This paper presents a new explanatory model for schizophrenia based upon philosophical, molecular and neurobiological hypotheses as well as on years of experience in observing and treating these patients. To start wit...This paper presents a new explanatory model for schizophrenia based upon philosophical, molecular and neurobiological hypotheses as well as on years of experience in observing and treating these patients. To start with, a novel interpretation of the Hegelian concept of mediation is presented. Mediation is defined as the rejection of non-realizable programs, such as thoughts and ideas, at a certain point in time in the evolution of a living system. Whenever a system treats non-realizable programs as if they were realizable, its ability to “test the reality” is lost, and consequently a loss of ego-boundaries may occur. On the molecular level, I will try to show how “non-splicing” of introns during the mRNA splicing process is equivalent to a loss of the rejection function corresponding to mediation. At the cellular level in the brain, mediation can be explained in terms of glial-neuronal interactions. Glia exert a spatio-temporal boundary setting function determining the grouping of neurons into functional units. Mutations in genes that result in non-splicing of introns can produce truncated (“chimeric”) neurotransmitter receptors. I propose that such dysfunctional receptors are generated in glial cells and that they cannot interact properly with their cognate neurotransmitters. The glia will then lose their inhibitory-rejecting function with respect to the information processing within neuronal networks. This loss of glial boundary setting could be an explanation for the loss of ego or body boundaries in schizophrenia. Pertinent examples of case studies are given attempting to deduce the main symptoms of schizophrenia from the proposed hypothesis. Some implications for the design of delusional robots are also discussed. Finally, the evolutionary potency of non-coding introns is philosophically interpreted that schizophrenics may be “too soon on earth”.展开更多
IgG4-related disease(IgG4-RD)is a chronic immune-mediated disorder characterized by progressive tissue fibrosis.Current treatments like glucocorticoids and rituximab focus on remission,yet reversing fibrosis remains c...IgG4-related disease(IgG4-RD)is a chronic immune-mediated disorder characterized by progressive tissue fibrosis.Current treatments like glucocorticoids and rituximab focus on remission,yet reversing fibrosis remains challenging[1,2].While interactions between immune cells and fibroblasts are known to drive fibrosis,the role of epithelial cells remains poorly understood[1].展开更多
文摘This paper presents a new explanatory model for schizophrenia based upon philosophical, molecular and neurobiological hypotheses as well as on years of experience in observing and treating these patients. To start with, a novel interpretation of the Hegelian concept of mediation is presented. Mediation is defined as the rejection of non-realizable programs, such as thoughts and ideas, at a certain point in time in the evolution of a living system. Whenever a system treats non-realizable programs as if they were realizable, its ability to “test the reality” is lost, and consequently a loss of ego-boundaries may occur. On the molecular level, I will try to show how “non-splicing” of introns during the mRNA splicing process is equivalent to a loss of the rejection function corresponding to mediation. At the cellular level in the brain, mediation can be explained in terms of glial-neuronal interactions. Glia exert a spatio-temporal boundary setting function determining the grouping of neurons into functional units. Mutations in genes that result in non-splicing of introns can produce truncated (“chimeric”) neurotransmitter receptors. I propose that such dysfunctional receptors are generated in glial cells and that they cannot interact properly with their cognate neurotransmitters. The glia will then lose their inhibitory-rejecting function with respect to the information processing within neuronal networks. This loss of glial boundary setting could be an explanation for the loss of ego or body boundaries in schizophrenia. Pertinent examples of case studies are given attempting to deduce the main symptoms of schizophrenia from the proposed hypothesis. Some implications for the design of delusional robots are also discussed. Finally, the evolutionary potency of non-coding introns is philosophically interpreted that schizophrenics may be “too soon on earth”.
基金supported by the National Natural Science Foundation of China(82271848,823B2037,and 82471829)the Beijing Natural Science Foundation(7232113)+2 种基金the National High Level Hospital Clinical Research Funding(2022-PUMCH-C-006)the National Key Research and Development Program of China(2022YFC2703104)the Peking Union Medical College Hospital Young Reserve Talent Development Program(UHB12076)。
文摘IgG4-related disease(IgG4-RD)is a chronic immune-mediated disorder characterized by progressive tissue fibrosis.Current treatments like glucocorticoids and rituximab focus on remission,yet reversing fibrosis remains challenging[1,2].While interactions between immune cells and fibroblasts are known to drive fibrosis,the role of epithelial cells remains poorly understood[1].
