Talk about Rube Goldberg approach! While the method is somewhat innovative, the structures have been known for at least 30 years. The catenans are easily made when preparing plasmid dna in bacteria. In a regular preparation of plasmid DNA about 1- 2% of DNA is in the form of catenan. They do not interfere with usual applications of plasmid DNA and so people do not pay attention to it's presence.
You are right about the central dogma. It was formulated in 1958 and states that information flows from DNA->RNA->protein. Since that time it has been ammended many times. Just because it is genereally not true, does not mean it is not useful. For example, Newton's mechanics is generally not true, but it is quite usefull for some applications.
Just running some numbers (based on the abstract) 4 x 10^7 reads * 50 b/read = 2 x 10^9 b. Error rate (general ballpark for RNA replication/translation, number comes from personal experience in the field and memory of published data) = 1 x 10^-5 errors/b Expected number of detectable errors = 2 x10^9 * 1 x 10^-5 = 2 x 10^4, that's within order of magnitude from observed rate! Practically an exact hit in molecular biology.
Randomness of distribution of errors: should not be random. Several described and known factors impact frequency of errors, such as base composition around the site, secondary and tertiary structures of RNA and DNA (yes, even DNA! although many seem to believe that DNA is a plain old double stranded DNA, it does have a tertiary structure, including during transcription to RNA).
This statistical analysis (albeit a brief one) does not disprove the presence of RNA -editing, but might emphasize the need for a more careful analysis and interpretation of data. RNA editing has been described before, and in some cases plays a vital role in making an organism function at all (e.g. some viruses have RNA-editing to regulate activity of polymerases and expression of viral proteins).
In conclusion, it is not an earth-shattering, dogma overthrowing finding, but rather an additional piece of information about expression of the genome and translation of it into phenotype.
Just in case one thinks that I do not know what I am talking about, here are my credentials: my @a = ('A'..'Z', " ",'a'..'z'); my @r = (15, 7, 3, 26, 12, 41, 38, 31, 29, 47, 38, 27, 44, 26, 1, 35, 41, 38, 41, 33, 51); map {print $a[$_];}(@r); print "\n";
No, I do not know if they were classified at all. Logically thinking, they were not living at extreme temperature, right? They should not be classified as extremophiles. Longevity, - that's different story.
When you freeze mammalian cells, you do not have to use DMSO, 100% FBS will do. Besides, mammalian cells have not adopted to being frozen. Bacteria often do, especially soil ones. In addition, some organisms sporulate and spores are very resistant to harsh treatment. It is not surprising to me that bacteria sutvived that long, although it is definetely unusual.
I agree with you friend. There are several good things about debt (for public companies): it might increase return on equity by providing additional capital for growth; reduce cost of capital if interest rate is lower than the cost of equity; provide tax benefits. There are, of course, costs associated with debt, so it is always a balance of things. In general, a company should choose debt/equity ratio which is appropriate for its business plan. If they have too much cash on hand, they should either invest it in projects that provide return greater than market, or return it to investors (in form of dividends or share buy-back).
I am neither programmer nor accountant, but I am almost an MBA (85%) and certified (computer) geek.
I hope that the problem is fixed too. I am amazed at all the "feel good" rethoric, that the teams did the best they can. It is not enough, the success is measured by achieving the goals, not whether you tried hard or not. I understand that it is a complex task, but they got the best engineers, right? And a lot of money. Maybe they need to review performance measures. As it is said: "Performance measures drive performance". Can you imagine buying a car which runs only to the first intersection?
Silica stuff works great when you do not want to think, or you do not have time for error. Just buy a kit from Qiagen. They use essentially the same columns for dna exctraction from blood, tissue, cells etc. For a relatively low sensitivity simple methods often work great. e.g. for PCR detection of Hepatitis B virus, one can incubate serum with 50 mM NaOH for 30 min at 37C, neutralize and go. But if you need to get a single-copy gene or low titer virus - silica columns or absorption on paper is your best bet.
To be exact, [H30+]*[OH-] = 10^-14, which in the case of ultrapure water means concentration of [H3O+] or [OH-] is 10^-7 M. BTW, [H2O]=55.55(5)M. If you want it in %, do the math.
To be exact, exactly half of genomic DNA comes from each parent. Extra-chromasomal DNA (e.g. mitochondrial DNA) is contributed by mother. Machinery which is required for DNA replication does not really matter; half-life of proteins is relatively short, and new proteins that make up the machinery will be made from the genomic DNA. Although the is some extra-chromasomal DNA which comes from maternal side, it's effects are small compared to the effects of the genomic DNA.
They had to take cells from the embryo; the analysis is destructive (probably Polymerase Chain Reaction, or PCR). One cannot take too many cells from the embyo, have to leave some for the embryo to develop. This limits number of screens. Since the woman had family history of Alzheimer's it is the obvious choice.
Well, let's see:
a search for "cure" at www.dictionary.com gives, among other meanings, these:
- An agent, such as a drug, that restores health; a remedy.
- Something that corrects or relieves a harmful or disturbing situation.
my example with AZT is an example of a drug, that restores health of HIV patients. You are right in the sense that it does not cure HIV completely, one has to take the drug all the time. But there are some people who live for 20 years with HIV! (BTW, AZT is only a first generation HIV drug, now it is HAART).
Another example, with vaccine, illustrates the second meaning of the word "cure". Vaccines do correct a harmfull situation of unprotected organism susceptible for infection.
So, I think I did give examples of cures.
Couple examples of cures developed in the last 50 years:
1. Hepatitis B vaccine; radically different from vaccinia (~1880) and polio (~1950).
2. HIV drugs, e.g. AZT, other antiviral drugs, like picovir (Viropharma Inc); there is a number of drugs designed to target a specific gene product. BTW, 'enabling' discovery - DNA structure - was done in 1953 (Crick and Watson)
Another example, in technology: satellites.
The point I would like to make is that it is hard to see grandious things from close distance. Wait 30-50 years to see what things as important as transistor were developed in late 20th century.
My son (he is not MIT student yet, only high school:)) suggested to install reservation system. Before you head off, change the state to something like "On my way..."
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Talk about Rube Goldberg approach! While the method is somewhat innovative, the structures have been known for at least 30 years. The catenans are easily made when preparing plasmid dna in bacteria. In a regular preparation of plasmid DNA about 1- 2% of DNA is in the form of catenan. They do not interfere with usual applications of plasmid DNA and so people do not pay attention to it's presence.
You are right about the central dogma. It was formulated in 1958 and states that information flows from DNA->RNA->protein. Since that time it has been ammended many times. Just because it is genereally not true, does not mean it is not useful. For example, Newton's mechanics is generally not true, but it is quite usefull for some applications.
Just running some numbers (based on the abstract)
4 x 10^7 reads * 50 b/read = 2 x 10^9 b.
Error rate (general ballpark for RNA replication/translation, number comes from personal experience in the field and memory of published data) = 1 x 10^-5 errors/b
Expected number of detectable errors = 2 x10^9 * 1 x 10^-5 = 2 x 10^4, that's within order of magnitude from observed rate! Practically an exact hit in molecular biology.
Randomness of distribution of errors: should not be random. Several described and known factors impact frequency of errors, such as base composition around the site, secondary and tertiary structures of RNA and DNA (yes, even DNA! although many seem to believe that DNA is a plain old double stranded DNA, it does have a tertiary structure, including during transcription to RNA).
This statistical analysis (albeit a brief one) does not disprove the presence of RNA -editing, but might emphasize the need for a more careful analysis and interpretation of data. RNA editing has been described before, and in some cases plays a vital role in making an organism function at all (e.g. some viruses have RNA-editing to regulate activity of polymerases and expression of viral proteins).
In conclusion, it is not an earth-shattering, dogma overthrowing finding, but rather an additional piece of information about expression of the genome and translation of it into phenotype.
Just in case one thinks that I do not know what I am talking about, here are my credentials:
my @a = ('A'..'Z', " ",'a'..'z');
my @r = (15, 7, 3, 26, 12, 41, 38, 31, 29, 47, 38, 27, 44, 26, 1, 35, 41, 38, 41, 33, 51);
map {print $a[$_];}(@r);
print "\n";
Sure it's possible. It is not necessarily scary though, the bactria will be very unadapted to the environment if it was dormant couple billion years.
No, I do not know if they were classified at all. Logically thinking, they were not living at extreme temperature, right? They should not be classified as extremophiles. Longevity, - that's different story.
When you freeze mammalian cells, you do not have to use DMSO, 100% FBS will do. Besides, mammalian cells have not adopted to being frozen. Bacteria often do, especially soil ones. In addition, some organisms sporulate and spores are very resistant to harsh treatment. It is not surprising to me that bacteria sutvived that long, although it is definetely unusual.
I agree with you friend. There are several good things about debt (for public companies): it might increase return on equity by providing additional capital for growth; reduce cost of capital if interest rate is lower than the cost of equity; provide tax benefits. There are, of course, costs associated with debt, so it is always a balance of things. In general, a company should choose debt/equity ratio which is appropriate for its business plan.
If they have too much cash on hand, they should either invest it in projects that provide return greater than market, or return it to investors (in form of dividends or share buy-back).
I am neither programmer nor accountant, but I am almost an MBA (85%) and certified (computer) geek.
I hope that the problem is fixed too.
I am amazed at all the "feel good" rethoric, that the teams did the best they can. It is not enough, the success is measured by achieving the goals, not whether you tried hard or not. I understand that it is a complex task, but they got the best engineers, right? And a lot of money. Maybe they need to review performance measures. As it is said: "Performance measures drive performance".
Can you imagine buying a car which runs only to the first intersection?
Silica stuff works great when you do not want to think, or you do not have time for error. Just buy a kit from Qiagen. They use essentially the same columns for dna exctraction from blood, tissue, cells etc. For a relatively low sensitivity simple methods often work great. e.g. for PCR detection of Hepatitis B virus, one can incubate serum with 50 mM NaOH for 30 min at 37C, neutralize and go. But if you need to get a single-copy gene or low titer virus - silica columns or absorption on paper is your best bet.
To be exact, [H30+]*[OH-] = 10^-14, which in the case of ultrapure water means concentration of [H3O+] or [OH-] is 10^-7 M. BTW, [H2O]=55.55(5)M. If you want it in %, do the math.
To be exact, exactly half of genomic DNA comes from each parent. Extra-chromasomal DNA (e.g. mitochondrial DNA) is contributed by mother. Machinery which is required for DNA replication does not really matter; half-life of proteins is relatively short, and new proteins that make up the machinery will be made from the genomic DNA. Although the is some extra-chromasomal DNA which comes from maternal side, it's effects are small compared to the effects of the genomic DNA.
They had to take cells from the embryo; the analysis is destructive (probably Polymerase Chain Reaction, or PCR). One cannot take too many cells from the embyo, have to leave some for the embryo to develop. This limits number of screens. Since the woman had family history of Alzheimer's it is the obvious choice.
Well, let's see:
a search for "cure" at www.dictionary.com gives, among other meanings, these:
- An agent, such as a drug, that restores health; a remedy.
- Something that corrects or relieves a harmful or disturbing situation.
my example with AZT is an example of a drug, that restores health of HIV patients. You are right in the sense that it does not cure HIV completely, one has to take the drug all the time. But there are some people who live for 20 years with HIV! (BTW, AZT is only a first generation HIV drug, now it is HAART).
Another example, with vaccine, illustrates the second meaning of the word "cure". Vaccines do correct a harmfull situation of unprotected organism susceptible for infection.
So, I think I did give examples of cures.
Couple examples of cures developed in the last 50 years:
1. Hepatitis B vaccine; radically different from vaccinia (~1880) and polio (~1950).
2. HIV drugs, e.g. AZT, other antiviral drugs, like picovir (Viropharma Inc); there is a number of drugs designed to target a specific gene product. BTW, 'enabling' discovery - DNA structure - was done in 1953 (Crick and Watson)
Another example, in technology: satellites.
The point I would like to make is that it is hard to see grandious things from close distance. Wait 30-50 years to see what things as important as transistor were developed in late 20th century.
My son (he is not MIT student yet, only high school :)) suggested to install reservation system. Before you head off, change the state to something like "On my way..."