Sunday 14 October 2007

BIRTH OF DNA IDEA

//////////////A Structure for Deoxyribose Nucleic Acid
J. D. WatsonF. H. C. Crick
April 25, 1953, Nature, Vol. 171, page 737
WE wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.A structure for nucleic acid has already been proposed by Pauling and Corey1. They kindly made their manuscript available to us in advance of publication. Their model consists of three intertwined chains, with the phosphates near the fibre axis, and the bases on the outside. In our opinion, this structure is unsatisfactory for two reasons: (1) We believe that the material which gives the X-ray diagrams is the salt, not the free acid. Without the acidic hydrogen atoms it is not clear what forces would hold the structure together, especially as the negatively charged phosphates near the axis will repel each other. (2) Some of the van der Waals distances appear to be too small.Another three-chain structure has also been suggested by Fraser (in the press). In his model the phosphates are on the outside and the bases on the inside, linked together by hydrogen bonds. This structure as described is rather ill-defined, and for this reason we shall not comment on it.

This figure is purely diagrammatic. The two ribbons symbolize the two phophate-sugar chains, and the horizonal rods the pairs of bases holding the chains together. The vertical line marks the fibre axis.



We wish to put forward a radically different structure for the salt of deoxyribose nucleic acid. This structure has two helical chains each coiled round the same axis (see diagram). We have made the usual chemical assumptions, namely, that each chain consists of phosphate diester groups joining beta-D-deoxyribofuranose residues with 3',5' linkages. The two chains (but not their bases) are related by a dyad perpendicular to the fibre axis. Both chains follow right-handed helices, but owing to the dyad the sequences of the atoms in the two chains run in opposite directions. Each chain loosely resembles Furberg's2 model No. 1; that is, the bases are on the inside of the helix and the phosphates on the outside. The configuration of the sugar and the atoms near it is close to Furberg's "standard configuration," the sugar being roughly perpendicular to the attached base. There is a residue on each every 3.4 A. in the z-direction. We have assumed an angle of 36° between adjacent residues in the same chain, so that the structure repeats after 10 residues on each chain, that is, after 34 A. The distance of a phosphorus atom from the fibre axis is 10 A. As the phosphates are on the outside, cations have easy access to them.The structure is an open one, and its water content is rather high. At lower water contents we would expect the bases to tilt so that the structure could become more compact.The novel feature of the structure is the manner in which the two chains are held together by the purine and pyrimidine bases. The planes of the bases are perpendicular to the fibre axis. They are joined together in pairs, a single base from one chain being hydroden-bonded to a single base from the other chain, so that the two lie side by side with identical z-coordinates. One of the pair must be a purine and the other a pyrimidine for bonding to occur. The hydrogen bonds are made as follows: purine position 1 to pyrimidine position 1; purine position 6 to pyrimidine position 6.
If it is assumed that the bases only occur in the structure in the most plausible tautomeric forms (that is, with the keto rather than the enol configurations) it is found that only specific pairs of bases can bond together. These pairs are: adenine (purine) with thymine (pyrimidine), and guanine (purine) with cytosine (pyrimidine).In other words, if an adenine forms one member of a pair, on either chain, then on these assumptions the other member must be thymine; similarly for guanine and cytosine. The sequence of bases on a single chain does not appear to be restricted in any way. However, if only specific pairs of bases can be formed, it follows that if the sequence of bases on one chain is given, then the sequence on the other chain is automatically determined.It has been found experimentally3,4 that the ratio of the amounts of adenine to thymine, and the ratio of guanine to cytosine, are always very close to unity for deoxyribose nucleic acid.It is probably impossible to build this structure with a ribose sugar in place of the deoxyribose, as the extra oxygen atom would make too close a van der Waals contact. The previously published X-ray data5,6 on deoxyribose nucleic acid are insufficient for a rigorous test of our structure. So far as we can tell, it is roughly compatible with the experimental data, but it must be regarded as unproved until it has been checked against more exact results. Some of these are given in the following communications. We were not aware of the details of the results presented there when we devised our structure, which rests mainly though not entirely on published experimental data and stereochemical arguments.It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.Full details of the structure, including the conditions assumed in building it, together with a set of coordinates for the atoms, will be published elsewhere.We are much indebted to Dr. Jerry Donohue for constant advice and criticism, especially on interatomic distances. We have also been stimulated by a knowledge of the general nature of the unpublished experimental results and ideas of Dr. M. H. F. Wilkins, Dr. R. E. Franklin and their co-workers at King’s College, London. One of us (J. D. W.) has been aided by a fellowship from the National Foundation for Infantile Paralysis.1 Pauling, L., and Corey, R. B., Nature, 171, 346 (1953); Proc. U.S. Nat. Acad. Sci., 39, 84 (1953).2 Furberg, S., Acta Chem. Scand., 6, 634 (1952).3 Chargaff, E., for references see Zamenhof, S., Brawerman, G., and Chargaff, E., Biochim. et Biophys. Acta, 9, 402 (1952).4 Wyatt, G. R., J. Gen. Physiol., 36, 201 (1952).5 Astbury, W. T., Symp. Soc. Exp. Biol. 1, Nucleic Acid, 66 (Camb. Univ. Press, 1947).6 Wilkins, M. H. F., and Randall, J. T., Biochim. et Biophys. Acta, 10, 192 (1953).



//////////////////Migrations influenced immune evolution
by Melissa Lee Phillips
Reposted from:http://www.the-scientist.com/news/home/53680/Human innate immunity differs between Africans and others, perhaps due to different infectious environmentsAn important component of the innate immune system evolved differently in different human populations, depending on the infectious diseases that each population has encountered, suggests a study published online this week in the Proceedings of the National Academy of Sciences. The authors found that variants of an immune receptor protect against bacterial infection in Europeans and Asians, while Africans often possess a version of the receptor that protects against malaria."Our study demonstrates that during migration out of Africa, the immune system has been changed by the infections it has encountered," senior author Mihai Netea of Radboud University Nijmegen Medical Center in the Netherlands told The Scientist in an Email.Toll-like receptors (TLRs) defend hosts by recognizing molecules that all pathogens possess. One of these receptors, TLR4, protects against Gram-negative bacteria, mycobacteria, fungi, and malaria parasites.Previous work has identified two common single nucleotide polymorphisms (SNPs) in TLR4, which appear to change the receptor's activity and alter susceptibility to infectious diseases. Different human populations also show different frequencies of these two SNPs.To see if infectious disease pressures could have influenced TLR4's evolution in different human populations, researchers led by Bart Ferwerda, also of Radboud, analyzed TLR4 polymorphisms in individuals from Africa, Eurasia, and the Americas.They found a high frequency of one of the SNPs in Africans, while Europeans showed high frequencies of both SNPs. The two SNPs appeared to cosegregate in European populations: people with one SNP always had the other. Most Asians and Americans showed neither SNP, instead expressing the ancestral alleles.It was a bit of a surprise to find no Europeans with the single SNP found in Africans, Betea said, but it indicated "a strong evolutionary pressure."The researchers next looked for functional differences between the TLR4 variant with one SNP, common among Africans, and the TLR4 variant with both SNPs, common among Europeans. They found that the African variant caused cells to produce high levels of a proinflammatory factor, while the European variant did not differ functionally from the ancestral TLR4.The second SNP found in Europeans must somehow neutralize the proinflammatory effects of the first SNP, according to Igor Mokrousov of St. Petersburg Pasteur Institute in Russia, who was not involved in the work.Other work has shown that enhanced inflammatory responses can contribute to death from septic shock, and the authors propose that this may explain why most populations do not possess the single SNP that leads to inflammation.In Africa, however, the threat of malaria may have overridden the threat of bacterial infection. Previous research has suggested that people with the single SNP suffer lower mortality rates from malaria than do people with ancestral alleles, although the mechanism of this protection is unknown.According to Calogero Caruso of the University of Palermo in Italy, the authors' hypothesis that malaria shaped TLR4 variants is "not completely convincing," because malaria was present in places other than sub-Saharan Africa during much of human history. Also, studies have conflicting findings on the role of inflammation in bacterial infection, said Caruso, who was not involved in the word. "Too much inflammation is dangerous as well as not enough inflammation, depending on the kind of bacteria and the individual phenotype.""The interplay is very complex as [other] environmental factors also played a role" in shaping humans' immune evolution, Mokrousov told The Scientist. But the study presents "very interesting, exciting results," he said. "Pressure from infectious diseases was one of the forces that shaped the human immune system."Melissa Lee Phillipsmail@the-scientist.com




////////////////////To have the most children, men should find a partner six years younger and women a mate four years older, Austrian researchers said on Wednesday.
The researchers tried to use evolution to explain why men often prefer younger women and what typically drives women's desire for older men, said their leader, Vienna University anthropologist Martin Fieder.



///////////////////Parallel universes: What's it mean?Sat, 2007-10-13 12:28
A quick question for a lazy Saturday afternoon. This article says mathematicians have found strong evidence that parallel universes exist, in which all possible outcomes coexist in separate universes. " A motorist who has a near miss, for instance, might feel relieved at his lucky escape. But in a parallel universe, another version of the same driver will have been killed. Yet another universe will see the motorist recover after treatment in hospital. The number of alternative scenarios is endless."
At the risk of posing a "Can God create a stone so heavy even He can't lift it?" type question, does this also mean that universes exist in which this same research was conducted and found to conclusively show that parallel universes do not exist? I'm hoping the Fred Bortz's of the world will chime in.


//////////////////Rejection sets off alarms for folks with low self-esteemSat, 2007-10-13 08:54
Few can tolerate such romantic or professional rebuffs as "It's not you, it's me" and "we regret to inform you that your application was not successful." But while a healthy dose of self-esteem can absorb the shock of rejection, poor self-esteem can trigger the primal fight-or-flight response, according to a new study from the University of California, Berkeley.


//////////////////Nanoengineers mine tiny diamonds for drug deliveryFri, 2007-10-12 14:04
Northwestern University researchers have shown that nanodiamonds -- much like the carbon structure as that of a sparkling 14 karat diamond but on a much smaller scale -- are very effective at delivering chemotherapy drugs to cells without the negative effects associated with current drug delivery agents.




/////////////////////Many places in the city, including Behala Bank Colony, Shibtala, Sapgachhia, Martinpara, Kalagachhia, Garia and Rabindra Palli, are still waterlogged. Metro profiles a few families living with the filthy water in different parts of the city since the rains last week.
The Saha family, Lake Town
What would it be like, being a guest in your own house? The Sahas of Lake Town came close to that, living as guests at a hotel a couple of kilometres away from home since Wednesday.
“Water entered our Block B apartment (in Ward 29) on Sunday. Some neighbours said over the phone that the place is still inundated,” says Debashis Saha, a senior consultant with Apollo Hospitals.
His wife, Suchandra, also a doctor, is attached with Bankura Medical College. The couple moved to Hotel Host in Baguiati with their two daughters and Suchandra’s mother after putting up with the waterlogging for three days. “Both my cars, a Santro and a Maruti 800, were fully immersed. There was no drinking water and our stock of food was going down,” says Debashis. “The electricity would be cut off for hours and I spotted a snake in the garage. That did it for me,” he adds.



//////////////////Uorygraph


//////////////////We should not call ourselves "secularists." We should not call ourselves "humanists," or "secular humanists," or "naturalists," or "skeptics," or "anti-theists," or "rationalists," or "freethinkers," or "brights." We should not call ourselves anything. We should go under the radar—for the rest of our lives. And while there, we should be decent, responsible people who destroy bad ideas wherever we find them.



///////////////////ELEPHANT MAN=Whatever the merits of his own diagnosis, Merrick can count himself extremely unlucky. Neurofibromatosis only affects one in 4000 people, while Proteus syndrome is even rarer – to date there have only been 90 cases documented worldwide.
We can take some comfort from the rarity of genetic disorders. Even for the more common genetic diseases such as sickle-cell anaemia and cystic fibrosis, the overall numbers of people affected are relatively small. Worldwide, for example, about one in 2000 people are born with cystic fibrosis. These figures are slightly misleading, however, since the numbers can vary enormously among different ethnic groups. In Scandinavia, for example, type 1 diabetes affects about one in 500 people, whereas in Japan only about one in 35,000 is affected



/////////////////Non-belief in religions is not the normal rest-state of all life. We non-believers in religion (atheists) are a very, very small minority in the world.The normal rest-state of all life seems to be belief in the religion you were brainwashed with since your early childhood.


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In the second half of the 20th Century, worldwide meat production increased
roughly fivefold; per capita consumption more than doubled. Even though the
industrialisation of farming has allowed vast numbers of animals to be reared in
relatively small areas, those kept in factory farms cannot forage for their own food
or live on scraps or waste products - as was traditionally largely the case.
Consequently, massive areas of land are given over to growing crops to feed them.
Livestock production has become the world's largest user of agricultural land.
The farm animal population has expanded dramatically to meet demand. Today, the growing human population -
already in excess of 6 billion - shares the planet and its resources at any one time with nearly 1 billion pigs, 1.3
billion cows, 1.8 billion sheep and goats and 15.4 billion chickens. As the intensive poultry industry (in particular)
spreads to and within many areas of the world, there are already twice as many chickens as there are humans on
earth to eat them. Consumption of dairy produce, eggs and seafood have also increased rapidly.
Before the 1990s, the vast majority of animal products were consumed in rich countries, yet in the last decade
many in developing nations have also adopted what was once known as the Western diet. Even though per capita
consumption of beef, pork and chicken remains at only a third of the quantities eaten in the industrial world, it has
doubled in poorer countries in little more than a decade. All indications are that this trend will continue apace for
the foreseeable future, encouraged by governments and large-scale international agricultural interests.
0.1 Current policies are unsustainable
The scale of this expansion is unsustainable and will reduce the future prospects of healthily feeding an expanding
human population. The main problems can be summarised as follows:
In the developed world, inappropriate diet is increasingly accepted as a cause of ill-health and morbidity.
Meat, meat products and dairy foods make up the greatest percentage of saturated fat intake and there is
now general consensus among nutritionists that this contributes significantly to several diseases which have
reached epidemic proportions. All informed opinion stresses the desirability of reduced consumption of
animal products and increased intake of fibre-rich carbohydrates, fresh fruit and vegetables in order to
minimise risk of heart disease, mature onset diabetes, obesity and (possibly) some cancers.
Rather than adding to our capacity to feed the world's human population, putting animal products at the
centre of food policy diminishes the possibility of doing so. Just as growth in the human population inevitably
puts a strain on the earth's resources, (leading many experts to cite control of numbers as crucial to the fight
against human hunger), so a spiralling farm animal population is also threatening stability. Apart from those
who feed predominantly on pasture where it is difficult to grow crops, and others who feed on scraps and
waste products as part of rotational mixed farming, farm animals utilise considerably more food calories than
they produce in the form of meat. Meat is the most resource costly form of food because livestock waste
8
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