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Objective Atherosclerosis is a major cause of cardiovascular disease. Monocyte-endothelial cell interactions are partly mediated by expression of monocyte CX3CR1 and endothelial cell fractalkine (CX3CL1). Interrupting the interaction between this ligand–receptor pair should reduce monocyte binding to the endothelial wall and reduce atherosclerosis. We sought to reduce atherosclerosis by preventing monocyte-endothelial cell interactions through use of a long-acting CX3CR1 agonist. Methods In this study, the chemokine domain of CX3CL1 was fused to the mouse Fc region to generate a long-acting soluble form of CX3CL1 suitable for chronic studies. CX3CL1-Fc or saline was injected twice a week (30 mg/kg) for 4 months into Ldlr knockout (KO) mice on an atherogenic western diet. Results CX3CL1-Fc-treated Ldlr KO mice showed decreased en face aortic lesion surface area and reduced aortic root lesion size with decreased necrotic core area. Flow cytometry analyses of CX3CL1-Fc-treated aortic wall cell digests revealed a decrease in M1-like polarized macrophages and T cells. Moreover, CX3CL1-Fc administration reduced diet-induced atherosclerosis after switching from an atherogenic to a normal chow diet. In vitro monocyte adhesion studies revealed that CX3CL1-Fc treatment caused fewer monocytes to adhere to a human umbilical vein endothelial cell monolayer. Furthermore, a dorsal window chamber model demonstrated that CX3CL1-Fc treatment decreased in vivo leukocyte adhesion and rolling in live capillaries after short-term ischemia-reperfusion. Conclusion These results indicate that CX3CL1-Fc can inhibit monocyte/endothelial cell adhesion as well as reduce atherosclerosis., Highlights • Long-acting FKN-Fc reduced atherosclerosis in LDLR KO mice in a prevention model. • FKN-Fc administration accelerated diet-induced regression of established atherosclerosis. • Monocyte adhesion in vitro and in vivo is reduced in the presence of FKN-Fc.

We have previously reported that the fractalkine (FKN)/CX3CR1 system represents a novel regulatory mechanism for insulin secretion and β cell function. Here, we demonstrate that chronic administration of a long-acting form of FKN, FKN-Fc, can exert durable effects to improve glucose tolerance with increased glucose-stimulated insulin secretion and decreased β cell apoptosis in obese rodent models. Unexpectedly, chronic FKN-Fc administration also led to decreased α cell glucagon secretion. In islet cells, FKN inhibited ATP-sensitive potassium channel conductance by an ERK-dependent mechanism, which triggered β cell action potential (AP) firing and decreased α cell AP amplitude. This results in increased glucose-stimulated insulin secretion and decreased glucagon secretion. Beyond its islet effects, FKN-Fc also exerted peripheral effects to enhance hepatic insulin sensitivity due to inhibition of glucagon action. In hepatocytes, FKN treatment reduced glucagon-stimulated cAMP production and CREB phosphorylation in a pertussis toxin-sensitive manner. Together, these results raise the possibility of use of FKN-based therapy to improve type 2 diabetes by increasing both insulin secretion and insulin sensitivity.

Attacks by aquatic predators generate frontal water disturbances characterised by low-frequency gradients in pressure and particle motion. Low-frequency hearing is highly developed in cephalopods. Thus, we examined behavioural responses in juvenile cuttlefish to infrasonic accelerations mimicking main aspects of the hydrodynamic signals created by predators. In the experimental set-up, animals and their surrounding water moved as a unit to minimise lateral line activation and to allow examination of the contribution by the inner ear. Behavioural responses were tested in light versus darkness and after food deprivation following a ‘simulated’ hunting opportunity. At low acceleration levels, colour change threshold at 3, 5 and 9 Hz was 0.028, 0.038 and 0.035 m s−2, respectively. At higher stimulus levels, jet-propulsed escape responses thresholds in daylight were 0.043, 0.065 and 0.069 m s−2 at 3, 5 and 9 Hz, respectively, and not significantly different from the corresponding darkness thresholds of 0.043, 0.071 and 0.064 m s−2. In a simulated hunting mode, escape thresholds were significantly higher at 3 Hz (0.118 m s−2) but not at 9 Hz (0.134 m s−2). Escape responses were directional, and overall followed the direction of the initial particle acceleration, with mean escape angles from 313 to 33 deg for all three experiments. Thus, in the wild, particle acceleration might cause escape responses directed away from striking predators but towards suction-feeding predators. We suggest that cuttlefish jet-propulsed escape behaviour has evolved to be elicited by the early hydrodynamic disturbances generated during predator encounters, and that the inner ear plays an essential role in the acoustic escape responses.

To improve conservation strategies for threatened sea turtles, more knowledge on their ecology, behavior, and how they cope with severe and changing weather conditions is needed. Satellite and animal motion datalogging tags were used to study the inter-nesting behavior of two female loggerhead turtles in the Gulf of Mexico, which regularly has hurricanes and tropical storms during nesting season. We contrast the behavioral patterns and swimming energetics of these two turtles, the first tracked in calm weather and the second tracked before, during and after a tropical storm. Turtle 1 was highly active and swam at the surface or submerged 95% of the time during the entire inter-nesting period, with a high estimated specific oxygen consumption rate (0.95 ml min-1 kg-0.83). Turtle 2 was inactive for most of the first 9 days of the inter-nesting period, during which she rested at the bottom (80% of the time) with low estimated oxygen consumption (0.62 ml min-1 kg-0.83). Midway through the internesting period, turtle 2 encountered a tropical storm and became highly active (swimming 88% of the time during and 95% after the storm). Her oxygen consumption increased significantly to 0.97 ml min-1 kg-0.83 during and 0.98 ml min-1 kg-0.83 after the storm. However, despite the tropical storm, turtle 2 returned to the nesting beach, where she successfully re-nested 75 m from her previous nest. Thus, the tropical storm had a minor effect on this female's individual nesting success, even though the storm caused 90% loss nests at Casey Key.

To improve conservation strategies for threatened sea turtles, more knowledge on their ecology, behavior, and how they cope with severe and changing weather conditions is needed. Satellite and animal motion datalogging tags were used to study the inter-nesting behavior of two female loggerhead turtles in the Gulf of Mexico, which regularly has hurricanes and tropical storms during nesting season. We contrast the behavioral patterns and swimming energetics of these two turtles, the first tracked in calm weather and the second tracked before, during and after a tropical storm. Turtle 1 was highly active and swam at the surface or submerged 95% of the time during the entire inter-nesting period, with a high estimated specific oxygen consumption rate (0.95 ml min

Field work in Norway was funded by the Carlsberg Foundation and the National Danish Research Council to PTM. The NMFS study was funded by the U.S. Mineral Management Service. MJ is funded by the Marine Alliance for Science and Technology, Scotland, and by a Marie Curie Career Integration Grant. MW was funded by the Danish Council for Independent Research, Natural Science and NAS is currently funded by a EU Horizon 2020 MSC Fellowship. The sperm whale carries a hypertrophied nose that generates powerful clicks for long-range echolocation. However, it remains a conundrum how this bizarrely shaped apex predator catches its prey. Several hypotheses have been advanced to propose both active and passive means to acquire prey, including acoustic debilitation of prey with very powerful clicks. Here we test these hypotheses by using sound and movement recording tags in a fine-scale study of buzz sequences to relate the acoustic behaviour of sperm whales with changes in acceleration in their head region during prey capture attempts. We show that in the terminal buzz phase, sperm whales reduce inter-click intervals and estimated source levels by 1-2 orders of magnitude. As a result, received levels at the prey are more than an order of magnitude below levels required for debilitation, precluding acoustic stunning to facilitate prey capture. Rather, buzzing involves high-frequency, low amplitude clicks well suited to provide high-resolution biosonar updates during the last stages of capture. The high temporal resolution helps to guide motor patterns during occasionally prolonged chases in which prey are eventually subdued with the aid of fast jaw movements and/or buccal suction as indicated by acceleration transients (jerks) near the end of buzzes. Publisher PDF

Toothed whales use intense ultrasonic clicks to echolocate prey and it has been hypothesized that they also acoustically debilitate their prey with these intense sound pulses to facilitate capture. Cephalopods are an important food source for toothed whales, and there has probably been an evolutionary selection pressure on cephalopods to develop a mechanism for detecting and evading sound–emitting toothed whale predators. Ultrasonic detection has evolved in some insects to avoid echolocating bats, and it can be hypothesized that cephalopods might have evolved similar ultrasound detection as an anti–predation measure. We test this hypothesis in the squid Loligo pealeii in a playback experiment using intense echolocation clicks from two squid–eating toothed whale species. Twelve squid were exposed to clicks at two repetition rates (16 and 125 clicks per second) with received sound pressure levels of 199–226 dB re 1 μPa (pp) mimicking the sound exposure from an echolocating toothed whale as it approaches and captures prey. We demonstrate that intense ultrasonic clicks do not elicit any detectable anti–predator behaviour in L. pealeii and that clicks with received levels up to 226 dB re 1 μPa (pp) do not acoustically debilitate this cephalopod species.

SUMMARYToothed whales emit high-powered ultrasonic clicks to echolocate a wide range of prey. It may be hypothesized that some of their prey species have evolved capabilities to detect and respond to such ultrasonic pulses in a way that reduces predation, akin to the situation for many nocturnal insects and echolocating bats. Using high-speed film recordings and controlled exposures, we obtained behavioural evidence that simulated toothed whale biosonar clicks elicit highly directional anti-predator responses in an ultrasound-sensitive allis shad (Alosa alosa). Ten shad were exposed to 192 dB re. 1 μPa (pp) clicks centred at 40 kHz at repetition rates of 1, 20, 50 and 250 clicks s–1 with summed energy flux density levels of 148, 161, 165 and 172 dB re. 1 μPa2 s. The exposures mimicked the acoustic exposure from a delphinid toothed whale in different phases of prey search and capture. The response times of allis shad were faster for higher repetition rates of clicks with the same sound pressure level. None of the fish responded to a single click, but had median response times of 182, 93 and 57 ms when exposed to click rates of 20, 50 and 250 clicks s–1, respectively. This suggests that the ultrasound detector of allis shad is an energy detector and that shad respond faster when exposed to a nearby fast-clicking toothed whale than to a slow-clicking toothed whale far away. The findings are thus consistent with the hypothesis that shad ultrasound detection is used for reducing predation from echolocating toothed whales.

Lungfishes are the closest living relatives of the tetrapods, and the ear of recent lungfishes resembles the tetrapod ear more than the ear of ray-finned fishes and is therefore of interest for understanding the evolution of hearing in the early tetrapods. The water-to-land transition resulted in major changes in the tetrapod ear associated with the detection of air-borne sound pressure, as evidenced by the late and independent origins of tympanic ears in all of the major tetrapod groups. To investigate lungfish pressure and vibration detection, we measured the sensitivity and frequency responses of five West African lungfish ( Protopterus annectens ) using brainstem potentials evoked by calibrated sound and vibration stimuli in air and water. We find that the lungfish ear has good low-frequency vibration sensitivity, like recent amphibians, but poor sensitivity to air-borne sound. The skull shows measurable vibrations above 100 Hz when stimulated by air-borne sound, but the ear is apparently insensitive at these frequencies, suggesting that the lungfish ear is neither adapted nor pre-adapted for aerial hearing. Thus, if the lungfish ear is a model of the ear of early tetrapods, their auditory sensitivity was limited to very low frequencies on land, mostly mediated by substrate-borne vibrations.

Clupeiform fish species, including the Gulf menhaden (Brevoortia patronus) that belong to the subfamily Alosinae, can detect ultrasound. Clupeiform fishes are unique in that they have specialized gas-filled bullae in the head associated with the ear via the bulla membrane and with the lateral line via the lateral recess membrane. It has been hypothesized that the utricle of the inner ear is responsible for ultrasound detection through a specialized connection to the gas-filled bullae complex. Here, we show that the lateral line and its connection to the gas-filled bullae complex via the lateral recess are involved in ultrasound detection in Gulf menhaden. Removal of a small portion of the lateral line overlying the lateral recess membrane eliminates the ability of Gulf menhaden to detect ultrasound. We further show that the gas-filled bullae vibrates in response to ultrasound, that the gas-filled bullae are necessary for detecting ultrasound, and that the bullae connections to the lateral line via the lateral recess membrane play an important role in ultrasound detection. These results add a new dimension to the role of the lateral line and bullae as part of the ultrasonic detection system in Gulf menhaden

Most fish cannot hear frequencies above 3 kHz, but a few species belonging to the subfamily Alosinae (family Clupeidae) can detect intense ultrasound. The response of adult specimens of the European allis shad (Alosa alosa) to sinusoidal ultrasonic pulses at 70 and 120 kHz is tested. The fish showed an intensity-graded response to the ultrasonic pulses with a response threshold between 161 and 167 dB re 1 µPa (pp) for both frequencies. These response thresholds are similar to thresholds derived from juvenile American shad (Alosa sapidissima) in previous studies, supporting the suggestion that these members of Alosinae have evolved a dedicated ultrasound detector adapted to detect and respond to approaching echolocating toothed whales.