Published 2005 .
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Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein which, following an apoptotic stimulus, translocates to the nucleus and mediates chromatin degradation. The physiological functions of AIF within the mitochondrion and in programmed cell death (PCD), however, remain unknown. In this thesis, I report the targeted deletion of the gene orthologs encoding AIF in mice and Drosophila. Embryoid bodies differentiated from Aif -/Y mouse embryonic stem (ES) cells fail to cavitate due to a cell-autonomous defect in PCD of inner core cells. In contrast, embryoid bodies differentiated from ES cells deficient in Apaf-1 or caspase-9, two key effectors of PCD, cavitate normally, and AIF translocates to the nuclei of dying cells. Furthermore, Apaf-1 and caspase-9 are dispensible for some morphological features of apoptosis including partial chromatin condensation and membrane blebbing, indicating a potential role for AIF in these apoptotic manifestations. These results indicate an essential requirement for AIF in PCD during cavitation of embryoid bodies. I next analyzed mice which carry a gene-targeted conditional allele of Aif. Mice in which Aif has been inactivated specifically in muscle develop dilated cardiomyopathy, heart failure, skeletal muscle atrophy and lactic acidosis. These pathologies are accompanied by a severe defect in respiratory chain complex I activity and a significant reduction in the level of complex I proteins in mutant tissues. These data point to an essential requirement for AIF in mitochondrial respiration and energy metabolism essential for normal tissue function. In the final section of this thesis, we identify and genetically characterize the Drosophila Aif ortholog DmAif. Like mammalian AIF, DmAIF is a mitochondrial protein that can induce PCD when overexpressed in cells. Transgenic flies which misexpress in the eye an N-terminally-truncated DmAIF lacking the presumptive mitochondrial import sequence (DeltaN-DmAIF) exhibit severely reduced eye size due to ectopic PCD. This cell death can occur in the absence of caspase function. Unlike mammalian AIF, however, DmAIF does not translocate from the mitochondrion to the nucleus following a death-inducing stimulus, as shown in an insect cell line. Finally, we generated and analyzed a Drosophila mutant carrying a loss-of-function mutation in DmAif. Loss of zygotic expression of DmAIF results in growth arrest during early larval stages and lethality. DmAIF mutant animals exhibit severe defects in respiratory complex I and complex IV function, accompanied by diminished levels of cellular ATP. (Abstract shortened by UMI.)
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Download Genetic elucidation of the roles of apoptosis-inducing factor (AIF) in mitochondrial respiration and programmed cell death.
The roles played by Aspergillus nidulans apoptosis-inducing factor (AIF)-like mitochondrial oxidoreductase (AifA) and NADH-ubiquinone oxidoreductases (NdeA. Apoptosis plays critical roles in the initiation, progression and remission of autoimmune diseases. On the one hand, apotosis of resident tissue cells in diseased organs contributes to the.
Publisher Summary. This chapter focuses on the convergence of growth-factor signaling pathways in developmental systems and pathogenesis. The dynamics of differentiation and growth along with the initiation and progression of disease processes involves a harmonized mobilization and activity of a wide variety of mediators and biological response modifiers such.
This specific type of programmed cell death may involve specific mitochondrial factors. In experimental models, apoptosis-inducing factor (AIF) and endonuclease G promote this type of cell death; however, Smac/DIABLO and HtrA2/Omi may also contribute (Ravagnan et al., ; van Loo et al., b).Cited by: Genetic elucidation of the roles of apoptosis-inducing factor book chapter discusses apoptosis, which is a program for cell deletion triggered by either physiological or noxious signals.
The chapter discusses several related concepts, including morphological characterization of cell death, regulation of programmed cell death, roles of physiological cell death, and frontiers in the study of apoptosis.
Neuroblastoma is a notably malignant cancer originates from neuroblastoma stem cells during embryogenesis. It can originate from any region of the peripheral nervous system. Neuroblastoma is a heterogeneous cancer.
The cells responsible for heterogeneous structure are neuroblastoma stem cells that initiate the cancer and generate into all the cancer cells and have self‐renewal Author: Bakiye Goker Bagca, Cigir Biray Avci.
Mouse. With its small size and ease of genetic manipulation, the mouse is currently the most frequently used model in atherosclerosis research .Development of atherosclerosis is influenced by a number of genes, which interact with each other and the environment to affect the disease phenotype .Manipulation can take place for single genes, Cited by: As the most common noncutaneous form of cancer in men, prostate cancer is the subject of over US$ million in research funding annually from both the NIH and the National Cancer Institute in the USA, with comparable funding levels in other nations worldwide [,].Despite these significant efforts, the exact mechanism of carcinogenesis is unknown, although it is believed Cited by: Other important modulators of the immune system development and function are death receptors such as Fas (CD95/APO-1) and Tumour necrosis factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL).
The death receptor system is essential for the regulation of the lymphoid system homeostasis [ 76 ].Cited by: 2. In the resolution stage of liver fibrosis, they are able to undergo (1) apoptosis by Fas (clusters of differentiation [CD]95), tumor necrosis factor (TNF) receptor 1, p75(neurotrophin receptor; p75NTR), and tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL) receptors by combining with their ligands 27; (2) senescence 28; and (3 Cited by: 6.
MicroRNAs (miRNAs) are non-coding RNAs that play essential roles in modulating the gene expression in almost all biological events. In the past decade, the involvement of miRNAs in various cardiovascular disorders has been explored in numerous in vitro and in vivo studies. In this paper, studies focused upon the discovery of miRNAs, their target genes, and functionality Cited by: Selenium is an essential trace element for humans and animals, and selenium deficiency is associated with several disease conditions such as immune impairment.
In addition, selenium intakes that are greater than the recommended daily allowance (RDA) appear to protect against certain types of cancers.
In humans and animals, cell proliferation and death must be Cited by: If the address matches an existing account you will receive an email with instructions to retrieve your username. Transforming growth factor (TGF) β1 is a potent growth inhibitor, with tumor-suppressing activity. Cancers are often refractile to this growth inhibition either because of genetic loss of TGF-β signaling components or, more commonly, because of downstream perturbation of the signaling pathway, such as by Ras activation.
The apoptotic demolition of the nucleus is accomplished by diverse proapoptotic factors, most of which are activated in the cytoplasm and gain access to the nucleoplasm during the cell death by: The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors.
The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing Cited by: You can write a book review and share your experiences.
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The majority of individuals who become acutely infected with hepatitis C virus (HCV) develop chronic infection and suffer from progressive liver damage while approximately 25% are able to eliminate the virus spontaneously.
Despite the recent introduction of new direct-acting antivirals, there is still no vaccine for HCV. As a result, new infections and reinfections Cited by: Chronic exposure to nickel(II), chromium(VI), or inorganic arsenic (iAs) has long been known to increase cancer incidence among affected individuals.
Recent epidemiological studies have found that carcinogenic risks associated with chromate and iAs exposures were substantially higher than previously thought, which led to major revisions of the federal standards regulating Cited by: Title:Editorial (Thematic Issue: Targeting Vascular Calcification: Up-Date) VOLUME: 20 ISSUE: 37 Author(s):Yuri V.
Bobryshev Affiliation:Faculty of Medicine University of New South Wales and St Vincent's Hospital Sydney SydneyNSW Australia. Keywords:Calcification, blood vessels, arteries, targets, biomarkers. Abstract:Our society faces a growing burden of Cited by: 2.
This banner text can have markup. web; books; video; audio; software; images; Toggle navigation. Abstract. Elimination of cells through apoptosis is crucial for tissue homeostasis.
The process of cell removal is regulated by the expression of recognition signals on the dying cell and corresponding phagocytosis receptors on the engulfing cell; in addition, chemotactic factors emitted by apoptotic cell corpses serve to attract macrophages to the site of cell by: 2.
We found that the flavoprotein apoptosis-inducing factor mitochondria-associated 2 (AIFM2) is a previously unrecognized anti-ferroptotic gene. AIFM2, which we renamed ferroptosis suppressor protein 1 (FSP1) and which was initially described as a pro-apoptotic gene11, confers protection against ferroptosis elicited by GPX4 deletion.
The backbone of cancer therapy in pediatric oncology has been stepwise integration of multimodality therapies (eg, chemotherapy, surgery, radiation therapy) into carefully designed treatment regimens tested sequentially through multicenter randomized trials.
Although chemotherapy has been effective in eradicating micrometastatic disease in so. Apart from potential roles in anti-tumor surveillance, the TNF-related apoptosis-inducing ligand (TRAIL) has important regulatory functions in the host immune response.
We studied antiinflammatory effects of endogenous and. How Does Cannabis Kill Cancer Cells. by Jeffrey Dach MD. An Exciting Time for Medicinal Cannabis.
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The study of each of these pathways may be complex and laborious since free radicals are extremely short-lived. Recently, genetic manipulation of wild-type animals has yielded species that over- or under-express genes such as, copper-zinc Superoxide dismutase, manganese Superoxide dismutase, nitric oxide synthase, and the Bcl-2 by: Cloning of plant caspase-like proteases and elucidation of the mechanisms through which mitochondria may regulate cell death in both systems should shed light on the evolution of cell death control in eukaryotes and may help to identify essential components that are highly conserved in by: The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential.
Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. Physician-Scientist Workforce (PSW) Report ACD Biomedical Workforce Working Group Data Investigators and Trainees Data Book: The NIH-Funded Research Workforce Data Book: NIH Research Training Grants and Fellowships Data Book.
A Modular Platform for the Rapid Site-Specific Radiolabeling of Proteins with 18 F Exemplified by Quantitative Positron Emission Tomography of Human Epidermal Growth Factor Receptor 2 Herman S. Gill Jeff N. Tinianow.
Editorial boards: present: Histochemistry and Cell Biology: present: Journal of Structural Biology: present: Methods in Applications in Fluorescence.
A novel risk factor for severity of autoimmune hepatitis (AIH): a high expression macrophage migration inhibitory factor (MIF) allele is associated with inflammatory markers in both American and Japanese patients David N.
Assis, Hiroki Takahashi, Lin Leng, Richard Bucala, Mikio Zeniya, James L. Boyer. Alexander Rich, MD: Alexander Rich MD, Director of Biology Department, MIT Keynote Speaker Along with decades of pioneering work in structural molecular biology at MIT, NIH, and Linus Pauling's lab, Dr.
Rich has co-founded Repligen [RGEN], Alkermes[ALKS], and over publications, his discoveries include Z-DNA and its editor effects on RNA, the first.
Digitoxin is only found in individuals that have used or taken this drug. It is a cardiac glycoside sometimes used in place of has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting.(From Martindale, The Extra Pharmacopoeia, 30th ed, p)Digitoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in.
Particle Carriers for Combating Multidrug-Resistant CancerCited by: Resveratrol Scientific Update By Longevinex Octo © Dosage Extremely high doses (~ mg/day) of resveratrol are being touted by some makers of resveratrol supplements.
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Since its first purification inadditional studies have refined the phenotype and functionality of HSCs and characterized all of their downstream progeny. The hematopoietic lineage is divided into two main branches: Cited by: The advances in biochemistry facilitated further elucidation about the mechanisms of the ‘catalase’ enzymatic reaction.
Thus, the work carried out by Chance’s lab led to the discovery of the formation of the ‘Compound I’ that occurred during the reaction between catalase and the first molecule of H 2 O 2.A few years later, he also discovered the ‘compounds II and III’ (Chance.
Apoptosis-inducing factor 1, mitochondrial is a protein that in humans is encoded by the AIFM1 gene on the X chromosome. New!!: Redox and AIFM1 See more» Air freshener.
Air fresheners are consumer products used in homes, or commercial products used in restrooms, that typically emit fragrance. New!!: Redox and Air freshener See more.Parkinson Disease Society (March ), “Elucidation of PINK-1 and LRRK2 function in Parkinson disease by a combined genetic and biochemical approach in the C.
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