The existence of an internal biological clock has been known since ancient times, but the inner workings of that clock—what makes life on earth tick—remained a mystery until the three American geneticists investigated the clock’s inner workings and explained how plants, mammals, and humans adapt their circadian rhythm to synchronize with the Earth’s rotation. In the 18th century, a French astronomer Jean Jacques d’Ortous de Mairan observed how mimosa plants opened and closed their leaves in response to sunrise and sunset, even when placed in complete darkness. He concluded that the plant had its own biological mechanism— the circadian rhythm—that enabled it to respond to these fluctuations. Over 200 years later, American researchers Seymour Benzer and Ronald Konopka demonstrated how mutations in an unknown gene disrupted the circadian clock of fruit flies. They named the mutation period, but their findings did not apply to humans nor did they explain how the phenomenon came about. These studies on fruit flies formed the foundation for Hall and Rosbash’s work in the early 1980s at Brandeis University in Boston. Young, meanwhile, was working independently at Rockefeller University in New York to isolate the period gene. Hall and Rosbash discovered that PER, the protein encoded by period, accumulated during the night and degraded during the day and that it oscillated over a 24-h cycle in synchronization with the circadian rhythm. How these circadian oscillations could be generated and sustained remained unclear. The pair hypothesized that the PER protein blocked the activity of the period gene via an ‘inhibitory feedback loop’ and could thus prevent its own synthesis and thereby regulate its own level in a continuous, cyclic rhythm (Figure 1). However, in order to block the activity of the period gene, PER protein, which is produced in the cytoplasm, would have to reach the genetic material in the cell nucleus. To fully understand how PER protein builds up in the nucleus during the night, Hall and Rosbash needed to identify how it got there. In 1994, Young discovered a second clock gene, timeless, encoding the TIM protein that was required for a normal circadian rhythm. He showed that when TIM bound to PER, the two proteins were able to enter the cell nucleus where they blocked period gene activity to close the inhibitory feedback loop (Figure 2). This however, failed to identify what controlled the frequency of the oscillations until Young identified another gene, doubletime, encoding the DBT protein that delayed the accumulation of the PER protein. This explained how an oscillation is more closely adjusted to match a 24-h cycle. Together, these discoveries provided a ‘key’ by establishing the mechanistic principles which ‘unlocked’ the inner workings of the biological clock and identified how the component parts work together. These ‘fundamental brilliant studies’ were credited with solving one of the great puzzles in physiology and were judged to
{"title":"Nobel Laureate Series What Makes Us Tick?","authors":"Jeffrey C. Hall, M. Rosbash, Michael W. Young","doi":"10.5860/choice.27-6684","DOIUrl":"https://doi.org/10.5860/choice.27-6684","url":null,"abstract":"The existence of an internal biological clock has been known since ancient times, but the inner workings of that clock—what makes life on earth tick—remained a mystery until the three American geneticists investigated the clock’s inner workings and explained how plants, mammals, and humans adapt their circadian rhythm to synchronize with the Earth’s rotation. In the 18th century, a French astronomer Jean Jacques d’Ortous de Mairan observed how mimosa plants opened and closed their leaves in response to sunrise and sunset, even when placed in complete darkness. He concluded that the plant had its own biological mechanism— the circadian rhythm—that enabled it to respond to these fluctuations. Over 200 years later, American researchers Seymour Benzer and Ronald Konopka demonstrated how mutations in an unknown gene disrupted the circadian clock of fruit flies. They named the mutation period, but their findings did not apply to humans nor did they explain how the phenomenon came about. These studies on fruit flies formed the foundation for Hall and Rosbash’s work in the early 1980s at Brandeis University in Boston. Young, meanwhile, was working independently at Rockefeller University in New York to isolate the period gene. Hall and Rosbash discovered that PER, the protein encoded by period, accumulated during the night and degraded during the day and that it oscillated over a 24-h cycle in synchronization with the circadian rhythm. How these circadian oscillations could be generated and sustained remained unclear. The pair hypothesized that the PER protein blocked the activity of the period gene via an ‘inhibitory feedback loop’ and could thus prevent its own synthesis and thereby regulate its own level in a continuous, cyclic rhythm (Figure 1). However, in order to block the activity of the period gene, PER protein, which is produced in the cytoplasm, would have to reach the genetic material in the cell nucleus. To fully understand how PER protein builds up in the nucleus during the night, Hall and Rosbash needed to identify how it got there. In 1994, Young discovered a second clock gene, timeless, encoding the TIM protein that was required for a normal circadian rhythm. He showed that when TIM bound to PER, the two proteins were able to enter the cell nucleus where they blocked period gene activity to close the inhibitory feedback loop (Figure 2). This however, failed to identify what controlled the frequency of the oscillations until Young identified another gene, doubletime, encoding the DBT protein that delayed the accumulation of the PER protein. This explained how an oscillation is more closely adjusted to match a 24-h cycle. Together, these discoveries provided a ‘key’ by establishing the mechanistic principles which ‘unlocked’ the inner workings of the biological clock and identified how the component parts work together. These ‘fundamental brilliant studies’ were credited with solving one of the great puzzles in physiology and were judged to","PeriodicalId":76257,"journal":{"name":"Nursing mirror","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71035245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I like nothing so much as a good philosophical discussion. For one thing, it just feels so delightfully scientific to be bandying about high minded terms like "epistemology," "ontology," "realism," "relativism," and "paradigm" with great abandon. For another thing, it is simply essential in my view of the world of science to which I enjoy belonging that one should be fully engaged in the ethical and normative underpinnings of scientific practice. That, to me, operationally characterizes philosophy of science. Our scientific philosophies facilitate the debating, codifying, and explicating of our "agreed-to rules of the road" for doing our work. They are our scientific code of conduct, so to speak. In my way of thinking, the rules of the road are important for all good researchers to understand and share if we are to hew faithfully to our paradigms and do good normal science research. The problem for me is that I see the emerging debate over whether our field is a science or not through two distinct lenses, and I'm getting some parallax out of it. I've earned two doctorates at two different stages of my career; one in marketing when I was much younger, and one more recently in information systems. That does not make me any smarter than the average bear, and it could certainly be argued that it's a sure sign of not being smarter, since one could say I had to do it twice to get it right. Yet, it has afforded me a very unique perspective on the emerging ontological debate about our discipline because, quite literally, I Have Been There Before! I've studied the Philosophy of Science two fulsome times in my career, and I've gotten some interesting perspectives each time as each was in the midst of an existential debate over status, and both of these experience bear upon my agenda-setting here, as an editor. While learning my scientific craft as a first-time doctoral student in marketing, I reveled in the debate that much of academic marketing was enmeshed in during the 80s on whether marketing was a science or a technology and if a science, how best to be practiced. We future scientists all read Kuhn (1970) in our philosophy of science seminar, as well as Dubin (1978) and a flock of excellent philosophical essays collected in a tome edited by the redoubtable Jagdish Sheth (Sheth & Garrett, 1986) - a philosophy of science volume that many in marketing and elsewhere still use, aged though it might be. We marketers also saw a collection of philosophical essays by thought leaders of the field under such titles as "Marketing, Scientific Progress, and the Scientific Method" (Anderson, 1983), "On Making Marketing Science more Scientific" (Arndt, 1985), "Paradigms Lost" (Deshpande, 1983), and "Metatheory and Metamethodology in Marketing" (Leong, 1985). The debate in marketing continued well past that point and has extended into recent years (e.g., Brown, 1996; Easton, 2002), indicating that the debate we have now in information systems has years yet to go. I
{"title":"Philosophically Speaking...","authors":"Thomas F. Stafford","doi":"10.1145/3290768.3290770","DOIUrl":"https://doi.org/10.1145/3290768.3290770","url":null,"abstract":"I like nothing so much as a good philosophical discussion. For one thing, it just feels so delightfully scientific to be bandying about high minded terms like \"epistemology,\" \"ontology,\" \"realism,\" \"relativism,\" and \"paradigm\" with great abandon. For another thing, it is simply essential in my view of the world of science to which I enjoy belonging that one should be fully engaged in the ethical and normative underpinnings of scientific practice. That, to me, operationally characterizes philosophy of science. Our scientific philosophies facilitate the debating, codifying, and explicating of our \"agreed-to rules of the road\" for doing our work. They are our scientific code of conduct, so to speak. In my way of thinking, the rules of the road are important for all good researchers to understand and share if we are to hew faithfully to our paradigms and do good normal science research.\u0000 The problem for me is that I see the emerging debate over whether our field is a science or not through two distinct lenses, and I'm getting some parallax out of it. I've earned two doctorates at two different stages of my career; one in marketing when I was much younger, and one more recently in information systems. That does not make me any smarter than the average bear, and it could certainly be argued that it's a sure sign of not being smarter, since one could say I had to do it twice to get it right. Yet, it has afforded me a very unique perspective on the emerging ontological debate about our discipline because, quite literally, I Have Been There Before! I've studied the Philosophy of Science two fulsome times in my career, and I've gotten some interesting perspectives each time as each was in the midst of an existential debate over status, and both of these experience bear upon my agenda-setting here, as an editor. \u0000 While learning my scientific craft as a first-time doctoral student in marketing, I reveled in the debate that much of academic marketing was enmeshed in during the 80s on whether marketing was a science or a technology and if a science, how best to be practiced. We future scientists all read Kuhn (1970) in our philosophy of science seminar, as well as Dubin (1978) and a flock of excellent philosophical essays collected in a tome edited by the redoubtable Jagdish Sheth (Sheth & Garrett, 1986) - a philosophy of science volume that many in marketing and elsewhere still use, aged though it might be. We marketers also saw a collection of philosophical essays by thought leaders of the field under such titles as \"Marketing, Scientific Progress, and the Scientific Method\" (Anderson, 1983), \"On Making Marketing Science more Scientific\" (Arndt, 1985), \"Paradigms Lost\" (Deshpande, 1983), and \"Metatheory and Metamethodology in Marketing\" (Leong, 1985). The debate in marketing continued well past that point and has extended into recent years (e.g., Brown, 1996; Easton, 2002), indicating that the debate we have now in information systems has years yet to go. I","PeriodicalId":76257,"journal":{"name":"Nursing mirror","volume":"151 12 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2018-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1145/3290768.3290770","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41710499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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