Recognising the attraction of sugars at the cell surface.
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Animals↗
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Results for “Autobiography”
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Mutation frequency decline revisited.
'Mutation frequency decline' (MFD) was discovered about forty years ago, and described as the disappearance of a particular class of ultraviolet light-induced mutations in Escherichia coli that occurred whenever protein synthesis was briefly inhibited immediately after irradiation. Later, MFD was interpreted as an excision repair anomaly uniquely affecting nonsense suppressor mutations induced in certain tRNA genes. Never fully understood, MFD has recently been linked to the newly discovered transcription-coupled rapid repair of ultraviolet damage on the template strand of active genes. This article recalls the emergence and development of the MFD story, and offers a new way to explain it and its relation to strand-specific excision repair.
Bacterial Proteins↗
The thymus: maestro of the immune system.
The thymus has been an enigmatic organ for centuries. Its true function was revealed only in 1961 when it was shown to be responsible for the proper development of the immune system. This finding has revolutionized the science of immunology and has led to a better understanding of the mechanisms involved in resistance to infections and of the pathogenesis of autoimmune and immunodeficiency diseases.
Animals↗
The discovery of protein phosphatases: from chaos and confusion to an understanding of their role in cell regulation and human disease.
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Animals↗
Surrogate cells or Trojan horses. The discovery of liposomes.
An autobiographical account of the liposome, from the perplexities of a blood smear to the growth of a multi-million pound business.
History, 20th Century↗
DNA filter elution: a window on DNA damage in mammalian cells.
This personal account traces a series of studies that led from DNA physical chemistry to anticancer drug mechanisms. Chemical crosslinking as a basis for anticancer drug actions had been suspected since the time of the first clinical reports of the effectiveness of nitrogen mustard in 1946. After the elucidation of the DNA helix-coil transition, several nearly concurrent findings in the early 1960s established the paradigm of DNA interstrand crosslinking. The DNA filter elution phenomenon was discovered in the early 1970s, and lent itself to the development of practical assays for DNA crosslinks and other DNA lesions in mammalian cells. The assays allowed studies of the effects of DNA damaging agents at pharmacologically or toxicologically relevant doses, and have been widely applied in studies of mutagenic and chemotherapeutic agents. During the period 1979-1986, DNA filter elution studies led to the paradigm of DNA topoisomerases as targets of anticancer drug action, and this has become one of the most active areas of anticancer drug development.
Animals↗
In pursuit of influenza: Fort Monmouth to Valhalla (and back).
In reviewing 50 years of personal research on influenza, I have journeyed, literally and figuratively, from an army camp epidemic in Fort Monmouth NJ in 1947 to a (literal and figurative) Valhalla, where I now conduct my research. Having entered the field as a physician, I have always sought practical applications of my work, yet in every instance, such applications have led me to seek further answers in basic research as new questions arose. I entered the area of influenza virus genetics by the back door through an interest in the effects of corticosteroid hormones on viral replication, used the genetic approach in analyzing the morphological variation of the virus and, in so doing, exploited the finding of a linkage of high-yield growth to spherical morphology. Today, all influenza vaccine viruses are high-yield genetic reassortants. Subsequent study of reassortant viruses facilitated the identification and isolation of the two major antigens of the virus in antigenic hybrids and showed their differing functions in the induction of immunity. In turn, a new approach to influenza vaccination has been discovered and is presently under clinical investigation.
Adrenal Cortex Hormones↗
From bioenergetics to philosophy of science: a brief report of an exciting cultural journey.
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Animals↗
Molecular dynamics of biological macromolecules: a brief history and perspective.
A description of the origin of my interest in and the development of molecular dynamics simulations of biomolecules is presented with a historical overview, including the role of my interactions with Shneior Lifson and his group in Israel. Some early applications of the methodology by members of my group are summarized, followed by a description of examples of recent applications and some discussion of possible future directions.
Biopolymers↗
No thank you kindly.
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Angioplasty, Balloon, Coronary↗
Mechanisms of flagellar motility probed with microtechniques.
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Animals↗
Social phobia and the recall of autobiographical memories.
Although cognitive theories of anxiety suggest that anxious individuals are characterized by the biased tendency to recall negative experiences with perceived threat, few empirical studies have confirmed this notion. To investigate personal memories associated with threatening experiences, individuals with socio phobia (n=16) and nonanxious individuals (n=17) completed an autobiographical memory-cueing procedure. Participants were presented with 15 social threat words and 15 neutral words, and they recorded the first specific memory that came to mind. Autobiographical memories were coded for specificity and affective tone. There were no group differences in the extent to which participants retrieved specific memories. A greater number of memories cued by social threat words were characterized by negative affect in the social phobia group than in the nonanxious group. However, examination of the means suggests that this effect was small and most likely not of practical significance. It is suggested that memory biases toward threat are not a prominent part of cognitive symptoms that characterize individuals with social phobia.
Affect↗
Interview between Lindsay Peer and Bob Turney.
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Adult↗
From bacteria to humans: lessons learned from a reductionist's view of ultraviolet light-induced DNA lesions.
What follows is a personal remembrance of how Dr. Richard Setlow influenced me as a young postdoctoral fellow at Oak Ridge National laboratory between 1963 and 1966. The narrative tries to place my "maturation" as a young, inexperienced scientist in the context of the cultural upheaval caused by the Vietnam war, of a Northerner facing a "culture-shock" living in the South and in a revolution in molecular and radiation biology taking place at Oak Ridge National Laboratory at that time. The unique historic juxtaposition of Dr. Setlow's contribution of the discovery of UV-induced pyrimidine dimers in bacterial DNA, being potentially the molecular lesion responsible for cell killing and mutagenesis, occurring as I was at Oak Ridge, and the wonderful working relationship I had with William Carrier, his technician, led to our discovery with James Regan that normal human cells repaired these lesion from their DNA. Amazingly, because of Dr. Setlow's challenge to me about my thoughts of the implications of his findings in bacteria, the chance visit to Oak Ridge National Laboratory by Dr. James Cleaver and my background as a human geneticist provided me the extraordinary opportunity to carry out a collaboration to test if human cancer prone syndromes might be deficient in the repair of these UV-induced DNA lesions. With our finding that the direct demonstration of a lack of repair of UV-induced pyrimidine dimers in cells from the skin cancer prone syndrome, xeroderma pigmentosum, opened up a new paradigm for the understanding of the molecular mechanism of carcinogenesis of both radiation and chemical carcinogenesis. From this investigator's vantage point in the history of the understanding of carcinogenesis, which has led us to the present point of "oncogenes" and "tumor suppressor genes", the old adage by Newton, "I only saw further because I stood on the shoulder of giants", is so applicable here. Dr. Setlow's shoulders were indeed among those of all of us that have made some small contribution in trying to understand this extremely complex process of human carcinogenesis.
Bacteria↗
At the birth of molecular radiation biology.
Rational thinking builds on feelings, too. This article starts with a tribute to Richard Setlow, an eminent scientist; it retraces as well some studies in molecular genetics that helped to understand basic questions of radiation biology. In the mid-1950s, the induction of a dormant virus (prophage) by irradiation of its host was an intriguing phenomenon. Soon, it was found that prophage induction results from the inactivation of the prophage repressor. Similarly, a score of induced cellular SOS functions were found to be induced when the LexA repressor is inactivated. Repressor inactivation involves the formation of a newly formed distinctive structure: a RecA-polymer wrapped around single-stranded DNA left by the arrest of replication at damaged sites. By touching this RecA nucleofilament, the LexA repressor is inactivated, triggering the sequential expression of SOS functions. The RecA nucleofilament acts as a chaperone, allowing recombinational repair to occur after nucleotide excision repair is over. The UmuD'C complex, synthesized slowly and parsimoniously, peaks at the end of recombinational repair, ready to be positioned at the tip of a RecA nucleofilament, placing the UmuD'C complex right at a lesion. At this location, UmuD'C prevents recombinational repair, and now acts as an error-prone paucimerase that fills the discontinuity opposite the damaged DNA. Finally, the elimination of lesions from the path of DNA polymerase, allows the resumption of DNA replication, and the SOS repair cycle switches to a normal cell cycle.
Animals↗
Concern for environmental mutagens: some personal reminiscences.
This article is a personal, anecdotal account of the early days of concern for environmental mutagenesis. The history of the original National Academy of Sciences Committee on the Biological Effects of Atomic Radiations (BEAR) and its early controversies are reviewed, along with the initial establishment of principles for discovering potential chemical mutagens. Although it emphasizes the great advances in cellular and molecular understanding over the past 35 years, the article ends with a pessimistic assessment of any possibility of quantitative assessment of mutational impacts on future generations.
Carcinogens, Environmental↗
Reminiscences of a mouse specific-locus test addict.
This paper describes some of the historical events surrounding the development of and achievements with the mouse specific-locus test in radiation and chemical mutagenesis. Some ongoing and future contributions of the test to research in molecular genetics are also mentioned.
Animals↗