Observe.Think.Touch Nature

September 20, 2011

Huxly — pondering upon human’s position in nature

Filed under: Humanity,Science Related — hebin @ 5:22 pm

from Huxley “Man and the Lowest Animals” (1861)

……

Perhaps no order of mammals presents us with so extraordinary a series of gradations as this–leading us insensibly from the crown and summit of the animal creation down to creatures, from which there is but a step, as it seems, to the lowest, smallest, and least intelligent of the placental Mammalia. It is as if nature herself had foreseen the arrogance of man, and with Roman severity had provided that his intellect by its very triumphs, should call into prominence the slaves, admonishing the conqueror that he is but dust.

These are the chief facts, this the immediate conclusion from them to which I adverted in the commencement of this Essay. The facts, I believe, cannot be disputed; and if so, the conclusion appears to me to be inevitable.

But if Man be separated by no greater structural barrier from the brutes than they are from one another–then it seems to follow that if any process of physical causation can be discovered by which the genera and families of ordinary animals have been produced, that process of causation is [147] amply sufficient to account for the origin of Man. In other words, if it could be shown that the Marmosets, for example, have arisen by gradual modification of the ordinary Platyrhini, or that both Marmosets and Platyrhini are modified ramifications of a primitive stock–then, there would be no rational ground for doubting that man might have originated, in the one case, by the gradual modification of a man-like ape; or, in the other case, as a ramification of the same primitive stock as those apes.

At the present moment, but one such process of physical causation has any evidence in its favour; or, in other words, there is but one hypothesis regarding the origin of species of animals in general which has any scientific existence–that propounded by Mr. Darwin. For Lamarck, sagacious as many of his views were, mingled them with so much that was crude and even absurd, as to neutralize the benefit which his originality might have effected, had he been a more sober and cautious thinker; and though I have heard of the announcement of a formula touching “the ordained continuous becoming of organic forms,” it is obvious that it is the first duty of a hypothesis to be intelligible, and that a qua-quâ-versal proposition of this kind, which may be read backwards, or forwards, or sideways, with exactly the same amount of signification, does not really exist, though it may seem to do so.

[148] At the present moment, therefore, the question of the relation of man to the lower animals resolves itself, in the end, into the larger question of the tenability, or untenability, of Mr. Darwin’s views. But here we enter upon difficult ground, and it behoves us to define our exact position with the greatest care.

It cannot be doubted, I think, that Mr. Darwin has satisfactorily proved that what he terms selection, or selective modification, must occur, and does occur, in nature; and he has also proved to superfluity that such selection is competent to produce forms as distinct, structurally, as some genera even are. If the animated world presented us with none but structural differences, I should have no hesitation in saying that Mr. Darwin had demonstrated the existence of a true physical cause, amply competent to account for the origin of living species, and of man among the rest.

……

On all sides I shall hear the cry–”We are men [152] and women, not a mere better sort of apes, a little longer in the leg, more compact in the foot, and bigger in brain than your brutal Chimpanzees and Gorillas. The power of knowledge–the conscience of good and evil–the pitiful tenderness of human affections, raise us out of all real fellowship with the brutes, however closely they may seem to approximate us.”

To this I can only reply that the exclamation would be most just and would have my own entire sympathy, if it were only relevant. But, it is not I who seek to base Man’s dignity upon his great toe, or insinuate that we are lost if an Ape has a hippocampus minor. On the contrary, I have done my best to sweep away this vanity. I have endeavoured to show that no absolute structural line of demarcation, wider than that between the animals which immediately succeed us in the scale, can be drawn between the animal world and ourselves; and I may add the expression of my belief that the attempt to draw a psychical distinction is equally futile, and that even the highest faculties of feeling and of intellect begin to germinate in lower forms of life.8 At the same [153] time, no one is more strongly convinced than I am of the vastness of the gulf between civilized man and the brutes; or is more certain that whether from them or not, he is assuredly not of them. No one is less disposed to think lightly of the present dignity, or desparingly of the future hopes, of the only consciously intelligent denizen of this world.

Barak Cohen — Learning Regulatory Code from Synthetic Promoters

Filed under: Papers — hebin @ 12:06 pm

Gertz, J., Siggia, E. D. & Cohen, B. A. Analysis of combinatorial cis-regulation in synthetic and genomic promoters. Nature 457, 215-218 (2008). URLhttp://dx.doi.org/10.1038/nature07521.

  • a technical note
    the expression level was measured by fluorescence to cell volume ratio for 25,000 cells in flowcytometry and take the mean. The reason to use the ratio is that the number of transcripts, i.e. expression level, depends on not only the promoter strength but also the cell’s “developmental stage”. Naively, one would expect that a cell grows its size and linearly increases its transcript number. Therefore the logic behind this ratio measure.
  • 1st result — Mig1 binds cooperatively

    Hill equation with a Hill coefficient of 3.4 and K 5 1.8 (red) fits the observed data (blue) well, compared to a Hill equation with a Hill coefficient of 1 (green).

  • Role of weak binding sites
    It’s a bit different than what I used to understand. Here is my current (I think correct) understanding: weak sites, when nearby a strong site, doesn’t get promoted to be a strong site, at least according to the model. This is what I used to believe what they suggest. But in fact, they estimated a free parameter that measures the ratio of affinity of MIG1 protein to the weak site to its affinity to a strong site, which gives 6.7. They claim that this is in the 95% CI of the PWM prediction, which suggests 9 fold lower affinity for the weaker site. The reason they suggest a weak site is useful is through its cooperative binding with the strong site. ( how is this the case? ) See figure below:

    Plots of expression for pairs of promoters that are almost identical except that either one strong Mig1 site or two strong Mig1 sites replace one strong and one weak Mig1 site. A blue circle represents one promoter pair and the red line represents equal expression.

  • Role of weak binding sites in vivo
    They have two strategies to link their findings from the synthetic libraries to the in vivo biology
    (1) compare the number of co-occurrence of weak site in promoters that harbor a strong site with that of shuffled promoters
    (2) they did a slightly trickier comparison: they found 359 promoters that contain at least one strong Mig1 site from all yeast promoters. They then applied their thermodynamic model through all the promoters, rank them by the predicted Mig1 repression and take the top ranking 359. As a test, they had 136 documented Mig1 target genes (perhaps by some microarray assays). They use this as a reference set and ask how much could the two 359 promoters sets overlap with the 136 biologically defined targets. In the end, their thermodynamic model predicted set predicts 8 more promoters out of the 136 (41 vs 33). This demonstrates that the thermodynamic model captures more features of repression than a simple look for strong hit.

Theme: Rubric. Blog at WordPress.com.

Follow

Get every new post delivered to your Inbox.