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Robert H Horvitz - One of the best experts on this subject based on the ideXlab platform.
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spk 1 an sr protein kinase inhibits Programmed Cell Death in caenorhabditis elegans
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Brendan D Galvin, Daniel P Denning, Robert H HorvitzAbstract:To identify genes involved in protecting Cells from Programmed Cell Death in Caenorhabditis elegans, we performed a genetic screen to isolate mutations that cause an increase in the number of Programmed Cell Deaths. We screened for suppressors of the Cell-Death defect caused by a partial loss-of-function mutation in ced-4, which encodes an Apaf-1 homolog that promotes Programmed Cell Death by activating the caspase CED-3. We identified one extragenic ced-4 suppressor, which has a mutation in the gene spk-1. The spk-1 gene encodes a protein homologous to serine-arginine-rich (SR) protein kinases, which are thought to regulate splicing. Previous work suggests that ced-4 can be alternatively spliced and that the splice variants function oppositely, with the longer transcript (ced-4L) inhibiting Programmed Cell Death. spk-1 might promote Cell survival by increasing the amount of the protective ced-4L splice variant. We conclude that Programmed Cell Death in C. elegans is regulated by an alternative splicing event controlled by the SR protein kinase SPK-1.
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the engulfment process of Programmed Cell Death in caenorhabditis elegans
Annual Review of Cell and Developmental Biology, 2004Co-Authors: Peter W Reddien, Robert H HorvitzAbstract:▪ Abstract Programmed Cell Death involves the removal of Cell corpses by other Cells in a process termed engulfment. Genetic studies of the nematode Caenorhabditis elegans have led to a framework not only for the killing step of Programmed Cell Death but also for the process of Cell-corpse engulfment. This work has defined two signal transduction pathways that act redundantly to control engulfment. Signals expressed by dying Cells probably regulate these C. elegans pathways. Components of the Cell-corpse recognition system of one of the C. elegans pathways include the CED-7 ABC transporter, which likely presents a Death ligand on the surface of the dying Cell; the CED-1 transmembrane receptor, which recognizes this signal; and the CED-6 adaptor protein, which may transduce a signal from CED-1. The second C. elegans pathway acts in parallel and involves a novel Rac GTPase signaling pathway, with the components CED-2 CrkII, CED-5 DOCK180, CED-12 ELMO, and CED-10 Rac. The Cell-corpse recognition system that ...
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phagocytosis promotes Programmed Cell Death in c elegans
Nature, 2001Co-Authors: Peter W Reddien, S Cameron, Robert H HorvitzAbstract:In the nematode Caenorhabditis elegans Programmed Cell Death requires the killer genes egl-1, ced-4 and ced-3 (refs 1 and 2), and the engulfment of dying Cells requires the genes ced-1, ced-2, ced-5, ced-6, ced-7, ced-10 and ced-12 (refs 3,4,5). Here we show that engulfment promotes Programmed Cell Death. Mutations that cause partial loss of function of killer genes allow the survival of some Cells that are Programmed to die, and mutations in engulfment genes enhance the frequency of this Cell survival. Furthermore, mutations in engulfment genes alone allow the survival and differentiation of some Cells that would normally die. Engulfment genes probably act in engulfing Cells to promote Death, as the expression in engulfing Cells of ced-1, which encodes a receptor that recognizes Cell corpses6, rescues the Cell-killing defects of ced-1 mutants. We propose that engulfing Cells act to ensure that Cells triggered to undergo Programmed Cell Death by the CED-3 caspase7 die rather than recover after the initial stages of Death.
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translocation of c elegans ced 4 to nuclear membranes during Programmed Cell Death
Science, 2000Co-Authors: Fangli Chen, Bradley M Hersh, Barbara Conradt, Zheng Zhou, Dieter Riemer, Yosef Gruenbaum, Robert H HorvitzAbstract:The Caenorhabditis elegans Bcl-2-like protein CED-9 prevents Programmed Cell Death by antagonizing the Apaf-1-like Cell-Death activator CED-4. Endogenous CED-9 and CED-4 proteins localized to mitochondria in wild-type embryos, in which most Cells survive. By contrast, in embryos in which Cells had been induced to die, CED-4 assumed a perinuclear localization. CED-4 translocation induced by the Cell-Death activator EGL-1 was blocked by a gain-of-function mutation in ced-9 but was not dependent on ced-3 function, suggesting that CED-4 translocation precedes caspase activation and the execution phase of Programmed Cell Death. Thus, a change in the subCellular localization of CED-4 may drive Programmed Cell Death.
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genetic control of Programmed Cell Death in the nematode caenorhabditis elegans
Cancer Research, 1999Co-Authors: Robert H HorvitzAbstract:Naturally-occurring or “Programmed” Cell Death appears to be a universal aspect of animal development (e.g., Ref. 1). For example, massive Cell Death occurs during the development of the mammalian fetus, particularly in the fetal brain; in areas of the developing vertebrate nervous system as many as 85% of the developing neurons die. Similarly, about 95% of developing thymocytes die without ever leaving the thymus. Why such Cell Deaths occur and how they are regulated are fundamental problems in developmental biology.
Osman Parlak - One of the best experts on this subject based on the ideXlab platform.
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fenoxycarb modulates ecdysone receptor b1 and Programmed Cell Death of the anterior silk gland of silkworm bombyx mori
Entomological Science, 2011Co-Authors: Ebru Goncu, Osman ParlakAbstract:Fenoxycarb, O-ethyl N-(2-(4-phenoxyphenoxy)-ethyl) carbamate has been shown to be one of the most potent juvenile hormone analogues against a variety of insect species. In the present study, topical application of fenoxycarb to fifth-instar larvae of the silkworm Bombyx mori (Lepidoptera: Bombycidae) was performed immediately after the fourth ecdysis (on day 0), day 3 and day 6 of the instar and then its effects on the anterior silk glands (ASG) and ecdysone receptor B1 (EcR-B1) protein were investigated during larval pupal development. Fenoxycarb application increased the instar length and prevented metamorphic events, depending on the application time. The ASGs of B. mori undergo Programmed Cell Death during the larval–pupal metamorphosis and an insect steroid, 20-hydroxyecdysone (20E), triggers this Cell Death. The exact mechanism by which 20E and juvenile hormone regulates Programmed Cell Death in insect tissues is poorly understood. To gain insights into how juvenile hormone regulates metamorphic events like Programmed Cell Death in the anterior silk glands, we analyzed the progression of Programmed Cell Death with morphological observations and biochemical experiments like acid phosphatase activity and DNA electrophoresis. Then we examined the EcR-B1 protein levels and their relationships with Programmed Cell Death. Our results indicated that fenoxycarb modulates Programmed Cell Death of the anterior silk glands and EcR-B1 protein level, depending on the application time. Fenoxycarb may exhibit its effects in at least two different ways: (i) acting on prothoracic gland secretory activity; and/or (ii) regulation of EcR-B1 expression in the anterior silk glands for Programmed Cell Death process.
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morphological changes and patterns of ecdysone receptor b1 immunolocalization in the anterior silk gland undergoing Programmed Cell Death in the silkworm bombyx mori
Acta Histochemica, 2009Co-Authors: Ebru Goncu, Osman ParlakAbstract:The silk gland is a specific larval tissue of Lepidopteran insects and begins to degenerate shortly before pupation. The steroid hormone ecdysone triggers the stage specific Programmed Cell Death of the anterior silk glands during metamorphosis in the silkworm, Bombyx mori. The anterior silk gland expresses ecdysone receptors, which are involved in regulation processes in response to ecdysone. In this study, the morphological changes, immunohistochemical localization and protein levels of ecdysone receptor B1 (EcR-B1) in the anterior silk gland of B. mori were investigated during Programmed Cell Death. Morphological changes observed during the degeneration process involve the appearance of large vacuoles, probably autophagic vacuoles, which increase in number in pupal anterior silk glands. No macrophages were found in the silk gland during the prepupal and pupal stage unlike in apoptosis, which strongly suggests that Programmed Cell Death of the anterior silk gland is carried out by autophagy. Morphological changes of the silk glands were accompanied by changes in the immunolocalization and protein levels of EcR-B1. The differences in tissue distribution and protein levels of EcR-B1 during the Programmed Cell Death indicate that the receptor plays a major role in the modulation and function of ecdysone activity in Bombyx anterior silk glands. Our results indicate that EcR-B1 expression may be important for the process of Programmed Cell Death in the anterior silk glands.
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some autophagic and apoptotic features of Programmed Cell Death in the anterior silk glands of the silkworm bombyx mori
Autophagy, 2008Co-Authors: Ebru Goncu, Osman ParlakAbstract:Programmed Cell Death has been subdivided into two major groups: apoptosis and autophagic Cell Death. The anterior silk gland of Bombyx mori degenerates during larval-pupal metamorphosis. Our findings indicate that two types of Programmed Cell Death features are observed during this physiological process. During the prepupal period, pyknosis of the nucleus, Cell detachment,and membrane blebbing occur and they are the first signs of Programmed Cell Death in the anterior silk glands. According to previous studies, all of these morphological appearances are common for both Cell-Death types. Autophagy features are also exhibited during the prepupal period. Levels of one of the lysosomal marker enzymes-acid phosphatase-are high during this period then decrease gradually. Vacuole formation begins to appear first at the basal surface of the Cell, then expands to the apical surface just before the larval pupal ecdysis. After larval-pupal ecdysis, DNA fragmentation, which is the obvious biochemical marker of apoptosis, is detected in agarose gel electrophoresis, which also shows that caspase-like enzyme activities occur during the Programmed Cell Death process of the anterior silk glands. Apoptosis and autophagic Cell Death interact with each other during the degeneration process of the anterior silk gland in Bombyx mori and this interaction occurs at a late phase of Cell Death. We suggest that apoptotic Cell Death only is not enough for whole gland degeneration and that more effective degeneration occurs with this cooperation.
Chul Woo Kim - One of the best experts on this subject based on the ideXlab platform.
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clinicopathological analysis of Programmed Cell Death 1 and Programmed Cell Death ligand 1 expression in the tumour microenvironments of diffuse large b Cell lymphomas
Histopathology, 2016Co-Authors: Dohee Kwon, Sehui Kim, Pil Kim, Soo Jeong Nam, Jin Ho Paik, Young A Kim, Tae Min Kim, Dae Seog Heo, Chul Woo KimAbstract:Aims To investigate the clinicopathological characteristics of Programmed Cell Death ligand 1 (PD-L1) and Programmed Cell Death 1 (PD-1) expression in the tumour microenvironments of diffuse large B Cell lymphoma (DLBCL). Methods and results Tumour tissues from 126 DLBCL patients were immunostained for PD-L1 and PD-1. The expression of PD-L1 by tumour Cells and/or tumour-infiltrating immune Cells (mainly macrophages) was evaluated, and the number of tumour-infiltrating PD-1(+) Cells was assessed. PD-L1 expression in tumour Cells was observed in 61.1% of DLBCLs, with a weak intensity in 29.4%, moderate intensity in 21.4% and strong intensity in 10.3% of cases. Strong PD-L1 expression in tumour Cells was associated significantly with the presence of B symptoms (adjusted P = 0.005) and Epstein-Barr virus (EBV) infection (adjusted P = 0.015), and tended to be higher in activated B Cell-like immunophenotype (16.7%) than germinal centre B Cell-like immunophenotype (2.5%) (adjusted P = 0.271). DLBCLs with PD-L1 expression in tumour Cells/macrophages showed similar clinicopathological characteristics. The quantity of PD-1(+) tumour-infiltrating lymphocytes correlated positively with the level of PD-L1 expression in tumour Cells (P = 0.042) or in tumour Cells/macrophages (P = 0.03). Increased infiltration of PD-1(+) Cells was associated with prolonged progression-free survival (P = 0.005) and overall survival (P = 0.026) in DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), whereas PD-L1 expression had no prognostic significance. Conclusions PD-L1 and PD-1 were expressed variably in DLBCLs by tumour Cells and tumour-infiltrating immune Cells and might be potential therapeutic targets using PD-1/PD-L1 blockade.
Ebru Goncu - One of the best experts on this subject based on the ideXlab platform.
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fenoxycarb modulates ecdysone receptor b1 and Programmed Cell Death of the anterior silk gland of silkworm bombyx mori
Entomological Science, 2011Co-Authors: Ebru Goncu, Osman ParlakAbstract:Fenoxycarb, O-ethyl N-(2-(4-phenoxyphenoxy)-ethyl) carbamate has been shown to be one of the most potent juvenile hormone analogues against a variety of insect species. In the present study, topical application of fenoxycarb to fifth-instar larvae of the silkworm Bombyx mori (Lepidoptera: Bombycidae) was performed immediately after the fourth ecdysis (on day 0), day 3 and day 6 of the instar and then its effects on the anterior silk glands (ASG) and ecdysone receptor B1 (EcR-B1) protein were investigated during larval pupal development. Fenoxycarb application increased the instar length and prevented metamorphic events, depending on the application time. The ASGs of B. mori undergo Programmed Cell Death during the larval–pupal metamorphosis and an insect steroid, 20-hydroxyecdysone (20E), triggers this Cell Death. The exact mechanism by which 20E and juvenile hormone regulates Programmed Cell Death in insect tissues is poorly understood. To gain insights into how juvenile hormone regulates metamorphic events like Programmed Cell Death in the anterior silk glands, we analyzed the progression of Programmed Cell Death with morphological observations and biochemical experiments like acid phosphatase activity and DNA electrophoresis. Then we examined the EcR-B1 protein levels and their relationships with Programmed Cell Death. Our results indicated that fenoxycarb modulates Programmed Cell Death of the anterior silk glands and EcR-B1 protein level, depending on the application time. Fenoxycarb may exhibit its effects in at least two different ways: (i) acting on prothoracic gland secretory activity; and/or (ii) regulation of EcR-B1 expression in the anterior silk glands for Programmed Cell Death process.
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morphological changes and patterns of ecdysone receptor b1 immunolocalization in the anterior silk gland undergoing Programmed Cell Death in the silkworm bombyx mori
Acta Histochemica, 2009Co-Authors: Ebru Goncu, Osman ParlakAbstract:The silk gland is a specific larval tissue of Lepidopteran insects and begins to degenerate shortly before pupation. The steroid hormone ecdysone triggers the stage specific Programmed Cell Death of the anterior silk glands during metamorphosis in the silkworm, Bombyx mori. The anterior silk gland expresses ecdysone receptors, which are involved in regulation processes in response to ecdysone. In this study, the morphological changes, immunohistochemical localization and protein levels of ecdysone receptor B1 (EcR-B1) in the anterior silk gland of B. mori were investigated during Programmed Cell Death. Morphological changes observed during the degeneration process involve the appearance of large vacuoles, probably autophagic vacuoles, which increase in number in pupal anterior silk glands. No macrophages were found in the silk gland during the prepupal and pupal stage unlike in apoptosis, which strongly suggests that Programmed Cell Death of the anterior silk gland is carried out by autophagy. Morphological changes of the silk glands were accompanied by changes in the immunolocalization and protein levels of EcR-B1. The differences in tissue distribution and protein levels of EcR-B1 during the Programmed Cell Death indicate that the receptor plays a major role in the modulation and function of ecdysone activity in Bombyx anterior silk glands. Our results indicate that EcR-B1 expression may be important for the process of Programmed Cell Death in the anterior silk glands.
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some autophagic and apoptotic features of Programmed Cell Death in the anterior silk glands of the silkworm bombyx mori
Autophagy, 2008Co-Authors: Ebru Goncu, Osman ParlakAbstract:Programmed Cell Death has been subdivided into two major groups: apoptosis and autophagic Cell Death. The anterior silk gland of Bombyx mori degenerates during larval-pupal metamorphosis. Our findings indicate that two types of Programmed Cell Death features are observed during this physiological process. During the prepupal period, pyknosis of the nucleus, Cell detachment,and membrane blebbing occur and they are the first signs of Programmed Cell Death in the anterior silk glands. According to previous studies, all of these morphological appearances are common for both Cell-Death types. Autophagy features are also exhibited during the prepupal period. Levels of one of the lysosomal marker enzymes-acid phosphatase-are high during this period then decrease gradually. Vacuole formation begins to appear first at the basal surface of the Cell, then expands to the apical surface just before the larval pupal ecdysis. After larval-pupal ecdysis, DNA fragmentation, which is the obvious biochemical marker of apoptosis, is detected in agarose gel electrophoresis, which also shows that caspase-like enzyme activities occur during the Programmed Cell Death process of the anterior silk glands. Apoptosis and autophagic Cell Death interact with each other during the degeneration process of the anterior silk gland in Bombyx mori and this interaction occurs at a late phase of Cell Death. We suggest that apoptotic Cell Death only is not enough for whole gland degeneration and that more effective degeneration occurs with this cooperation.
Azadeh Namakydoust - One of the best experts on this subject based on the ideXlab platform.
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lesion level response dynamics to Programmed Cell Death protein pd 1 blockade
Journal of Clinical Oncology, 2019Co-Authors: Juan C Osorio, Kathryn C Arbour, Jennifer N Durham, Andrew J Plodkowski, Darragh F Halpenny, Michelle S Ginsberg, Peter Sawan, Joseph G Crompton, Azadeh NamakydoustAbstract:PURPOSEResponse to Programmed Cell Death protein 1 (PD-1) blockade is often conceptualized as resulting from reinvigoration of tumor-infiltrating lymphocytes. However, recruited antitumor immunity ...