Polyunsaturated fatty acids in stream food webs – high dissimilarity among producers and consumers

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藏药七十味珍珠丸改善APP/PS1小鼠学习记忆能力

藏药七十味珍珠丸（ratanasampil,RNSP）可改善大脑氧化应激水平,改善大脑功能,有安神和促进学习记忆的功效,然而RNSP是否可改善阿尔茨海默症（AD）小鼠的学习记忆功能,尚缺乏系统研究。本研究采用APP/PS 1转基因小鼠为研究对象,并随机将其分为实验组和对照组。对实验组进行为期12周的RNSP灌胃给药,对照组进行12周的蒸馏水灌胃,采用Morris水迷宫与开场实验评价小鼠学习记忆能力,比较小鼠体重与相关器官质量,并比较器官质量指数,通过分子生物学检测指标评价小鼠脑内老年斑数量,Aβ生成量及BACE1表达水平。本研究证实,与对照组相比,给药组小鼠定位航行潜伏期明显缩短（22.60±13.26 vs. 46.44±8.41, P<0.01, day 5）,穿越平台次数明显增加（1.29±0.37 vs. 0.54±0.29, P<0.01）,探洞次数明显增加（32.11±9.85 vs. 20.89±8.78, P<0.05）,表明RNSP提高了APP/PS 1小鼠的学习记忆能力和空间探索能力。与对照组相比,给药组小鼠大脑重量及脑质量指数均增高（0.4135±0.0102 vs. 0.3833±0.0254, P<0.05;2.04±0.08 vs. 1.84±0.15, P<0.05）,脑内老年斑数量减少（18.70±7.88 vs. 38.83±6.15, P<0.05）,Aβ1- 42水平及BACE1表达均显著降低（0.19±0.08 vs. 0.41±0.12, P<0.05; 0.136±0.04 vs. 0.206±0.02, P<0.05）,表明RNSP延缓了APP/PS 1小鼠的脑萎缩进程,降低脑内老年斑的形成,下调脑内Aβ1-42水平和BACE1裂解酶的蛋白质表达量。本研究提示,RNSP可改善APP/PS 1小鼠的学习记忆能力,其机制可能和RNSP抑制脑萎缩,降低BACE1蛋白表达以及减少脑内Aβ沉积有关。     

Cryopreservation of Shoot Tips from Six Endangered Australian Species using a Modified Vitrification Protocol

An efficient vitrification procedure was developed and successfullyapplied to cryopreserve six endangered West Australian species(family Haemodoraceae: Anigozanthos humilis ssp. chrysanthusHopper;A. kalbarriensis Hopper;A. viridis ssp. terraspectansHopper;Conostylis dielsia ssp.teres Hopper;C. micrantha Hopperand C. wonganensis Hopper). Species were initially evaluatedfor cryostorage using a basic vitrification protocol involving:culturing plantlets in vitro for 21 d; excision of shoot apices;preculture of apical tips on 0.4 M sorbitol for 2 d, followedby incubation in PVS2 (plant vitrification solution 2) for 25min at 0 °C, then direct immersion in liquid nitrogen (LN).Warming of retrieved material was for 1 min in a 40 °C waterbath. Using this protocol five of the six species exhibitedlow post-storage survival, while the sixth species, A. viridisssp. terraspectans posted higher survival (61.1%). Using A.viridis ssp. terraspectans as an indicator species, the initialprotocol was modified to include: 3 d preculture on 0.80 M glycerol,loading treatment with 2.0 M glycerol plus 0.4 M sucrose solutionfor 20 min, followed by 25 min exposure to a modified PVS2.Survival was significantly improved in the test species, andin further experiments three other species also showed significantimprovements with the new protocol. Key findings include: effectivenessof glycerol in the preculture medium; the effect of precultureduration; the importance of a loading stage for these species;and the successful use of modified PVS2 solutions with reducedor zero dimethyl sulfoxide (DMSO). Copyright 2001 Annals ofBotany Company A. humilis ssp. chrysanthus, A. kalbarriensis, A. viridis ssp.terraspectans , Conostylis dielsia ssp. teres, C. micrantha, C. wonganensis, kangaroo paws, Haemodoraceae, vitrification, cryopreservation, rare and endangered, conservation     

Bradykinin-related compounds as new drugs for cancer and inflammation

Bradykinin (BK) (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) is an important growth factor for small-cell lung cancer (SCLC) and prostate cancer (PC). These cancers have cells of neuroendocrine origin and express receptors for a variety of neuropeptides. BK receptors are expressed on almost all lung cancer cell lines and on many PC cells. Our very potent BK antagonist B9430 (D-Arg-Arg-Pro-Hyp-Gly-lgl-Ser-D-Igl-Oic-Arg) (Hyp, trans-4-hydroxy-L-proline; Ig1, alpha-2-indanylglycine; Oic, octahydroindole-2-carboxylic acid) is a candidate anti-inflammatory drug but does not inhibit growth of SCLC or PC. When B9430 is dimerized by N-terminal cross-linking with a suberimide linker, the product B9870 is a potent growth inhibitor for SCLC both in vitro and in vivo in athymic nude mice. Daily i.p. injection at 5 mg x kg(-1) day(-1) beginning on day 8 after SCLC SHP-77 cell implantation gave 65% inhibition of tumor growth. B9870 stimulates apoptosis in SCLC by a novel "biased agonist" action. We have also developed new small mimetic antagonists. BKM-570 (F5C-OC2Y-Atmp) (F5C, pentafluorocinnamic acid; OC2Y, O-2,6-dichlorobenzyl tyrosine; Atmp, 4-amino-2,2,6,6-tetramethylpiperidine) is very potent for inhibition of SHP-77 growth in nude mice. When injected daily i.p. at 5 mg x kg(-1), M-570 gave 90% suppression of tumor growth. M-570 is more potent than the well-known anticancer drug cisPlatin (60% inhibition) or the recently developed SU5416 (40% inhibition) in this model. M-570 also showed activity against various other cancer cell lines in vitro (SCLC, non-SCLC, lung, prostate, colon, cervix) and inhibited growth of prostate cell line PC3 in nude mice. M-570 and related compounds evidently act in vivo through pathways other than BK receptors. These compounds have clinical potential for treatment of human lung and prostate cancers.     

Transmembrane organization of the Bacillus subtilis chemoreceptor McpB deduced by cysteine disulfide crosslinking

The Bacillus subtilis chemoreceptor McpB is a dimer of identical subunits containing two transmembrane (TM) segments (TM1, residues 17-34: TM2, residues 280-302) in each monomer with a 2-fold axis of symmetry. To study the organization of the TM domains, the wild-type receptor was mutated systematically at the membrane bilayer/extracytoplasmic interface with 15 single cysteine (Cys) substitutions in each of the two TM domains. Each single Cys substitution was capable of complementing a null allele in vivo, suggesting that no significant perturbation of the native tertiary or quaternary structure of the chemoreceptor was introduced by the mutations. On the basis of patterns of disulfide crosslinking between subunits of the dimeric receptor, an alpha-helical interface was identified between TM1 and TM1' (containing residues 32, 36, 39, and 43) and between TM2 and TM2' (containing residues 276, 277, 280, 283 and 286). Pairs of cysteine substitutions (positions 34/280 and 38/273) in TM1 and TM2 were used to further elucidate specific contacts within a monomer subunit, enabling a model to be constructed defining the organization of the TM domain. Crosslinking of residues that were 150-180 degrees removed from position 32 (positions 37, 41, and 44) suggested that the receptors may be organized as an array of trimers of dimers in vivo. All crosslinking was unaffected by deletion of cheB and cheR (loss of receptor demethylation/methylation enzymes) or by deletion of cheW and cheV (loss of proteins that couple receptors with the autophosphorylating kinase). These findings indicate that the organization of the transmembrane region and the stability of the quaternary complex of receptors are independent of covalent modifications of the cytoplasmic domain and conformations in the cytoplasmic domain induced by the coupling proteins.     

Effects of palmitate and oleate on the respiratory quotient during acute feeding

Objective: Using tracers, we showed, over 9 hours, that palmitic acid (PA) is oxidized at a lower rate than oleic acid (OA). Our subsequent clinical trial showed that enriching the diet for 28 days with PA, relative to OA, lowered fatty acid (FA) oxidation. However, because this conclusion was based on indirect calorimetry for 7 hours after a test meal, transient differences in the kinetics of oxidation of OA and PA could explain these results. Thus, we hypothesized that increasing PA vs. OA would decrease FA oxidation during the first day of feeding the diets. Research Methods and Procedures: A double‐masked trial was conducted in 20 adults, who, after a baseline diet, were randomized to one of two experimental formula diets: high (HI) OA (PA = 1.7% kcal, OA = 31.4% kcal; N = 11) or HI PA (PA = 16.8% kcal, OA = 16.4% kcal; N = 9). Respiratory quotient (RQ) was measured over the first 14 hours of feeding the experimental diets (7:00 am to 9:00 pm ). To determine whether these subjects were representative of the subjects in the previous trial, we assessed RQ 28 days after beginning either diet. Results: During the first 14 hours of feeding the diets, time (p = 0.026) but not diet group had an effect on the difference between the RQ post‐feeding and the fasting pre‐value. However, RQ in the fed state was significantly higher in the HI PA group after 28 days of feeding. Discussion: Chronically increasing dietary PA for 28 days, but not acute meal feeding, lowers total FA oxidation.