Synthesis and properties of novel antisense oligonucleotides bearing an anthraquinone moiety at an internucleotide linkage.

Antisense oligonucleotides bearing an anthraquinone moiety at an internucleotide linkage were synthesized utilizing the stereoisomers of anthraquinone incorporated T-C dimer phosphoramidite derivatives. Some physicochemical properties of the anthraquinon bearing oligomers were investigated.     

江苏沿海地区生态承载力空间分异特征及优化

区域生态承载能力空间格局与优化研究是推动经济转型升级和生态保护修复统筹发展的需要.本研究以江苏沿海区域自然-社会-经济复合生态系统为研究对象,建立生态承载压力-状态-潜力(PSP)概念模型,用15项指标表征3个层面状态的交互关系,在GIS等空间技术支持下,通过分项和多项综合评价,分析研究区域生态承载力的量级、空间分异特...     

Eccentric exercise training as a countermeasure to non-weight-bearing soleus muscle atrophy.

Although various exercise paradigms have been tested, none has completely prevented muscle atrophy during non-weight bearing. Because loaded eccentric contractions occur during normal daily activity but are absent during non-weight bearing, this investigation tested whether eccentric resistance training could prevent soleus muscle atrophy during non-weight bearing. Adult female rats were randomly assigned to either weight bearing +/- intramuscular electrodes or non-weight bearing +/- intramuscular electrodes groups. Electrically stimulated maximal eccentric contractions (4 sets of 6 repetitions at approximately 0.2 fiber lengths/s, 128 degrees range of motion) were performed on anesthetized animals at 48-h intervals during the 10-day experiment. Non-weight bearing significantly reduced soleus muscle wet weight (28-31%) and noncollagenous protein content (30-31%) compared with controls. Eccentric exercise training during non-weight bearing attenuated but did not prevent the loss of soleus muscle wet weight and noncollagenous protein by 77 and 44%, respectively. The potential of eccentric exercise training as an effective and highly efficient counter-measure to non-weight-bearing atrophy is demonstrated in the 44% attenuation of soleus muscle noncollagenous protein loss by eccentric exercise during only 0.035% of the total non-weight-bearing time period.     

Preparation of carbohydrate-oligonucleotide conjugates using the squarate spacer

Attachment of carbohydrates to oligonucleotides has proven to induce receptor-mediated endocytosis. A facile method for the formation of covalent linkages between glycans and oligonucleotides is herein described. Thus, use of 3,4-diethoxy-3-cyclobutene-1,2-dione as a linking reagent provides easy conjugation between carbohydrates bearing an amino group at the reducing end and oligonucleotides bearing an aminoalkyl modification.     

Preparation of a DNA matrix via an electrochemically directed copolymerization of pyrrole and oligonucleotides bearing a pyrrole group.

A new methodology for the preparation of addressed DNA matrices is described. The process includes an electrochemically directed copolymerization of pyrrole and oligonucleotides bearing on their 5' end a pyrrole moiety introduced by phosphoramidite chemistry. The electro-controlled synthesis of the copolymer (poly-pyrrole) gives, in one step, a solid conducting film deposited on the surface of an electrode. The resulting polymer consists of pyrrole chains bearing covalently linked oligonucleotide. The polymer growth is limited to the electrode surface, so that it is possible to prepare a DNA matrix on a multiple electrode device by successive copolymerizations. A support bearing four oligonucleotides was used to detect three ras mutations on a synthetic DNA fragment.     

Distribution of surface IgM and IgD on single cells from lymphocyte subpopulations.

The surface immunoglobulin heavy chains on individual spleen cells fractionated by velocity sedimentation were studied using fluorescent antisera. In adult mice, cells bearing both mu and delta chains were found in all fractions. While there was an increase in the proportion of cells bearing mu only in the medium to large cell fractions, the majority of cells bearing mu only were small lymphocytes. Results obtained using 3-week-old mice were basically similar, but showed both a marked decrease in small mu + delta + cells and a marked increase in small mu + delta - cells when compared with adult animals.     

Holococcolithophore‐heterococcolithophore (Haptophyta) life cycles: Flow cytometric analysis of relative ploidy levels

Several coccolithophore species are known to exhibit heteromorphic life cycles. In certain species, notably Emiliania huxleyi, the heterococcolith‐bearing phase alternates with a non‐calcifying stage, whereas in others the heterococcolith‐bearing phase alternates with a holococcolith‐bearing phase. Heterococcolithophore‐holococcolithophore life cycles have previously been observed for only one species in culture, but have also been inferred from an increasing number of observations of combination coccospheres. 18S rDNA sequences from pure cultures of both the heterococcolith‐bearing and holococcolith‐bearing phases of Coccolithus pelagicus were identical, providing an additional indication of their identity as different life cycle stages of the same species. Flow cytometric analyses have been undertaken on SybrGreen‐stained nuclei isolated from pure cultures of the two phases of four coccolithophore species (Coccolithus pelagicus, Calcidiscus leptoporus, Coronosphaera mediterranea and Emiliania huxleyi) in order to determine relative DNA content. Results confirm the hypothesis that holococcolithophore‐heterococcolithophore life cycles are haplo‐diploid in nature. Light microscope observations of the processes of sexual fusion and meiosis are reported for two of the experimental species. The results are discussed in the context of the evolution of bio‐mineralization in the coccolithophores and the possible ubiquity of haplo‐diploidy in the haptophytes.     

Genetic control of biennial bearing in apple

Although flowering in mature fruit trees is recurrent, floral induction can be strongly inhibited by concurrent fruiting, leading to a pattern of irregular fruiting across consecutive years referred to as biennial bearing. The genetic determinants of biennial bearing in apple were investigated using the 114 flowering individuals from an F(1) population of 122 genotypes, from a 'Starkrimson' (strong biennial bearer)×'Granny Smith' (regular bearer) cross. The number of inflorescences, and the number and the mass of harvested fruit were recorded over 6 years and used to calculate 26 variables and indices quantifying yield, precocity of production, and biennial bearing. Inflorescence traits exhibited the highest genotypic effect, and three quantitative trait loci (QTLs) on linkage group (LG) 4, LG8, and LG10 explained 50% of the phenotypic variability for biennial bearing. Apple orthologues of flowering and hormone-related genes were retrieved from the whole-genome assembly of 'Golden Delicious' and their position was compared with QTLs. Four main genomic regions that contain floral integrator genes, meristem identity genes, and gibberellin oxidase genes co-located with QTLs. The results indicated that flowering genes are less likely to be responsible for biennial bearing than hormone-related genes. New hypotheses for the control of biennial bearing emerged from QTL and candidate gene co-locations and suggest the involvement of different physiological processes such as the regulation of flowering genes by hormones. The correlation between tree architecture and biennial bearing is also discussed.     

Seasonal dynamics of photosynthesis and total carbon gain in bearing and nonbearing pistachio (<Emphasis Type="Italic">Pistacia vera</Emphasis> L.) shoots

Seasonal changes in leaf gas exchange, assimilation response to light and leaf area were monitored in bearing and nonbearing pistachio shoots. Shoot bearing status did not directly affect leaf photosynthetic rate. However, photosynthetic light-response curves strongly varied during the season demonstrating the dominant effect of the tree’s seasonal phenology on assimilation. Early in the season low photosynthetic rates were associated with high rates of dark respiration indicating limited photosynthesis in the young leaves. As leaves matured, dark respiration decreased and assimilation reached maximum values. Photosynthetic efficiency was strongly reduced late in the season due to leaf age and senescence. Fruit load precipitated an early leaf senescence and drop that resulted in a 53% decrease in leaf area in bearing vs. nonbearing shoots, strongly decreasing the seasonal photosynthetic performance of bearing shoots. Bearing shoots produced a 26% lower seasonal carbon gain compared to nonbearing shoots.     

Peptide chemistry applied to a new family of phenothiazine-containing inhibitors of human farnesyltransferase

Novel phenothiazine derivatives bearing an amino acid residue were synthesized via peptide chemistry, and evaluated for their inhibitory potential on human farnesyltransferase. The phenothiazine unit proved to be an important bulky unit in the structure of the synthesized inhibitors. Propargyl ester 20 bearing a tyrosine residue exhibited the best biological potential in vitro in the present study. Further syntheses and biological evaluation of phenothiazine derivatives are necessary in order to gain a full view of SAR in this family of farnesyltransferase inhibitors.     

A within-species warning function for an aposematic signal

Aposematic, or warning, signals are generally interspecific in form: one species advertises noxiousness to a predator or parasite species. In a study of the pipevine swallowtail butterfly (Battus philenor), we show that a pattern of colouration in the caterpillars that is considered to be aposematic in the context of attack by natural enemies also deters oviposition by conspecific females. In field and laboratory assays, females avoided oviposition on plants bearing live conspecific larvae. Females avoided oviposition on plants bearing artificially constructed models identical to larvae in shape, size and colour pattern. Finally, oviposition on plants harbouring a model bearing the larval colour pattern was reduced relative to plants bearing a leaf-green model, suggesting that the larval colour pattern was essential for avoidance. We discuss how intraspecific and interspecific processes might interact in the evolution of an aposematic signal.     

Anthranilate sulfonamide hydroxamate TACE inhibitors. Part 2: SAR of the acetylenic P1' group

The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing novel acetylenic P1' groups was explored. In particular, compound 4t bearing a butynyloxy P1' moiety has excellent in vitro potency against isolated TACE enzyme and in cells, good selectivity over MMP-1 and oral activity in an in vivo model of TNF-alpha production.     

Effect of clofibrate treatment on chronic hyperlipidemia induced by an ACTH-producing tumor.

Plasma triglyceride and cholesterol levels were significantly increased in rats bearing an MtT-F4 tumor for 31-41 days. Addition of clofibrate at a dose of 30 mg kg-1 to the diet of rats bearing the tumor resulted in the complete elimination of the tumor effect on the plasma triglycerides, and to a great extent prevented the rise in the plasma cholesterol.     

Synthesis and activity on rat aorta rings and rat pancreatic beta-cells of ring-opened analogues of benzopyran-type potassium channel activators

Ring-opened analogues of dihydrobenzopyran potassium channel openers (PCOs) were prepared and evaluated as putative PCOs on rat aorta rings (myorelaxant effect) and rat pancreatic beta-cells (inhibition of insulin secretion). These derivatives are characterized by the presence of a sulfonylurea, a urea or an amide function. Some compounds bearing an arylurea moiety provoked vasorelaxant effects and a marked inhibition of insulin release. Derivatives bearing a sulfonylurea or an amide function were, however, poorly active on both tissues. Structure-activity relationships and apparent tissue selectivity are discussed.     

Aromatase inhibition by R 83 842, the dextro isomer of R 76 713, in JEG-3 choriocarcinoma grown in ovariectomized nude mice

The effects of repeated (5 days) dosing with the non-steroidal aromatase inhibitor R 83 842 (the dextro isomer of R 76 713) on tumor aromatase and uterus weight in ovariectomized nude mice bearing JEG-3 tumors were examined. In animals bearing an androstenedione implant the presence of a JEG-3 tumor significantly increased uterus weight, proving that tumor aromatase indeed converted androgens to estrogens. Oral administration of R 76 713 (10 mg/kg) for 5 days reduced the increase in uterus weight by 84% in tumor bearing mice revealing true in vivo aromatase inhibition by R 76 713.

Experiments performed in the absence of exogenously added androgens gave similar results. Uterus weights in tumor bearing mice were significantly higher than in control mice. Oral administration of R 83 842 (5 mg/kg) for 5 days reduced uterus weight in the tumor bearing animals. Ex vivo aromatase measurements performed in JEG-3 tumors from these animals showed an aromatase inhibition of 93.9% in treated mice as compared to untreated mice. Five days oral treatment with R 83 842 dose-dependently lowered both aromatase activity and uterus weight. Doses of 5 and 0.5 mg/kg inhibited tumor aromatase by 94.1 and 74.7%, respectively, and reduced uterus weight. After a dose of 0.05 mg/kg aromatase activity and uterus weight were similar to those in the control group.     

Pharmacological characteristics of the hind paw weight bearing difference induced by chronic constriction injury of the sciatic nerve in rats

AimsWe examined the possible involvement of spontaneous on-going pain in the rat chronic constriction injury (CCI) model of neuropathic pain.Main methodsThe development of weight bearing deficit, as an index of spontaneous on-going pain, was investigated in comparison to that of mechanical allodynia in CCI rats. We also examined the effects of morphine and a gabapentin analogue (1S, 3R)-3-methyl-gabapentin (3-M-gabapentin) on both the CCI-induced weight bearing deficit and mechanical allodynia.Key findingsRats with CCI demonstrated a significant reduction in weight bearing of the injured limb with a peak at a week post-operation, which was followed by a gradual recovery for over 7 weeks. The time course of development and recovery of CCI-induced weight bearing deficit appeared to follow that of foot deformation of the affected hind limb. CCI also evoked mechanical allodynia that was fully developed on a week post-operation, but showed no recovery for at least 8 weeks. 3-M-gabapentin significantly inhibited CCI-induced mechanical allodynia, but not weight bearing deficit, at 100 mg/kg p.o. Likewise, morphine was without significant effect on CCI-induced weight bearing deficit at the dose (3 mg/kg, s.c.) that could almost completely inhibit mechanical allodynia, whereas it inhibited both mechanical allodynia and weight bearing deficit at 6 mg/kg, s.c.SignificanceThe present findings suggest that CCI-induced weight bearing deficit is not a consequence of mechanical allodynia, but is attributable to spontaneous on-going pain. The rat CCI model of neuropathic pain thus represents both spontaneous on-going pain and mechanical allodynia.     

Transfection of cultured fish cells RBCF-1 with exogenous oncogene and their resistance to malignant transformation

1. Plasmids bearing the G418-resistant gene neo were transfected into cultured fish cells RBCF-1 by electroporation at an efficiency comparable to that in NIH3T3 cells. 2. Transfection of plasmids bearing both neo and activated human c-Ha-ras into NIH3T3 and RBCF-1 cells resulted in the malignant transformation of the former but not of the latter cells.     

Enhanced hydrolytic stability and water solubility of an aromatic nitrogen mustard by conjugation with molecular umbrellas

Chlorambucil, an aromatic nitrogen mustard, has been conjugated to putrescine- and spermidine-based scaffolds bearing one, two, and four persulfated cholic acid units. Those conjugates bearing two or four sterols show improved hydrolytic stability and water solubility relative to chlorambucil. A similar conjugate that contained only one sterol unit shows negligible improvement in hydrolytic stability but a significant increase in water solubility. Qualitatively, the hydrolytic stability within this series of conjugates parallels the shielding effects that have previously been found for related conjugates bearing a pendant, hydrophobic fluorescent probe. In vitro studies indicate that these conjugates possess modest to moderate activity against certain human lymphoblastic leukemia and human colon carcinoma cells.     

Targeting of plant glycoside-bearing liposomes to specific cellular and subcellular sites

The possibility of using liposomes as an effective drug delivery system has been studied by incorporation of two plant glycosides of varying terminal sugar residues onto the surface of liposomes and examination of their distribution in different tissues. The two glycosides, corchorusin D and asiaticoside having glucose and rhamnose respectively at the terminal ends wee selected for the purpose. The hepatic uptake of liposomes made from egg lecithin, cholesterol and dicetyl phosphate and either of the two glycosides was compared. The hepatic uptake of asiaticoside bearing liposomes was reduced, whereas that of corchorusin D bearing liposomes was enhanced and was specific for glucose. Liver perfusion followed by cell separation showed that the uptake is mostly into the non-parenchymal cells of liver. The distribution of corchorusin D bearing liposomes was maximal in the lysosomal fraction of the non-parenchymal cells. Ways of using corchorusin D bearing liposomes as delivery systems for drugs or enzymes to lysosomes have been sought.