We here review primary methods used in quantifying and mapping 5‐hydroxymethylcytosine (5hmC), including global quantification, restriction enzyme‐based detection, and methods involving DNA‐enrichment strategies and the genome‐wide sequencing of 5hmC. As discovered in the mammalian genome in 2009, 5hmC, oxidized from 5‐methylcytosine (5mC) by ten‐eleven translocation (TET) dioxygenases, is increasingly being recognized as a biomarker in biological processes from development to pathogenesis, as its various detection methods have shown. We focus in particular on an ultrasensitive single‐molecule imaging technique that can (...) detect and quantify 5hmC from trace samples and thus offer information regarding the distance‐based relationship between 5hmC and 5mC when used in combination with fluorescence resonance energy transfer. (shrink)

5‐methylcytosine (5mC) was long thought to be the only enzymatically created modified DNA base in mammalian cells. The discovery of 5‐hydroxymethylcytosine, 5‐formylcytosine, and 5‐carboxylcytosine as reaction products of the TET family 5mC oxidases has prompted extensive searches for proteins that specifically bind to these oxidized bases. However, only a few of such “reader” proteins have been identified and verified so far. In this review, we discuss potential biological functions of oxidized 5mC as well as the role the presumed reader (...) proteins may play in interpreting the genomic signals of 5mC oxidation products. (shrink)

To decode the function and molecular recognition of several recently discovered cytosine derivatives in the human genome – 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine – a detailed understanding of their effects on the structural, chemical, and biophysical properties of DNA is essential. Here, we review recent literature in this area, with particular emphasis on features that have been proposed to enable the specific recognition of modified cytosine bases by DNA-binding proteins. These include electronic factors, modulation of base-pair stability, flexibility, and radical (...) changes in duplex conformation. We explore these proposals and assess whether or not they are supported by current biophysical data. This analysis is focused primarily on the properties of epigenetically modified DNA itself, which provides a basis for discussion of the mechanisms of recognition by different proteins. 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine have recently been discovered in mammalian DNA and appear to have essential regulatory roles. Here, we summarize recent investigations into their effects on the structural, chemical, and biophysical properties of DNA, an understanding of which is essential to decoding their behavior in the genome. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:BOOK REVIEWS 91 The passage which permitted such an interpretation is the following: This self-command is very different at different times.... Can we give any reason for these variations, except experience? Where then is the power of which we pretend to be conscious? Is there not here, either in a spiritual or a material substance, or both, some secret mechanism or structure of parts, upon which the effect depends...?" (...) (Enquiry, p. 68). This rhetorical question is, on the contrary, intended as the part of the third argument for the thesis "that even this command of the will gives us no real idea of force or energy" (Enquiry, p. 67). There is no evidence in the Enquiries that Hume concluded that self is a substance. On p. 45, Anderson "suggests that Hume employs 'impression'...in a less frequent usage, however.., to be a pressure, or pattern of light, or other means whereby objects are applied to the external organs of sense"t On p. 65 and also on p. 173, it is argued fallaciously that, "Hume considers mathematical ideas, like all other ideas, to be existences. If this be true, then the necessary relations ~mpposed to obtain among mathematical ideas cannot be discerned even though these ideas themselves be fully known." Now it is a matter of debate whether Hume believed that all mathematical ideas are derived from impressions (see my controversy with Flew on this issue, in Ratio, Vol. VI, No. 2, "Hume on Pure and Applied Geometry," and Flew's article, "Did Hume Distinguish Pure and Applied Geometry?," Ratio, Vol. VIII, No. 1). But even if we assume that this is his belief, it does not follow at all that the logical relations among these ideas are contingent. As Pap argued a long time ago, "A sensationalist might maintain that all the concepts that constitute a given proposition are derived from experience and might nevertheless admit that proposition itself is a priori in the sense of requiring no empirical verification in order to be assertable as true." Thus, Hume the sensationalist admitted that a priori knowledge is possible in mathematics, which is conversant exclusively about "relations of ideas" and not about "matters of fact." Finally, in the last chapter, it is argued that, "Hume's own suggestion concerning these three natural relations (resemblance, contiguity, and cause and effect) is that they are fundamentally material--that they consist in a certain characteristic movement of the animal spirit in the brain" (p. 163)I1 That, "The necessity is the relationship between cause and effect, Hume's remarks suggest, is ultimately their identity in essence. One passage which we have noted indicates that cause and effect are inseparable, and by use of Hume's own maxims we may strictly infer from their inseparability their identity" (p. 165)II And that, "Although Hume's doctrine of matter is ultimately of central importance in his system, his beginnings in moral philosophy doubtless led him to turn his attention away from the topic of matter" (p. 175). This book, though replete with quotations from Hume's works and exhibiting a great amount of microscopic observations, represents a mistaken view of Hume's epistemology. ~ARHANG ZABEEIq Roosevelt University, Chicago Hegel's Phenomenology. Dialogues on the Life of Mind. By Jacob Loewenberg. (La Salle, Ill. : The Open Court Publ. Co., 1965.Pp. xv + 377.) Hegel's Phenomenology o] Spirit, intriguing in its richness, has long remained one of the most forbidding of philosophical classics. Unfortunately, commentaries, though altogether indispensable, are sparse. Heretofore, the reader found himself referred mainly to two foreign language studies, G. A. Gabler's Kritik des Be~usst~ein~ of 1835, and J. Hyppolite's Gen~se et structure de la Phdnomdnologie de l'esprit; no full-scale work in English was available. And 92 HISTORY OF PHILOSOPHY even the reader prepared to turn to these works might register disenchantment: Gabler deals with two fifths of the book only, and Hyppolite is at times too close to the text to be much help. What remains is comment in the framework of more general studies of Hegel's philosophy (Royce, Haering, Kroner, Stace, Findlay and others). In this situation Loewenberg's contribution marks a... (shrink)

A nationalist theory of the modern state holds that territorial states should be constituted as nations composed of people who in some sense belong with each other as members of their country. Liberal philosophers have defended this view on the grounds that nationality creates the solidarity necessary for social justice. Their argument is troubled by the case of the United States, where nationality is strong but solidarity weak. According to the best empirical studies, the fundamental reason for the American exception (...) is not libertarian political culture, but white anti-black racism. This essay makes the case that an open border policy with Mexico and other Latina/o states is likely to weaken the national identity now widely held in the United States, but increase the political prospects for racial justice. It follows that a liberal nationalist justification for excluding undocumented Latina/o immigrants from membership in U.S. society should be rejected. (shrink)