The Genetic Component of the Forced Diving Bradycardia Response in Mammals

We contrasted the forced diving bradycardia between two genetically similar (inbred) rat strains (Fischer and Buffalo), compared to that of outbred rats (Wistar). The animals were habituated to forced diving for 4 weeks. Each animal was then tested during one 40 s dive on each of 3 days. The heart rate (fH) was measured before, during, and after each dive. Fischer and Buffalo exhibited marked difference in dive bradycardia (Fischer: 120.9 ± 14.0 beats min−1 vs. Buffalo: 92.8 ± 12.8 beats min−1, P < 0.05). Outbred rats showed an intermediate response (103.0 ± 30.9 beats min−1) but their between-animal variability in mean dive fH and pre-diving resting fH were higher than the inbred strains (P < 0.05), which showed no difference (P > 0.05). The decreased variability in fH in inbred rats as compared with the outbred group indicates that reduced genetic variability minimizes variability of the diving bradycardia between individuals. Heritability within strains was assessed by the repeatability (R) index and was 0.93 ± 0.05 for the outbred, 0.84 ± 0.16 for Buffalo, and 0.80 ± 0.12 for Fischer rats for fH during diving. Our results suggest that a portion of the mammalian diving bradycardia may be a heritable trait

First gene-edited calf with reduced susceptibility to a major viral pathogen

Bovine viral diarrhea virus (BVDV) is one of the most important viruses affecting the health and well-being of bovine species throughout the world. Here, we used CRISPR-mediated homology-directed repair and somatic cell nuclear transfer to produce a live calf with a six amino acid substitution in the BVDV binding domain of bovine CD46. The result was a gene-edited calf with dramatically reduced susceptibility to infection as measured by reduced clinical signs and the lack of viral infection in white blood cells. The edited calf has no off-target edits and appears normal and healthy at 20 months of age without obvious adverse effects from the on-target edit. This precision bred, proof-of-concept animal provides the first evidence that intentional genome alterations in the CD46 gene may reduce the burden of BVDV-associated diseases in cattle and is consistent with our stepwise, in vitro and ex vivo experiments with cell lines and matched fetal clones

Behaviour and Physiology: The Thermal Strategy of Leatherback Turtles

Background: Adult leatherback turtles (Dermochelys coriacea) exhibit thermal gradients between their bodies and the environment of $8uC in sub-polar waters and #4uC in the tropics. There has been no direct evidence for thermoregulation in leatherbacks although modelling and morphological studies have given an indication of how thermoregulation may be achieved. Methodology/Principal Findings: We show for the first time that leatherbacks are indeed capable of thermoregulation from studies on juvenile leatherbacks of 16 and 37 kg. In cold water (, 25uC), flipper stroke frequency increased, heat loss through the plastron, carapace and flippers was minimized, and a positive thermal gradient of up to 2.3uC was maintained between body and environment. In warm water (25 – 31uC), turtles were inactive and heat loss through their plastron, carapace and flippers increased. The thermal gradient was minimized (0.5uC). Using a scaling model, we estimate that a 300 kg adult leatherback is able to maintain a maximum thermal gradient of 18.2uC in cold sub-polar waters. Conclusions/Significance: In juvenile leatherbacks, heat gain is controlled behaviourally by increasing activity while heat flux is regulated physiologically, presumably by regulation of blood flow distribution. Hence, harnessing physiology and behaviour allows leatherbacks to keep warm while foraging in cold sub-polar waters and to prevent overheating in

Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons

Background: Alterations in neurotransmitter phenotypes of specific neurons can cause imbalances in excitation and inhibition in the central nervous system (CNS), leading to diseases. Therefore, the correct specification and maintenance of neurotransmitter phenotypes is vital. As with other neuronal properties, neurotransmitter phenotypes are often specified and maintained by particular transcription factors. However, the specific molecular mechanisms and transcription factors that regulate neurotransmitter phenotypes remain largely unknown. Methods: In this paper we use single mutant, double mutant and transgenic zebrafish embryos to elucidate the functions of Lmx1ba and Lmx1bb in the regulation of spinal cord interneuron neurotransmitter phenotypes. Results: We demonstrate that lmx1ba and lmx1bb are both expressed in zebrafish spinal cord and that lmx1bb is expressed by both V0v cells and dI5 cells. Our functional analyses demonstrate that these transcription factors are not required for neurotransmitter fate specification at early stages of development, but that in embryos with at least two lmx1ba and/or lmx1bb mutant alleles there is a reduced number of excitatory (glutamatergic) spinal interneurons at later stages of development. In contrast, there is no change in the numbers of V0v or dI5 cells. These data suggest that lmx1b-expressing spinal neurons still form normally, but at least a subset of them lose, or do not form, their normal excitatory fates. As the reduction in glutamatergic cells is only seen at later stages of development, Lmx1b is probably required either for the maintenance of glutamatergic fates or to specify glutamatergic phenotypes of a subset of later forming neurons. Using double labeling experiments, we also show that at least some of the cells that lose their normal glutamatergic phenotype are V0v cells. Finally, we also establish that Evx1 and Evx2, two transcription factors that are required for V0v cells to acquire their excitatory neurotransmitter phenotype, are also required for lmx1ba and lmx1bb expression in these cells, suggesting that Lmx1ba and Lmx1bb act downstream of Evx1 and Evx2 in V0v cells. Conclusions: Lmx1ba and Lmx1bb function at least partially redundantly in the spinal cord and three functional lmx1b alleles are required in zebrafish for correct numbers of excitatory spinal interneurons at later developmental stages. Taken together, our data significantly enhance our understanding of how spinal cord neurotransmitter fates are regulated

Bionic bodies, posthuman violence and the disembodied criminal subject

This article examines how the so-called disembodied criminal subject is given structure and form through the law of homicide and assault. By analysing how the body is materialised through the criminal law’s enactment of death and injury, this article suggests that the biological positioning of these harms of violence as uncontroversial, natural, and universal conditions of being ‘human’ cannot fully appreciate what makes violence wrongful for us, as embodied entities. Absent a theory of the body, and a consideration of corporeality, the criminal law risks marginalising, or altogether eliding, experiences of violence that do not align with its paradigmatic vision of what bodies can and must do when suffering its effects. Here I consider how the bionic body disrupts the criminal law’s understanding of human violence by being a body that is both organic and inorganic, and capable of experiencing and performing violence in unexpected ways. I propose that a criminal law that is more receptive to the changing, technologically mediated conditions of human existence would be one that takes the corporeal dimensions of violence more seriously and, as an extension of this, adopts an embodied, embedded, and relational understanding of human vulnerability to violence

All data was simultaneously recorded.

<p>Activity, water and body temperature and heat fluxes recorded simultaneously from the 37 kg leatherback during stepwise increases in water temperature.</p

Experimental setup.

<p>(A) An illustration of the turtles harnessed in their tanks. (B) The placement of the heat flux transducers (HFT) on the animals.</p

The leatherbacks were exposed to stepwise changes in water temperature.

<p>The complete water temperature profile for the experiment performed on the 37 kg leatherback.</p

Recorded and calculated values at each water temperature for the 16 kg leatherback.

<p>Recorded and calculated values at each water temperature for the 16 kg leatherback.</p