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University of Medicine and Dentistry of New Jersey
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About: University of Medicine and Dentistry of New Jersey is a based out in . It is known for research contribution in the topics: Population & Pregnancy. The organization has 14634 authors who have published 19610 publications receiving 1041794 citations.
Topics: Population, Pregnancy, Poison control, Gene, Receptor
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TL;DR: It is found that metabolic stress is a potent trigger of apoptotic cell death, defects in which enable long-term survival that is dependent on autophagy both in vitro and in tumors in vivo, and raises the conundrum whereby inactivation of a survival pathway (autophagy) promotes tumorigenesis.
Abstract: Human breast, ovarian, and prostate tumors display allelic loss of the essential autophagy gene beclin1 with high frequency, and an increase in the incidence of tumor formation is observed in beclin1(+/-) mutant mice. These findings suggest a role for beclin1 and autophagy in tumor suppression; however, the mechanism by which this occurs has been unclear. Autophagy is a bulk degradation process whereby organelles and cytoplasm are engulfed and targeted to lysosomes for proteolysis,(1,2) There is evidence that autophagy sustains cell survival during nutrient deprivation through catabolism, but also that autophagy is a means of achieving cell death when executed to completion. If or how either of these diametrically opposing functions proposed for autophagy may be related to tumor suppression is unknown. We found that metabolic stress is a potent trigger of apoptotic cell death, defects in which enable long-term survival that is dependent on autophagy both in vitro and in tumors in vivo.(3) These findings raise the conundrum whereby inactivation of a survival pathway (autophagy) promotes tumorigenesis. Interestingly, when cells with defects in apoptosis are denied autophagy, this creates the inability to tolerate metabolic stress, reduces cellular fitness, and activates a necrotic pathway to cell death. This necrosis in tumors is associated with inflammation and enhancement of tumor growth, due to the survival of a small population of surviving, but injured, cells in a microenvironment that favors oncogenesis. Thus, by sustaining metabolism through autophagy during periods of metabolic stress, cells can limit energy depletion, cellular damage, and cell death by necrosis, which may explain how autophagy can prevent cancer, and how loss of a survival function can be tumorigenic.
378 citations
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TL;DR: The National Institute of Mental Health convened a meeting in October 2005 to review the literature on obesity, nutrition, and physical activity among those with mental disorders, and the findings of this meeting and subsequent update of the literature review are summarized here.
378 citations
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TL;DR: Physical interaction and mutual functional repression may provide an underlying mechanism for many hitherto poorly understood PAH-induced toxic responses, and may also provide a mechanistic explanation for alteration of xenobiotic metabolism by cytokines and compounds that regulate NF-κB.
377 citations
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TL;DR: The possibility of a link between amyloid plaques in the brains of patients with Alzheimer's disease and the findings of previous studies is investigated.
Abstract: Aims Amyloid has recently been shown to accumulate intracellularly in the brains of patients with Alzheimer's disease (AD), yet amyloid plaques are generally thought to arise from gradual extracellular amyloid deposition. We have investigated the possibility of a link between these two apparently conflicting observations. Methods and results Immunohistochemistry and digital image analysis was used to examine the detailed localization of beta-amyloid(42) (A beta 42), a major component of amyloid plaques, in the entorhinal cortex and hippocampus of AD brains. A beta 42 first selectively accumulates in the perikaryon of pyramidal cells as discrete, granules that appear to be cathepsin D-positive, suggesting that they may represent lysosomes or lysosome-derived structures. AD brain regions abundantly populated with pyramidal neurones exhibiting excessive A beta 42 accumulations also contained evidence of neuronal lysis. Lysis of these A beta 42-burdened neurones apparently resulted in a local, radial dispersion of their cytoplasmic contents, including A beta 42 and lysosomal enzymes, into the surrounding extracellular space. A nuclear remnant was found at the dense core of many amyloid plaques, strengthening the idea that each amyloid plaque represents the end product of a single neuronal cell lysis. The inverse relationship between the amyloid plaque density and pyramidal cell density in the AD brain regions also supports this possibility, as does the close correlation between plaque size and the size of local pyramidal cells. Conclusions Our findings suggest that excessive intracellular accumulation of A beta 42-positive material in pyramidal cells can result in cell lysis, and that cell lysis is an important source of amyloid plaques and neuronal loss in AD brains.
376 citations
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TL;DR: Findings suggest that decreased calbindin gene expression may lead to a failure of calcium buffering or intraneuronal calcium homeostasis, which contributes to calcium-mediated cytotoxic events during aging and in the pathogenesis of neurodegenerative diseases.
Abstract: The present studies establish that there are specific, significant decreases in the neuronal calcium-binding protein (28-kDa calbindin-D) gene expression in aging and in neurodegenerative diseases. The specificity of the changes observed in calbindin mRNA levels was tested by reprobing blots with calmodulin, cyclophilin, and B-actin cDNAs. Gross brain regions of the aging rat exhibited specific, significant decreases (60-80%) in calbindin mRNA and protein levels in the cerebellum, corpus striatum, and brain-stem region but not in the cerebral cortex or hippocampus. Discrete areas of the aging human brain exhibited significant decreases (50-88%) in calbindin protein and mRNA in the cerebellum, corpus striatum, and nucleus basalis but not in the neocortex, hippocampus, amygdala, locus ceruleus, or nucleus raphe dorsalis. Comparison of diseased human brain tissue with age- and sex-matched controls yielded significant decreases (60-88%) in calbindin protein and mRNA in the substantia nigra (Parkinson disease), in the corpus striatum (Huntington disease), in the nucleus basalis (Alzheimer disease), and in the hippocampus and nucleus raphe dorsalis (Parkinson, Huntington, and Alzheimer diseases) but not in the cerebellum, neocortex, amygdala, or locus ceruleus. Since calbindin gene expression decreased specifically in brain areas known to be particularly affected in aging and in each of the neurodegenerative diseases, these findings suggest that decreased calbindin gene expression may lead to a failure of calcium buffering or intraneuronal calcium homeostasis, which contributes to calcium-mediated cytotoxic events during aging and in the pathogenesis of neurodegenerative diseases.
376 citations
Authors
Showing all 14639 results
Name | H-index | Papers | Citations |
---|---|---|---|
John Q. Trojanowski | 226 | 1467 | 213948 |
Virginia M.-Y. Lee | 194 | 993 | 148820 |
Danny Reinberg | 145 | 342 | 68201 |
Michael F. Holick | 145 | 767 | 107937 |
Tasuku Honjo | 141 | 712 | 88428 |
Arnold J. Levine | 139 | 485 | 116005 |
Aaron T. Beck | 139 | 536 | 170816 |
Charles J. Yeo | 136 | 672 | 76424 |
Jerry W. Shay | 133 | 639 | 74774 |
Chung S. Yang | 128 | 560 | 56265 |
Paul G. Falkowski | 127 | 378 | 64898 |
Csaba Szabó | 123 | 958 | 61791 |
William C. Roberts | 122 | 1117 | 55285 |
Bryan R. Cullen | 121 | 371 | 50901 |
John R. Perfect | 119 | 573 | 52325 |