The Experts below are selected from a list of 34974 Experts worldwide ranked by ideXlab platform
D Mcdonald - One of the best experts on this subject based on the ideXlab platform.
-
pulmonary lymphangiectasia resulting from vascular endothelial growth factor c overexpression during a critical periodnovelty and significance
Circulation Research, 2014Co-Authors: Lichin Yao, Chiara Testini, Denis Tvorogov, Andrey Anisimov, Sara O Vargas, Peter Baluk, Bronislaw Pytowski, Lena Claessonwelsh, Kari Alitalo, D McdonaldAbstract:Rationale: Lymphatic vessels in the respiratory tract normally mature into a functional network during the neonatal period, but under some pathological conditions they can grow as enlarged, dilated sacs that result in the potentially lethal condition of pulmonary lymphangiectasia. Objective: We sought to determine whether overexpression of the lymphangiogenic growth factor (vascular endothelial growth factor-C [VEGF-C]) can promote lymphatic growth and maturation in the respiratory tract. Unexpectedly, Perinatal overexpression of VEGF-C in the respiratory epithelium led to a condition resembling human pulmonary lymphangiectasia, a life-threatening disorder of the newborn characterized by respiratory distress and the presence of widely dilated lymphatics. Methods and Results: Administration of doxycycline to Clara cell secretory protein-reverse tetracycline-controlled transactivator/tetracycline operator-VEGF-C double-transgenic mice during a critical period from embryonic day 15.5 to postnatal day 14 was accompanied by respiratory distress, chylothorax, pulmonary lymphangiectasia, and high mortality. Enlarged sac-like lymphatics were abundant near major airways, pulmonary vessels, and visceral pleura. Side-by-side comparison revealed morphological features similar to pulmonary lymphangiectasia in humans. The condition was milder in mice given doxycycline after age postnatal day 14 and did not develop after postnatal day 35. Mechanistic studies revealed that VEGF recptor (VEGFR)-3 alone drove lymphatic growth in adult mice, but both VEGFR-2 and VEGFR-3 were required for the Development of lymphangiectasia in neonates. VEGFR-2/VEGFR-3 heterodimers were more abundant in the dilated lymphatics, consistent with the involvement of both receptors. Despite the dependence of lymphangiectasia on VEGFR-2 and VEGFR-3, the condition was not reversed by blocking both receptors together or by withdrawing VEGF-C. Conclusions: The findings indicate that VEGF-C overexpression can induce pulmonary lymphangiectasia during a critical period in Perinatal Development.
-
pulmonary lymphangiectasia resulting from vegf c overexpression during a critical period
Circulation Research, 2014Co-Authors: Lichin Yao, Chiara Testini, Denis Tvorogov, Andrey Anisimov, Sara O Vargas, Peter Baluk, Bronislaw Pytowski, Lena Claessonwelsh, Kari Alitalo, D McdonaldAbstract:Rationale: Lymphatic vessels in the respiratory tract normally mature into a functional network during the neonatal period, but under some pathological conditions can grow as enlarged, dilated sacs that result in the potentially lethal condition of pulmonary lymphangiectasia. Objective: We sought to determine whether overexpression of the lymphangiogenic growth factor VEGF-C can promote lymphatic growth and maturation in the respiratory tract. Unexpectedly, Perinatal overexpression of VEGF-C in the respiratory epithelium led to a condition resembling human pulmonary lymphangiectasia, a life-threatening disorder of the newborn characterized by respiratory distress and the presence of widely dilated lymphatics. Methods and Results: Administration of doxycycline to CCSP-rtTA/tetO-VEGF-C double transgenic mice during a critical period from E15.5 to P14 was accompanied by respiratory distress, chylothorax, pulmonary lymphangiectasia, and high mortality. Enlarged sac-like lymphatics were abundant near major airways, pulmonary vessels, and visceral pleura. Side-by-side comparison revealed morphologic features similar to pulmonary lymphangiectasia in humans. The condition was milder in mice given doxycycline after age P14 and did not develop after P35. Mechanistic studies revealed that VEGFR-3 alone drove lymphatic growth in adult mice, but both VEGFR-2 and VEGFR-3 were required for the Development of lymphangiectasia in neonates. VEGFR-2/VEGFR-3 heterodimers were more abundant in the dilated lymphatics, consistent with the involvement of both receptors. Despite the dependence of lymphangiectasia on VEGFR-2 and VEGFR-3, the condition was not reversed by blocking both receptors together or by withdrawing VEGF-C. Conclusions: : The findings indicate that VEGF-C overexpression can induce pulmonary lymphangiectasia during a critical period in Perinatal Development.
Jianke Zhang - One of the best experts on this subject based on the ideXlab platform.
-
TRADD regulates Perinatal Development and adulthood survival in mice lacking RIPK1 and RIPK3
Nature Communications, 2019Co-Authors: John P. Dowling, Mohamed Alsabbagh, Christina Del Casale, Jianke ZhangAbstract:TRADD is an adaptor for TNFR1-induced apoptosis and NFκB activation. However, TRADD-deficient mice undergo normal Development and contain normal lymphoid populations, which contrasts with an embryonic defect in mice lacking FADD, the shared adaptor mediating apoptosis. Recent studies indicate FADD suppresses embryonic necroptosis mediated by RIPK1. TRADD was suggested to also mediate necroptosis. Here we report that targeting TRADD fails to rescue Fadd−/− embryos from necroptosis, and ablation of TRADD rescues Ripk1−/− mice from Perinatal lethality when RIPK3-mediated necroptosis is disabled. The resulting Ripk1−/−Ripk3−/−Tradd−/− mice survive until early adulthood, but die thereafter. A single allele of Tradd is optimal for survival of Ripk1−/−Ripk3−/−Tradd+/− mice. We show that TRADD plays a more dominating role in NFκB-signaling than RIPK1. While RIPK1 protects thymocytes from TNFα-induced apoptosis, TRADD promotes this process. The data demonstrate that TRADD is critical in Perinatal and adult mice lacking RIPK1 and RIPK3, which has not been appreciated in prior studies.
-
TRADD regulates Perinatal Development and adulthood survival in mice lacking RIPK1 and RIPK3
Nature Publishing Group, 2019Co-Authors: John P. Dowling, Mohamed Alsabbagh, Christina Del Casale, Zheng-gang Liu, Jianke ZhangAbstract:Programmed cell death regulates early Development but how various factors (for example, TRADD, FADD and RIPKs) regulate this is unclear. Here, the authors show that a single allele of Tradd is essential for survival, when both Ripk3 and Ripk1 are knocked out in mice, and RIPK1 protects thymocytes from TNF-induced apoptosis
Lichin Yao - One of the best experts on this subject based on the ideXlab platform.
-
pulmonary lymphangiectasia resulting from vascular endothelial growth factor c overexpression during a critical periodnovelty and significance
Circulation Research, 2014Co-Authors: Lichin Yao, Chiara Testini, Denis Tvorogov, Andrey Anisimov, Sara O Vargas, Peter Baluk, Bronislaw Pytowski, Lena Claessonwelsh, Kari Alitalo, D McdonaldAbstract:Rationale: Lymphatic vessels in the respiratory tract normally mature into a functional network during the neonatal period, but under some pathological conditions they can grow as enlarged, dilated sacs that result in the potentially lethal condition of pulmonary lymphangiectasia. Objective: We sought to determine whether overexpression of the lymphangiogenic growth factor (vascular endothelial growth factor-C [VEGF-C]) can promote lymphatic growth and maturation in the respiratory tract. Unexpectedly, Perinatal overexpression of VEGF-C in the respiratory epithelium led to a condition resembling human pulmonary lymphangiectasia, a life-threatening disorder of the newborn characterized by respiratory distress and the presence of widely dilated lymphatics. Methods and Results: Administration of doxycycline to Clara cell secretory protein-reverse tetracycline-controlled transactivator/tetracycline operator-VEGF-C double-transgenic mice during a critical period from embryonic day 15.5 to postnatal day 14 was accompanied by respiratory distress, chylothorax, pulmonary lymphangiectasia, and high mortality. Enlarged sac-like lymphatics were abundant near major airways, pulmonary vessels, and visceral pleura. Side-by-side comparison revealed morphological features similar to pulmonary lymphangiectasia in humans. The condition was milder in mice given doxycycline after age postnatal day 14 and did not develop after postnatal day 35. Mechanistic studies revealed that VEGF recptor (VEGFR)-3 alone drove lymphatic growth in adult mice, but both VEGFR-2 and VEGFR-3 were required for the Development of lymphangiectasia in neonates. VEGFR-2/VEGFR-3 heterodimers were more abundant in the dilated lymphatics, consistent with the involvement of both receptors. Despite the dependence of lymphangiectasia on VEGFR-2 and VEGFR-3, the condition was not reversed by blocking both receptors together or by withdrawing VEGF-C. Conclusions: The findings indicate that VEGF-C overexpression can induce pulmonary lymphangiectasia during a critical period in Perinatal Development.
-
pulmonary lymphangiectasia resulting from vegf c overexpression during a critical period
Circulation Research, 2014Co-Authors: Lichin Yao, Chiara Testini, Denis Tvorogov, Andrey Anisimov, Sara O Vargas, Peter Baluk, Bronislaw Pytowski, Lena Claessonwelsh, Kari Alitalo, D McdonaldAbstract:Rationale: Lymphatic vessels in the respiratory tract normally mature into a functional network during the neonatal period, but under some pathological conditions can grow as enlarged, dilated sacs that result in the potentially lethal condition of pulmonary lymphangiectasia. Objective: We sought to determine whether overexpression of the lymphangiogenic growth factor VEGF-C can promote lymphatic growth and maturation in the respiratory tract. Unexpectedly, Perinatal overexpression of VEGF-C in the respiratory epithelium led to a condition resembling human pulmonary lymphangiectasia, a life-threatening disorder of the newborn characterized by respiratory distress and the presence of widely dilated lymphatics. Methods and Results: Administration of doxycycline to CCSP-rtTA/tetO-VEGF-C double transgenic mice during a critical period from E15.5 to P14 was accompanied by respiratory distress, chylothorax, pulmonary lymphangiectasia, and high mortality. Enlarged sac-like lymphatics were abundant near major airways, pulmonary vessels, and visceral pleura. Side-by-side comparison revealed morphologic features similar to pulmonary lymphangiectasia in humans. The condition was milder in mice given doxycycline after age P14 and did not develop after P35. Mechanistic studies revealed that VEGFR-3 alone drove lymphatic growth in adult mice, but both VEGFR-2 and VEGFR-3 were required for the Development of lymphangiectasia in neonates. VEGFR-2/VEGFR-3 heterodimers were more abundant in the dilated lymphatics, consistent with the involvement of both receptors. Despite the dependence of lymphangiectasia on VEGFR-2 and VEGFR-3, the condition was not reversed by blocking both receptors together or by withdrawing VEGF-C. Conclusions: : The findings indicate that VEGF-C overexpression can induce pulmonary lymphangiectasia during a critical period in Perinatal Development.
-
dynamics of airway blood vessels and lymphatics lessons from Development and inflammation
Proceedings of the American Thoracic Society, 2011Co-Authors: Donald M. Mcdonald, Lichin Yao, Peter BalukAbstract:Blood vessels and lymphatic vessels in the respiratory tract play key roles in inflammation. By undergoing adaptive remodeling and growth, blood vessels undergo changes that enable the extravasation of plasma and leukocytes into inflamed tissues, and lymphatic vessels adjust to the increased fluid clearance and cell traffic involved in immune responses. Blood vessels and lymphatics in adult airways are strikingly different from those of late-stage embryos. Before birth, blood vessels in mouse airways make up a primitive plexus similar to that of the yolk sac. This plexus undergoes rapid and extensive remodeling at birth. In the early neonatal period, parts of the plexus regress. Capillaries then rapidly regrow, and with arterioles and venules form the characteristic adult vascular pattern. Lymphatic vessels of the airways also undergo rapid changes around birth, when lymphatic endothelial cells develop button-like intercellular junctions specialized for efficient fluid uptake. Among the mechanisms that underlie the onset of rapid vascular remodeling at birth, changes in tissue oxygen tension and mechanical forces associated with breathing are likely to be involved, along with growth factors that promote the growth and maturation of blood vessels and lymphatics. Whatever the mechanisms, the dynamic nature of airway blood vessels and lymphatics during Perinatal Development foretells the extraordinary vascular plasticity found in many diseases.
Wolfgang A Linke - One of the best experts on this subject based on the ideXlab platform.
-
Plasticity of cardiac titin/connectin in heart Development q
2013Co-Authors: Christiane A Opitz, Wolfgang A LinkeAbstract:Many sarcomeric proteins in the myocardium alter their isoform pattern during Perinatal Development to adjust to the intensified pump function of the postnatal heart. These changes also involve the giant protein titin/connectin. Here we show by low-percentage polyacrylamide-gel electrophoresis that Developmentally regulated switching of cardiac titin/connectin size occurs in the hearts of mouse, rat, pig, and chicken. Mammalian hearts express, well before birth, large foetal ( 3.7 MDa) N2BA-titin/connectin isoform but no N2B-isoform (3.0 MDa). During Perinatal heart Development the 3.7-MDa N2BA-isoform is replaced by a mix of smaller isoforms. At birth a plethora of intermediate-size N2BA-isoforms appears together with the N2B-isoform. In postnatal heart Development the larger-size N2BA-isoforms disappear and smaller-size N2BA-isoforms are upregulated, whereas the proportion of N2B-titin/connectin increases to species-specific adult levels. The time courses of isoform switching are faster in small than in large mammals. Titin/connectin isoform switching also takes place in developing chicken hearts, but the largest embryonic isoform found here was less than 3.4 MDa. At hatching, various smaller-size isoforms appeared and within a week the adult expression pattern was established representing a major 3.0-MDa isoform and a minor 3.15-MDa isoform. The ratio between the two adult isoforms differed between the left ventricle and the right atrium. The Perinatal changes toward smaller cardiac titin/connectin isoforms in mammals and chicken greatly increase the myofibrillar passive tension of postnatal hearts. Plasticity of titin/connectin at approximately the time of birth thus affects myocardial mechanics but could also be an important factor in Developmentally regulated assembly and signalling processes
-
plasticity of cardiac titin connectin in heart Development
Journal of Muscle Research and Cell Motility, 2006Co-Authors: Christiane A Opitz, Wolfgang A LinkeAbstract:Many sarcomeric proteins in the myocardium alter their isoform pattern during Perinatal Development to adjust to the intensified pump function of the postnatal heart. These changes also involve the giant protein titin/connectin. Here we show by low-percentage polyacrylamide-gel electrophoresis that Developmentally regulated switching of cardiac titin/connectin size occurs in the hearts of mouse, rat, pig, and chicken. Mammalian hearts express, well before birth, large foetal (approximately 3.7 MDa) N2BA-titin/connectin isoform but no N2B-isoform (3.0 MDa). During Perinatal heart Development the 3.7-MDa N2BA-isoform is replaced by a mix of smaller isoforms. At birth a plethora of intermediate-size N2BA-isoforms appears together with the N2B-isoform. In postnatal heart Development the larger-size N2BA-isoforms disappear and smaller-size N2BA-isoforms are upregulated, whereas the proportion of N2B-titin/connectin increases to species-specific adult levels. The time courses of isoform switching are faster in small than in large mammals. Titin/connectin isoform switching also takes place in developing chicken hearts, but the largest embryonic isoform found here was less than 3.4 MDa. At hatching, various smaller-size isoforms appeared and within a week the adult expression pattern was established representing a major 3.0-MDa isoform and a minor 3.15-MDa isoform. The ratio between the two adult isoforms differed between the left ventricle and the right atrium. The Perinatal changes toward smaller cardiac titin/connectin isoforms in mammals and chicken greatly increase the myofibrillar passive tension of postnatal hearts. Plasticity of titin/connectin at approximately the time of birth thus affects myocardial mechanics but could also be an important factor in Developmentally regulated assembly and signalling processes.
Janice M Juraska - One of the best experts on this subject based on the ideXlab platform.
-
long term effects of adolescent exposure to bisphenol a on neuron and glia number in the rat prefrontal cortex differences between the sexes and cell type
Neurotoxicology, 2016Co-Authors: Leslie M Wise, Renee N Sadowski, Taehyeon Kim, Jari Willing, Janice M JuraskaAbstract:Bisphenol A (BPA), an endocrine disruptor used in a variety of consumer products, has been found to alter the number of neurons in multiple brain areas in rats following exposure in Perinatal Development. Both the number of neurons and glia also change in the medial prefrontal cortex (mPFC) during adolescence, and this process is known to be influenced by gonadal hormones which could be altered by BPA. In the current study, we examined Long-Evans male and female rats that were administered BPA (0, 4, 40, or 400μg/kg/day) during adolescent Development (postnatal days 27-46). In adulthood (postnatal day 150), the number of neurons and glia in the mPFC were stereologically assessed in methylene blue/azure II stained sections. There were no changes in the number of neurons, but there was a significant dose by sex interaction in number of glia in the mPFC. Pairwise comparisons between controls and each dose showed a significant increase in the number of glia between 0 and 40μg/kg/day in females, and a significant decrease in the number of glia between 0 and 4μg/kg/day in males. In order to determine the type of glial cells that were changing in these groups in response to adolescent BPA administration, adjacent sections were labelled with S100β (astrocytes) and IBA-1 (microglia) in the mPFC of the groups that differed. The number of microglia was significantly higher in females exposed to 40μg/kg/day than controls and lower in males exposed to 4μg/kg/day than controls. There were no significant effects of adolescent exposure to BPA on the number of astrocytes in male or females. Thus, adolescent exposure to BPA produced long-term alterations in the number of microglia in the mPFC of rats, the functional implications of which need to be explored.
-
sexual differentiation of the adolescent rodent brain hormonal influences and Developmental mechanisms
Hormones and Behavior, 2013Co-Authors: Janice M Juraska, Cheryl L Sisk, Lydia L DoncarlosAbstract:Abstract This article is part of a Special Issue “Puberty and Adolescence”. Sexual differentiation is the process by which the nervous system becomes structurally and functionally dissimilar in females and males. In mammals, this process has been thought to occur during prenatal and early postnatal Development, when a transient increase in testosterone secretion masculinizes and defeminizes the developing male nervous system. Decades of research have led to the views that structural sexual dimorphisms created during Perinatal Development are passively maintained throughout life, and that ovarian hormones do not play an active role in feminization of the nervous system. Furthermore, Perinatal testosterone was thought to determine sex differences in neuron number by regulating cell death and cell survival, and not by regulating cell proliferation. As investigations of neural Development during adolescence became more prominent in the late 20th century and revealed the extent of brain remodeling during this time, each of these tenets has been challenged and modified. Here we review evidence from the animal literature that 1) the brain is further sexually differentiated during puberty and adolescence; 2) ovarian hormones play an active role in the feminization of the brain during puberty; and 3) hormonally modulated, sex-specific addition of new neurons and glial cells, as well as loss of neurons, contribute to sexual differentiation of hypothalamic, limbic, and cortical regions during adolescence. This architectural remodeling during the adolescent phase of sexual differentiation of the brain may underlie the known sex differences in vulnerability to addiction and psychiatric disorders that emerge during this Developmental period.