Ice thickness monitoring for cryo-EM grids by interferometry imaging.

While recent technological developments contributed to breakthrough advances in single particle cryo-electron microscopy (cryo-EM), sample preparation remains a significant bottleneck for the structure determination of macromolecular complexes. A critical time factor is sample optimization that requires the use of an electron microscope to screen grids prepared under different conditions to achieve the ideal vitreous ice thickness containing the particles. Evaluating sample quality requires access to cryo-electron microscopes and a strong expertise in EM. To facilitate and accelerate the selection procedure of probes suitable for high-resolution cryo-EM, we devised a method to assess the vitreous ice layer thickness of sample coated grids. The experimental setup comprises an optical interferometric microscope equipped with a cryogenic stage and image analysis software based on artificial neural networks (ANN) for an unbiased sample selection. We present and validate this approach for different protein complexes and grid types, and demonstrate its performance for the assessment of ice quality. This technique is moderate in cost and can be easily performed on a laboratory bench. We expect that its throughput and its versatility will contribute to facilitate the sample optimization process for structural biologists.

Does the Selection of the Procedure Impact the Return to Work in Unemployed Patients Undergoing Bariatric Surgery?

PURPOSE: Obesity and its comorbidities are risk factors for absenteeism and unemployment. Bariatric surgery might help to intervene in the vicious circle of unemployment, social disadvantage and increasing obesity. The most common bariatric procedures are sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). This survey analyzes the influence of the bariatric procedure on return to work. METHODS: The data of a German nationwide multicenter registry StuDoQ|MBE from 2015 to 2020 are evaluated. Patients are surveyed who underwent a primary SG or RYGB while being unemployed: 782 patients are included. Primary endpoint is any form of return to work within 1 year after treatment. The surgical procedure acts as the binary main treatment variable. A multivariate binary logistic regression model was performed with age, sex, vocational training and weight loss as third variables so that odds ratios (OR) and adjusted ORs were determined. RESULTS: Of the patients, 41.56% received a RYGB, 58.44% a SG. One year after bariatric surgery, 39.39% of the patients with SG and 33.85% with RYGB reached a return to work. The OR for return to work is 1.27 (p = 0.11) non-significant in favor of SG. The adjusted OR is 1.26 (p = 0.15), indicating that there is no significant influence of the difference between the two surgical procedures on the outcome of return to work. CONCLUSION: There is a positive effect regarding return to work in bariatric patients: More than a third of the previously unemployed patients were employed 1 year after surgery. Procedure-specific influences could not be determined.

The Spatial Resolution of Bat Biosonar Quantified with a Visual-Resolution Paradigm.

Bats are navigation super-performers, flying at high speed through nocturnal forests. Numerous field observations and formal experiments have impressively shown how well bats tackle navigation in 3D with biosonar, i.e., the auditory analysis of self-generated ultrasonic emissions [1-7]. However, unlike in the visual system, where space is explicitly coded at very high resolution in the retinal fovea, the inner ear encodes frequency and time, not space. Spatial attributes of echoes are represented in the space-dependent filtering of the bats' pinnae [8, 9] and binaural computations, like interaural time and level differences [10, 11], as first proposed by Lord Rayleigh [12]. Remarkably, Rayleigh also provided a clear definition of spatial resolution: based on the shape of optical diffraction patterns arising from two closely spaced light sources, Rayleigh defined resolution as the capability to detect a trough in their joint light diffraction patterns [13, 14]. Here, we recruit Rayleigh's classical resolution paradigm to quantify how well bats can resolve multiple simultaneously presented reflectors in space. We show that biosonar spatial resolution in azimuth is no better than about 80° compared to a human visual resolution down to 0.02° [14]. We suggest that bats compensate this effective lack of spatial resolution by sequentially probing their environment in flight. Our data show that low-resolution environment perception is a viable alternative to high-resolution vision to support intelligent behavior in complex environments.

Optic and echo-acoustic flow interact in bats.

Echolocating bats are known to fly and forage in complete darkness, using the echoes of their actively emitted calls to navigate and to detect prey. However, under dim light conditions many bats can also rely on vision. Many flying animals have been shown to navigate by optic flow information and, recently, bats were shown to exploit echo-acoustic flow to navigate through dark habitats. Here, we show for the bat Phyllostomus discolor that, in lighted habitats where self-motion-induced optic flow is strong, optic and echo-acoustic flow interact to guide navigation. Echo-acoustic flow showed a surprisingly strong effect compared with optic flow. We thus demonstrate multimodal interaction between two far-ranging spatial senses, vision and echolocation, available in this combination almost exclusively in bats and toothed whales. Our results highlight the importance of merging information from different sensory systems in a sensory-specialist animal to successfully navigate and hunt under difficult conditions.

Echo-acoustic scanning with noseleaf and ears in phyllostomid bats.

The mammalian visual system is highly directional and mammals typically employ rapid eye movements to scan their environment. Both sound emission and hearing in echolocating bats are directional but not much is known about how bats use ear movements and possibly movements of the sound-emitting structures to scan space. Here, we investigated in a tightly controlled behavioural experiment how Phyllostomusdiscolor bats employ their echolocation system while being moved through differently structured environments: we monitored and reconstructed both a close-up of the facial structures in 3D, including the motile noseleaf and outer ears, and the sonar-beam of the bat while it was moved along reflectors. Despite the simple linear movement of the bats in the setup, the bats pointed their beam quite variably in azimuth with a standard deviation of about ±20 deg. This variation arises from yaw-type head rotations. Video analyses show that the bat's noseleaf twitches with every echolocation call. Second, we show that the bat's ears are raised to a rather stereotypical head-centred position with every echolocation call. Surprisingly, P. discolor can adjust the timing and the magnitude of these ear movements to the distance of the reflectors with millisecond precision. Our findings reveal echolocation-specific specialisations as well as general principles of scanning and stabilisation of a directional remote sense. The call-correlated movements of the facial structures may lead to a higher directionality of the echolocation system and may enable the bats to adjust their echo-acoustic gaze to dynamic environments.

Echo-acoustic flow affects flight in bats.

Flying animals need to react fast to rapid changes in their environment. Visually guided animals use optic flow, generated by their movement through structured environments. Nocturnal bats cannot make use of optic flow, but rely mostly on echolocation. Here, we show that bats exploit echo-acoustic flow to negotiate flight through narrow passages. Specifically, bats' flight between lateral structures is significantly affected by the echo-acoustic salience of those structures, independent of their physical distance. This is true even though echolocation, unlike vision, provides explicit distance cues. Moreover, the bats reduced the echolocation sound levels in stronger flow, probably to compensate for the increased summary target strength of the lateral reflectors. However, bats did not reduce flight velocity under stronger echo-acoustic flow. Our results demonstrate that sensory flow is a ubiquitous principle for flight guidance, independent of the fundamentally different peripheral representation of flow across the senses of vision and echolocation.

Concurrent Acoustic Activation of the Medial Olivocochlear System Modifies the After-Effects of Intense Low-Frequency Sound on the Human Inner Ear.

>Human hearing is rather insensitive for very low frequencies (i.e. below 100 Hz). Despite this insensitivity, low-frequency sound can cause oscillating changes of cochlear gain in inner ear regions processing even much higher frequencies. These alterations outlast the duration of the low-frequency stimulation by several minutes, for which the term 'bounce phenomenon' has been coined. Previously, we have shown that the bounce can be traced by monitoring frequency and level changes of spontaneous otoacoustic emissions (SOAEs) over time. It has been suggested elsewhere that large receptor potentials elicited by low-frequency stimulation produce a net Ca(2+) influx and associated gain decrease in outer hair cells. The bounce presumably reflects an underdamped, homeostatic readjustment of increased Ca(2+) concentrations and related gain changes after low-frequency sound offset. Here, we test this hypothesis by activating the medial olivocochlear efferent system during presentation of the bounce-evoking low-frequency (LF) sound. The efferent system is known to modulate outer hair cell Ca(2+) concentrations and receptor potentials, and therefore, it should modulate the characteristics of the bounce phenomenon. We show that simultaneous presentation of contralateral broadband noise (100 Hz-8 kHz, 65 and 70 dB SPL, 90 s, activating the efferent system) and ipsilateral low-frequency sound (30 Hz, 120 dB SPL, 90 s, inducing the bounce) affects the characteristics of bouncing SOAEs recorded after low-frequency sound offset. Specifically, the decay time constant of the SOAE level changes is shorter, and the transient SOAE suppression is less pronounced. Moreover, the number of new, transient SOAEs as they are seen during the bounce, are reduced. Taken together, activation of the medial olivocochlear system during induction of the bounce phenomenon with low-frequency sound results in changed characteristics of the bounce phenomenon. Thus, our data provide experimental support for the hypothesis that outer hair cell calcium homeostasis is the source of the bounce phenomenon.

Low-frequency sound affects active micromechanics in the human inner ear.

Noise-induced hearing loss is one of the most common auditory pathologies, resulting from overstimulation of the human cochlea, an exquisitely sensitive micromechanical device. At very low frequencies (less than 250 Hz), however, the sensitivity of human hearing, and therefore the perceived loudness is poor. The perceived loudness is mediated by the inner hair cells of the cochlea which are driven very inadequately at low frequencies. To assess the impact of low-frequency (LF) sound, we exploited a by-product of the active amplification of sound outer hair cells (OHCs) perform, so-called spontaneous otoacoustic emissions. These are faint sounds produced by the inner ear that can be used to detect changes of cochlear physiology. We show that a short exposure to perceptually unobtrusive, LF sounds significantly affects OHCs: a 90 s, 80 dB(A) LF sound induced slow, concordant and positively correlated frequency and level oscillations of spontaneous otoacoustic emissions that lasted for about 2 min after LF sound offset. LF sounds, contrary to their unobtrusive perception, strongly stimulate the human cochlea and affect amplification processes in the most sensitive and important frequency range of human hearing.

Amplitude-modulation detection by gerbils in reverberant sound fields.

Reverberation can dramatically reduce the depth of amplitude modulations which are critical for speech intelligibility. Psychophysical experiments indicate that humans' sensitivity to amplitude modulation in reverberation is better than predicted from the acoustic modulation depth at the receiver position. Electrophysiological studies on reverberation in rabbits highlight the contribution of neurons sensitive to interaural correlation. Here, we use a prepulse-inhibition paradigm to quantify the gerbils' amplitude modulation threshold in both anechoic and reverberant virtual environments. Data show that prepulse inhibition provides a reliable method for determining the gerbils' AM sensitivity. However, we find no evidence for perceptual restoration of amplitude modulation in reverberation. Instead, the deterioration of AM sensitivity in reverberant conditions can be quantitatively explained by the reduced modulation depth at the receiver position. We suggest that the lack of perceptual restoration is related to physical properties of the gerbil's ear input signals and inner-ear processing as opposed to shortcomings of their binaural neural processing.