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Re: [evol-psych] News: Resurrecting ancient proteins, team finds just two mutations set stage for evolution of modern hormone signaling

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  • Edgar Owen
    O my God, more evidence of MUTATIONS causing genetic change! As if there wasn t overwhelming evidence of it already.... Kohl must be biting his tongue! Edgar
    Message 1 of 10 , Jun 25, 2013
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      O my God, more evidence of MUTATIONS causing genetic change! As if there wasn't overwhelming evidence of it already....

      Kohl must be biting his tongue!

      Edgar



      On Jun 24, 2013, at 9:34 PM, Robert Karl Stonjek wrote:

       


      Resurrecting ancient proteins, team finds just two mutations set stage for evolution of modern hormone signaling

      June 24th, 2013 in Biology / Evolution

      Evolution, it seems, sometimes jumps instead of crawls. A research team led by a University of Chicago scientist has discovered two key mutations that sparked a hormonal revolution 500 million years ago.

      In a feat of "molecular time travel," the researchers resurrected and analyzed the functions of the ancestors of genes that play key roles in modern human reproduction, development, immunity and cancer. By re-creating the same DNA changes that occurred during those genes' ancient history, the team showed that two mutations set the stage for hormones like estrogen, testosterone and cortisol to take on their crucial present-day roles.

      "Changes in just two letters of the genetic code in our deep evolutionary past caused a massive shift in the function of one protein and set in motion the evolution of our present-day hormonal and reproductive systems," said Joe Thornton, PhD, professor of human genetics and ecology & evolution at the University of Chicago, who led the study.

      "If those two mutations had not happened, our bodies today would have to use different mechanisms to regulate pregnancy, libido, the response to stress, kidney function, inflammation, and the development of male and female characteristics at puberty," Thornton said.

      The findings were published online June 24 in the Proceedings of the National Academy of Sciences.

      Understanding how the genetic code of a protein determines its functions would allow biochemists to better design drugs and predict the effects of mutations on disease. Thornton said the discovery shows how evolutionary analysis of proteins' histories can advance this goal, Before the group's work, it was not previously known how the various steroid receptors in modern species distinguish estrogens from other hormones.

      The team, which included researchers from the University of Oregon, Emory University and the Scripps Research Institute, studied the evolution of a family of proteins called steroid hormone receptors, which mediate the effects of hormones on reproduction, development and physiology. Without receptor proteins, these hormones cannot affect the body's cells.

      Thornton's group traced how the ancestor of the entire receptor family—which recognized only estrogens—evolved into descendant proteins capable of recognizing other steroid hormones, such as testosterone, progesterone and the stress hormone cortisol.

      To do so, the group used a gene "resurrection" strategy. They first inferred the genetic sequences of ancient receptor proteins, using computational methods to work their way back up the tree of life from a database of hundreds of present-day receptor sequences. They then biochemically synthesized these ancient DNA sequences and used molecular assays to determine the receptors' sensitivity to various hormones.

      Thornton's team narrowed down the time range during which the capacity to recognize non-estrogen steroids evolved, to a period about 500 million years ago, before the dawn of vertebrate animals on Earth. They then identified the most important mutations that occurred during that interval by introducing them into the reconstructed ancestral proteins. By measuring how the mutations affected the receptor's structure and function, the team could re-create ancient molecular evolution in the laboratory.

      They found that just two changes in the ancient receptor's gene sequence caused a 70,000-fold shift in preference away from estrogens toward other steroid hormones. The researchers also used biophysical techniques to identify the precise atomic-level mechanisms by which the mutations affected the protein's functions. Although only a few atoms in the protein were changed, this radically rewired the network of interactions between the receptor and the hormone, leading to a massive change in function.

      "Our findings show that new molecular functions can evolve by sudden large leaps due to a few tiny changes in the genetic code," Thornton said. He pointed out that, along with the two key changes in the receptor, additional mutations, the precise effects of which are not yet known, were necessary for the full effects of hormone signaling on the body to evolve.

      More information: Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors, www.pnas.org/cgi/doi/10.1073/pnas.1303930110

      Provided by University of Chicago Medical Center

      "Resurrecting ancient proteins, team finds just two mutations set stage for evolution of modern hormone signaling." June 24th, 2013. http://phys.org/news/2013-06-resurrecting-ancient-proteins-team-mutations.html

      Posted by
      Robert Karl Stonjek



    • james kohl
      Use of the word mutation in the context of nutrient-dependent pheromone-controlled adaptive evolution of hormone-organized and hormone-activated behavior is
      Message 2 of 10 , Jun 25, 2013
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        Use of the word 'mutation' in the context of nutrient-dependent pheromone-controlled adaptive evolution of hormone-organized and hormone-activated behavior is merely an attestation to a long-standing misrepresentation of cause and effect. Clearly, mutated genes are not responsible for adaptively evolved sex differences. Pheromonal communication in microbes set the stage for hormone signaling in multicellular organisms. Only a fool would suggest that mutations are responsible for genetic changes manifested in sex differences in hormones.

         
        James V. Kohl
        Medical laboratory scientist (ASCP)
        Independent researcher
        Kohl, J.V. (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors. Socioaffective Neuroscience & Psychology, 2: 17338.


        From: Edgar Owen <edgarowen@...>
        To: evolutionary-psychology@yahoogroups.com
        Sent: Tuesday, June 25, 2013 7:07 AM
        Subject: Re: [evol-psych] News: Resurrecting ancient proteins, team finds just two mutations set stage for evolution of modern hormone signaling

         
        O my God, more evidence of MUTATIONS causing genetic change! As if there wasn't overwhelming evidence of it already....

        Kohl must be biting his tongue!

        Edgar



        On Jun 24, 2013, at 9:34 PM, Robert Karl Stonjek wrote:

         


        Resurrecting ancient proteins, team finds just two mutations set stage for evolution of modern hormone signaling

        June 24th, 2013 in Biology / Evolution

        Evolution, it seems, sometimes jumps instead of crawls. A research team led by a University of Chicago scientist has discovered two key mutations that sparked a hormonal revolution 500 million years ago.
        In a feat of "molecular time travel," the researchers resurrected and analyzed the functions of the ancestors of genes that play key roles in modern human reproduction, development, immunity and cancer. By re-creating the same DNA changes that occurred during those genes' ancient history, the team showed that two mutations set the stage for hormones like estrogen, testosterone and cortisol to take on their crucial present-day roles.
        "Changes in just two letters of the genetic code in our deep evolutionary past caused a massive shift in the function of one protein and set in motion the evolution of our present-day hormonal and reproductive systems," said Joe Thornton, PhD, professor of human genetics and ecology & evolution at the University of Chicago, who led the study.
        "If those two mutations had not happened, our bodies today would have to use different mechanisms to regulate pregnancy, libido, the response to stress, kidney function, inflammation, and the development of male and female characteristics at puberty," Thornton said.
        The findings were published online June 24 in the Proceedings of the National Academy of Sciences.
        Understanding how the genetic code of a protein determines its functions would allow biochemists to better design drugs and predict the effects of mutations on disease. Thornton said the discovery shows how evolutionary analysis of proteins' histories can advance this goal, Before the group's work, it was not previously known how the various steroid receptors in modern species distinguish estrogens from other hormones.
        The team, which included researchers from the University of Oregon, Emory University and the Scripps Research Institute, studied the evolution of a family of proteins called steroid hormone receptors, which mediate the effects of hormones on reproduction, development and physiology. Without receptor proteins, these hormones cannot affect the body's cells.
        Thornton's group traced how the ancestor of the entire receptor family—which recognized only estrogens—evolved into descendant proteins capable of recognizing other steroid hormones, such as testosterone, progesterone and the stress hormone cortisol.
        To do so, the group used a gene "resurrection" strategy. They first inferred the genetic sequences of ancient receptor proteins, using computational methods to work their way back up the tree of life from a database of hundreds of present-day receptor sequences. They then biochemically synthesized these ancient DNA sequences and used molecular assays to determine the receptors' sensitivity to various hormones.
        Thornton's team narrowed down the time range during which the capacity to recognize non-estrogen steroids evolved, to a period about 500 million years ago, before the dawn of vertebrate animals on Earth. They then identified the most important mutations that occurred during that interval by introducing them into the reconstructed ancestral proteins. By measuring how the mutations affected the receptor's structure and function, the team could re-create ancient molecular evolution in the laboratory.
        They found that just two changes in the ancient receptor's gene sequence caused a 70,000-fold shift in preference away from estrogens toward other steroid hormones. The researchers also used biophysical techniques to identify the precise atomic-level mechanisms by which the mutations affected the protein's functions. Although only a few atoms in the protein were changed, this radically rewired the network of interactions between the receptor and the hormone, leading to a massive change in function.
        "Our findings show that new molecular functions can evolve by sudden large leaps due to a few tiny changes in the genetic code," Thornton said. He pointed out that, along with the two key changes in the receptor, additional mutations, the precise effects of which are not yet known, were necessary for the full effects of hormone signaling on the body to evolve.
        More information: Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors, www.pnas.org/cgi/doi/10.1073/pnas.1303930110
        Provided by University of Chicago Medical Center
        "Resurrecting ancient proteins, team finds just two mutations set stage for evolution of modern hormone signaling." June 24th, 2013. http://phys.org/news/2013-06-resurrecting-ancient-proteins-team-mutations.html
        Posted by
        Robert Karl Stonjek




      • james kohl
        Abstract excerpt: Here we show that this shift in function was driven primarily by two historical amino acid changes, which caused a ∼70,000-fold change in
        Message 3 of 10 , Jun 25, 2013
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          Abstract excerpt: "Here we show that this shift in function was driven primarily by two historical amino acid changes, which caused a ∼70,000-fold change in the ancestral protein’s specificity."

          JK: The amino acid changes are nutrient-dependent. Pheromone control of the changes is required for epistasis.
           
          James V. Kohl
          Medical laboratory scientist (ASCP)
          Independent researcher
          Kohl, J.V. (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors. Socioaffective Neuroscience & Psychology, 2: 17338.


          From: Robert Karl Stonjek <stonjek@...>
          To: Evolutionary-Psychology <evolutionary-psychology@yahoogroups.com>; Evolutionary Psychology News <evol_psch_news@yahoogroups.com>
          Sent: Monday, June 24, 2013 9:34 PM
          Subject: [evol-psych] News: Resurrecting ancient proteins, team finds just two mutations set stage for evolution of modern hormone signaling

           

          Resurrecting ancient proteins, team finds just two mutations set stage for evolution of modern hormone signaling

          June 24th, 2013 in Biology / Evolution
          Evolution, it seems, sometimes jumps instead of crawls. A research team led by a University of Chicago scientist has discovered two key mutations that sparked a hormonal revolution 500 million years ago.
          In a feat of "molecular time travel," the researchers resurrected and analyzed the functions of the ancestors of genes that play key roles in modern human reproduction, development, immunity and cancer. By re-creating the same DNA changes that occurred during those genes' ancient history, the team showed that two mutations set the stage for hormones like estrogen, testosterone and cortisol to take on their crucial present-day roles.
          "Changes in just two letters of the genetic code in our deep evolutionary past caused a massive shift in the function of one protein and set in motion the evolution of our present-day hormonal and reproductive systems," said Joe Thornton, PhD, professor of human genetics and ecology & evolution at the University of Chicago, who led the study.
          "If those two mutations had not happened, our bodies today would have to use different mechanisms to regulate pregnancy, libido, the response to stress, kidney function, inflammation, and the development of male and female characteristics at puberty," Thornton said.
          The findings were published online June 24 in the Proceedings of the National Academy of Sciences.
          Understanding how the genetic code of a protein determines its functions would allow biochemists to better design drugs and predict the effects of mutations on disease. Thornton said the discovery shows how evolutionary analysis of proteins' histories can advance this goal, Before the group's work, it was not previously known how the various steroid receptors in modern species distinguish estrogens from other hormones.
          The team, which included researchers from the University of Oregon, Emory University and the Scripps Research Institute, studied the evolution of a family of proteins called steroid hormone receptors, which mediate the effects of hormones on reproduction, development and physiology. Without receptor proteins, these hormones cannot affect the body's cells.
          Thornton's group traced how the ancestor of the entire receptor family—which recognized only estrogens—evolved into descendant proteins capable of recognizing other steroid hormones, such as testosterone, progesterone and the stress hormone cortisol.
          To do so, the group used a gene "resurrection" strategy. They first inferred the genetic sequences of ancient receptor proteins, using computational methods to work their way back up the tree of life from a database of hundreds of present-day receptor sequences. They then biochemically synthesized these ancient DNA sequences and used molecular assays to determine the receptors' sensitivity to various hormones.
          Thornton's team narrowed down the time range during which the capacity to recognize non-estrogen steroids evolved, to a period about 500 million years ago, before the dawn of vertebrate animals on Earth. They then identified the most important mutations that occurred during that interval by introducing them into the reconstructed ancestral proteins. By measuring how the mutations affected the receptor's structure and function, the team could re-create ancient molecular evolution in the laboratory.
          They found that just two changes in the ancient receptor's gene sequence caused a 70,000-fold shift in preference away from estrogens toward other steroid hormones. The researchers also used biophysical techniques to identify the precise atomic-level mechanisms by which the mutations affected the protein's functions. Although only a few atoms in the protein were changed, this radically rewired the network of interactions between the receptor and the hormone, leading to a massive change in function.
          "Our findings show that new molecular functions can evolve by sudden large leaps due to a few tiny changes in the genetic code," Thornton said. He pointed out that, along with the two key changes in the receptor, additional mutations, the precise effects of which are not yet known, were necessary for the full effects of hormone signaling on the body to evolve.
          More information: Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors, www.pnas.org/cgi/doi/10.1073/pnas.1303930110
          Provided by University of Chicago Medical Center
          "Resurrecting ancient proteins, team finds just two mutations set stage for evolution of modern hormone signaling." June 24th, 2013. http://phys.org/news/2013-06-resurrecting-ancient-proteins-team-mutations.html
          Posted by
          Robert Karl Stonjek


        • anonymous_9001
          What nutrient causes what change through what mechanism using what pathway with which enzyme(s)? Until you can answer that, you ve explained nothing. You ve
          Message 4 of 10 , Jun 25, 2013
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            What nutrient causes what change through what mechanism using what pathway with which enzyme(s)?

            Until you can answer that, you've explained nothing. You've yet to describe any mechanism in your papers that make genomic changes.

            "Chromatin remodeling? Epigenetic. Does not alter base sequence at all. All it
            does is change how the genome is packaged to regulate access of transcription
            factors and RNA polymerases. Does not alter genome sequence.

            Silencing? Epigenetic. Silencing can be a result of chromatin remodeling,
            production of repressors/breakdown of activators, RNA interference, etc. Does
            not alter genome sequence.

            Alternate splicing? Epigenetic. Splicing is post-translational. Does not alter
            genome sequence."

            ""Reversible switching between EPIGENETIC states..."


            "Me: You still have not shown how your model accounts for observable GENOMIC changes.

            JK: Of course I have Mr. or Mrs. anonymous_9001. I have made it perfectly clear that the epigenetic landscape becomes the physical landscape of DNA via the effects of olfactory/pheromonal input associated with food odors and social odors on the microRNA/messenger RNA balance and alterations in the thermodynamic control of protein biosynthesis and degradation, which leads to differences in stochastic gene expression. Why don't you pay attention to what I have detailed, and stop trying to convince others that I have not shown how my model accounts for observable GENOMIC changes because you cannot grasp the complexity of the model and prefer to believe that mutations are somehow involved in adaptive evolution via ecological, social, neurogenic, and socio-cognitive niche construction. Is there a model that shows how mutations account for observable GENOMIC changes?

            I asked: Do you understand why people exemplify facts by using model organisms? Did you make any attempt at all to understand " Reversible switching between epigenetic states in honeybee behavioral
            subcastes" http://dx.doi.org/10.1038/nn.3218> which are obviously nutrient-dependent and pheromone-controlled. What kind of idiot says "You still have not shown how your model accounts for observable GENOMIC changes." -- after it is perfectly clear that I have done precisely that in species from microbes to man?"

            Epigenetic processes DO NOT MAKE GENOME SEQUENCE CHANGES. Your model has never explained how genomic changes are made and never will. This is a fatal flaw in your model, as it directly contradicts observed evidence.

            --- In evolutionary-psychology@yahoogroups.com, james kohl <jvkohl@...> wrote:

            >
            > JK: The amino acid changes are nutrient-dependent. Pheromone control of the changes is required for epistasis.
            >
            >  
            > James V. Kohl
            > Medical laboratory scientist (ASCP)
            > Independent researcher
            > Kohl, J.V. (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors. Socioaffective Neuroscience & Psychology, 2: 17338.
          • james kohl
            You have not identified yourself as someone with the minimal intelligence required to understand anything I have written. You have also not commented on
            Message 5 of 10 , Jun 25, 2013
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              You have not identified yourself as someone with the minimal intelligence required to understand anything I have written. You have also not commented on anything included in my published works.

               
              James V. Kohl
              Medical laboratory scientist (ASCP)
              Independent researcher
              Kohl, J.V. (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors. Socioaffective Neuroscience & Psychology, 2: 17338.


              From: anonymous_9001 <anonymous_9001@...>
              To: evolutionary-psychology@yahoogroups.com
              Sent: Tuesday, June 25, 2013 4:30 PM
              Subject: [evol-psych] Re: News: Resurrecting ancient proteins, team finds just two mutations set stage for evolution of modern hormone signaling

               
              What nutrient causes what change through what mechanism using what pathway with which enzyme(s)?

              Until you can answer that, you've explained nothing. You've yet to describe any mechanism in your papers that make genomic changes.

              "Chromatin remodeling? Epigenetic. Does not alter base sequence at all. All it
              does is change how the genome is packaged to regulate access of transcription
              factors and RNA polymerases. Does not alter genome sequence.

              Silencing? Epigenetic. Silencing can be a result of chromatin remodeling,
              production of repressors/breakdown of activators, RNA interference, etc. Does
              not alter genome sequence.

              Alternate splicing? Epigenetic. Splicing is post-translational. Does not alter
              genome sequence."

              ""Reversible switching between EPIGENETIC states..."

              "Me: You still have not shown how your model accounts for observable GENOMIC changes.

              JK: Of course I have Mr. or Mrs. anonymous_9001. I have made it perfectly clear that the epigenetic landscape becomes the physical landscape of DNA via the effects of olfactory/pheromonal input associated with food odors and social odors on the microRNA/messenger RNA balance and alterations in the thermodynamic control of protein biosynthesis and degradation, which leads to differences in stochastic gene expression. Why don't you pay attention to what I have detailed, and stop trying to convince others that I have not shown how my model accounts for observable GENOMIC changes because you cannot grasp the complexity of the model and prefer to believe that mutations are somehow involved in adaptive evolution via ecological, social, neurogenic, and socio-cognitive niche construction. Is there a model that shows how mutations account for observable GENOMIC changes?

              I asked: Do you understand why people exemplify facts by using model organisms? Did you make any attempt at all to understand " Reversible switching between epigenetic states in honeybee behavioral
              subcastes" http://dx.doi.org/10.1038/nn.3218> which are obviously nutrient-dependent and pheromone-controlled. What kind of idiot says "You still have not shown how your model accounts for observable GENOMIC changes." -- after it is perfectly clear that I have done precisely that in species from microbes to man?"

              Epigenetic processes DO NOT MAKE GENOME SEQUENCE CHANGES. Your model has never explained how genomic changes are made and never will. This is a fatal flaw in your model, as it directly contradicts observed evidence.

              --- In evolutionary-psychology@yahoogroups.com, james kohl <jvkohl@...> wrote:

              >
              > JK: The amino acid changes are nutrient-dependent. Pheromone control of the changes is required for epistasis.
              >
              >  
              > James V. Kohl
              > Medical laboratory scientist (ASCP)
              > Independent researcher
              > Kohl, J.V. (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors. Socioaffective Neuroscience & Psychology, 2: 17338.



            • anonymous_9001
              It s a very simple question that you either refuse to answer or cannot answer. Since you can t bring forth a logical reason as to why you refuse to answer,
              Message 6 of 10 , Jun 25, 2013
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                It's a very simple question that you either refuse to answer or cannot answer. Since you can't bring forth a logical reason as to why you refuse to answer, that leaves only one conclusion.

                --- In evolutionary-psychology@yahoogroups.com, james kohl <jvkohl@...> wrote:
                >
                > You have not identified yourself as someone with the minimal intelligence required to understand anything I have written. You have also not commented on anything included in my published works.
                >
                >
                >  
                > James V. Kohl
                > Medical laboratory scientist (ASCP)
                > Independent researcher
                > Kohl, J.V. (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors. Socioaffective Neuroscience & Psychology, 2: 17338.
              • anonymous_9001
                Also, you spend a lot of time avoiding questions under the guise of you wouldn t understand anyway, so why would I explain myself? It shouldn t be all that
                Message 7 of 10 , Jun 25, 2013
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                  Also, you spend a lot of time avoiding questions under the guise of "you wouldn't understand anyway, so why would I explain myself?"

                  It shouldn't be all that taxing to type up an explanation, so what harm is there in putting it out there regardless? Why does it matter if the possibility of people not understanding it exists? That's a cop out and you know it. Unless, of course, you're incapable of explaining it in the first place due to your own lack of understanding.
                • Edgar Owen
                  Anon, Kohl did slip a few times and state his model in simple English but he resists doing it because when stated simply its absurdity is apparent. A few
                  Message 8 of 10 , Jun 26, 2013
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                    Anon,

                    Kohl did slip a few times and state his "model" in simple English but he resists doing it because when stated simply its absurdity is apparent.

                    A few paraphrases of the Kohl "model" when he's slipped and stated what he really believes in simple English...

                    The universe was created by God the Creator
                    Olfaction is by far the most important sense even in humans.
                    The book of Genesis is his (Kohl's) microbiology textbook (admitting he never took a college course in biology because of his "learning disablity [sic]")
                    The universe exists because if it didn't it wouldn't (Kohl's logico-psycho theory of the universe)
                    All genetic changes are caused not by mutations but by the creator God tinkering with his creation.
                    All changes to the genome responsible for the evolution of new species are caused by what individual animals eat and smell.
                    Anyone who doesn't agree is a FOOL!
                    :-)

                    There are others even more ludicrous  ...

                    Edgar






                    On Jun 25, 2013, at 11:10 PM, anonymous_9001 wrote:

                     

                    Also, you spend a lot of time avoiding questions under the guise of "you wouldn't understand anyway, so why would I explain myself?"

                    It shouldn't be all that taxing to type up an explanation, so what harm is there in putting it out there regardless? Why does it matter if the possibility of people not understanding it exists? That's a cop out and you know it. Unless, of course, you're incapable of explaining it in the first place due to your own lack of understanding.


                  • james kohl
                    From: Edgar Owen   Anon, The universe exists because if it didn t it wouldn t (Kohl s logico-psycho theory of the universe) Edgar wrote:
                    Message 9 of 10 , Jun 26, 2013
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                      From: Edgar Owen <edgarowen@...>

                       
                      Anon,

                      The universe exists because if it didn't it wouldn't (Kohl's logico-psycho theory of the universe)

                      Edgar wrote: "... the physical universe is a complete consistent logico-mathematical system (if it wasn't it would tear itself apart and couldn't exist),...  He would like to attribute his nonsense to me, but clearly the logico-psycho theory of a universe that exists because if it didn't it wouldn't, is something only someone like Edgar (the antique dealer) would propose.
                      James V. Kohl
                      Medical laboratory scientist (ASCP)
                      Independent researcher
                      Kohl, J.V. (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors. Socioaffective Neuroscience & Psychology, 2: 17338.




                      On Jun 25, 2013, at 11:10 PM, anonymous_9001 wrote:

                       
                      Also, you spend a lot of time avoiding questions under the guise of "you wouldn't understand anyway, so why would I explain myself?"

                      It shouldn't be all that taxing to type up an explanation, so what harm is there in putting it out there regardless? Why does it matter if the possibility of people not understanding it exists? That's a cop out and you know it. Unless, of course, you're incapable of explaining it in the first place due to your own lack of understanding.




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