The Reification of Non-Human Animals.

This paper takes up Axel Honneth's suggestion that we, in the 21st century Western world, should revisit the Marxian idea of reification; unlike Honneth, however, this paper applies reification to the ways in which humans relate to non-human animals, particularly in the context of scientific experiments. Thinking about these practices through the lens of reification, the paper argues, yields a more helpful understanding of what is regarded as problematic in those practices than the standard animal rights approaches. The second part of the paper offers ways of overcoming reification that go beyond Honneth's idea of recognition by introducing Iris Murdoch's idea of attention. This proposed strategy makes the ethical relevance of reification more salient and makes it possible to counter reification through a practice such as attention which, unlike recognition, can be consciously established.

Assembly defects of human tRNA splicing endonuclease contribute to impaired pre-tRNA processing in pontocerebellar hypoplasia.

Introns of human transfer RNA precursors (pre-tRNAs) are excised by the tRNA splicing endonuclease TSEN in complex with the RNA kinase CLP1. Mutations in TSEN/CLP1 occur in patients with pontocerebellar hypoplasia (PCH), however, their role in the disease is unclear. Here, we show that intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers independently of CLP1. Splice site recognition involves the mature domain and the anticodon-intron base pair of pre-tRNAs. The 2.1-Å resolution X-ray crystal structure of a TSEN15-34 heterodimer and differential scanning fluorimetry analyses show that PCH mutations cause thermal destabilization. While endonuclease activity in recombinant mutant TSEN is unaltered, we observe assembly defects and reduced pre-tRNA cleavage activity resulting in an imbalanced pre-tRNA pool in PCH patient-derived fibroblasts. Our work defines the molecular principles of intron excision in humans and provides evidence that modulation of TSEN stability may contribute to PCH phenotypes.

If Veganism Is Not a Choice: The Moral Psychology of Possibilities in Animal Ethics.

In their daily practices, many ethical vegans choose what to eat, wear, and buy among a range that is limited to the exclusion of animal products. Rather than considering and then rejecting the idea of using such products, doing so often does not occur to them as a possibility at all. In other cases, when confronted with the possibility of consuming animal products, vegans have claimed to reject it by saying that it would be impossible for them to do so. I refer to this phenomenon as 'moral impossibility'. An analysis of moral impossibility in animal ethics shows that it arises when one's conception of 'what animals are' shifts-say through encounter with other animals. It also arises when individuals learn more about animals and what happens to them in production facilities. This establishes a link between increased knowledge, understanding, and imaginative exploration on the one hand, and the exclusion of the possibility of using animals as resources on the other. Taking moral impossibility in veganism seriously has two important consequences: one is that the debate around veganism needs to shift from choice and decision, to a prior analysis of concepts and moral framing; the other is that moral psychology is no longer seen as empirical psychology plus ethical analysis, but the contents of psychological findings are understood as being influenced and framed by moral reflection.

Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery.

An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks.

Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination.

Meiotic recombination between homologous chromosomes initiates via programmed DNA double-strand breaks (DSBs), generated by complexes comprising Spo11 transesterase plus accessory proteins. DSBs arise concomitantly with the development of axial chromosome structures, where the coalescence of axis sites produces linear arrays of chromatin loops. Recombining DNA sequences map to loops, but are ultimately tethered to the underlying axis. How and when such tethering occurs is currently unclear. Using ChIPchip in yeast, we show that Spo11-accessory proteins Rec114, Mer2, and Mei4 stably interact with chromosome axis sequences, upon phosphorylation of Mer2 by S phase Cdk. This axis tethering requires meiotic axis components (Red1/Hop1) and is modulated in a domain-specific fashion by cohesin. Loss of Rec114, Mer2, and Mei4 binding correlates with loss of DSBs. Our results strongly suggest that hotspot sequences become tethered to axis sites by the DSB machinery prior to DSB formation.

Analysis of protein-DNA interactions during meiosis by quantitative chromatin immunoprecipitation (qChIP).

During meiotic prophase a number of important events require recombination between maternal and paternal chromosomes, which is initiated through the introduction of DNA double-strand breaks (DSBs). The majority of DSBs, which mostly occur at so-called hotspots, have been located between cohesin binding sites. qChIP (chromatin immunoprecipitation quantified by real-time PCR) is a sensitive, accurate, and cost-efficient alternative to ChIP-on-Chip for the analysis of noncovalent protein-DNA interactions at defined binding sites in vivo. Here we use qChIP to study Mre11 binding to three chromosomal loci during meiosis. We show that Mre11 interacts with a known hotspot region (UpsilonCR048) in the R-band of chromosome III, but not with a cold region in the G-band (UpsilonCR011). Interestingly Mre11 binds to a cohesin binding site (UpsilonCR067), 20 kb distal to UpsilonCR048, with similar intensity as to the hotspot, despite the absence of DSBs in this region.

A rare case of penile fracture with complete urethral rupture during sexual intercourse.

Fracture of the penis during intercourse is a relatively uncommon condition. We report a rare case with laceration of bilateral corpora cavernosa and associated complete urethral rupture. The patient underwent immediate surgical repair of the penile fracture with primary urethroplasty. After 1 year follow-up he presents excellent results with normal sexual function and normal postoperative urethrogram with no voiding problems.