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Graham Sinden - One of the best experts on this subject based on the ideXlab platform.
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the contribution of PAS 2050 to the evolution of international greenhouse gas emission standards
International Journal of Life Cycle Assessment, 2009Co-Authors: Graham SindenAbstract:Background, aim, and scope The assessment of greenhouse gas (GHG) emissions arising from products (goods and services) is emerging as a high profile application of life cycle assessment (LCA), with an increasing desire from retailers and other supply chain organizations to better understand, and in some cases communicate, the carbon footprint of products. Publicly Available Specification 2050:2008, Specification for the assessment of the life cycle greenhouse gas emissions of goods and services, addresses the single-impact category of global warming to provide a standardized and simplified implementation of process LCA methods for assessing GHG emissions from products. This paper briefly reviews the development process followed for PAS 2050, before examining the treatment of GHG-specific contribution of PAS 2050 to product carbon footprinting.
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the contribution of PAS 2050 to the evolution of international greenhouse gas emission standards
International Journal of Life Cycle Assessment, 2009Co-Authors: Graham SindenAbstract:The assessment of greenhouse gas (GHG) emissions arising from products (goods and services) is emerging as a high profile application of life cycle assessment (LCA), with an increasing desire from retailers and other supply chain organizations to better understand, and in some cases communicate, the carbon footprint of products. Publicly Available Specification 2050:2008, Specification for the assessment of the life cycle greenhouse gas emissions of goods and services, addresses the single-impact category of global warming to provide a standardized and simplified implementation of process LCA methods for assessing GHG emissions from products. This paper briefly reviews the development process followed for PAS 2050, before examining the treatment of GHG-specific contribution of PAS 2050 to product carbon footprinting. PAS 2050 was jointly sponsored by the Carbon Trust and the UK Department for Environment, Food and Rural Affairs and was published by the British Standards Institution on 29 October 2008. An independent steering group oversaw the development of the specification, including the establishment of an expert workgroup program, comprehensive international consultation, and expert input on the requirements of the specification. The development process for PAS 2050 resulted in a specification that includes specific requirements that limit the interpretation of the underlying LCA approach to product carbon footprinting. These requirements, including goal setting and life cycle inventory assessment, aspects of system boundary identification and temporal aspects of GHG emissions, clarify the approach to be taken by organizations implementing product carbon footprinting, and simplify the application of LCA procedures in relation to product carbon footprinting. Assessment of the emissions arising from the life cycle of products has a clear international component, and delivering consistent results across the supply chain requires the application of consistent methods. There is an emerging recognition that further standardization of methods for product carbon footprinting is needed, and the specific requirements resulting from the PAS 2050 development process make a valuable contribution across a range of GHG assessment issues. The widespread interest in PAS 2050 from individuals and organizations, together with the development of similar guidance by other organizations, confirmed that there is a need for clarification, certainty, and requirements in the field of product carbon footprint analysis. The use of PAS 2050 to refine, clarify, and simplify existing LCA methods and standards has resulted in specific approaches to key GHG assessment issues being developed; it is important that future standards development work considers the impact of these approaches and their further refinement. It is the consumption of goods and services by individuals around the world that drives global GHG emission, and PAS 2050 is a first attempt to provide integrated, consistent approaches that directly address the role of consumption at the product level in contributing to GHG emissions. Climate science and GHG assessment techniques are both evolving areas and it will be necessary to review the approach taken by PAS 2050 in the future: a formal review process for PAS 2050 will commence towards the end of 2009 and practitioners are encouraged to participate in this review process.
Murray L Whitelaw - One of the best experts on this subject based on the ideXlab platform.
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hif has biff crosstalk between hif1a and the family of bhlh PAS proteins
Experimental Cell Research, 2017Co-Authors: Emily L Button, David C Bersten, Murray L WhitelawAbstract:Two decades of research into functions of the ubiquitous transcription factor HIF have revealed pervasive roles in development, oxygen homeostasis, metabolism, cancer and responses to ischemia. Unsurprisingly, HIF activities impinge on many pathologies, for which underlying molecular mechanisms are actively sought. HIF is a member of the heterodimeric bHLH/PAS family of transcription factors, a set of proteins that commonly function in developmental pathways and adaptive responses to environmental or physiological stress. Similarities in the mechanisms that regulate gene targeting by these transcription factors create opportunities for extensive crosstalk between family members. Data supporting pathway interactions between HIF1a and other bHLH/PAS factors, both collaborative and antagonistic, is beginning to surface in the areas of cancer, circadian rhythm, and immune responses. This review summarises the status of HIF1a-bHLH/PAS protein crosstalk and is dedicated to the memory of Lorenz Poellinger, a pioneer investigator into the molecular mechanisms of HIF, AHR, and ARNT bHLH/PAS factors.
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bhlh PAS proteins in cancer
Nature Reviews Cancer, 2013Co-Authors: David C Bersten, Adrienne E Sullivan, Daniel J Peet, Murray L WhitelawAbstract:Mammalian basic HLH (helix-loop-helix)-PER-ARNT-SIM (bHLH-PAS) proteins are heterodimeric transcription factors that sense and respond to environmental signals (such as pollutants) or to physiological signals (for example, hypoxia and circadian rhythms) through their two PAS domains. PAS domains form a generic three-dimensional fold, which commonly contains an internal cavity capable of small-molecule binding and outer surfaces adept at protein-protein interactions. These proteins are important in several pro-tumour and antitumour pathways and their activities can be modulated by both natural metabolites and oncometabolites. Recently determined structures and successful small-molecule screening programmes are now providing new opportunities to discover selective agonists and antagonists directed against this multitasking family of transcription factors.
Lorenz Poellinger - One of the best experts on this subject based on the ideXlab platform.
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inhibitory PAS domain protein iPAS is a hypoxia inducible splicing variant of the hypoxia inducible factor 3α locus
Journal of Biological Chemistry, 2002Co-Authors: Yuichi Makino, Arvydas Kanopka, William J Wilson, Hirotoshi Tanaka, Lorenz PoellingerAbstract:Abstract The inhibitory PAS (Per/Arnt/Sim) domain protein, IPAS, functions as a dominant negative regulator of hypoxia-inducible transcription factors (HIFs) by forming complexes with those proteins that fail to bind to hypoxia response elements of target genes. We have previously observed that IPAS is predominantly expressed in mice in Purkinje cells of the cerebellum and in corneal epithelium of the eye where it appears to play a role in negative regulation of angiogenesis and maintenance of an avascular phenotype. Sequencing of the mouse IPAS genomic structure revealed that IPAS is a splicing variant of the HIF-3α locus. Thus, in addition to three unique exons (1a, 4a, and 16) IPAS shares three exons (2, 4, and 5) with HIF-3α as well as alternatively spliced variants of exons 3 and 6. In experiments using normal mice and mice exposed to hypoxia (6% O2) for 6 h we observed alternative splicing of the HIF-3α transcript in the heart and lung. The alternatively spliced transcript was only observed under hypoxic conditions, thus defining a novel mechanism of hypoxia-dependent regulation of gene expression. Importantly, this mechanism may establish negative feedback loop regulation of adaptive responses to hypoxia/ischemia in these tissues.
David C Bersten - One of the best experts on this subject based on the ideXlab platform.
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hif has biff crosstalk between hif1a and the family of bhlh PAS proteins
Experimental Cell Research, 2017Co-Authors: Emily L Button, David C Bersten, Murray L WhitelawAbstract:Two decades of research into functions of the ubiquitous transcription factor HIF have revealed pervasive roles in development, oxygen homeostasis, metabolism, cancer and responses to ischemia. Unsurprisingly, HIF activities impinge on many pathologies, for which underlying molecular mechanisms are actively sought. HIF is a member of the heterodimeric bHLH/PAS family of transcription factors, a set of proteins that commonly function in developmental pathways and adaptive responses to environmental or physiological stress. Similarities in the mechanisms that regulate gene targeting by these transcription factors create opportunities for extensive crosstalk between family members. Data supporting pathway interactions between HIF1a and other bHLH/PAS factors, both collaborative and antagonistic, is beginning to surface in the areas of cancer, circadian rhythm, and immune responses. This review summarises the status of HIF1a-bHLH/PAS protein crosstalk and is dedicated to the memory of Lorenz Poellinger, a pioneer investigator into the molecular mechanisms of HIF, AHR, and ARNT bHLH/PAS factors.
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bhlh PAS proteins in cancer
Nature Reviews Cancer, 2013Co-Authors: David C Bersten, Adrienne E Sullivan, Daniel J Peet, Murray L WhitelawAbstract:Mammalian basic HLH (helix-loop-helix)-PER-ARNT-SIM (bHLH-PAS) proteins are heterodimeric transcription factors that sense and respond to environmental signals (such as pollutants) or to physiological signals (for example, hypoxia and circadian rhythms) through their two PAS domains. PAS domains form a generic three-dimensional fold, which commonly contains an internal cavity capable of small-molecule binding and outer surfaces adept at protein-protein interactions. These proteins are important in several pro-tumour and antitumour pathways and their activities can be modulated by both natural metabolites and oncometabolites. Recently determined structures and successful small-molecule screening programmes are now providing new opportunities to discover selective agonists and antagonists directed against this multitasking family of transcription factors.
Kevin H. Gardner - One of the best experts on this subject based on the ideXlab platform.
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arnt PAS b has a fragile native state structure with an alternative β sheet register nearby in sequence space
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Matthew R Evans, Paul B Card, Kevin H. GardnerAbstract:The aryl hydrocarbon receptor nuclear translocator (ARNT) is a basic helix–loop–helix Period/ARNT/Single-minded (bHLH-PAS) protein that controls various biological pathways as part of dimeric transcriptional regulator complexes with other bHLH-PAS proteins. The two PAS domains within ARNT, PAS-A and PAS-B, are essential for the formation of these complexes because they mediate protein–protein interactions via residues located on their β-sheet surfaces. While investigating the importance of residues in ARNT PAS-B involved in these interactions, we uncovered a point mutation (Y456T) on the solvent-exposed β-sheet surface that allowed this domain to interconvert with a second, stable conformation. Although both conformations are present in equivalent quantities in the Y456T mutant, this can be shifted almost completely to either end point by additional mutations. A high-resolution solution structure of a mutant ARNT PAS-B domain stabilized in the new conformation revealed a 3-residue slip in register and accompanying inversion of the central Iβ-strand. We have demonstrated that the new conformation has >100-fold lower in vitro affinity for its heterodimerization partner, hypoxia-inducible factor 2α PAS-B. We speculate that the pliability in β-strand register is related to the flexibility required of ARNT to bind to several partners and, more broadly, to the abilities of some PAS domains to regulate their activities in response to small-molecule cofactors.
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PAS kinase an evolutionarily conserved PAS domain regulated serine threonine kinase
Proceedings of the National Academy of Sciences of the United States of America, 2001Co-Authors: Jared Rutter, Kevin H. Gardner, C. H. Michnoff, Shannon M. Harper, Steven L McknightAbstract:PAS domains regulate the function of many intracellular signaling pathways in response to both extrinsic and intrinsic stimuli. PAS domain-regulated histidine kinases are common in prokaryotes and control a wide range of fundamental physiological processes. Similarly regulated kinases are rare in eukaryotes and are to date completely absent in mammals. PAS kinase (PASK) is an evolutionarily conserved gene product present in yeast, flies, and mammals. The amino acid sequence of PASK specifies two PAS domains followed by a canonical serine/threonine kinase domain, indicating that it might represent the first mammalian PAS-regulated protein kinase. We present evidence that the activity of PASK is regulated by two mechanisms. Autophosphorylation at two threonine residues located within the activation loop significantly increases catalytic activity. We further demonstrate that the N-terminal PAS domain is a cis regulator of PASK catalytic activity. When the PAS domain-containing region is removed, enzyme activity is significantly increased, and supplementation of the purified PAS-A domain in trans selectively inhibits PASK catalytic activity. These studies define a eukaryotic signaling pathway suitable for studies of PAS domains in a purified in vitro setting.