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101.
Pontillo J Marinkovic D Tran JA Arellano M Fleck BA Wen J Tucci FC Nelson J Saunders J Foster AC Chen C 《Bioorganic & medicinal chemistry letters》2005,15(20):4615-4618
Piperazinebenzylamines bearing a small N-(1-methoxy-2-propyl) side chain were found to be potent and selective antagonists of the human melanocortin-4 (MC4) receptor. Compound 7b, having K(i) values of 6.9 and 2800 nM at the human MC4 and MC3 receptors, respectively, has moderate oral bioavailability in mice, which is improved relative to the arylethyl analogues. 相似文献
102.
Tucci FC White NS Markison S Joppa M Tran JA Fleck BA Madan A Dyck BP Parker J Pontillo J Arellano LM Marinkovic D Jiang W Chen CW Gogas KR Goodfellow VS Saunders J Foster AC Chen C 《Bioorganic & medicinal chemistry letters》2005,15(19):4389-4395
The melanocortin-4 receptor (MC4R) plays an important role in the regulation of energy homeostasis. Recent studies have shown that blockade of the MC4R reverses tumor-induced weight loss in mice. Herein, we describe the synthesis and identification of potent and selective non-peptide antagonists of the human MC4R from a series of 2-ethoxycarbonylcyclohexyl-piperazines. Compound 12i was found to possess low nanomolar affinity for the MC4R, and exhibit oral bioavailability in rats. More importantly, when administered orally to mice (10 mg/kg), it led to statistically significant increases in food intake over a 24-h period. 相似文献
103.
The mismatch repair (MMR) system ensures genome integrity by removing mispaired and unpaired bases that originate during replication. A major source of mutational changes is strand slippage in repetitive DNA sequences without concomitant repair. We established a genetic assay that allows measuring the stability of GT repeats in the ade6 gene of Schizosaccharomyces pombe. In repair-proficient strains most of the repeat variations were insertions, with addition of two nucleotides being the most frequent event. GT repeats were highly destabilized in strains defective in msh2 or pms1. In these backgrounds, mainly 2-bp insertions and 2-bp deletions occurred. Surprisingly, essentially the same high mutation rate was found with mutants defective in msh6. In contrast, a defect in swi4 (a homologue of Msh3) caused only slight effects, and instability was not further increased in msh6 swi4 double mutants. Also inactivation of exo1, which encodes an exonuclease that has an MMR-dependent function in repair of base-base mismatches, caused only slightly increased repeat instability. We conclude that Msh2, Msh6, and Pms1 have an important role in preventing tract length variations in dinucleotide repeats. Exo1 and Swi4 have a minor function, which is at least partially independent of MMR. 相似文献
104.
The phylogeny of Anisoptera, dragonflies in the strict sense, has proven to be notoriously difficult to resolve. Based on morphological characters, several recent publications dealing with the phylogeny of dragonflies proposed contradicting inter- and intrafamily relationships. We explored phylogenetic information content of mitochondrial large-subunit (LSU) and small-subunit (SSU) ribosomal gene fragments for these systematic problems. Starting at published universal primers, we developed primer sets suitable for amplifying large parts of the LSU and SSU rRNA genes within dragonflies. These fragments turned out to harbor sufficient phylogenetic information to satisfyingly resolve intrafamily relationships, but they contain insufficient phylogenetic structure to permit reliable conclusions about several interfamily relationships. We demonstrate that decay of phylogenetic signal progresses from intrafamily to interfamily to outgroup relationships and is correlated with an increase of genetic distances. As expected, signal decay is most pronounced in fast-changing sites. Additionally, base composition among fast-changing sites significantly deviates from the expected homogeneity. Homogeneity of base composition among all included taxa was restored only after removing fast-changing sites from the data set. The molecular data tentatively support interfamily relationships proposed by the most recent publication based on morphological characters of fossil and extant dragonflies. 相似文献
105.
Summary. The effects of sodium dichromate (chromate; 1 mg/100 g b. wt. s.c.) and cisdiamminedichloroplatinum(II) (CP; 0.6 mg/100 g
b. wt. i.p.) on renal amino acid excretion and plasma amino acid composition were investigated in 10- and 55-day-old anaesthetised
rats. On the basis of diuresis experiments on conscious rats the mentioned doses and times (1st day after chromate in both age groups and in 10-day-old rats after CP and 3rd day after CP in adult rats) were found out to be optimal for the characterisation of amino acid transport after heavy metal
poisoning. Interestingly, in conscious 10-day-old rats chromate nephrotoxicity is not detectable after 1 mg/100 g b. wt. whereas
all of the other experimental groups showed nephrotoxic effects of chromate and CP in conscious rats. Urine volumes are lower,
but not significantly, in anaesthetised immature rats, independently of the administered nephrotoxin. But GFR is significantly
lower in 10-day-old rats, both in controls and after CP, whereas after chromate GFR is significantly reduced only in adult
rats and age differences disappeared. In principle the renal fractional excretion (FE) of amino acids was distinctly higher
in immature rats as a sign of lower amino acid reabsorption capacity. Nevertheless, the amino acid plasma concentrations were
relatively high in immature rats. However, both chromate and CP did not distinctly influence amino acid plasma concentrations.
But in both age groups the administration of chromate and CP significantly decreased amino acid reabsorption capacity (increase
in FE) as a sign of nephrotoxicity, most pronounced in adult rats after CP. The investigation of renal amino acid handling
confirms (1) that both CP and chromate are nephrotoxins, (2) that CP was more nephrotoxic in 55-day-old animals compared to
immature rats as could be demonstrated before using other parameters for nephrotoxicity testing and showed (3) that determination
of renal amino acid handling is a highly sensitive marker for nephrotoxicity testing, especially in immature rats.
Received March 3, 2000 Accepted October 11, 2000 相似文献
106.
Physiological aspects of hydrocarbon emulsification, metal resistance and DNA profile of biodegrading bacteria isolated from oil polluted sites 总被引:4,自引:0,他引:4
Leonardo Colombo Fleck Flávio Correa Bicca Marco Antônio Zachia Ayub 《Biotechnology letters》2000,22(4):285-289
The production of biosurfactants was evaluated for seven bacterial strains isolated from different oil contaminated sites by the Emulsification Index using diesel oil as the hydrocarbon source. Minimum Inhibitory Concentrations of Mg2+, Cr3+ and Cu2+ were determined to identify the less sensitive bacteria in order to select the best strains for bioremediation. Plasmid extraction was also performed in order to search for gene sequences involved with biosurfactant synthesis. All strains were able to emulsify diesel oil. Rhodococcus ruber AC239 presented the best index (58%), followed by other Rhodococcus strains. Pseudomonas aeruginosa, R. ruber AC239, AC87 and R. erytropolis AC272 presented smallest sensitivities to heavy metals used, being suitable for use in sites contaminated with high concentrations of them. No plasmid DNA was detected showing that biosurfactant coding genes should be in the chromosomal DNA. 相似文献
107.
108.
Pintó-Marijuan M de Agazio M Zacchini M Santos MA Torné JM Fleck I 《Physiologia plantarum》2007,131(1):159-169
In order to further study a previously observed relationship between polyamine (PA) content and changes in irradiation, we examined the level of free and bound PAs, the activity of transglutaminase (TGase, EC 2.3.2.13) and chlorophyll fluorescence in holm oak ( Quercus ilex L.) leaves in response to different levels of light intensity and amount. A diurnal trend of free and bound putrescine (F-Put and B-Put, respectively) and TGase activity was observed in plants under natural conditions in the forest, with the highest value corresponding to the maximum light intensity and amount of light received by the leaves. In another set of experiments, potted Q. ilex plants in experimental fields were subjected to a range of periods of natural photosynthetic photon flux density (PPFD) by covering or not covering the whole trees. Under a natural photoperiod (uncovered leaves), B-Put content and TGase activity paralleled the diurnal PPFD pattern, reaching a maximum at the highest PPFD; prior to this maximum, free PAs showed a significant rise. Plants that were in darkness until midday and suddenly exposed to high light intensity showed enhanced TGase activity, resulting in the maximum accumulation of B-Put. The involvement of the accumulation of B-Put reflected in the changes of the B-Put/bound spermidine ratio during the photoprotective responses to high light stress in forest plants is discussed in relation to the chlorophyll fluorescence parameters observed. 相似文献
109.
San Juan AF Fleck SJ Chamorro-Viña C Maté-Muñoz JL Moral S García-Castro J Ramírez M Madero L Lucia A 《Journal of strength and conditioning research / National Strength & Conditioning Association》2007,21(1):173-177
Improvements in chemotherapy and radiotherapy have contributed to the high survival rate (approximately 70%) of childhood acute lymphoblastic leukemia (ALL). However, during treatment, lack of physical activity and treatment cause various short- to long-term side effects, such as muscle atrophy and physical deconditioning. The purpose of this study was to determine the effects of an intrahospital, short-duration (8 weeks) exercise training program on muscle strength and endurance and functional mobility of children with ALL. Seven children (4 boys and 3 girls; 4-7 years of age) who were in the maintenance phase of treatment for ALL were selected as subjects. Three training sessions of 90- to 120-minute duration were performed each week. Each session included 11 different strength exercises engaging the major muscle groups and aerobic training. Gains in strength and endurance were assessed with a 6 repetition maximum test for upper (seated bench press and seated lateral row) and lower extremities (leg press). Gains in functional mobility were assessed with the time up and go test (TUG) and the timed up and down stairs test (TUDS). Performance was significantly improved after the training program in all strength tests (p < 0.01 for seated bench press and p < 0.05 for both seated lateral row and seated leg press) and in the TUG test (p < 0.05). In summary, a period of time as short as 8 weeks is enough to produce clinically relevant early-phase adaptations in children receiving treatment against ALL (i.e., improved functional mobility and muscle strength). Although more research is needed in the area of exercise training and pediatric cancer, exercise sciences can play a beneficial role in assisting both oncologists in treating cancer and improving children's quality of life during and after treatment. 相似文献
110.
Characterization of human embryonic stem cell lines by the International Stem Cell Initiative 总被引:1,自引:0,他引:1
International Stem Cell Initiative Adewumi O Aflatoonian B Ahrlund-Richter L Amit M Andrews PW Beighton G Bello PA Benvenisty N Berry LS Bevan S Blum B Brooking J Chen KG Choo AB Churchill GA Corbel M Damjanov I Draper JS Dvorak P Emanuelsson K Fleck RA Ford A Gertow K Gertsenstein M Gokhale PJ Hamilton RS Hampl A Healy LE Hovatta O Hyllner J Imreh MP Itskovitz-Eldor J Jackson J Johnson JL Jones M Kee K King BL Knowles BB Lako M Lebrin F Mallon BS Manning D Mayshar Y McKay RD Michalska AE 《Nature biotechnology》2007,25(7):803-816
The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue-nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected. 相似文献