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71.
Kemp S Wheate NJ Buck DP Nikac M Collins JG Aldrich-Wright JR 《Journal of inorganic biochemistry》2007,101(7):1049-1058
Fifteen platinum(II)-based metallointercalators have been synthesised that utilise substituted 1,10-phenanthroline (phen) ligands, including 5-chloro-1,10-phenanthroline (5-Cl-phen), 5-methyl-1,10-phenanthroline (5-CH3-phen), 5-amino-1,10-phenanthroline (5-NH2-phen), 5-nitro-1,10-phenanthroline (5-NO2-phen) and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), and achiral ethylenediamine (en) and the chiral ancillary ligands 1S,2S-diaminocyclohexane (S,S-dach) and 1R,2R-diaminocyclohexane (R,R-dach). Their cytotoxicity in the L1210 murine leukaemia cell line was determined using growth inhibition assays. The most cytotoxic metal complexes are those that contain S,S-dach ancillary ligands and 5-CH3-phen intercalating ligands. One metallointercalator [Pt(5-CH3-phen)(S,S-dach)]Cl2 (5MESS), displays a 5-10-fold increase in cytotoxicity compared to the clinical agent cisplatin. From DNA binding experiments there appears to be no significant difference between any of the metal complexes, indicating that neither DNA binding affinity nor the mode of binding/DNA adduct formed is the sole determinant of the cytotoxicity of this family of platinum(II)-based metallointercalators. 相似文献
72.
Melles DC van Leeuwen WB Snijders SV Horst-Kreft D Peeters JK Verbrugh HA van Belkum A 《Journal of microbiological methods》2007,69(2):371-375
We compared multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and amplified fragment length polymorphism (AFLP) for typing of Staphylococcus aureus and show that the methods yield similar results, although with differences in resolving power and reproducibility. Epidemiological conditions should determine which is the optimal typing method to be used. 相似文献
73.
Deterministic and stochastic models motivated by Salmonella transmission in unmanaged/managed populations are studied. The SIRS models incorporate three routes of transmission (direct, vertical and indirect via free-living infectious units in the environment). With deterministic models we are able to understand the effects of different routes of transmission and other epidemiological factors on infection dynamics. In particular, vertical transmission has little influence on this dynamics, whereas the higher the indirect (direct) transmission rate the greater the tendency to persistent oscillation (stable endemic states). We show that the sustained cycles are also prone to demographic effect, i.e., persistent oscillation becomes impossible in the managed case (in the sense of balanced recruitment and death rates) by comparing with results in unmanaged populations (exponential population dynamics). Further, approximations of quasi-stationary distributions are derived for stochastic versions of the proposed models based on a diffusion approximation to the infection process. The effect of transmission parameters on the ratio of mean to standard deviation of the approximating distribution, used to judge the validity of the approximations and the expected time until fade out of infection, is further discussed. We conclude that strengthening any route of transmission may or may not reduce the expected time to fade out of infection, depending on the population dynamics. 相似文献
74.
Based on universal thermodynamic principles (Schwarz in Biophys Chem 86:119–129, 2000) it is shown how measured enthalpy changes can be utilized to determine the relevant binding isotherm as well as the variation
of the molar enthalpy change. This is carried out in a novel way involving multiple titration experiments whose evaluation
requires no beforehand assumptions or models whatever. An appropriate specific model mechanism may be discussed afterwards
and developed in view of the given experimental results. The pertinent procedure is demonstrated using micro-calorimetric
data obtained in the case of the local anesthetic dibucaine as it associates with POPC liposomes. Mutual interactions of the
bound ligand molecules could be described in terms of repulsive enthalpic and entropic activity coefficients. Apparently these
are induced by electrostatic forces and by the finite size of binding sites, respectively. 相似文献
75.
The spatial-temporal dynamics of farm animal diseases depend both on disease specific processes and the underlying contact network between farms. Indirect transmission via free-living bacteria in the environment is an important transmission route and contributes significantly to the dynamics. The pair-wise model has been developed to include both direct transmission and indirect transmission via free stages. The model is compared with stochastic simulations of epidemics on contact networks. The network framework is applied to the investigation of the epidemiological dynamics of between-herd transmission of Salmonella spp. The main results help to explain differences in observed epidemiological patterns and to identify possible causes for different strains of Salmonella developing so much variation in their infection dynamics in UK dairy herds. Numerical results show that shorter infectious period, more persistent immune response and more rapid removal of faeces result in a lower prevalence of infection and a greater tendency for (damped) oscillation. A possible control strategy is consequently suggested. Furthermore, the effect of network structure on long-term dynamics is examined. 相似文献
76.
Both linear and discontinuous ribosome scanning are used for translation initiation from bicistronic human immunodeficiency virus type 1 env mRNAs 下载免费PDF全文
Human immunodeficiency virus type 1 (HIV-1) generates 16 alternatively spliced isoforms of env mRNA that contain the same overlapping open reading frames for Vpu and Env proteins but differ in their 5' untranslated regions (UTR). A subset of env mRNAs carry the extra upstream Rev initiation codon in the 5' UTR. We explored the effect of the alternative UTR on the translation of Vpu and Env proteins from authentic env mRNAs expressed from cDNA constructs. Vpu expression from the subset of env mRNA isoforms with exons containing an upstream Rev AUG codon was minimal. However, every env mRNA isoform expressed similar levels of Env protein. Mutations that removed, altered the strength of, or introduced upstream AUG codons dramatically altered Vpu expression but had little impact on the consistent expression of Env. These data show that the different isoforms of env mRNA are not redundant but instead regulate Vpu production in HIV-1-infected cells. Furthermore, while the initiation of Vpu translation conforms to the leaky ribosome-scanning model, the consistent Env synthesis infers a novel, discontinuous ribosome-scanning mechanism to translate Env. 相似文献
77.
Different cytochromes P450 are involved in steroid biosynthesis. These cytochromes have heme as the prosthetic group. We previously reported that ACTH, an activator of glucocorticoid biosynthesis in adrenal, requires heme biosynthesis for a maximal response. In the present study, we investigated the effect of ACTH, and the effect of two activators of the adrenal mineralocorticoid synthesis, endothelin-1 and low sodium diet on 5-aminolevulinate-synthase (ALA-s) mRNA. ALA-s is the rate-limiting enzyme in heme biosynthesis. It was found that infusion of rats with ACTH for 1 h caused an increase of adrenal ALA-s mRNA and activity accompanied by an increase in plasma corticosterone. CYP21, a cytochrome involved in the synthesis of both corticosterone and aldosterone, was not modified at the RNA level in adrenal glands by 1 h of ACTH infusion. Consistently, infusion of endothelin-1 for 1 h increased ALA-s mRNA and aldosterone content in adrenal gland without modifying CYP21 mRNA levels. To study if ALA-s is also regulated by the main physiological stimuli that increase adrenal mineralocorticoid secretion, we fed rats with low salt diet for 2 or 15 days. Low salt diet treatment increased adrenal gland ALA-s mRNA levels. On the other hand, the rapid stimulation of ALA-s mRNA by ACTH which acts through cyclic AMP was confirmed in H295R human adrenocortical cells, the only human adrenal cell line that has a steroid secretion pattern and regulation similar to primary cultures of adrenal cells. Our findings suggest that the acute activation of adrenal steroidogenic cytochromes by trophic hormones involves an increase in heme biosynthesis which will favor the production of active cytochromes. 相似文献
78.
Jesudason EP Baben B Ashok BS Masilamoni JG Kirubagaran R Jebaraj WC Jayakumar R 《Molecular and cellular biochemistry》2007,298(1-2):69-81
Aβ vaccination as a therapeutic intervention of Alzheimer’s has many challenges, key among them is the regulation of inflammatory
processes concomitant with excessive generation of free radicals seen during such interventions. Here we report the beneficial
effects of melatonin on inflammation associated with Aβ vaccination in the central and peripheral nervous system of mice.
Mice were divided into three groups (n = 8 in each): control, inflammation (IA), and melatonin-treated (IAM). The brain, liver, and spleen samples were collected
after 5 days for quantitative assessment of plasma lipid peroxides (LPO), an oxidative stress marker, and antioxidant enzymes
such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (Gpx). IA group mice have
shown the elevated concentration of LPO significantly while there was a reduction at antioxidant enzyme levels. In addition,
a significant (P < 0.05) reduction in neurotransmitters like dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) was also observed
in the IA group mice. Nevertheless, their metabolites, such as homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA)
increased significantly (P < 0.05) as compared to control. Samples were further evaluated at microscopic level to examine the neuropathological changes
by immunohistochemical methods. Melatonin treatment effectively reversed these above changes and normalized the LPO and antioxidant
enzyme levels (P < 0.05). Furthermore, melatonin salvaged the brain cells from inflammation. Our Immunohistochemical findings in the samples
of melatonin-treated animals (IAM group) indicated diminished expression of glial fibrillary acidic protein (GFAP) and nuclear
factor kappa B (NfκB) than those observed in the IA group samples. Our results suggest that administration of melatonin protects
inflammation associated with Aβ vaccination, through its direct and indirect actions and it can be an effective adjuvant in
the development of vaccination in immunotherapy for Alzheimer’s disease (AD). 相似文献
79.
Justus E Awad D Hohnholt M Schaffran T Edwards K Karlsson G Damian L Gabel D 《Bioconjugate chemistry》2007,18(4):1287-1293
A new class of lipids, containing the closo-dodecaborate cluster, has been synthesized. Two lipids, S-(N, N-(2-dimyristoyloxyethyl)acetamido)thioundecahydro-closo-dodecaborate (2-) (B-6-14) and S-(N, N-(2-dipalmitoyloxyethyl)acetamido)thioundecahydro-closo-dodecaborate (2-) (B-6-16) are described. Both of them have a double-tailed lipophilic part and a headgroup carrying two negative charges. Differential scanning calorimetry shows that B-6-14 and B-6-16 bilayers have main phase transition temperatures of 18.8 and 37.9 degrees C, respectively. Above the transition temperature of 18.8 degrees C, B-6-14 can form liposomal vesicles, representing the first boron-containing lipid with this capability. Upon cooling below the transition temperature, stiff bilayers are formed. When incorporated into liposomal formulations with equimolar amounts of distearoyl phosphatidylcholine (DSPC) and cholesterol, stable liposomes are obtained. The zeta-potential measurements indicate that both B-6-14- and B-6-16-containing vesicles are negatively charged, with the most negative potential described of any liposome so far. The liposomes are of high potential value as transporters of boron to tumor cells in treatments based on boron neutron capture therapy (BNCT). Liposomes prepared from B-6-14 were slightly less toxic in V79 Chinese hamster cells (IC50 5.6 mM) than unformulated Na2B12H11SH (IC50 3.9 mM), while liposomes prepared from B-6-16 were not toxic even at 30 mM. 相似文献
80.
Knowledge of the genetic population structure lies at the heart of mapping studies aiming genes responsible for Mendelian and complex traits. The Quebec population, which is of mostly French descent, is considered an excellent model for such genetic epidemiological endeavours because it is a young founder population. Yet, the assessment of the founder effect has relied mostly on the observed distribution of monogenic diseases and on the analysis of the underlying mutations with investigations focusing on the Saguenay region. To eliminate this clinical bias and to obtain a more complete image of the genetic diversity, different regional populations of Quebec were investigated by analysing neutral markers that represent maternal, paternal and X chromosome lineages. Results indicate that Quebec does not appear more homogeneous nor significantly different from European populations. However, a series of regional founder effects, particularly visible at the level of rare variants, are observed. These effects can be explained by the successive migrations of descendants of the first immigrants from the initial sites of settlement towards the outer regions. Depending on the number of founders and their diversity, as well as on the degree of isolation and the magnitude of the interbreeding with the neighbouring or local populations, such as Amerindians or later migrants, the consequences of these regional founder effects are more or less detectable in the contemporary population. 相似文献