Author
Michael H. Hastings
Other affiliations: Vanderbilt University, University of Cambridge, Rowett Research Institute ...read more
Bio: Michael H. Hastings is an academic researcher from Laboratory of Molecular Biology. The author has contributed to research in topics: Circadian rhythm & Circadian clock. The author has an hindex of 78, co-authored 226 publications receiving 23486 citations. Previous affiliations of Michael H. Hastings include Vanderbilt University & University of Cambridge.
Papers published on a yearly basis
Papers
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TL;DR: It is determined that two mouse cryptochrome genes, mCry1 and mCry2, act in the negative limb of the clock feedback loop, and the mPER and mCRY proteins appear to inhibit the transcriptional complex differentially.
1,507 citations
TL;DR: Analysis of Clock/Clock mutant mice, homozygous Period2(Brdm1) mutants, and Cryptochrome-deficient mice reveals substantially altered Bmal1 rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the Bmal 1 loop.
Abstract: We show that, in the mouse, the core mechanism for the master circadian clock consists of interacting positive and negative transcription and translation feedback loops. Analysis of Clock/Clock mutant mice, homozygous Period2(Brdm1) mutants, and Cryptochrome-deficient mice reveals substantially altered Bmal1 rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the Bmal1 loop. In vitro analysis of CRYPTOCHROME inhibition of CLOCK: BMAL1-mediated transcription shows that the inhibition is through direct protein:protein interactions, independent of the PERIOD and TIMELESS proteins. PERIOD2 is a positive regulator of the Bmal1 loop, and CRYPTOCHROMES are the negative regulators of the Period and Cryptochrome cycles.
1,320 citations
TL;DR: The discovery of these local circadian clocks forces a re-appraisal of established models of circadian biology and presents new avenues for therapeutic intervention in conditions where disturbance of circadian gene expression is an important cause of morbidity.
Abstract: The hypothalamic suprachiasmatic nuclei (SCN) are our principal circadian oscillator, coordinating daily cycles of physiology and behaviour that adapt us to the world. Local versions of the SCN clockwork are also active in peripheral, non-neural tissues, driving the tissue-specific cycles of gene expression that underpin circadian organization. These local oscillators are tuned to each other, and to solar time, by neuroendocrine and metabolic cues that depend on the SCN. The discovery of these local circadian clocks forces a re-appraisal of established models of circadian biology. It also presents new avenues for therapeutic intervention in conditions where disturbance of circadian gene expression is an important cause of morbidity.
1,100 citations
TL;DR: It is confirmed that mPER1 influences rhythmicity primarily through interaction with other clock proteins, while mPER2 positively regulates rhythmic gene expression, and there is partial compensation between products of these two genes.
858 citations
TL;DR: Temporally complex, circadian programming of the transcriptome in a peripheral organ is imposed across a wide range of core cellular functions and is dependent on an interaction between intrinsic, tissue-specific factors and extrinsic regulation by the SCN central pacemaker.
789 citations
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TL;DR: The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or her own research.
Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or
7,563 citations
Book•
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TL;DR: The brain's default state: self-organized oscillations in rest and sleep, and perturbation of the default patterns by experience.
Abstract: Prelude. Cycle 1. Introduction. Cycle 2. Structure defines function. Cycle 3. Diversity of cortical functions is provided by inhibition. Cycle 4. Windows on the brain. Cycle 5. A system of rhythms: from simple to complex dynamics. Cycle 6. Synchronization by oscillation. Cycle 7. The brain's default state: self-organized oscillations in rest and sleep. Cycle 8. Perturbation of the default patterns by experience. Cycle 9. The gamma buzz: gluing by oscillations in the waking brain. Cycle 10. Perceptions and actions are brain state-dependent. Cycle 11. Oscillations in the "other cortex:" navigation in real and memory space. Cycle 12. Coupling of systems by oscillations. Cycle 13. The tough problem. References.
4,266 citations
TL;DR: Circadian rhythms are generated by one of the most ubiquitous and well-studied timing systems and are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input it receives from the outside world.
Abstract: Time in the biological sense is measured by cycles that range from milliseconds to years. Circadian rhythms, which measure time on a scale of 24 h, are generated by one of the most ubiquitous and well-studied timing systems. At the core of this timing mechanism is an intricate molecular mechanism that ticks away in many different tissues throughout the body. However, these independent rhythms are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input it receives from the outside world.
3,962 citations
TL;DR: It used to be that research in chronobiology moved biochemical functions [transcriptional activators], the along at a gentlemanly pace, but by mid 1997 the word in determining what the authors perceive as time was PASWCCLK.
2,723 citations
TL;DR: Recent advances in the study of mitogen-activated protein kinase cascades include the cloning of genes encoding novel members of the cascades, further definition of the roles of the cascade in responses to extracellular signals, and examination of cross-talk between different cascades.
2,569 citations