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41.
Singaram?Gopalakrishnan Napo?KM?Cheung Bill?WP?Yip Doris?WT?AuEmail author 《Frontiers in zoology》2013,10(1):78
Introduction
Females having a longer telomere and lifespan than males have been documented in many animals. Such linkage however has never been reported in fish. Progressive shortening of telomere length is an important aging mechanism. Mounting in vitro evidence has shown that telomere shortening beyond a critical length triggered replicative senescence or cell death. Estrogen has been postulated as a key factor contributing to maintenance of telomere and sex-dependent longevity in animals. This postulation remains unproven due to the lack of a suitable animal system for testing. Here, we introduce a teleost model, the Japanese medaka Oryzias latipes, which shows promise for research into the molecular mechanism(s) controlling sex difference in aging.Results
Using the medaka, we demonstrate for the first time in teleost that (i) sex differences (female?>?male) in telomere length and longevity also exist in fish, and (ii) a natural, ‘menopause’-like decline of plasma estrogen was evident in females during aging. Estrogen levels significantly correlated with telomerase activity as well as telomere length in female organs (not in males), suggesting estrogen could modulate telomere length via telomerase activation in a sex -specific manner. A hypothetical in vivo ‘critical’ terminal restriction fragment (TRF, representing telomere) length of approximately 4 kb was deduced in medaka liver for prediction of organismal mortality, which is highly comparable with that for human cells. An age conversion model was also established to enable age translation between medaka (in months) and human (in years). These novel tools are useful for future research on comparative biology of aging using medaka.Conclusion
The striking similarity in estrogen profile between aging female O. latipes and women enables studying the influence of “postmenopausal” decline of estrogen on telomere and longevity without the need of invasive ovariectomy. Medaka fish is advantageous for studying the direct effect of increased estrogen on telomere length and longevity without the breast cancer complications reported in rodents. The findings strongly support the notion that O. latipes is a unique non-mammalian model for validation of estrogenic influence on telomere and longevity in vertebrates. This laboratory model fish is of potential significance for deciphering the ostensibly conserved mechanism(s) of sex-associated longevity in vertebrates.42.
43.
Evolutionary transfer of ORF-containing group I introns between different subcellular compartments (chloroplast and mitochondrion) 总被引:10,自引:2,他引:8
Turmel M; Cote V; Otis C; Mercier JP; Gray MW; Lonergan KM; Lemieux C 《Molecular biology and evolution》1995,12(4):533-545
We describe here a case of homologous introns containing homologous open
reading frames (ORFs) that are inserted at the same site in the large
subunit (LSU) rRNA gene of different organelles in distantly related
organisms. We show that the chloroplast LSU rRNA gene of the green alga
Chlamydomonas pallidostigmatica contains a group I intron (CpLSU.2)
encoding a site-specific endonuclease (I-CpaI). This intron is inserted at
the identical site (corresponding to position 1931-1932 of the Escherichia
coli 23S rRNA sequence) as a group I intron (AcLSU.m1) in the mitochondrial
LSU rRNA gene of the amoeboid protozoon Acanthamoeba castellanii. The
CpLSU.2 intron displays a remarkable degree of nucleotide similarity in
both primary sequence and secondary structure to the AcLSU.m1 intron;
moreover, the Acanthamoeba intron contains an ORF in the same location
within its secondary structure as the CpLSU.2 ORF and shares with it a
strikingly high level of amino acid similarity (65%; 42% identity). A
comprehensive survey of intron distribution at site 1931 of the chloroplast
LSU rRNA gene reveals a rather restricted occurrence within the
polyphyletic genus Chlamydomonas, with no evidence of this intron among a
number of non- Chlamydomonad green algae surveyed, nor in land plants. A
parallel survey of homologues of a previously described and similar
intron/ORF pair (C. reinhardtii chloroplast CrLSU/A. castellanii
mitochondrial AcLSU.m3) also shows a restricted occurrence of this intron
(site 2593) among chloroplasts, although the intron distribution is
somewhat broader than that observed at site 1931, with site-2593 introns
appearing in several green algal branches outside of the Chlamydomonas
lineage. The available data, while not definitive, are most consistent with
a relatively recent horizontal transfer of both site-1931 and site- 2593
introns (and their contained ORFs) between the chloroplast of a
Chlamydomonas-type organism and the mitochondrion of an Acanthamoeba- like
organism, probably in the direction chloroplast to mitochondrion. The data
also suggest that both introns could have been acquired in a single event.
相似文献
44.
The spores of Anabaena doliolum formed in light (light spores)and after transfer to darkness (dark spores) are biochemicallydifferent in that the light spores contain chlorophyll a andphycocyanin, while dark spores seem to lack them. The apparentbiosyntheses accompanying dark-spore germination seem to proceedin the following order: RNA, chlorophyll a, phycocyanin andDNA. Results of chloramphenicol treatment indicate that proteinsynthesis precedes RNA synthesis. The biosynthetic events followingRNA synthesis show a requirement for light. 相似文献
45.
McErlane V Yakkundi A McCarthy HO Hughes CM Patterson LH Hirst DG Robson T McKeown SR 《The journal of gene medicine》2005,7(7):851-859
BACKGROUND: AQ4N is metabolised in hypoxic cells by cytochrome P450s (CYPs) to the cytotoxin AQ4. Most solid tumours are known to contain regions of hypoxia whereas levels of CYPs have been found to vary considerably. Enhancement of CYP levels may be obtained using gene-directed enzyme prodrug therapy (GDEPT). We have therefore examined the potential of a CYP2B6-mediated GDEPT strategy to enhance the anti-tumour effect of the combination of AQ4N with radiation or cyclophosphamide (CPA). METHODS: In vitro and in vivo transient transfection of human CYP2B6 +/- CYP reductase (CYPRED) was investigated in RIF-1 mouse tumours. Efficacy in vitro was assessed using the alkaline comet assay (ACA). In vivo, the time to reach 4x the treatment volume (quadrupling time; VQT) was used as the end point. RESULTS: When CYP2B6 was transfected into RIF-1 cells and treated with AQ4N under hypoxic conditions there was a significant increase in DNA damage (measured by the ACA) compared with non-transfected cells. In vivo, a single intra-tumoural injection of a CYP2B6 vector construct significantly enhanced tumour growth delay in combination with AQ4N (100 mg/kg) and 10 Gy X-rays. AQ4N (100 mg/kg) and CPA (100 mg/kg) with CYP2B6 and CYPRED also enhanced tumour growth delay; this effect became significant when the schedule was repeated 14 days later (p = 0.0197). CONCLUSIONS: The results show the efficacy of a CYP2B6-mediated GDEPT strategy for bioreduction of AQ4N; this may offer an additional approach to target radiation- and chemo-resistant hypoxic tumours that should enhance overall tumour control. 相似文献
46.
The main objective of this paper is to report the identification and synthesis of norhydromorphone, a novel metabolite of hydromorphone, and its antinociceptive activities when tested in the formalin test as compared to other known analgesics. In addition, we are reporting for the first time the lack of antinociceptive activities of hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide in the rat formalin test. Norhydromorphone was isolated and identified as a metabolite of hydromorphone in a cancer patient's urine. An authentic standard of norhydromorphone was synthesized. The identity of norhydromorphone in the urine sample was confirmed by comparing the LC retention time and MS ion fragmentation with the synthetic standard using a liquid chromatographic-mass spectrometric-mass spectrometric (LC-MS-MS) assay. Norhydromorphone was found to be a minor metabolite of hydromorphone in the urine. Additionally, the antinociceptive activities of norhydromorphone, hydromorphone, morphine, dihydromorphine, dihydroisomorphine, hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide were determined in the rat formalin test following intraperitoneal (i.p.) administration. Only limited antinociception was observed and no significant increase in antinociception was detected at the three doses tested. The increased polarity of norhydromorphone as compared to hydromorphone due to the primary piperidine nitrogen may make it less favorable to cross the blood-brain-barrier (BBB), which may be partly responsible. In addition, lower intrinsic antinociceptive activity, which remains to be determined, could also contribute to the low antinociception. Our results also show that hydromorphone was five times as potent as morphine in the formalin test, while dihydromorphine and dihydroisomorphine were equipotent to and 36% as potent as morphine, respectively. Hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide did not exhibit any antinociceptive effect at the doses tested. The results further underscore the importance of a free C3-OH to the analgesic effect of morphine alkaloids. 相似文献
47.
M Morgan Conn Joe Kappock Dale Drueckhammer Richard Cammack Dennis Hall Tony Cass Jon D Stewart Graham RL Cousins Jeremy KM Sanders Sabine Flitsch Philip AS Lowden Richard Newman 《Current opinion in chemical biology》1999,3(6):631
A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in chemical biology. 相似文献
48.
KM Abha Mishra Runesh Podili Teja S. Pathlavath Kalyan K. Sethi 《Journal of biochemical and molecular toxicology》2023,37(8):e23409
Since the outbreak of highly virulent coronaviruses, significant interest was assessed to the brain and heart axis (BHA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected patients. The majority of clinical reports accounted for unusual symptoms associated with SARS-CoV-2 infections which are of the neurological type, such as headache, nausea, dysgeusia, anosmia, and cerebral infarction. The SARS-CoV-2 enters the cells through the angiotensin-converting enzyme (ACE-2) receptor. Patients with prior cardiovascular disease (CVD) have a higher risk of COVID-19 infection and it has related to various cardiovascular (CV) complications. Infected patients with pre-existing CVDs are also particularly exposed to critical health outcomes. Overall, COVID-19 affected patients admitted to intensive care units (ICU) and exposed to stressful environmental constraints, featured with a cluster of neurological and CV complications. In this review, we summarized the main contributions in the literature on how SARS-CoV-2 could interfere with the BHA and its role in affecting multiorgan disorders. Specifically, the central nervous system involvement, mainly in relation to CV alterations in COVID-19-affected patients, is considered. This review also emphasizes the biomarkers and therapy options for COVID-19 patients presenting with CV problems. 相似文献
49.