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31.
Tumor suppressor genes 总被引:12,自引:0,他引:12
Macleod K 《Current opinion in genetics & development》2000,10(1):81-93
Although tumor suppressor genes continue to be discovered, the most recent advances have been made in attributing new and exciting functions to existing ones - such as the apparent role of VHL as a regulator of proteolysis. Great insights have also come from piecing genes together into pathways and networks. For instance the discovery that cyclin D1 is regulated by beta-catenin/Tcf-4 allows us to tie the APC pathway to the RB pathway and cell cycle control. Similarly, tumor suppressor genes have been fitted together with oncogenes into the various pathways that regulate apoptosis such that tumor suppressor function is now attributed to some of the basic components of the apoptotic machinery, such as caspases and Apaf-1. The great pace at which mouse models of tumorigenesis continue to advance our knowledge of tumor suppressor gene function has led us to look anew at the role of genes such as TCF-1 and SMAD-3 in human cancer. Finally, the realisation that different growth regulatory pathways give rise to generic signals suggests that future work may lie in integrating the signals from different pathways and in understanding the importance of protein levels to cellular function. 相似文献
32.
33.
A wide-ranging examination of plastid (pt)DNA sequence homologies within
higher plant nuclear genomes (promiscuous DNA) was undertaken. Digestion
with methylation-sensitive restriction enzymes and Southern analysis was
used to distinguish plastid and nuclear DNA in order to assess the extent
of variability of promiscuous sequences within and between plant species.
Some species, such as Gossypium hirsutum (cotton), Nicotiana tabacum
(tobacco), and Chenopodium quinoa, showed homogenity of these sequences,
while intraspecific sequence variation was observed among different
cultivars of Pisum sativum (pea), Hordeum vulgare (barley), and Triticum
aestivum (wheat). Hypervariability of plastid sequence homologies was
identified in the nuclear genomes of Spinacea oleracea (spinach) and Beta
vulgaris (beet), in which individual plants were shown to possess a unique
spectrum of nuclear sequences with ptDNA homology. This hypervariability
apparently extended to somatic variation in B. vulgaris. No sequences with
ptDNA homology were identified by this method in the nuclear genome of
Arabidopsis thaliana.
相似文献
34.
35.
Hanna M. Vesterinen Peter Connick Cadi M. J. Irvine Emily S. Sena Kieren J. Egan Gary G. Carmichael Afiyah Tariq Sue Pavitt Jeremy Chataway Malcolm R. Macleod Siddharthan Chandran 《PloS one》2015,10(4)
Objective
To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis.Design
Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action.Results
We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil) as lead candidates for clinical evaluation.Conclusions
We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders. 相似文献36.
Malcolm R. Macleod Aaron Lawson McLean Aikaterini Kyriakopoulou Stylianos Serghiou Arno de Wilde Nicki Sherratt Theo Hirst Rachel Hemblade Zsanett Bahor Cristina Nunes-Fonseca Aparna Potluru Andrew Thomson Julija Baginskitae Kieren Egan Hanna Vesterinen Gillian L. Currie Leonid Churilov David W. Howells Emily S. Sena 《PLoS biology》2015,13(10)
37.
Kojo Yeboah-Antwi Portipher Pilingana William B. Macleod Katherine Semrau Kazungu Siazeele Penelope Kalesha Busiku Hamainza Phil Seidenberg Arthur Mazimba Lora Sabin Karen Kamholz Donald M. Thea Davidson H. Hamer 《PLoS medicine》2010,7(9)
Background
Pneumonia and malaria, two of the leading causes of morbidity and mortality among children under five in Zambia, often have overlapping clinical manifestations. Zambia is piloting the use of artemether-lumefantrine (AL) by community health workers (CHWs) to treat uncomplicated malaria. Valid concerns about potential overuse of AL could be addressed by the use of malaria rapid diagnostics employed at the community level. Currently, CHWs in Zambia evaluate and treat children with suspected malaria in rural areas, but they refer children with suspected pneumonia to the nearest health facility. This study was designed to assess the effectiveness and feasibility of using CHWs to manage nonsevere pneumonia and uncomplicated malaria with the aid of rapid diagnostic tests (RDTs).Methods and Findings
Community health posts staffed by CHWs were matched and randomly allocated to intervention and control arms. Children between the ages of 6 months and 5 years were managed according to the study protocol, as follows. Intervention CHWs performed RDTs, treated test-positive children with AL, and treated those with nonsevere pneumonia (increased respiratory rate) with amoxicillin. Control CHWs did not perform RDTs, treated all febrile children with AL, and referred those with signs of pneumonia to the health facility, as per Ministry of Health policy. The primary outcomes were the use of AL in children with fever and early and appropriate treatment with antibiotics for nonsevere pneumonia. A total of 3,125 children with fever and/or difficult/fast breathing were managed over a 12-month period. In the intervention arm, 27.5% (265/963) of children with fever received AL compared to 99.1% (2066/2084) of control children (risk ratio 0.23, 95% confidence interval 0.14–0.38). For children classified with nonsevere pneumonia, 68.2% (247/362) in the intervention arm and 13.3% (22/203) in the control arm received early and appropriate treatment (risk ratio 5.32, 95% confidence interval 2.19–8.94). There were two deaths in the intervention and one in the control arm.Conclusions
The potential for CHWs to use RDTs, AL, and amoxicillin to manage both malaria and pneumonia at the community level is promising and might reduce overuse of AL, as well as provide early and appropriate treatment to children with nonsevere pneumonia.Trial registration
ClinicalTrials.gov Please see later in the article for the Editors'' Summary NCT00513500相似文献38.
39.
Marine sediment samples collected from various sites at 2 Atlantic salmon farms in Tasmania were analysed for the presence of Neoparamoeba sp., an amoeba associated with amoebic gill disease (AGD) in farmed Atlantic salmon. Environmental variables of the sediment layer at each site, including redox potential and sulphide concentration, were measured and the general biological condition assessed by video observation. Sediments and environmental data were collected on 4 occasions at each site over a 12 mo period. Neoparamoeba sp. was detected in populations of amoebae recovered by culture from all sites and in 50% of all sediment samples taken. There was evidence of a seasonal influence on the presence of the amoeba, but this was different at each farm. No Neoparamoeba sp. was recovered from any sites at Farm 1 during the winter of 2002 whereas at Farm 2 this was the case for the summer of 2003. There appeared to be no relationship between the presence of Neoparamoeba sp., salmon farming activities and environmental parameters. 相似文献
40.
Maclean JA Chen MA Wayne CM Bruce SR Rao M Meistrich ML Macleod C Wilkinson MF 《Cell》2005,120(3):369-382