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1دورية أكاديمية
المؤلفون: BAYRİ, YAŞAR, ŞAHİN, YENER
المساهمون: Jin, Sheng Chih, Dong, Weilai, Kundishora, Adam J., Panchagnula, Shreyas, Moreno-De-Luca, Andres, Furey, Charuta G., Allocco, August A., Walker, Rebecca L., Nelson-Williams, Carol, Smith, Hannah, Dunbar, Ashley, Conine, Sierra, Lu, Qiongshi, Zeng, Xue, Sierant, Michael C., Knight, James R., Sullivan, William, Duy, Phan Q., DeSpenza, Tyrone, Reeves, Benjamin C., Karimy, Jason K., Marlier, Arnaud, Castaldi, Christopher, Tikhonova, Irina R., Li, Boyang, Pena, Helena Perez, Broach, James R., Kabachelor, Edith M., Ssenyonga, Peter, Hehnly, Christine, Ge, Li, Keren, Boris, Timberlake, Andrew T., Goto, June, Mangano, Francesco T., Johnston, James M., Butler, William E., Warf, Benjamin C., Smith, Edward R., Schiff, Steven J., Limbrick, David D., Jr., Heuer, Gregory, Jackson, Eric M., Iskandar, Bermans J., Mane, Shrikant, Haider, Shozeb, Guclu, Bulent, Bayri, Yasar, Sahin, Yener, Duncan, Charles C., Apuzzo, Michael L. J., DiLuna, Michael L., Hoffman, Ellen J., Sestan, Nenad, Ment, Laura R., Alper, Seth L., Bilguvar, Kaya, Geschwind, Daniel H., Gunel, Murat, Lifton, Richard P., Kahle, Kristopher T.
مصطلحات موضوعية: DE-NOVO MUTATION, VENTRICULAR ZONE DISRUPTION, COWDEN-SYNDROME, PTEN, SPECTRUM, AUTISM, CHILDREN, PATHWAY, RARE, EXPRESSION
الوصف: Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to similar to 22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.
وصف الملف: application/pdf
العلاقة: NATURE MEDICINE; https://hdl.handle.net/11424/243170Test; WOS:000579706700002
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2دورية أكاديمية
المؤلفون: Montserrat Guerra, Maria, Henzi, Roberto, Ortloff Trautmann, Alexander, Lichtin, Nicole, Vio, Karin, Jimenez, Antonio J., Dolores Dominguez Pinos, Maria, Gonzalez, Cesar, Clara Jara, Maria, Hinostroza, Fernando, Rodriguez, Sara, Jara, Maryoris, Ortega, Eduardo, Guerra, Francisco, Sival, Deborah A., den Dunnen, Wilfred F. A., Perez Figares, Jose M., McAllister, James P., Johanson, Conrad E., Rodriguez, Esteban M.
المصدر: JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
مصطلحات موضوعية: Cerebrospinal fluid, Congenital hydrocephalus, HTx rat, Human, Junction pathology, Neural stem cells, Neurospheres, Ventricular zone disruption
الوصف: Fetal-onset hydrocephalus affects 1 to 3 per 1,000 live births. It is not only a disorder of cerebrospinal fluid dynamics but also a brain disorder that corrective surgery does not ameliorate. We hypothesized that cell junction abnormalities of neural stem cells (NSCs) lead to the inseparable phenomena of fetal-onset hydrocephalus and abnormal neurogenesis. We used bromodeoxyuridine labeling, immunocytochemistry, electron microscopy, and cell culture to study the telencephalon of hydrocephalic HTx rats and correlated our findings with those in human hydrocephalic and nonhydrocephalic human fetal brains (n = 12 each). Our results suggest that abnormal expression of the intercellular junction proteins N-cadherin and connexin-43 in NSC leads to 1) disruption of the ventricular and subventricular zones, loss of NSCs and neural progenitor cells; and 2) abnormalities in neurogenesis such as periventricular heterotopias and abnormal neuroblast migration. In HTx rats, the disrupted NSC and progenitor cells are shed into the cerebrospinal fluid and can be grown into neurospheres that display intercellular junction abnormalities similar to those of NSC of the disrupted ventricular zone; nevertheless, they maintain their potential for differentiating into neurons and glia. These NSCs can be used to investigate cellular and molecular mechanisms underlying this condition, thereby opening the avenue for stem cell therapy.
العلاقة: JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY,Vol.74,653-671,2015; http://repositoriodigital.uct.cl/handle/10925/4028Test
الإتاحة: https://doi.org/10.1097/NEN.0000000000000203Test
http://repositoriodigital.uct.cl/handle/10925/4028Test -
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المؤلفون: William J. Sullivan, Bermans J. Iskandar, Yasar Bayri, James R. Knight, James M. Johnston, Michael L.J. Apuzzo, Kristopher T. Kahle, Boyang Li, Andrew T. Timberlake, Sheng Chih Jin, Steven J. Schiff, Shreyas Panchagnula, Rebecca L. Walker, Shozeb Haider, Li Ge, Daniel H. Geschwind, Hannah Smith, Richard P. Lifton, Seth L. Alper, Carol Nelson-Williams, Boris Keren, Christine Hehnly, Arnaud Marlier, Bulent Guclu, Laura R. Ment, Ellen J. Hoffman, Francesco T. Mangano, Xue Zeng, Edith Mbabazi Kabachelor, Kaya Bilguvar, August A Allocco, Ashley Dunbar, James R. Broach, Benjamin C. Warf, William E. Butler, Helena Perez Pena, Sierra B Conine, David D. Limbrick, Qiongshi Lu, Edward R. Smith, Jason K. Karimy, Christopher Castaldi, Eric M. Jackson, Yener Sahin, Murat Gunel, Adam J. Kundishora, Charles C. Duncan, Michael L. DiLuna, Shrikant Mane, Michael C. Sierant, Gregory G. Heuer, June Goto, Charuta G. Furey, Andres Moreno-De-Luca, Peter Ssenyonga, Weilai Dong, Nenad Sestan, Phan Q. Duy, Benjamin C. Reeves, Tyrone DeSpenza, Irina Tikhonova
المساهمون: Jin, Sheng Chih, Dong, Weilai, Kundishora, Adam J., Panchagnula, Shreyas, Moreno-De-Luca, Andres, Furey, Charuta G., Allocco, August A., Walker, Rebecca L., Nelson-Williams, Carol, Smith, Hannah, Dunbar, Ashley, Conine, Sierra, Lu, Qiongshi, Zeng, Xue, Sierant, Michael C., Knight, James R., Sullivan, William, Duy, Phan Q., DeSpenza, Tyrone, Reeves, Benjamin C., Karimy, Jason K., Marlier, Arnaud, Castaldi, Christopher, Tikhonova, Irina R., Li, Boyang, Pena, Helena Perez, Broach, James R., Kabachelor, Edith M., Ssenyonga, Peter, Hehnly, Christine, Ge, Li, Keren, Boris, Timberlake, Andrew T., Goto, June, Mangano, Francesco T., Johnston, James M., Butler, William E., Warf, Benjamin C., Smith, Edward R., Schiff, Steven J., Limbrick, David D., Jr., Heuer, Gregory, Jackson, Eric M., Iskandar, Bermans J., Mane, Shrikant, Haider, Shozeb, Guclu, Bulent, Bayri, Yasar, Sahin, Yener, Duncan, Charles C., Apuzzo, Michael L. J., DiLuna, Michael L., Hoffman, Ellen J., Sestan, Nenad, Ment, Laura R., Alper, Seth L., Bilguvar, Kaya, Geschwind, Daniel H., Gunel, Murat, Lifton, Richard P., Kahle, Kristopher T.
المصدر: Nat Med
مصطلحات موضوعية: EXPRESSION, 0301 basic medicine, Male, PTEN, Cell type, Neurogenesis, Ubiquitin-Protein Ligases, CHILDREN, Disease, VENTRICULAR ZONE DISRUPTION, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, Article, COWDEN-SYNDROME, Cerebral Ventricles, PATHWAY, Tripartite Motif Proteins, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, RARE, Neural Stem Cells, Pregnancy, Exome Sequencing, Medicine, Humans, Genetic Predisposition to Disease, Exome, AUTISM, Exome sequencing, Gliogenesis, SPECTRUM, Fetus, business.industry, Brain, General Medicine, medicine.disease, Neural stem cell, DE-NOVO MUTATION, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Female, business, Neuroglia, Ventriculomegaly, Transcription Factors, Hydrocephalus
الوصف: Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to similar to 22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa5ffd2d8f3b89a9eace21cef26b4737Test
https://europepmc.org/articles/PMC7871900Test/ -
4دورية أكاديمية
المؤلفون: Montserrat Guerra, Maria, Henzi, Roberto, Ortloff, Alexander, Lichtin, Nicole, Vio, Karin, Jimenez, Antonio J., Dolores Dominguez-Pinos, Maria, Gonzalez, Cesar, Clara Jara, Maria, Hinostroza, Fernando, Rodriguez, Sara, Jara, Maryoris, Ortega, Eduardo, Guerra, Francisco, Sival, Deborah A., den Dunnen, Wilfred F. A., Perez-Figares, Jose M., McAllister, James P., Johanson, Conrad E., Rodriguez, Esteban M.
المصدر: Montserrat Guerra , M , Henzi , R , Ortloff , A , Lichtin , N , Vio , K , Jimenez , A J , Dolores Dominguez-Pinos , M , Gonzalez , C , Clara Jara , M , Hinostroza , F , Rodriguez , S , Jara , M , Ortega , E , Guerra , F , Sival , D A , den Dunnen , W F A , Perez-Figares , J M , McAllister , J P , Johanson , C E & Rodriguez , E M 2015 , ' Cell Junction Pathology of Neural ....
مصطلحات موضوعية: Cerebrospinal fluid, Congenital hydrocephalus, HTx rat, Human, Junction pathology, Neural stem cells, Neurospheres, Ventricular zone disruption, ARNOLD-CHIARI MALFORMATION, CENTRAL-NERVOUS-SYSTEM, HUMAN FETAL EPENDYMA, SUBVENTRICULAR ZONE, ADHERENS JUNCTIONS, NEUROBLAST MIGRATION, CORTICAL DEVELOPMENT, CEREBROSPINAL-FLUID, BLOOD-VESSELS
الوصف: Fetal-onset hydrocephalus affects 1 to 3 per 1,000 live births. It is not only a disorder of cerebrospinal fluid dynamics but also a brain disorder that corrective surgery does not ameliorate. We hypothesized that cell junction abnormalities of neural stem cells (NSCs) lead to the inseparable phenomena of fetal-onset hydrocephalus and abnormal neurogenesis. We used bromodeoxyuridine labeling, immunocytochemistry, electron microscopy, and cell culture to study the telencephalon of hydrocephalic HTx rats and correlated our findings with those in human hydrocephalic and nonhydrocephalic human fetal brains (n = 12 each). Our results suggest that abnormal expression of the intercellular junction proteins N-cadherin and connexin-43 in NSC leads to 1) disruption of the ventricular and subventricular zones, loss of NSCs and neural progenitor cells; and 2) abnormalities in neurogenesis such as periventricular heterotopias and abnormal neuroblast migration. In HTx rats, the disrupted NSC and progenitor cells are shed into the cerebrospinal fluid and can be grown into neurospheres that display intercellular junction abnormalities similar to those of NSC of the disrupted ventricular zone; nevertheless, they maintain their potential for differentiating into neurons and glia. These NSCs can be used to investigate cellular and molecular mechanisms underlying this condition, thereby opening the avenue for stem cell therapy.
الإتاحة: https://doi.org/10.1097/NEN.0000000000000203Test
https://hdl.handle.net/11370/1f9af1fe-c8f1-4e16-9e90-58a6262eab62Test
https://research.rug.nl/en/publications/1f9af1fe-c8f1-4e16-9e90-58a6262eab62Test