We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate (...) assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

This 1979 text addresses the ways in which the dominant theories in large areas of Western social science have been subject to strong criticisms, particularly ...

Despite the remarkable achievements of novel targeted anti‐cancer drugs, most therapies only produce remission for a limited time, resistance to treatment, and relapse, often being the ultimate outcome. Drug resistance is due to highly efficient adaptive strategies utilized by cancer cells. Exogenous and endogenous stress stimuli are known to induce first‐line responses, capable of re‐establishing cellular homeostasis and determining cell fate decisions. Cancer cells may also mount second‐line adaptive strategies, such as the mutator response. Hypermutable subpopulations of cells may expand (...) under severe selective stress, thereby accelerating the emergence of adapted clones. As with first‐line protective responses, these strategies appear highly conserved, and are found in yeasts and bacteria. We hypothesize that evolutionarily conserved programs rheostatically regulate mutability in fluctuating environments, and contribute to drug resistance in cancer cells. Elucidating the conserved genetic and molecular mechanisms may present novel opportunities to increase the effectiveness of cancer therapies. (shrink)

David Thomas takes a close look at the United Kingdom during the 1970s to examine the emergence of “electroculture.” Mapping class struggle, dispossession, and state violence onto a history of oil, Thomas makes the case that labor politics and energy politics are deeply intertwined.

Much has been written about prisoner research and the controversies surrounding prisoners as human subjects. The Institute of Medicine recently released a report addressing some of these issues. This report, which generated further controversy, needs to be fully discussed in the literature and certain aspects are examined in this work. Further, in the body of literature there has been little acknowledgement of the concept of the right of prisoners to be involved in research. This needs to be pursued from an (...) ethical perspective and eventually a legal one. This paper explores that concept and documents some facilities in which a prisoner's right to research has occurred. (shrink)

In this immensely readable and wide ranging book,Bernard Lewis charts the successive transformations of the Middle East,beginning with the two great empires,the Roman and the Persian,and covering the growth of Christianity,the rise and spread of Islam,the waves of invaders from the east,the Mongol hordes of Jengiz Khan,the rise of the Ottoman Turks,and the changing balance of power between the Muslim and Christian worlds.THE MIDDLE EAST is a brilliant survey of the history and civilisations of the region.

Malignant tumours are often characterised by significant rearrangement of the genome. This may be visible in the form of a deranged karyotype with both loss and gain of DNA sequences extending from chromosomal regions to whole chromosomes. In several tumour types, however, gross genomic derangements are minimal, and tumour cells contain one or more additional (supernumerary) chromosomes that may be unrecognisable in terms of a single origin. In this review we term such chromosomes cancer‐associated neochromosomes (CaNCs). In the absence of (...) other identified genomic abnormalities, and because the CaNC is a common feature of the cancer type, it is hypothesised that the genetic alterations required for cell transformation are contained within its structure. In this review, we discuss the potential impact of modern genomic technologies on our understanding of the nature and causes of CaNC formation, which is central to several cancer types, exemplified here by well‐differentiated liposarcoma. (shrink)

This is a biography of the works of Richard Price, 1723-1791, one of the leading radical intellectuals of the late-18th century. By profession a dissenting minister, he was also a mathematician, a political pamphleteer, particularly on the American and French Revolutions, and a moral philosopher.

This series of three articles describes the history of land law shared by the British and American legal systems, and how and why these legal traditions have diverged from each other in modern times. This Article - part 1 in this series - describes the emerging customs and laws regarding land rights among early inhabitants of Britain, and how succeeding invasions and occupation by Celtic, Roman, Germanic, and Norman peoples altered these customs and laws. The Article details the profound changes (...) in land law worked by massive economic changes in early British society, including sociological occurrences such as the Black Death, and the adoption of laws, such as the Statute of Uses in 1536. (shrink)

Christian-Muslim Relations, a Bibliographical History 1 is a history of all the known works on Christian-Muslim relations from 600 to 1500. It comprises introductory essays and over 200 detailed entries containing descriptions, assessments and compehensive bibliographical details of individual works.

It has been claimed that decisions reached democratically have the consent of those subject to them. It will be shown that arguments for this view rest on either a Kantian or a utilitarian conception of consent. When the distinct nature of these arguments is kept clearly in mind, it becomes apparent that little remains of any of them. Nothing remains of the argument based on the Kantian conception, at least in so far as it is used to support the view (...) that democratic government rests on the consent of the governed. Though something remains of the arguments based on the utilitarian conception, what remains is not what they often are thought to establish. The spurious plausibility of consent arguments for democracy is due to switches between the Kantian conception of consent and the utilitarian. (shrink)