MicroRNA (miRNA) encoding genes are abundant in vertebrate genomes but very few have been studied in any detail. Bioinformatic
tools allow prediction of miRNA targets and this information coupled with knowledge of miRNA expression profiles facilitates
formulation of hypotheses of miRNA function. Although the central nervous system (CNS) is a prominent site of miRNA expression,
virtually nothing is known about the spatial and temporal expression profiles of miRNAs in the brain. To provide an overview
of the breadth of miRNA expression in the CNS, we performed a comprehensive analysis of the neuroanatomical expression profiles
of 38 abundant conserved miRNAs in developing and adult zebrafish brain. 相似文献
The mortality of naked Anoplophora glabripennis Motschulsky (Coleoptera: Cerambycidae) larvae exposed to ethanedinitrile (cyanogen; C2N2) varied with temperature, time of exposure, and dose of ethanedinitrile. The concentration x time (Ct) product of ethanedinitrile over a range of temperatures (4.4, 10.1, 15.6, and 20.1 degrees C) decreased with increasing temperature, for both 3- and 6-h exposures. The Ct products varied with time of exposure at different temperatures. The variations in mortality at different temperatures are described with a slope ratio (Y = [slope]6h/ [slope]3h). At different temperatures, the concentration of ethanedinitrile and the duration of exposure play different roles in killing A. glabripennis larvae. These results suggest the control of A. glabripennis larvae within wood is achievable. 相似文献
Breast cancer accounts for 1 in 4 of all female cancers worldwide; approaching 13,000 women dying per year in the UK alone. Seventy five per cent of all diagnosed breast cancers are oestrogen receptor (ER) positive. Ovarian synthesis of oestrogens ceases at menopause and as breast cancer is more prevalent in postmenopausal women the non-ovarian sources of oestrogen are important in disease progression. There is now considerable evidence that associates increased breast cancer risk with prolonged exposure to oestrogens hence greater attention is now being given to determining whether the measurement of plasma oestrogen may assist in identifying chemoprevention target groups. Studies suggest that in most postmenopausal patients the intra-tumoural concentrations of oestrogens are up to 20-fold higher than those present in the plasma however, while the extent of biosynthesis of oestrogens within breast tissue is a major determinant of local exposure, plasma levels are a useful indicator of overall metabolism in peripheral tissues. As such it is important to understand factors that influence these measurements. This review summarises the impact of lifestyle such as body mass index, together with the role of genetic polymorphisms placed within the context of designing future epidemiological studies and breast cancer risk algorithms. 相似文献
1. Conservation of freshwater animal populations requires their access to, as well as sufficient availability of, critical habitats, such as those for reproduction. Abundant small-scale barriers may cause extensive fragmentation of freshwater habitat but, by comparison to larger structures their effects are rarely considered by catchment managers. The relationship between the distribution of, and access to, spawning habitat in a regulated river, characterized by abundant small barriers, was examined for river lamprey Lampetra fluviatilis , a threatened migratory fish. 2. Telemetry of adult lamprey in the River Derwent, North East England was used to quantify upriver migration and access to spawning habitat, together with surveys of spawning habitat availability and spawning activity between 2002 and 2007. 3. Access in to the Derwent appeared severely restricted by a tidal barrage, beyond which lamprey migrated rapidly in unobstructed reaches. Of all lamprey tagged in the lower 4 km of river, or ascending the barrage, 64% and 17% passed the first and second weirs respectively, with high flows crucial for this. Although over 98% of lamprey spawning habitat occurred more than 51 km upstream, on average just 1.8% of river lamprey spawners were recorded there. 4. In order to protect or rehabilitate species or species assemblages, greater attention needs to be paid to the relative spatial distribution of low-head barriers and the resultant availability of key habitats within individual catchments. This is particularly important given the renewed emphasis internationally on low-head hydropower solutions as a source of renewable energy, and the rapid growth in numbers of low-head barriers in many catchments. 相似文献
The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA), claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP) in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP), lipid peroxidation (measured as malondialdehyde; MDA) and leukocytic count (LC). Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein.
Results
EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg). Interestingly, DHA (125 mg/kg) markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85) and leukocytosis (r = 0.89), thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg) induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold), a rise in serum creatinine/urea levels (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying causal relationships.
Conclusion
DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels (thus implying a diagnostic/prognostic role for CRP). Further, this study is the first to reveal that DHA can obliterate the lethal CP-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing leukocytosis, systemic inflammation, and oxidative stress. 相似文献
We have established a reverse genetics approach for the routine generation of medaka (Oryzias latipes) gene knockouts. A cryopreserved library of N-ethyl-N-nitrosourea (ENU) mutagenized fish was screened by high-throughput resequencing for induced point mutations. Nonsense and splice site mutations were retrieved for the Blm, Sirt1, Parkin and p53 genes and functional characterization of p53 mutants indicated a complete knockout of p53 function. The current cryopreserved resource is expected to contain knockouts for most medaka genes. 相似文献
There is a need for efficient modeling strategies which quickly lead to reliable mathematical models that can be applied for design and optimization of (bio)-chemical processes. The serial gray box modeling strategy is potentially very efficient because no detailed knowledge is needed to construct the white box part of the model and because covenient black box modeling techniques like neural networks can be used for the black box part of the model. This paper shows for a typical biochemical conversion how the serial gray box modeling strategy can be applied efficiently to obtain a model with good frequency extrapolation properties. Models with good frequency extrapolation properties can be applied under dynamic conditions that were not present during the identification experiments. For a given application domain of a model, this property can be used to considerably reduce the number of identification experiments. The serial gray box modeling strategy is demonstrated to be successful for the modeling of the enzymatic conversion of penicillin G In the concentration range of 10-100 mM and temperature range of 298-335 K. Frequency extrapolation is shown by using only constant temperatures in the (batch) identification experiments, while the model can be used reliable with varying temperatures during the (batch) validation experiments. No reliable frequency extrapolation properties could be obtained for a black box model, and for a more knowledge-driven white box model reliable frequency extrapolation properties could only be obtained by incorporating more knowledge in the model. Copyright 1999 John Wiley & Sons, Inc. 相似文献
Third generation aromatase inhibitors have excellent specificity. Some reports indicate that letrozole may have a minor effect on cortisol synthesis but these were not confirmed: valid comparisons with other aromatase inhibitors requires randomised study.
The putative use of a third generation inhibitor as a single agent in premenopausal women has been investigated using YM511. It was hypothesised that in this situation site-specific suppression of estrogens in breast carcinomas, without systemic effects, may lead to a down-regulation of tumour proliferation. Plasma levels of androstenedione and testosterone were significantly increased by 2 weeks treatment with YM511. Mean plasma estrone levels were suppressed, but some plasma estradiol levels were abnormally high and others abnormally low. These differential effects of YM511 on circulating estrogens supported the concept that peripheral synthesis of estrogens might be suppressed while ovarian production remained high. However, YM511 did not demonstrate anti-proliferative effects in hormone sensitive breast carcinomas.
Consideration of the pharmacology of the estrogen receptor during tamoxifen therapy indicates that tamoxifen effectively saturates the receptor (>99.94% occupancy) in postmenopausal women. The addition of an aromatase inhibitor in this situation would be very unlikely to affect the biological activity of the estrogen receptor. This provides a possible explanation why the clinical efficacy of tamoxifen combined with an aromatase inhibitor appears to be equivalent to that of tamoxifen alone. 相似文献
We have employed a direct radiolabel binding assay to investigate the
interaction between3H-heparin and recombinant envelope glycoproteins,
rgp120s, derived from several different isolates of HIV-1. Comparable
dose-dependent binding is exhibited by rgp120s from isolates IIIB, GB8, MN
and SF-2. Under identical experimental conditions the binding of3H- heparin
to a recombinant soluble form of the cellular receptor for gp120, CD4, is
negligible. The binding of3H-heparin to rgp120 is competed for by excess
unlabeled heparin and certain other, but not all, glycosaminoglycan and
chemically modified heparins. Of a range of such polysaccharides tested,
ability to compete with3H-heparin for binding was strictly correlated with
inhibition of HIV-1 replication in vitro. Those possessing potent
anti-HIV-1 activity were effective competitors, whereas those having no or
little anti-HIV-1 activity were poor competitors. Scatchard analysis
indicates that the K d of the interaction between heparin and rgp120 is 10
nM. Binding studies conducted in increasing salt concentrations confirm
that the interaction is ionic in nature. Synthetic 33-35 amino acid
peptides based on the sequence of the V3 loop of gp120 also bind to heparin
with high affinity. V3 loop peptides that are cyclized due to terminal
cysteine residues show more selective binding than their uncyclized
counterparts. Overall, these data demonstrate further that heparin exerts
its anti-HIV-1 activity by binding to the envelope glycoprotein of HIV-1,
rather than its cellular receptor, CD4. This study confirms that the V3
loop of gp120 is the site at which heparin exerts its anti- HIV-1 activity.
Moreover, it reveals that high affinity binding to heparin is shared by all
four rgp120s examined, despite amino acid substitutions within the V3 loop.
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