JNCC guidelines for minimising the risk of injury and disturbance to marine mammals from seismic surveys: We can do better.

The U.K.'s Joint Nature Conservation Committee 1998 guidelines for minimising acoustic impacts from seismic surveys on marine mammals were the first of their kind. Covering both planning and operations, they included various measures for reducing the potential for damaging hearing - an appropriate focus at the time. Since introduction, the guidelines have been criticised for, among other things: the arbitrarily-sized safety zones; the lack of shut-down provisions; the use of mitigation measures that introduce more noise into the environment (e.g., soft-starts); inadequate observer training; and the lack of standardised data collection protocols. Despite the concerns, the guidelines have remained largely unchanged. Moreover, increasing scientific recognition of the scope and magnitude of non-injurious impacts of sound on marine life has become much more widespread since the last revisions in 2010. Accordingly, here we present feasible and realistic recommendations for such improvements, in light of the current state of knowledge.

A non-anesthetized mouse model for recording sensory urinary bladder activity.

The goal of this study was to develop an in vivo awake mouse model for extracellular bladder sensory nerve recording. A bipolar 125-µm silver electrode was positioned under a single postganglionic bladder nerve. Efferent nerve signals were eliminated by tying off the postganglionic bladder nerve between the major pelvic ganglion and the recording electrode. Sensory nerve activity was measured in the conscious animals 48 h after surgery during continuous intravesical infusion of 0.9% saline/0.5% acetic acid followed by 0.5% acetic acid with capsazepine (10 µM) at a rate of 0.75 ml/h. Continuous infusion of 0.9% NaCl led to a gradual increase in the frequency of sensory nerve firing that peaked upon reaching threshold pressure. Non-micturition contractions were observed in some animals during filling and other animals exhibited only minimal pressure fluctuations; both types of events were associated with a rise in sensory nerve activity. Intravesical infusion of 0.5% acetic acid reduced the intermicturition interval. This was associated with a 2.1-fold increase in bladder pressure during filling and a two-fold increase at both threshold and micturition pressures. Concurrent with these changes, sensory activity increased 2.8-fold during filling and 2.4-fold at threshold pressure. Subsequent intravesical infusion of capsazepine in 0.5% acetic acid reduced filling and threshold pressures by 21 and 31.2%, respectively, and produced corresponding decreases of 36 and 23.4% in sensory nerve activity. The current study shows that multifiber sensory nerve recordings can be reproducibly obtained from conscious mice.

Surface marker antigens in the characterization of human embryonic stem cells.

The use of cell surface antigens to characterise embryonic stem (ES) cells, and to monitor their differentiation, has had a long history, stretching back to the early studies of differentiation antigens in the haematopoietic system, and their application to teratocarcinomas and embryonal carcinoma (EC) cells in the laboratory mouse. A wide series of such antigens, which include both glycolipids and glycoproteins are now extensively used in studies of human ES cells. Many of these were first identified using both mouse and human EC cells, although the cell surface antigen phenotype of human EC and ES cells has proved to be significantly different from that of murine EC and ES cells.

Navy sonar and cetaceans: just how much does the gun need to smoke before we act?

Cetacean mass stranding events associated with naval mid-frequency sonar use have raised considerable conservation concerns. These strandings have mostly involved beaked whales, with common pathologies, including "bubble lesions" similar to decompression sickness symptoms and acoustic traumas. However, other cetacean species have also stranded coincident with naval exercises. Possible mechanisms for the strandings include a behavioral response that causes deep divers to alter their diving behavior, which then results in decompression sickness-like impacts. Current mitigation measures during military exercises are focused on preventing auditory damage (hearing loss), but there are significant flaws with this approach. Behavioral responses, which occur at lower sound levels than those that cause hearing loss, may be more critical. Thus, mitigation measures should be revised. A growing number of international bodies recognize this issue and have urged increasing scrutiny of sound-producing activities, but many national jurisdictions have resisted calls for increased protection.

Characterisation of receptor binding by the chemotaxis inhibitory protein of Staphylococcus aureus and the effects of the host immune response.

The chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) is reported to bind to the receptors for C5a and formylated peptides and has been proposed as a promising lead for the development of new anti-inflammatory compounds. Here we have examined the receptor specificity and mode of action of recombinant CHIPS(28-149) and also the immune response to CHIPS(28-149) in patients with S. aureus infections and in uninfected controls. Recombinant CHIPS(28-149) bound with high affinity to the human C5a receptor (C5aR), but had low affinity for the second C5a receptor, C5L2, and the formyl peptide receptor, FPR. Although ligand binding to C5aR was potently inhibited, CHIPS(28-149) had much weaker effects on ligand binding to C5L2 and FPR. Similarly, CHIPS(28-149) potently inhibited the ligand-induced activation of C5aR but was less potent at inhibition via FPR. NMR studies showed that CHIPS(28-149) bound directly to the N-terminus of C5aR but not C5L2, and CHIPS(28-149) residues involved in the interaction were identified by chemical shift analysis. All human sera examined contained high titres of IgG and IgA reactivity against CHIPS(28-149), and no correlation was observed between infection status at the time of serum collection and antibody titre. Individual serum samples promoted or inhibited the binding of CHIPS(28-149) to C5aR, or had no effect. IgG depletion of serum samples abrogated the effects on CHIPS binding, demonstrating that these were antibody mediated. Sera from infected individuals were more likely to inhibit CHIPS(28-149) binding than sera from healthy controls. However, high antibody titres correlated well with both inhibition and enhancement of CHIPS(28-149) binding to C5aR; this suggests that the inhibitory effect relates to epitope specificity rather than greater antibody binding. We conclude that CHIPS is likely to be too immunogenic to be used as an anti-inflammatory treatment but that some antibodies against CHIPS may be useful in the treatment of S. aureus infections.