on the data: Tajima's test, the HKA test, and the
McDonald-Kreitman test. About half of the loci fail to conform to the
expectations of neutral theory by one of the tests. We conclude that many
variables are affecting levels of DNA polymorphism in Drosophila, from
properties of nucleotides to population history and, perhaps, mating
structure. No simple, all encompassing explanation satisfactorily accounts
for the data.
相似文献
17.
Caccone A; Moriyama EN; Gleason JM; Nigro L; Powell JR 《Molecular biology and evolution》1996,13(9):1224-1232
Drosophila melanogaster belongs to a closely related group of eight species
collectively known as the melanogaster subgroup; all are native to
sub-Saharan Africa and islands off the east coast of Africa. The
phylogenetic relationships of most species in this subgroup have been well
documented; however, the three most closely related species, D. simulans,
D. sechellia, and D. mauritiana, have remained problematic from a
phylogenetic standpoint as no data set has unambiguously resolved them. We
present new DNA sequence data on the nullo and Serendipity-alpha genes and
combine them with all available nuclear DNA sequence data; the total data
encompass 12 genes and the ITS of rDNA. A methodological problem arose
because nine of the genes had information on intraspecific polymorphisms in
at least one species. We explored the effect of inclusion/exclusion of
polymorphic sites and found that it had very little effect on phylogenetic
inferences, due largely to the fact that 82% of polymorphisms are
autapomorphies (unique to one species). We have also reanalyzed our
previous DNA-DNA hybridization data with a bootstrap procedure. The
combined sequence data set and the DNA-DNA hybridization data strongly
support the sister status of the two island species, D. sechellia and D.
mauritiana. This at least partially resolves what had been a paradox of
parallel evolution in these two species.
相似文献
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19.
Yaqin Xu Christine Tertilt Anja Krause Luis EN Quadri Ronald G Crystal Stefan Worgall 《Respiratory research》2009,10(1):26
Background
Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Infections of the respiratory tract are a hallmark in CF. The host immune responses in CF are not adequate to eradicate pathogens, such as P. aeruginosa. Dendritic cells (DC) are crucial in initiation and regulation of immune responses. Changes in DC function could contribute to abnormal immune responses on multiple levels. The role of DC in CF lung disease remains unknown.Methods
This study investigated the expression of CFTR gene in bone marrow-derived DC. We compared the differentiation and maturation profile of DC from CF and wild type (WT) mice. We analyzed the gene expression levels in DC from naive CF and WT mice or following P. aeruginosa infection.Results
CFTR is expressed in DC with lower level compared to lung tissue. DC from CF mice showed a delayed in the early phase of differentiation. Gene expression analysis in DC generated from naive CF and WT mice revealed decreased expression of Caveolin-1 (Cav1), a membrane lipid raft protein, in the CF DC compared to WT DC. Consistently, protein and activity levels of the sterol regulatory element binding protein (SREBP), a negative regulator of Cav1 expression, were increased in CF DC. Following exposure to P. aeruginosa, expression of 3β-hydroxysterol-Δ7 reductase (Dhcr7) and stearoyl-CoA desaturase 2 (Scd2), two enzymes involved in the lipid metabolism that are also regulated by SREBP, was less decreased in the CF DC compared to WT DC.Conclusion
These results suggest that CFTR dysfunction in DC affects factors involved in membrane structure and lipid-metabolism, which may contribute to the abnormal inflammatory and immune response characteristic of CF. 相似文献20.