Sighing in interaction: Somatic, semiotic, and social

Participants in interaction routinely orient to gaze, bodily comportment, and nonlexical vocalizations as salient for developing an analysis of the unfolding course of action. In this article, I address the respiratory phenomenon of sighing, the aim being to describe sighing as a situated practice that contributes to the achievement of particular actions in interaction. I report on the various actions sighs implement or construct and how their positioning and delivery informs participants’ understandings of their significance for interaction. Data are in American Englis

“From sweet potatoes to God Almighty”: Roy Rappaport on being a hedgehog

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71618/1/ae.2007.34.3.581.pd

Biofabrication of vasculature in microphysiological models of bone

Bone contains a dense network of blood vessels that are essential to its homoeostasis, endocrine function, mineral metabolism and regenerative functions. In addition, bone vasculature is implicated in a number of prominent skeletal diseases, and bone has high affinity for metastatic cancers. Despite vasculature being an integral part of bone physiology and pathophysiology, it is often ignored or oversimplified in in vitro bone models. However, 3D physiologically relevant vasculature can now be engineered in vitro, with microphysiological systems (MPS) increasingly being used as platforms for engineering this physiologically relevant vasculature. In recent years, vascularised models of bone in MPSs systems have been reported in the literature, representing the beginning of a possible technological step change in how bone is modelled in vitro. Vascularised bone MPSs is a subfield of bone research in its nascency, however given the impact of MPSs has had in in vitro organ modelling, and the crucial role of vasculature to bone physiology, these systems stand to have a substantial impact on bone research. However, engineering vasculature within the specific design restraints of the bone niche is significantly challenging given the different requirements for engineering bone and vasculature. With this in mind, this paper aims to serve as technical guidance for the biofabrication of vascularised bone tissue within MPS devices. We first discuss the key engineering and biological considerations for engineering more physiologically relevant vasculature in vitro within the specific design constraints of the bone niche. We next explore emerging applications of vascularised bone MPSs, and conclude with a discussion on the current status of vascularised bone MPS biofabrication and suggest directions for development of next generation vascularised bone MPSs

From patent to patient: analysing access to innovative cancer drugs.

Analysis of cancer drugs licensed through the European Medicines Agency (EMA) in 2000-2016 shows that the number of authorisations increased over that timeframe. The median number of licensed drugs each year rose from six for 2000-2008 to 13.5 for 2009-2016. Over 2000-2016, there were 64 drug authorisations for haematological, 15 for breast, and 12 for skin cancer, but none for oesophageal, brain, bladder, or uterine cancer. Only 6% of authorisations included a paediatric indication. The average time for a drug to progress from patent priority date to availability on the National Health Service (NHS) increased from 12.8 years for drugs first licensed in 2000-2008 to 14.0 years for those licensed in 2009-2016. There was evidence that the most innovative drugs were not being prioritised for EMA licensing and NICE approval

Cascading predator effects in a Fijian coral reef ecosystem

Coral reefs are among Earth's best-studied ecosystems, yet the degree to which large predators influence the ecology of coral reefs remains an open and contentious question. Recent studies indicate the consumptive effects of large reef predators are too diffuse to elicit trophic cascades. Here, we provide evidence that such predators can produce non-consumptive (fear) effects that flow through herbivores to shape the distribution of seaweed on a coral reef. This trophic cascade emerged because reef topography, tidal oscillations, and shark hunting behaviour interact to create predictable "hot spots" of fear on the reef where herbivores withhold feeding and seaweeds gain a spatial refuge. Thus, in risky habitats, sharks can exert strong ecological impacts even though they are trophic generalists that rarely feed. These findings contextualize the debate over whether predators influence coral reef structure and function and move us to ask not if, but under what specific conditions, they generate trophic cascades

Centriole splitting caused by loss of the centrosomal linker protein C-NAP1 reduces centriolar satellite density and impedes centrosome amplification

Duplication of the centrosomes is a tightly regulated process. Abnormal centrosome numbers can impair cell division and cause changes in how cells migrate. Duplicated centrosomes are held together by a proteinaceous linker made up of rootletin filaments anchored to the centrioles by C-NAP1. This linker is removed in a NEK2A kinase-dependent manner as mitosis begins. To explore C-NAP1 activities in regulating centrosome activities, we used genome editing to ablate it. C-NAP1–null cells were viable and had an increased frequency of premature centriole separation, accompanied by reduced density of the centriolar satellites, with reexpression of C-NAP1 rescuing both phenotypes. We found that the primary cilium, a signaling structure that arises from the mother centriole docked to the cell membrane, was intact in the absence of C-NAP1, although components of the ciliary rootlet were aberrantly localized away from the base of the cilium. C-NAP1–deficient cells were capable of signaling through the cilium, as determined by gene expression analysis after fluid flow–induced shear stress and the relocalization of components of the Hedgehog pathway. Centrosome amplification induced by DNA damage or by PLK4 or CDK2 overexpression was markedly reduced in the absence of C-NAP1. We conclude that centriole splitting reduces the local density of key centriolar precursors to impede overduplication