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Sex, France, and Arab Men, 1962-1979. By TODD SHEPARD. Chicago: University of Chicago Tress, 2017. Pp. 317. $50.00 (cloth). Todd Shepard begins in 1962 with the formal end of the [...]

Jean-Pierre Le Goff, Malaise dans la democratie (Paris: Editions Stock, 2016). The mass murders committed in Paris in January and November 2015 demonstrated that terrorists--not their innocent victims or the [...]

Jean-Pierre Le Goff, La Fin du village: Une histoire francaise (Paris: Editions Gallimard, 2012). Jean-Pierre Le Goff is deservedly known as an acute analyst of the changes in post-World War [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tibs.2010.01.003 Byline: David M. Wilson, Michael M. Seidman Abstract: DNA interstrand crosslinks (ICLs) can arise from reactions with endogenous chemicals, such as malondialdehyde - a lipid peroxidation product - or from exposure to various clinical anti-cancer drugs, most notably bifunctional alkylators and platinum compounds. Because they covalently link the two strands of DNA, ICLs completely block transcription and replication, and, as a result, are lethal to the cell. It is well established that proteins that function in nucleotide excision repair and homologous recombination are involved in ICL resolution. Recent work, coupled with a much earlier report, now suggest an emerging link between proteins of the base excision repair pathway and crosslink processing. Author Affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, IRP, 251 Bayview Blvd, Suite #100, BRC, Baltimore, MD 21224, USA

Splice-site mutations in the beta-globin gene can lead to aberrant transcripts and decreased functional beta-globin, causing beta-thalassemia. Triplex-forming DNA oligonucleotides (TFOs) and peptide nucleic acids (PNAs) have been shown to stimulate recombination in reporter gene loci in mammalian cells via site-specific binding and creation of altered helical structures that provoke DNA repair. We have designed a series of triplex-forming PNAs that can specifically bind to sequences in the human beta-globin gene. We demonstrate here that these PNAs, when cotransfected with recombinatory donor DNA fragments, can promote single base-pair modification at the start of the second intron of the beta-globin gene, the site of a common thalassemia-associated mutation. This single base pair change was detected by the restoration of proper splicing of transcripts produced from a green fluorescent protein-beta-globin fusion gene. The ability of these PNAs to induce recombination was dependent on dose, sequence, cell-cycle stage, and the presence of a homologous donor DNA molecule. Enhanced recombination, with frequencies up to 0.4%, was observed with use of the lysomotropic agent chloroquine. Finally, we demonstrate that these PNAs were effective in stimulating the modification of the endogenous beta-globin locus in human cells, including primary hematopoietic progenitor cells. This work suggests that PNAs can be effective tools to induce heritable, site-specific modification of disease-related genes in human cells. beta-thalassemia | gene correction | triplex-forming oligonucleotides | gene targeting

A model of revolutionary process based on agency, choice, and game theory before engaging the details is summarized. The outcome of the revolutionary conflict can be best understood and explained by studying the inner workings of dual authority and the new political economy, and most especially the part played by the food supply as a weapon for coercing soldiers and civilians.

A threshold level of the triple helix forming oligonucleotides (TFOs), consisting of three or four 2'-AE residues, are 10-fold more active than those with just 2 2'-AE residues in a hypoxanthine phosphoribosyltransferase (HPRT) activity monitored gene knockout assays. Further, the frequencies of HPRT activity with the active TFOs are 300-400 fold higher than the background activity.

A study was conducted to analyze the effects of substitution of T with 5-(1-propynyl)-2'-deoxyuridine on triplex formation under physiologic conditions by pyrimidine triplex-forming oligonucleotides. Third-strand binding to the target duplexes was determined using gel mobility shift assays under native or denaturing conditions. Cells were then harvested for vector DNA isolation using an altered alkaline lysis process.

Psoralen-conjugated triple-helix-forming oligonucleotides have been used to generate site-specific mutations within mammalian cells. To investigate factors influencing the efficiency of oligonucleotide-mediated gene targeting, the processing of third-strand-directed psoralen adducts was compared in normal and repair-deficient human cells. An unusually high mutation frequency and an altered mutation pattern were seen in xeroderma pigmentosum variant (XPV) cells compared with normal, xeroderma pigmentosum group A (XPA), and Fanconi anemia cells. In XPV, targeted mutations were produced in the supF reporter gene carried in a simian virus 40 vector at a frequency of 30%, 3-fold above that in normal or Fanconi anemia cells and 6-fold above that in XPA. The mutations generated by targeted psoralen crosslinks and monoadducts in the XPV cells formed a pattern distinct from that in the other three cell lines, with mutations occurring not just at the damaged site but also at adjacent base pairs. Hence, the XPV cells may have an abnormality in translesion bypass synthesis during repair and/or replication, implicating a DNA polymerase or an accessory factor as a basis of the defect in XPV. These results may help to elucidate the repair deficiency in XPV, and they raise the possibility that genetic manipulation via triplex-targeted mutagenesis may be enhanced by modulation of the XPV-associated activity in normal cells.

When mammalian cells were treated with triplex-forming oligonucleotides of sufficient binding affinity, mutations were specifically induced in a simian virus 40 vector contained within the cells. Triplex-induced mutagenesis was not detected in xeroderma pigmentosum group A cells nor in Cockayne's syndrome group B cells, indicating a requirement for excision repair and for transcription-coupled repair, respectively, in the process. Triplex formation was also found to stimulate DNA repair synthesis in human cell extracts, in a pattern correlating with the inhibition of transcription in such extracts. These findings may have implications for therapeutic applications of triplex DNA and raise the possibility that naturally occurring triple helices are a source of genetic instability., Triple helices can be formed when oligo-nucleotides bind in the major groove of duplex DNA at polypurine-polypyrimidine sequences(1). Triple helix formation has been used to block transcription initiation and elongation(2) [...]

An examination of the actions of Parisian metallurgists in May--June 1968 reveals a working class uninterested in the global political and social project proposed by student and other revolutionaries. Instead, workers demonstrated their limited adaptation to what may be called the repressive society of seductions. Wage earners took advantage of the momentary weakness of state power in May to initiate the largest strike wave in French history. By June, state repression and the seductions of consumer society induced metal workers to return to their jobs. Thus a combination of coercion and the appeal of consumption forced and persuaded wage earners to reenter the factories. With the expansion of the mass market during the Fifth Republic, French workers entered an era where demands for commodities largely replaced any lingering revolutionary yearnings and proved much more popular than workers' control or autogestion.

The studies of the interstrand cross-links produced by phenylselenyl substituted derivatives of thymidine and 5-methyl-2'-deoxycytidine in duplex DNA when oxidized by Nal[O.sub.4] is reported. The versatile cross-linking reactions of thymidine and 5-methyl-2'-deoxycytidine molecules could be used as mechanistic probes and tools for biotechnology.

The ability of purified endogenous human replication protein A (RPA) to melt DNA triplexes and tetraplexes was examined to show that RPA destabilizes a DNA tripe helix structure in a specific and highly effective manner. The results revealed that the large quantity of RPA known to exist in vivo might likely be a strong deterrent to the stability of triplexes that could potentially form from human genomic DNA sequences.

Triple helix forming oligonucleotides (TFOs) are developed for gene targeting and their influence on bioactivity of the modifications is examined. The enhancement of TFO bioactivity has required chemical modifications that improve interaction with the specific targets while retaining selectivity against mismatched sequences.

The synthesis of triple helix forming oligonucleotide (TFOs) designed to target a site in the human beta-globin gene, which is the locus for mutations that underlie the beta-globinpathies, including sickle cell anemia is described. The results validate the modification format described and indicate that 2'-O-methylpseudoisocytidine substitutions are an effective solution to problem of targeting genomic sequences containing adjacent cystosines.

The development in living mammalian cells of triple helix-forming oligonucleotides as gene targeting reagents is studied. The results show that for optimal bioactivity, the 2'-0-[2-Aminoethyl] residues should be clustered rather than dispersed.

1968: The World Transformed. Edited by CAROLE FINK, PHILIPP GASSERT, and DETLEF JUNKER. Cambridge and New York: Cambridge University Press, 1998. Pp. xi + 477.$54.95 (cloth); $18.95 (paper). The editors […]

The Spanish Civil War was one of the great dramas of the twentieth century. The war erupted on 19 July 1936 when a large part of the Spanish military revolted [...]

The Spanish Republic at War, 1936-1939. By Helen Graham. (Cambridge: Cambridge University Press, 2003. Pp. 486. $70.00.) This work is essentially a traditional political and diplomatic history of the Spanish [...]

Creating Spaniards: Culture and National Identity in Republican Spain by Sandie Holguin. Madison, University of Wisconsin Press, 2002. 304 pp. Cloth, $45.00; paper, $21.95. This is a solid study of [...]

The history of workers' and peasants' agrarian collectives in Spain during the revolution and civil war is examined on the basis of recent research focusing on archives which were only opened in recent years.

Paul Preston THE SPANISH HOLOCAUST Inquisition and extermination in twentieth-century Spain 700pp. Harper Press. 30 [pounds sterling]. 978 0 00 2556347 US: Norton. $35. 978 0 393 06476 6 Paul [...]