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Temporal Requirements (temporal + requirement)

Distribution by Scientific Domains

Life Sciences	75%

Selected Abstracts

Temporal requirements of insulin/IGF-1 signaling for proteotoxicity protection

AGING CELL, Issue 2 2010
Ehud Cohen
Summary Toxic protein aggregation (proteotoxicity) is a unifying feature in the development of late-onset human neurodegenerative disorders. Reduction of insulin/IGF-1 signaling (IIS), a prominent lifespan, developmental and reproductive regulatory pathway, protects worms from proteotoxicity associated with the aggregation of the Alzheimer's disease-linked A, peptide. We utilized transgenic nematodes that express human A, and found that late life IIS reduction efficiently protects from A, toxicity without affecting development, reproduction or lifespan. To alleviate proteotoxic stress in the animal, the IIS requires heat shock factor (HSF)-1 to modulate a protein disaggregase, while DAF-16 regulates a presumptive active aggregase, raising the question of how these opposing activities could be co-regulated. One possibility is that HSF-1 and DAF-16 have distinct temporal requirements for protection from proteotoxicity. Using a conditional RNAi approach, we found an early requirement for HSF-1 that is distinct from the adult functions of DAF-16 for protection from proteotoxicity. Our data also indicate that late life IIS reduction can protect from proteotoxicity when it can no longer promote longevity, strengthening the prospect that IIS reduction might be a promising strategy for the treatment of neurodegenerative disorders caused by proteotoxicity. [source]

Protein degradation, as with protein synthesis, is required during not only long-term spatial memory consolidation but also reconsolidation

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2008
Julien Artinian
Abstract The formation of long-term memory requires protein synthesis, particularly during initial memory consolidation. This process also seems to be dependant upon protein degradation, particularly degradation by the ubiquitin-proteasome system. The aim of this study was to investigate the temporal requirement of protein synthesis and degradation during the initial consolidation of allocentric spatial learning. As memory returns to a labile state during reactivation, we also focus on the role of protein synthesis and degradation during memory reconsolidation of this spatial learning. Male CD1 mice were submitted to massed training in the spatial version of the Morris water maze. At various time intervals after initial acquisition or after a reactivation trial taking place 24 h after acquisition, mice received an injection of either the protein synthesis inhibitor anisomycin or the protein degradation inhibitor lactacystin. This injection was performed into the hippocampal CA3 region, which is specifically implicated in the processing of spatial information. Results show that, in the CA3 hippocampal region, consolidation of an allocentric spatial learning task requires two waves of protein synthesis taking place immediately and 4 h after acquisition, whereas reconsolidation requires only the first wave. However, for protein degradation, both consolidation and reconsolidation require only one wave, taking place immediately after acquisition or reactivation, respectively. These findings suggest that protein degradation is a key step for memory reconsolidation, as for consolidation. Moreover, as protein synthesis-dependent reconsolidation occurred faster than consolidation, reconsolidation did not consist of a simple repetition of the initial consolidation. [source]

The role of pdx1 and HNF6 in proliferation and differentiation of endocrine precursors

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2004
Laura Wilding
Abstract Ex vivo expansion of embryonic stem cells (ES cells) or pancreatic stem cells for insulin delivery to diabetic patients provides potential for the restoration of islet function in these individuals. Understanding the spatial and temporal requirements of crucial factors for endocrine progenitor specification, proliferation, and terminal differentiation remains a major challenge in the field of pancreas development. Here, we provide speculation as to the role of pdx1 and HNF6 in these different stages of pancreatic endocrine cell development. At the time when islets begin to form within the pancreas, the expression patterns of pdx1 and HNF6 diverge, suggesting distinct functions for each of the genes over the course of endocrine cell development. The current body of evidence provides support for a role of both factors in early endocrine specification as well as a requirement for pdx1 in the generation of mature pancreatic endocrine cells. The precise temporal requirement of HNF6 in the production of terminally differentiated endocrine cells remains unclear. Future studies in this area will rely on conditionally manipulatable systems in combination with lineage-tracing studies for a more accurate assessment of pdx1 and HNF6 function at different stages along the pathway of endocrine cell development. Copyright © 2004 John Wiley & Sons, Ltd. [source]