Glia-derived axonal growth inhibitory proteins limit functional repair following damage to the adult cen- tral nervous system （CNS）. Nogo proteins, myelin-as- sociated glycoprotein （MAG）, oligodendrocyte myelin gl...Glia-derived axonal growth inhibitory proteins limit functional repair following damage to the adult cen- tral nervous system （CNS）. Nogo proteins, myelin-as- sociated glycoprotein （MAG）, oligodendrocyte myelin glycoprotein （OMgp） and B lymphocyte stimulator （BLyS）, are 4 inhibitors that commonly interact with the neuronal receptor, Nogo receptor-1 （NgR1）, lead- ing to inhibition of axonal growth. Here, we demon- strate that lateral olfactory tract usher substance （LOTUS） binds to NgR1 and blocks the binding of all four ligands to NgR1, resulting in the suppression of axonal growth inhibition induced by these NgR1 li- gands. LOTUS allows neurons to overcome NgRl-me- diated axonal growth inhibition, raising the possibility that LOTUS may be useful in future therapeutic ap- proaches as an endogenous potent inhibitor of NgR1 for promoting neuronal regeneration.展开更多
It is well known that primates,including humans,hardly recover motor function after spinal cord injury（SCI）when compared with non-primate mammals such as rodents.This limited functional recovery is in part due to a ...It is well known that primates,including humans,hardly recover motor function after spinal cord injury（SCI）when compared with non-primate mammals such as rodents.This limited functional recovery is in part due to a non-permissive environment of the central nervous system（CNS）inhibiting axonal regrowth.展开更多
Acquired drug resistance is the major reason why patients fail to respond to cancer therapies.It is a challenging task to deter.mine the tipping point of endocrine resistance and detect the associated molecules.Derive...Acquired drug resistance is the major reason why patients fail to respond to cancer therapies.It is a challenging task to deter.mine the tipping point of endocrine resistance and detect the associated molecules.Derived from new systems biology theory, the dynamic network biomarker (DNB) method is designed to quantitatively identify the tipping point of a drastic system transition and can theoretically identify DNB genes that play key roles in acquiring drug resistance.We analyzed time-course mRNA sequence data generated from the tamoxifen-treated estrogen receptor (ER)-positive MCF-7 cell line, and identified the tipping point of endocrine resistance with its leading molecules.The results show that there is interplay between gene mutations and DNB genes, in which the accumulated mutations eventually affect the DNB genes that subsequently cause the change of transcriptional landscape, enabling full-blown drug resistance. Survival analyses based on clinical datasets validated that the DNB genes were associated with the poor survival of breast cancer patients.The results provided the detection for the pre-resistance state or early signs of endocrine resistance.Our predictive method may greatly benefit the scheduling of treatments for complex diseases in which patients are exposed to considerably different drugs and may become drug resistant.展开更多
基金supported by a grant-in-aid from the Ministry of Education,Culture,Sports,Science and Technology of Japangrants for Research and Development project of Yokohama City University
文摘Glia-derived axonal growth inhibitory proteins limit functional repair following damage to the adult cen- tral nervous system （CNS）. Nogo proteins, myelin-as- sociated glycoprotein （MAG）, oligodendrocyte myelin glycoprotein （OMgp） and B lymphocyte stimulator （BLyS）, are 4 inhibitors that commonly interact with the neuronal receptor, Nogo receptor-1 （NgR1）, lead- ing to inhibition of axonal growth. Here, we demon- strate that lateral olfactory tract usher substance （LOTUS） binds to NgR1 and blocks the binding of all four ligands to NgR1, resulting in the suppression of axonal growth inhibition induced by these NgR1 li- gands. LOTUS allows neurons to overcome NgRl-me- diated axonal growth inhibition, raising the possibility that LOTUS may be useful in future therapeutic ap- proaches as an endogenous potent inhibitor of NgR1 for promoting neuronal regeneration.
基金supported by a grant-in-aid from the Ministry of Education,Culture,Sports,Science and Technology of Japangrants for Research and Development project of Yokohama City University
文摘It is well known that primates,including humans,hardly recover motor function after spinal cord injury（SCI）when compared with non-primate mammals such as rodents.This limited functional recovery is in part due to a non-permissive environment of the central nervous system（CNS）inhibiting axonal regrowth.
基金This work was supported by grants from the National Key R&D Program of China (2017YFA0505500)Strategic Priority Research Program of the Chinese Academy of Sciences (XDBl3040700)+6 种基金the National Natural Science Foundation of China (11771152,91529303,31771476,31571363,31771469,91530320,61134013,81573023,81501203,and 11326035)Pearl River Science and Technology Nova Program of Guangzhou (201610010029)FISRT,Aihara Innovative Mathematical Modeling Project from Cabinet Office,JapanFundamental Research Funds for the Central Universities (2017ZD095)JSPS KAKENHI (15H05707)Grant-in-Aid for Scientific Research on Innovative Areas (3901) and SPS KAKENHI (15KT0084,17H06299,17H06302,and 18H04031)RIKEN Epigenome and Single Cell Project Grants to M.O.-H.This work was performed in part under the International Cooperative Research Program of Institute for Protein Research,Osaka University (ICRa-17-01 to L.C.and M.O.-H.).
文摘Acquired drug resistance is the major reason why patients fail to respond to cancer therapies.It is a challenging task to deter.mine the tipping point of endocrine resistance and detect the associated molecules.Derived from new systems biology theory, the dynamic network biomarker (DNB) method is designed to quantitatively identify the tipping point of a drastic system transition and can theoretically identify DNB genes that play key roles in acquiring drug resistance.We analyzed time-course mRNA sequence data generated from the tamoxifen-treated estrogen receptor (ER)-positive MCF-7 cell line, and identified the tipping point of endocrine resistance with its leading molecules.The results show that there is interplay between gene mutations and DNB genes, in which the accumulated mutations eventually affect the DNB genes that subsequently cause the change of transcriptional landscape, enabling full-blown drug resistance. Survival analyses based on clinical datasets validated that the DNB genes were associated with the poor survival of breast cancer patients.The results provided the detection for the pre-resistance state or early signs of endocrine resistance.Our predictive method may greatly benefit the scheduling of treatments for complex diseases in which patients are exposed to considerably different drugs and may become drug resistant.
