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[
Science,
1995]
Programmed cell death (PCD), or apoptosis, is a conserved terminal differentiation program that multicellular organisms have evolved to get rid of cells that are not needed, that are in the way, or that are potentially dangerous. PCD can be equated with cell suicide in the sense that the dying cell plays an active role in promoting its own demise and removal from the organism.
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[
Hist Philos Life Sci,
2000]
The transformation of embryology to developmental biology has been linked to the introduction of experimental approaches from molecular genetics to the study of development. This paper pursues this theme by analyzing the tools molecular biologists, moving from phage and bacterial genetics to the study of development in higher organisms, brought to their new field of investigations. The paper focuses on Sydney Brenner's move from molecular genetics to developmental biology. His attempt to turn the nematode worm Caenorhabditis elegans into a new tool for the study of development included a vast and ever expanding mapping program. Worm workers themselves did not distinguish sharply between mapping on the cellular, chromosomal or molecular level. Mapping, the paper argues, or more generally 'analytical/comparative' next to 'experimentalist' approaches (Pickstone) were not only part and parcel of Brenner's strategy to 'molecularize' the study of development, but also played a crucial role in 'classical' molecular biology.
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[
Int J Dev Biol,
2000]
1969 was a landmark year. But for me it was not Neil Armstrong's giant leap or Woodstock heralding the beginning of the end of the sixties that sticks in my mind. It was a visit I made to Cambridge to meet a "bloke who is starting a new project to study some sort of worm", as my head of department at the Medical Research Council's National Institute of Medical Research informed me...
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[
Science,
2002]
The nematode worm known as Caenorhabditis elegans is not much to look at. Just a millimeter long and transparent to boot, it is almost invisible to the naked eye. But in biological research the tiny worm looms large, providing a model system for studying everything from embryonic development to aging. Now, three researchers who pioneered the use of C. elegans as a model organism have won the Nobel Prize in Physiology or Medicine.
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[
Genetics,
1989]
Just over 21 years ago, in October of 1967, Sydney Brenner soaked a culture of hermaphroditic nematodes of the species Caenorhabditis elegans in a solution of ethyl methane sulfonate. A week later, examining their F2 descendants, he noticed a short, "dumpy" animal among the long, thin wild-type worms. The dumpy animal was picked to a separate culture plate and allowed to produce self-progeny, which were also dumpy: it was a true-breeding mutant. The new strain was given the name E1. Crosses with the parental wild-type strain showed that the mutant phenotype was due to a single autosomal recessive mutation - in modern nomenclature, allele
e1 of the gene
dpy-1.
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[
Genetics,
2015]
A little over 50 years ago, Sydney Brenner had the foresight to develop the nematode (round worm) Caenorhabditis elegans as a genetic model for understanding questions of developmental biology and neurobiology. Over time, research on C. elegans has expanded to explore a wealth of diverse areas in modern biology including studies of the basic functions and interactions of eukaryotic cells, host-parasite interactions, and evolution. C. elegans has also become an important organism in which to study processes that go awry in human diseases. This primer introduces the organism and the many features that make it an outstanding experimental system, including its small size, rapid life cycle, transparency, and well-annotated genome. We survey the basic anatomical features, common technical approaches, and important discoveries in C. elegans research. Key to studying C. elegans has been the ability to address biological problems genetically, using both forward and reverse genetics, both at the level of the entire organism and at the level of the single, identified cell. These possibilities make C. elegans useful not only in research laboratories, but also in the classroom where it can be used to excite students who actually can see what is happening inside live cells and tissues.
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[
Exp Oncol,
2012]
The story of cell death began with the origins of cell biology, including important observations by Elie (Ilya) Metchnikoff, who realized that phagocytes engulfed dying cells. Most of the early studies were observational. By the middle of the 20th C, researchers were beginning to explore how cells died, had recognized that cell death was a physiologically controlled process, that the most common mode of death ("shrinkage necrosis", later apoptosis) was tightly controlled, and were speculating whether lysosomes were "suicide bags". Just prior to 1990 several discoveries led to rapid expansion of interest in the field and elucidation of the mechanisms of apoptosis. Closer to the beginning of the 21st C comprehensive analysis of the molecules that controlled and effected apoptosis led to the conclusion that autophagic processes were linked to apoptosis and could serve to limit or increase cell death. Today, realizing that knowledge of the components of cell death has not yet produced pharmaceuticals of therapeutic value, research is turning to questions of what metabolic or other mechanisms indirectly control the activation or suppression of the cell death positive feedback loop. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later"
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[
Stud Hist Philos Biol Biomed Sci,
2012]
This paper argues that the history of the computer, of the practice of computation and of the notions of 'data' and 'programme' are essential for a critical account of the emergence and implications of data-driven research. In order to show this, I focus on the transition that the investigations on the worm C. elegans experienced in the Laboratory of Molecular Biology of Cambridge (UK). Throughout the 1980s, this research programme evolved from a study of the genetic basis of the worm's development and behaviour to a DNA mapping and sequencing initiative. By examining the changing computing technologies which were used at the Laboratory, I demonstrate that by the time of this transition researchers shifted from modelling the worm's genetic programme on a mainframe apparatus to writing minicomputer programs aimed at providing map and sequence data which was then circulated to other groups working on the genetics of C. elegans. The shift in the worm research should thus not be simply explained in the application of computers which transformed the project from hypothesis-driven to a data-intensive endeavour. The key factor was rather a historically specific technology-in-house and easy programmable minicomputers-which redefined the way of achieving the project's long-standing goal, leading the genetic programme to co-evolve with the practices of data production and distribution.
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[
Ecol Dis,
1983]
Medical records concerning filarial diseases in Ceylon date from the account of Davy[1], though there are hints as to the more obvious manifestations in the old chronicles of the country, too. A first survey was conducted in 1912/1913 concentrating on urban areas, followed by a second survey in the 1930s with emphasis on the rural parts. The results displayed a remarkable distribution pattern: Wuchereria bancrofti, the so-called "urban type", concentrated in Galle and Matara towns, whereas Brugia malayi, the "rural type", widespread along the southwest coast from Matara to Negombo, plus isolated pockets in the northwest, central north, east and south. The survey of the 1930s lead to the supposition that the occurrence of B. malayi must have something to do with the distribution of certain water plants, a suspicion later on confirmed in that Pistia stratiotes in particular--but other water plants as well--are essential for the survival of the vector (Taeniorhynchus (Mansonia) uniformis) during its early (submersed) stages of development. A determined effort to remove the water plants from tanks etc. reduced the rural type with encouraging results. At the same time, a combination of factors, in particular the war-time sojourn of masses of troops from Africa, already infected by filarial diseases, in the southwestern coastal areas triggered off an unexpected spread of the urban type out of its early "bridge-heads" in Galle and Matara towns to invade the southwest coastal areas, and, later on, supported by increased population mobility, to advance further inland too. At present, there is no remedy within sight to give some hope to come to grips with this problem as the vector, Culex pipiens fatigans, is ubiquitous and finds suitable breeding grounds practically everywhere. Research into the history of filarial diseases in Ceylon points as far as B. malayi is concerned, to an invasion by a Malayan army under the Kalinga kings during the days of close relations between Ceylon and southeast Asia, i.e. during the 12th and 13th centuries, and as far as W. bancrofti is concerned, a Chinese army, invading the southern coast in the early 15th century, is made responsible. Filarial diseases in Ceylon present a particular interesting case of geomedical research; but inspite of encouraging results in fighting the rural type, i.e. B. malayi, the urban type, W. bancrofti, seems to remain a problem of public health in the island for the forseeable future.