Deep homology in the age of next-generation sequencing

The principle of homology is central to conceptualizing the comparative aspects of morphological evolution. The distinctions between homologous or non-homologous structures have become blurred, however, as modern evolutionary developmental biology (evo-devo) has shown that novel features often result from modification of pre-existing developmental modules, rather than arising completely de novo. With this realization in mind, the term 'deep homology' was coined, in recognition of the remarkably conserved gene expression during the development of certain animal structures that would not be considered homologous by previous strict definitions. At its core, it can help to formulate an understanding of deeper layers of ontogenetic conservation for anatomical features that lack any clear phylogenetic continuity. Here, we review deep homology and related concepts in the context of a gene expression-based homology discussion. We then focus on how these conceptual frameworks have profited from the recent rise of high-throughput next-generation sequencing. These techniques have greatly expanded the range of organisms amenable to such studies. Moreover, they helped to elevate the traditional gene-by-gene comparison to a transcriptome-wide level. We will end with an outlook on the next challenges in the field and how technological advances might provide exciting new strategies to tackle these questions.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'

Assessment of Orbital Compartment Pressure: A Comprehensive Review.

The orbit is a closed compartment defined by the orbital bones and the orbital septum. Some diseases of the orbit and the optic nerve are associated with an increased orbital compartment pressure (OCP), e.g., retrobulbar hemorrhage or thyroid eye disease. Our aim was to review the literature on the different approaches to assess OCP. Historically, an assessment of the tissue resistance provoked by the retropulsion of the eye bulb was the method of choice for estimating OCP, either by digital palpation or with specifically designed devices. We found a total of 20 articles reporting direct OCP measurement in animals, cadavers and humans. In nine studies, OCP was directly measured in humans, of which five used a minimally invasive approach. Two groups used experimental/custom devices, whilst the others applied commercially available devices commonly used for monitoring the compartment syndromes of the limbs. None of the nine articles on direct OCP measurements in humans reported complications. Today, OCP is mainly estimated using clinical findings considered surrogates, e.g., elevated intraocular pressure or proptosis. These diagnostic markers appear to reliably indicate elevated OCP. However, particularly minimally invasive approaches show promises for direct OCP measurements. In the future, more sophisticated, specifically designed equipment might allow for even better and safer measurements and hence facilitate the diagnosis and monitoring of orbital diseases

Anatomy and systematics of the diplodocoid Amphicoelias altus supports high sauropod dinosaur diversity in the Upper Jurassic Morrison Formation of the USA

Sauropod dinosaurs were an abundant and diverse component of the Upper Jurassic Morrison Formation of the USA, with 24 currently recognized species. However, some authors consider this high diversity to have been ecologically unviable and the validity of some species has been questioned, with suggestions that they represent growth series (ontogimorphs) of other species. Under this scenario, high sauropod diversity in the Late Jurassic of North America is greatly overestimated. One putative ontogimorph is the enigmatic diplodocoid Amphicoelias altus, which has been suggested to be synonymous with Diplodocus. Given that Amphicoelias was named first, it has priority and thus Diplodocus would become its junior synonym. Here, we provide a detailed re-description of A. altus in which we restrict it to the holotype individual and support its validity, based on three autapomorphies. Constraint analyses demonstrate that its phylogenetic position within Diplodocoidea is labile, but it seems unlikely that Amphicoelias is synonymous with Diplodocus. As such, our re-evaluation also leads us to retain Diplodocus as a distinct genus. There is no evidence to support the view that any of the currently recognized Morrison sauropod species are ontogimorphs. Available data indicate that sauropod anatomy did not dramatically alter once individuals approached maturity. Furthermore, subadult sauropod individuals are not prone to stemward slippage in phylogenetic analyses, casting doubt on the possibility that their taxonomic affinities are substantially misinterpreted. An anatomical feature can have both an ontogenetic and phylogenetic signature, but the former does not outweigh the latter when other characters overwhelmingly support the affinities of a taxon. Many Morrison Formation sauropods were spatio-temporally and/or ecologically separated from one another. Combined with the biases that cloud our reading of the fossil record, we contend that the number of sauropod dinosaur species in the Morrison Formation is currently likely to be underestimated, not overestimated

Influence of thoracic epidural analgesia on cardiovascular autonomic control after thoracic surgery

Background. Thoracic epidural analgesia (TEA) is effective in alleviating pain after major thoracoabdominal surgery and may also reduce postoperative mortality and morbidity. This study investigated cardiovascular autonomic control in patients undergoing elective thoracic surgery and its modulation by continuous TEA. Methods. Thirty‐eight patients were randomly assigned to receive patient‐controlled analgesia (PCA group) or thoracic epidural analgesia (TEA group) with doses of bupivacaine (0.25% during operation, 0.125% after operation) and fentanyl (2 µgml-1). Heart rate variability (HRV), baroreflex function and pressure response to nitroglycerine and phenylephrine were assessed before operation, 4 h after the end of surgery (POD 0) and on the first and second postoperative days (POD1 and POD2). Results. Early after surgery, all HRV variables and baroreflex sensitivities were markedly decreased in both groups. In the TEA group, total HRV and its high‐frequency components (HF) increased towards preoperative values at POD1 and POD2, whereas the ratio of low to high frequencies (LF/HF) was significantly reduced (mean (sd), -44 (15)% at POD 0, -38 (17)% at POD1, -37 (18%) at POD2) and associated with blunting of the postoperative increase in heart rate and blood pressure. In the PCA group, the ratio of LF/HF remained unchanged and the decrements in HRV variables persisted until POD2. In the two groups, baroreflex sensitivities and pressure responses recovered preoperative values at POD2. Conclusions. In contrast with PCA management, TEA using low concentrations of bupivacaine and fentanyl blunted cardiac sympathetic neural drive, resulting in vagal predominance, while HRV variables were better restored after surgery. Br J Anaesth 2003; 91: 525-3

Smac Mimetics and TNFalpha: A Dangerous Liaison?

Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. It has been thought that small-molecule mimetics of Smac, an endogenous IAP antagonist, might potentiate apoptosis in cancer cells by promoting caspase activation. However, three recent papers, two in Cell (Vince et al., 2007; Varfolomeev et al., 2007) and one in Cancer Cell (Petersen et al., 2007), now report that Smac mimetics primarily kill cancer cells via a different mechanism, the induction of autoubiquitination and degradation of cIAPs, which culminates in TNFalpha-mediated cell death