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Mitochondrial DNA (mtDNA) has been reported to contain 5-methylcytosine (5mC) at CpG dinucleotides, as in the nuclear genome, but neither the mechanism generating mtDNA methylation nor its functional significance is known. We now report the presence of 5-hydroxymethylcytosine (5hmC) as well as 5mC in mammalian mtDNA, suggesting that previous studies underestimated the level of cytosine modification in this genome. DNA methyltransferase 1 (DNMT1) translocates to the mitochondria, driven by a mitochondrial targeting sequence located immediately upstream of the commonly accepted translational start site. This targeting sequence is conserved across mammals, and the encoded peptide directs a heterologous protein to the mitochondria. DNMT1 is the only member of the three known catalytically active DNA methyltransferases targeted to the mitochondrion. Mitochondrial DNMT1 (mtDNMT1) binds to mtDNA, proving the presence of mtDNMT1 in the mitochondrial matrix. mtDNMT1 expression is up-regulated by NRF1 and PGC1α, transcription factors that activate expression of nuclear-encoded mitochondrial genes in response to hypoxia, and by loss of p53, a tumor suppressor known to regulate mitochondrial metabolism. Altered mtDNMT1 expression asymmetrically affects expression of transcripts from the heavy and light strands of mtDNA. Hence, mtDNMT1 appears to be responsible for mtDNA cytosine methylation, from which 5hmC is presumed to be derived, and its expression is controlled by factors that regulate mitochondrial function.

I find much to admire in Michael W. Clune’s book A Defense of Judgment . I have some points of disagreement as well. I think the argument concedes too much to the bad idea that political egalitarianism implies a lack of difference among judgments of value. I have reservations about the idea of “expertise” (let alone deference to experts) in philosophy or literary studies. And I believe that Clune’s use of an essay of mine does not accurately portray its content or purpose. Nonetheless I think the book is a powerful and insightful intervention.

The ordinary human concerns with the past and the future can be seen both as forms of suffering (anxiety toward the future, regret toward the past, etc.) and as illusory because they involve the failure to appreciate the primary reality of the present. In this lecture I argue that while there are certainly ways of being occupied with past or future times that we have reason to criticize, such criticism cannot base itself on any metaphysical claim to the singular or exclusive reality of the present. The task of developing useful forms of describing and assessing the different ways we can go wrong in temporalizing our lives is hindered rather than helped by the suggestion that our concerns with the past and with the future are as such forms of attachment to the Unreal.

Moran discusses the idea of beauty according to Immanuel Kant and Marcel Proust. Both Kant and Proust are concerned with a sense of requirement or obligation in connection with the experience of the beautiful and see this as the primary difference between the beautiful and the (merely) agreeable or pleasant. For Kant, the requirement is described as something directed outwards, toward other people, in that they speak of the beautiful as such only when they are not speaking merely for themselves but are prepared to demand the agreement of all others.

In this article I reply to the comments of six philosophers on my book Authority and Estrangement: An Essay on Self-knowledge.

In the fourth book of this award-winning series, author Richard Konicek-Moran explores 15 new mysteries children and adults encounter in their daily lives. Relating the mysteries to experiences familiar to elementary and middle school students, the stories show how science is part of everyday life and initiate inquiry-based learning by leaving each mystery without an ending. Students identify the problem to be solved, formulate questions, form hypotheses, test their ideas, and come up with possible explanations.

The mechanical properties of human brain tissue are the subject of interest because of their use in understanding brain trauma and in developing therapeutic treatments and procedures. To represent the behavior of the tissue, we have developed hyperelastic mechanical models whose parameters are fitted in accordance with experimental test results. However, most studies available in the literature have fitted parameters with data of a single type of loading, such as tension, compression, or shear. Recently, Jin et al. (Journal of Biomechanics 46:2795−2801, 2013) reported data from ex vivo tests of human brain tissue under tension, compression, and shear loading using four strain rates and four different brain regions. However, they do not report parameters of energy functions that can be readily used in finite element simulations. To represent the tissue behavior for the quasi-static loading conditions, we aimed to determine the best fit of the hyperelastic parameters of the hyperfoam, Ogden, and polynomial strain energy functions available in ABAQUS for the low strain rate data, while simultaneously considering all three loading modes. We used an optimization process conducted in MATLAB, calling iteratively three finite element models developed in ABAQUS that represent the three loadings. Results showed a relatively good fit to experimental data in all loading modes using two terms in the energy functions. Values for the shear modulus obtained in this analysis (897−1653Pa) are in the range of those presented in other studies. These energy-function parameters can be used in brain tissue simulations using finite element models.

It is undeniable that the assumption of sincerity is important to assertion, and that assertion is central to the transmission of beliefs through human testimony. Discussions of testimony, however, often assume that the epistemic importance of sincerity to testimony is that of a (fallible) guarantee of access to the actual beliefs of the speaker. Other things being equal, we would do as well or better if we had some kind of unmediated access to the beliefs of the other person, without the risks involved in the overt act of speaking, and the assumption of sincerity in speech is the closest we can come to this access. Contrary to this picture, I argue that sincerity has a quite different epistemic role to play in testimony than that of an indicator of the speaker's beliefs. The epistemology of testimony requires reference to the speaker as agent, and not just the speaker's beliefs, as well as a sense of 'expression of belief' that links it to the specifically addressive relation to another person.