Mark1984_SRI
Member
Registered: 7th Feb 06
Location: Preston
User status: Offline
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Has anyone else got loads of work on at the moment (with uni) or just life to make me feel like im not the only one at the moment? i'm currently doing 2 essays one 2500 word one 3000 word. Also doing preparation work for for a presentation next friday then i've got two more essays before i finish one due 4th may, one due 12th may= 4essays 1 presentation Urgh i hate this english course 
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vibrio
Banned
Registered: 28th Feb 01
Location: POAH
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Methylation is is the major covalent modification of DNA and almost always found in a palindromic CpG sequence thus making the 5’met Cytosine found symmetrically on both strands (sinsheimer 1955). It was first proposed by scarano (1971) and later by Holliday & Pugh (1975) and Riggs (1975) to be involved in cell differention and gene function and later Yeivin and Razin (1993) showed that epigenetic control of gene expression in mammals involves DNA methylation associated with gene-specific methylation patterns. Recognition of methyl-DNA by MBD binding proteins specifically requires both cytosines to be methylated, however the passive demethylation action of DNA replication would strip the methyl group from 50% of the DNA after two rounds of replication. In order to protect this state of DNA modification addition of the methyl group by the enzyme DNA methyl transferase (Bestor and Ingram 1983). DNMT1 is associated with proliferating cell nuclear antigen during DNA replication at DNA replication foci with methylation occurring within one to two minutes of replication to restore a state of full methylation to the DNA (Chuang et al, 1997). It is through this process that methylated DNA induced gene repression is inherited from mother to daughter for many generations of actively dividing cells (Razin and Riggs 1980). DNMT1 is essential for mouse embryogenesis as targeted knockouts of DNMT1 results in death (Li et al, 1992, Bird & Wolffe, 1999). Methylated DNA does under go active demethylation (Oswald et al, 2000) but this is not necessarily associated with replication (Kafri et al. 1992). while the paternal genome in fertilized mouse eggs is stripped of DNA methylation prior to zygotic fusion and subsequent replication (Mayer et al, 2000). This demethylation of the paternal genome is a feature of mouse, rat, human, pig zygotes but surprisingly not of rabbit and sheep zygotes (Beaujean et al, 2005, Beaujean et al, 2004a, Young & Beaujean, 2004). Interestingly sheep paternal genome is significantly demethylated when injected into mouse oocytes (Beaujean et al, 2004b) suggesting it is not inherently resistant to demethylation. While DNMT1 is responsible for maintaining methylation patterns during DNA replication, de novo methylation at previously unmethylated sites during early embryogenesis is carried out by DNMT3a & DNMT3b (Okano et al, 1999).
Methylation occurs at 70-80% of mammalian CpG sites (Ehrlich and Wang 1981) with the remaining unmethylated CpG sites found in CpG rich islands usually found in promoter regions of house keeping genes (bird 1986). These CpG islands are found in somatic cells in the gametes and in embryonic cells through out embryogenesis and gameogenesis (Kafri et al. 1992). In contrast CpG islands of tissue specific genes are generally Methylated in non expressing cells but unmethylated in their expressing cells (Yeivin and Razin 1993). Why CpG Islands are not methylated at replication could be explained by their replication during G1/early S phase (Delgado et al, 1998) when DNMT1 levels are low (Szyf et al, 1991) while levels of the transcription factor p21 are high which could prevent DNMT binding to PCNA (Chuang et al, 1997). This could prevent DNMT1 being present at the replication foci of CpG islands thus preventing their methylation. This theory is strengthened by the fact that many CpG islands are replication origins (Delgado et al, 1998), however it does not explain the lack of methylated CpG islands which are located in promoters of genes which lack p21 recognition sites. Aberrant DNA methylation are of particular importance to cancer (Jones & Baylin, 2002). Hypomethylation can result in the switching on of genes while hypermethylation of CpG islands can switch off genes (Jones & baylin, 2002, Feinberg & Vogelstein, 1983). Hypermethylation of CpG island found in tumor suppressor gene promoters is a prevalent mechanism for the transcriptional silence of these genes (Robertson, 2001., Rountree et al, 2001., Esteller & Herman, 2002., Jones & Baylin, 2002.). Removal of methylatransferase activity from the human colorectal cancer cell line HCT116 by genetic (antisense/SiRNA against HNMT1) or pharmacologic methods (5-aza-2'-deoxycytidine) causes extensive hypomethylation through out the genome including hypermethylated regions (Robert et al, 2003., Ting et al, 2004) however controversy surrounds wither knocking out of DNMT1 is sufficient for this observed hypomethylation event. Ting et al (2004) suggests that DNMT1 is redundant due to a compensatory role by DNMT3b. In order to investigate this they produced a double knockout of DNMT1 & DNMT3b cells which showed greater than 95% reduction in genomic methylation and crucially these cells re-expressed the tumour suppressor gene Cdkn2a providing a direct link between the methylation of its promoter and its transcription. These Double knockout cells had a 90% reduction in growth compared to the wild type HCT1165 cells. DNMT1 might also be targeted to methylate DNA at H3-K9 methylated chromatin via interaction of the histone methyltransferase SUV39H1 (Fuks et al, 2003). This is supported by studies of Jeddeloh et al (1999) which shows that a mutation of the putative SNF2-like ATPase DDM1 in Arabidopsis leads to a severe reduction in DNA methylation and Dennis et al (2001) showed the targeted disruption of its mammalian homologue LSH causes loss of DNA methylation and lethality in mice.
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RichR
Premium Member
Registered: 17th Oct 01
Location: Waterhouses, Staffordshire
User status: Offline
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I have a Yacht Design Dissertation due on May 18th, a AeroHydrodynamics tank test lab on Hydrofoil craft write up due in a week today and a project management assignment due in a week today
plus a 1.5 exam in structural analysis in 4 weeks, a 3 hour exam in Hydrodynamics and a 3 hour exam in AeroHydrodynamics
all of which is to be done within the next 5 weeks
then 4 years of uni is over and done with!
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Mark1984_SRI
Member
Registered: 7th Feb 06
Location: Preston
User status: Offline
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point made, only read the first two lines, maybe english literature isn't so bad 
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RichR
Premium Member
Registered: 17th Oct 01
Location: Waterhouses, Staffordshire
User status: Offline
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trying to do some work no but can't be arsed - Project Management coursework is abotu relocating a boatyard - its ntohing to do with design/engineering; its emmensly dull and I cant get past the intro!
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ClaireF
Member
Registered: 1st Nov 05
Location: hurlford, scotland Drives: corsa again
User status: Offline
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yeah i have three assignments to do and not done them
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Mark1984_SRI
Member
Registered: 7th Feb 06
Location: Preston
User status: Offline
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i'm doing an essay now or at least should be, serious lack of motivation at the moment. 
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ClaireF
Member
Registered: 1st Nov 05
Location: hurlford, scotland Drives: corsa again
User status: Offline
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yep me to
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CorsAsh
Member
Registered: 19th Apr 02
Location: Munich
User status: Offline
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Less than a month to finish and render this:
and make a full presentation and display to back it all up.
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RichR
Premium Member
Registered: 17th Oct 01
Location: Waterhouses, Staffordshire
User status: Offline
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I'd get more doen if I wasnt being disturbed by dad who's decided to Decorate the Office I'm sat in trying to work - planing and sanding doors, fitting ne skirting and arcatrave, new floor - its dusty and loud
plus CS is too distracting
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Mark1984_SRI
Member
Registered: 7th Feb 06
Location: Preston
User status: Offline
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quote:
Originally posted by CorsAsh
Less than a month to finish and render this:
and make a full presentation and display to back it all up.
Crikey mate thought i had it bad!
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CorsAsh
Member
Registered: 19th Apr 02
Location: Munich
User status: Offline
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quote:
Originally posted by LiVe LeE
I'd get more doen if I wasnt being disturbed by dad who's decided to Decorate the Office I'm sat in trying to work - planing and sanding doors, fitting ne skirting and arcatrave, new floor - its dusty and loud
plus CS is too distracting
I feel your pain, parental bothering and CS, the two main distractions to my work  
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abdus
Member
Registered: 23rd Feb 06
User status: Offline
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catching up with Legal Theory and Jurisprudence, Administrative Law and 2 other ones... exams in less than 1 month...aaaahhhhhh
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RichR
Premium Member
Registered: 17th Oct 01
Location: Waterhouses, Staffordshire
User status: Offline
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I've finished my main 3D work now, but trying to do the structural design, Stability book, MCA codes of Practice, Velocity Prediction Programme, and loads of other shite, including GA which I started 6 months ago and get too bored doing - all to be i in 3 weeks time
along with the 2 other assignments for thursday
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vibrio
Banned
Registered: 28th Feb 01
Location: POAH
User status: Offline
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quote:
Originally posted by Mark1984_SRI
point made, only read the first two lines, maybe english literature isn't so bad
you'll find sciencey writing different but yes its crap lol
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