Unsolved Problems   Diverse Topics for Class Discussion    Nov 18, 2015

A) Try to invent a theory to explain sliding of limb bud grafts along the medio-lateral axis ("affinophoresis", Crawford and Stocum, 1988 Development vol. 102, pages 687-698) by means of whatever forces cause engulfment of more medial limb tissue fragments by more lateral tissues. (Nardi and Stocum, 1983 Differentiation 25, pages 27-31).

Both sets of phenomena require forces that pull (or push?) on limb tissues, with these forces becoming unbalanced where cells from one medio-lateral position are in contact with cells from another position.

B) Please read the Wikipedia article about "Levinthal's Paradox": Each kind of protein folds in a fraction of a second to whatever geometry minimizes Gibbs free energy. But trying out all possible combinations of angular bending, one by one (as textbooks teach), would take billions of years, even if each alternative configuration gets tested in only a millionth of a second.

Past theories include the following:

    * Only a tiny fraction of alternatives are actually tested?
    * Alternatives are tested simultaneously, not sequentially?
    * Conformations of smaller, ~25 amino acid "modules" are independently tested?
    * Only a tiny fraction of possible amino acid sequences are used, that have been selected for their ability to fold rapidly to a consistent three dimensional structure?
    * What other possibilities can you invent?

C) Fusion of two differentiated cells turns off differentiation: If they are not the same cell type, then both nuclei "turn off"expression (transcription) of all luxury genes (=genes not expressed in all differentiated cells. )
    * Hypothesize a function for this turning-off of luxury gene transcription.
    * Hypothesize a mechanism for this turning-off.
    * Hypothesize a way to use such turning-off in the treatment of cancer.
    * Hypothesize a way to use such turning-off in the treatment of an autoimmune disease.
* ...in the treatment of some other disease, perhaps muscular dystrophy.

D) Binding sites of antibodies have been reported to be lined entirely by pleated sheet folding patterns of proteins (based on x-ray diffraction studies). This is a paradox because the base sequences that code for the antibody binding sites are generated by random splicing of many V, D and J sequences, plus hypermutation. The explanation is supposed to be that binding site DNA is only transcribed when it codes for an amino acid sequence that happens to fold only into pleated sheets. But how is it possible for any mechanism to distinguish between DNA or RNA sequences based on the folding of the proteins for which they code? Even differences as drastic as chain terminations shouldn't be distinguishable until the protein is actually synthesized.

E) Computer programs exist which can correctly predict the three dimensional shape into which a protein will fold, based on its amino acid sequence, but only for around 80% of proteins. For many actual proteins, the computer predictions are very wrong.
Please read the (very well done) Wikipedia article titled "Protein Structure Prediction"
How does a protein know how to fold, if a computer can't predict it?
What peculiarities in a protein's structure would you expect should make it more difficult to predict?

F) How can human brains ever be anywhere near as smart as computers, considering that electrical impulses and transistors are thousands to millions times faster than nerve action potentials and synapses?

    * Maybe "parallel processing" (doing lots of independent calculations simultaneously)
    * Maybe brains can only understand other brains which are significantly less intelligent than they are?
    * The relation of computers to human intelligence is... Additive? Multiplicative?
    * Can brains understand what they can't transmit?

G) What if children were somehow able to learn correct grammar of a language before they have heard enough spoken sentences for computer programs to have deduced those grammatical rules?
Would that tell you something about the mind? ...Or something about languages? ... Or both?


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