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JournalISSN: 0892-6638

The FASEB Journal 

Federation of American Societies for Experimental Biology
About: The FASEB Journal is an academic journal published by Federation of American Societies for Experimental Biology. The journal publishes majorly in the area(s): Medicine & Biology. It has an ISSN identifier of 0892-6638. Over the lifetime, 38888 publications have been published receiving 1248867 citations. The journal is also known as: FASEB J & The FASEB Journal.


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Journal ArticleDOI
TL;DR: BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function, and is advocated as a factor when converting a dose for translation from animals to humans.
Abstract: As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.

5,054 citations

Journal ArticleDOI
Carl Nathan1
TL;DR: How different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule is reviewed.
Abstract: Evolution has resorted to nitric oxide (NO), a tiny, reactive radical gas, to mediate both servoregulatory and cytotoxic functions. This article reviews how different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule.

4,149 citations

Journal ArticleDOI
TL;DR: Sir Walter Bodmer shares his perspective regarding the principles of successful scientific management from his experience in leading the Imperial Cancer Research Fund (ICRF) as well as his being in the forefront of science.
Abstract: coupled with general fiscal difficulties are hindering realization of knowledge and benefit to society. The solution requires more than the corporate mold of The increasing politicization of the support of science has awakened many a scientist to the risks and realities of survival as an investigator and to the threats to the future of science. Effective management and wise leadership of the scientific enterprise are necessary solutions to the dilemma. Sir Walter Bodmer shares his perspective regarding the principles of successful scientific management from his experience in leading the Imperial Cancer Research Fund (ICRF) as well as his being in the forefront of science. Yes! Management is necessary. But to be effective it must not displace leadership or the recognition and pursuit of excellence. It must be nonintrusive. Naive management imperatives in management. It must encompass a variety of actions based in the fundamental principle that management supports the optimal conduct of science. Dr. Bodmer guides us through these principles with clarity, experience, and vision. The principles of excellence, balance, and strategic insight have each been key ingredients in the success of the ICRF and are applicable at large.

4,074 citations

Journal ArticleDOI
TL;DR: Recent developments that have widened considerably the understanding of the mechanisms that control V EGF production and VEGF signal transduction are focused on and recent studies that have shed light on the mechanisms by which VEGf regulates angiogenesis are reviewed.
Abstract: Vascular endothelial growth factor (VEGF) is a highly specific mitogen for vascular endothelial cells. Five VEGF isoforms are generated as a result of alternative splicing from a single VEGF gene. These isoforms differ in their molecular mass and in biological properties such as their ability to bind to cell-surface heparan-sulfate proteoglycans. The expression of VEGF is potentiated in response to hypoxia, by activated oncogenes, and by a variety of cytokines. VEGF induces endothelial cell proliferation, promotes cell migration, and inhibits apoptosis. In vivo VEGF induces angiogenesis as well as permeabilization of blood vessels, and plays a central role in the regulation of vasculogenesis. Deregulated VEGF expression contributes to the development of solid tumors by promoting tumor angiogenesis and to the etiology of several additional diseases that are characterized by abnormal angiogenesis. Consequently, inhibition of VEGF signaling abrogates the development of a wide variety of tumors. The various VEGF forms bind to two tyrosine-kinase receptors, VEGFR-1 (flt-1) and VEGFR-2 (KDR/flk-1), which are expressed almost exclusively in endothelial cells. Endothelial cells express in addition the neuropilin-1 and neuropilin-2 coreceptors, which bind selectively to the 165 amino acid form of VEGF (VEGF165). This review focuses on recent developments that have widened considerably our understanding of the mechanisms that control VEGF production and VEGF signal transduction and on recent studies that have shed light on the mechanisms by which VEGF regulates angiogenesis.

3,569 citations

Journal ArticleDOI
TL;DR: This review highlights primarily the first MAPK cascade to be discovered that uses the MEK and ERK isoforms and describes their involvement in different cellular processes, and it is now known that signaling pathways initiated by phorbol esters, iono‐phors, heat shock, and liganda for seven transmembrane receptors use distinct MAPK cascades with little or no cross‐reactivity between them.
Abstract: The transmission of extracellular signals into their intracellular targets is mediated by a network of interacting proteins that regulate a large number of cellular processes. Cumulative efforts from many laboratories over the past decade have allowed the elucidation of one such signaling mechanism, which involves activations of several membranal signaling molecules followed by a sequential stimulation of several cytoplasmic protein kinases collectively known as mitogen-activated protein kinase (MAPK) signaling cascade. Up to six tiers in this cascade contribute to the amplification and specificity of the transmitted signals that eventually activate several regulatory molecules in the cytoplasm and in the nucleus to initiate cellular processes such as proliferation, differentiation, and development. Moreover, because many oncogenes have been shown to encode proteins that transmit mitogenic signals upstream of this cascade, the MAPK pathway provides a simple unifying explanation for the mechanism of action...

3,548 citations

Performance
Metrics
No. of papers from the Journal in previous years
YearPapers
2023632
20226,405
2021928
20201,896
20191,765
20181,103