Landmarks, beacons, or panoramic views: What do pigeons attend to for guidance in familiar environments?

Birds and social insects represent excellent systems for understanding visually guided navigation. Both animal groups use surrounding visual cues for homing and foraging. Ants extract sufficient spatial information from panoramic views, which naturally embed all near and far spatial information, for successful homing. Although egocentric panoramic views allow for parsimonious explanations of navigational behaviors, this potential source of spatial information has been mostly neglected during studies of vertebrates. Here we investigate how distinct landmarks, a beacon, and panoramic views influence the reorientation behavior in pigeons (Columba livia). Pigeons were trained to search for a location characterized by a beacon and several distinct landmarks. Transformation tests manipulated aspects of the landmark configuration, allowing for a dissociation among navigational strategies. Quantitative image and path analyses provided support that the panoramic view was used by the pigeons. Although the results from some individuals support the use of beaconing, overall the pigeons relied predominantly on the panoramic view when spatial cues provided conflicting information regarding the goal location. Reorientation based on vector and bearing information derived from distinct landmarks as well as environmental geometry failed to account fully for the results. Thus, the results of our study support that pigeons can use panoramic views for reorientation in familiar environments. Given that the current model for landmark use by pigeons posits the use of different vectors from an object, a global panorama-matching strategy suggests a fundamental change in the theory of how pigeons use surrounding visual cues for localization.

Senescent Tumor Cells Are Frequently Present at the Invasion Front: Implications for Improving Disease Control in Patients with Locally Advanced Prostate Cancer.

INTRODUCTION: Local tumor invasion is a critical factor for the outcome of men with prostate cancer. In particular, seminal vesicle invasion (SVI) has been reported to be associated with a more unfavorable prognosis. A better understanding of the functional state of invading prostate cancer cells is crucial to develop novel therapeutic strategies for patients with locally advanced disease. METHODS: The prognostic impact of local tumor progression was ascertained in over 1,000 men with prostate cancer. Prostate cancer specimens were stained by double-immunohistochemistry for the proliferation marker Ki-67 and the senescence marker p16INK4A. The migratory properties of senescent prostate cancer cells were analyzed in vitro using a wound healing assay and immunofluorescence microscopy for p16INK4A. RESULTS: We confirm the notion that patients with SVI have a more unfavorable prognosis than patients with extraprostatic extension alone. Surprisingly, we found that the tumor invasion front frequently harbors p16INK4A-positive and Ki-67-negative, i.e., senescent, tumor cells. While the intraprostatic tumor periphery was a hotspot for both proliferation and expression of p16INK4A, the area of SVI showed less proliferative activity but was at the same time a hotspot of cells with increased nuclear p16INK4A expression. Senescence was associated with an accelerated migration of prostate cancer cells in vitro. CONCLUSION: This proof-of-concept study shows that invading prostate cancer cells frequently show signs of cellular senescence. This finding may open new avenues for neoadjuvant and adjuvant treatment concepts in men with locally advanced prostate cancer.

Long-term cost-effectiveness of matrix-associated chondrocyte implantation in the German health care system: a discrete event simulation.

INTRODUCTION: Cartilage defects in the knee can be caused by injury, various types of arthritis, or degeneration. As a long-term consequence of cartilage defects, osteoarthritis can develop over time, often leading to the need for a total knee replacement (TKR). The treatment alternatives of chondral defects include, among others, microfracture, and matrix-associated autologous chondrocyte implantation (M-ACI). The purpose of this study was to determine cost-effectiveness of M-ACI in Germany with available mid- and long-term outcome data, with special focus on the avoidance of TKR. MATERIALS AND METHODS: We developed a discrete-event simulation (DES) that follows up individuals with cartilage defects of the knee over their lifetimes. The DES was conducted with a status-quo scenario in which M-ACI is available and a comparison scenario with no M-ACI available. The model included 10,000 patients with articular cartilage defects. We assumed Weibull distributions for short- and long-term effects for implant failures. Model outcomes were costs, number of TKRs, and quality-adjusted life years (QALYs). All analyses were performed from the perspective of the German statutory health insurance. RESULTS: The majority of patients was under 45 years old, with defect sizes between 2 and 7 cm2 (mean: 4.5 cm2); average modeled lifetime was 48 years. In the scenario without M-ACI, 26.4% of patients required a TKR over their lifetime. In the M-ACI scenario, this was the case in only 5.5% of cases. Thus, in the modeled cohort of 10,000 patients, 2700 TKRs, including revisions, could be avoided. Patients treated with M-ACI experienced improved quality of life (22.53 vs. 21.21 QALYs) at higher treatment-related costs (18,589 vs. 14,134 € /patient) compared to those treated without M-ACI, yielding an incremental cost-effectiveness ratio (ICER) of 3376 € /QALY. CONCLUSION: M-ACI is projected to be a highly cost-effective treatment for chondral defects of the knee in the German healthcare setting.

Route-following ants respond to alterations of the view sequence.

Ants can navigate by comparing the currently perceived view with memorised views along a familiar foraging route. Models regarding route-following suggest that the views are stored and recalled independently of the sequence in which they occur. Hence, the ant only needs to evaluate the instantaneous familiarity of the current view to obtain a heading direction. This study investigates whether ant homing behaviour is influenced by alterations in the sequence of views experienced along a familiar route, using the frequency of stop-and-scan behaviour as an indicator of the ant's navigational uncertainty. Ants were trained to forage between their nest and a feeder which they exited through a short channel before proceeding along the homeward route. In tests, ants were collected before entering the nest and released again in the channel, which was placed either in its original location or halfway along the route. Ants exiting the familiar channel in the middle of the route would thus experience familiar views in a novel sequence. Results show that ants exiting the channel scan significantly more when they find themselves in the middle of the route, compared with when emerging at the expected location near the feeder. This behaviour suggests that previously encountered views influence the recognition of current views, even when these views are highly familiar, revealing a sequence component to route memory. How information about view sequences could be implemented in the insect brain, as well as potential alternative explanations to our results, are discussed.

Development of raw acceleration cut-points for wrist and hip accelerometers to assess sedentary behaviour and physical activity in 5-7-year-old children.

This study validated sedentary behaviour (SB), moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA) accelerometer cut-points in 5-7-year-old children. Participants (n = 49, 55% girls) wore an ActiGraph GT9X accelerometer, recording data at 100 Hz downloaded in 1 s epochs, on both wrists and the right hip during a standardised protocol and recess. Cut-points were generated using ROC analysis with direct observation as a criterion. Subsequently, cut-points were optimised using Confidence intervals equivalency analysis and then cross-validated in a cross-validation group. SB cut-points were 36 mg (Sensitivity (Sn) = 79.8%, Specificity (Sp) = 56.8%) for non-dominant wrist, 39 mg (Sn = 75.4%, Sp = 70.2%) for dominant wrist and 20 mg (Sn = 78%, Sp = 50.1%) for hip. MVPA cut-points were 189 mg (Sn = 82.6%, Sp = 78%) for non-dominant wrist, 181 mg (Sn = 79.1%, Sp = 76%) for dominant wrist and 95 mg (Sn = 79.3%, Sp = 75.6%) for hip. VPA cut-points were 536 mg (Sn = 75.1%, Sp = 68.7%) for non-dominant wrist, 534 mg (Sn = 67.6%, Sp = 95.6%) for dominant wrist and 325 mg (Sn = 78.2%, Sp = 96.1%) for hip. All placements demonstrated adequate levels of accuracy for SB and PA assessment.

Running paths to nowhere: repetition of routes shows how navigating ants modulate online the weights accorded to cues.

Ants are expert navigators, keeping track of the vector to home as they travel, through path integration, and using terrestrial panoramas in view-based navigation. Although insect learning has been much studied, the learning processes in navigation have not received much attention. Here, we investigate in desert ants (Melophorus bagoti) the effects of repeating a well-travelled and familiar route segment without success. We find that re-running a homeward route without entering the nest impacted subsequent trips. Over trips, ants showed more meandering from side to side and more scanning behaviour, in which the ant stopped and turned, rotating to a range of directions. In repeatedly re-running their familiar route, ants eventually gave up heading in the nestward direction as defined by visual cues and turned to walk in the opposite direction. Further manipulations showed that the extent and rate of this path degradation depend on (1) the length of the vector accumulated in the direction opposite to the food-to-nest direction, (2) the specific visual experience of the repeated segment of the route that the ants were forced to re-run, and (3) the visual panorama: paths are more degraded in an open panorama, compared with a visually cluttered scene. The results show that ants dynamically modulate the weighting given to route memories, and that fits well with the recent models, suggesting that the mushroom bodies provide a substrate for the reinforcement learning of views for navigation.

Multiple sources of celestial compass information in the Central Australian desert ant Melophorus bagoti.

The Central Australian desert ant Melophorus bagoti is known to use celestial cues for compass orientation. We manipulated the available celestial cues for compass orientation for ants that had arrived at a feeder, were captured and then released at a distant test site that had no useful terrestrial panoramic cues. When tested in an enclosed transparent box that blocked some or most of the ultraviolet light, the ants were still well oriented homewards. The ants were again significantly oriented homewards when most of the ultraviolet light as well as the sun was blocked, or when the box was covered with tracing paper that eliminated the pattern of polarised light, although in the latter case, their headings were more scattered than in control (full-cue) conditions. When the position of the sun was reflected 180° by a mirror, the ants headed off in an intermediate direction between the dictates of the sun and the dictates of unrotated cues. We conclude that M. bagoti uses all available celestial compass cues, including the pattern of polarised light, the position of the sun, and spectral and intensity gradients. They average multiple cues in a weighted fashion when these cues conflict.

Food selection in larval fruit flies: dynamics and effects on larval development.

Selecting food items and attaining a nutritionally balanced diet is an important challenge for all animals including humans. We aimed to establish fruit fly larvae (Drosophila melanogaster) as a simple yet powerful model system for examining the mechanisms of specific hunger and diet selection. In two lab experiments with artificial diets, we found that larvae deprived of either sucrose or protein later selectively fed on a diet providing the missing nutrient. When allowed to freely move between two adjacent food patches, larvae surprisingly preferred to settle on one patch containing yeast and ignored the patch providing sucrose. Moreover, when allowed to move freely between three patches, which provided either yeast only, sucrose only or a balanced mixture of yeast and sucrose, the majority of larvae settled on the yeast-plus-sucrose patch and about one third chose to feed on the yeast only food. While protein (yeast) is essential for development, we also quantified larval success on diets with or without sucrose and show that larvae develop faster on diets containing sucrose. Our data suggest that fruit fly larvae can quickly assess major nutrients in food and seek a diet providing a missing nutrient. The larvae, however, probably prefer to quickly dig into a single food substrate for enhanced protection over achieving an optimal diet.

Backtracking behaviour in lost ants: an additional strategy in their navigational toolkit.

Ants use multiple sources of information to navigate, but do not integrate all this information into a unified representation of the world. Rather, the available information appears to serve three distinct main navigational systems: path integration, systematic search and the use of learnt information--mainly via vision. Here, we report on an additional behaviour that suggests a supplemental system in the ant's navigational toolkit: 'backtracking'. Homing ants, having almost reached their nest but, suddenly displaced to unfamiliar areas, did not show the characteristic undirected headings of systematic searches. Instead, these ants backtracked in the compass direction opposite to the path that they had just travelled. The ecological function of this behaviour is clear as we show it increases the chances of returning to familiar terrain. Importantly, the mechanistic implications of this behaviour stress an extra level of cognitive complexity in ant navigation. Our results imply: (i) the presence of a type of 'memory of the current trip' allowing lost ants to take into account the familiar view recently experienced, and (ii) direct sharing of information across different navigational systems. We propose a revised architecture of the ant's navigational toolkit illustrating how the different systems may interact to produce adaptive behaviours.

An intrinsic oscillator underlies visual navigation in ants.

Many insects display lateral oscillations while moving, but how these oscillations are produced and participate in visual navigation remains unclear. Here, we show that visually navigating ants continuously display regular lateral oscillations coupled with variations of forward speed that strongly optimize the distance covered while simultaneously enabling them to scan left and right directions. This pattern of movement is produced endogenously and conserved across navigational contexts in two phylogenetically distant ant species. Moreover, the oscillations' amplitude can be modulated by both innate or learnt visual cues to adjust the exploration/exploitation balance to the current need. This lower-level motor pattern thus drastically reduces the degree of freedom needed for higher-level strategies to control behavior. The observed dynamical signature readily emerges from a simple neural circuit model of the insect's conserved pre-motor area known as the lateral accessory lobe, offering a surprisingly simple but effective neural control and endorsing oscillation as a core, ancestral way of moving in insects.

Polyelectrolyte coating of iron oxide nanoparticles for MRI-based cell tracking.

Iron oxide-based magnetic nanoparticles (MNPs) offer unique properties for cell tracking by magnetic resonance imaging (MRI) in cellular immunotherapy. In this study, we investigated the uptake of chemically engineered NPs into antigen-presenting dendritic cells (DCs). DCs are expected to perceive MNPs as foreign antigens, thus exhibiting the capability to immunologically sense MNP surface chemistry. To systematically evaluate cellular uptake and T2/T2(⁎) MR imaging properties of MNPs, we synthesized polymer-based MNPs by employing layer-by-layer (LbL) technology. Thereby, we achieved modification of particle shell parameters, such as size, surface charge, and chemistry. We found that subcellular packaging of MNPs rather than MNP content in DCs influences MR imaging quality. Increased local intracellular electron density as inferred from transmission electron microscopy (TEM) strongly correlated with enhanced contrast in MRI. Thus, LbL-tailoring of MNP shells using polyelectrolytes that impact on uptake and subcellular localization can be used for modulating MR imaging properties. FROM THE CLINICAL EDITOR: In this study, layer-by-layer tailoring of magnetic NP shells was performed using polyelectrolytes to improve uptake by dendritic cells for cell-specific MR imaging. The authors conclude that polyelectrolyte modified NP-s can be used for modulating improving MR imaging quality by increasing subcellular localization.

Aversive view memories and risk perception in navigating ants.

Many ants establish foraging routes through learning views of the visual panorama. Route models have focused primarily on attractive view use, which experienced foragers orient towards to return to known sites. However, aversive views have recently been uncovered as a key component of route learning. Here, Cataglyphis velox rapidly learned aversive views, when associated with a negative outcome, a period of captivity in vegetation, triggering increases in hesitation behavior. These memories were based on the accumulation of experiences over multiple trips with each new experience regulating forager hesitancy. Foragers were also sensitive to captivity time differences, suggesting they possess some mechanism to quantify duration. Finally, we analyzed foragers' perception of risky (i.e. variable) versus stable aversive outcomes by associating two sites along the route with distinct captivity schedules, a fixed or variable duration, with the same mean across training. Foragers exhibited fewer hesitations in response to risky outcomes compared to fixed ones, indicating they perceived risky outcomes as less severe. Results align with a logarithmic relationship between captivity duration and hesitations, suggesting that aversive stimulus perception is a logarithm of its actual value. We discuss how aversive view learning could be executed within the mushroom bodies circuitry following a prediction error rule.

Views, landmarks, and routes: how do desert ants negotiate an obstacle course?

The Australian desert ant Melophorus bagoti often follows stereotypical routes through a cluttered landscape containing both distant panoramic views and obstacles (plants) to navigate around. We created an artificial obstacle course for the ants between a feeder and their nest. Landmarks comprised natural objects in the landscape such as logs, branches, and tussocks. Many ants travelled stereotypical routes home through the obstacle course in training, threading repeatedly the same gaps in the landmarks. Manipulations altering the relations between the landmarks and the surrounding panorama, however, affected the routes in two major ways. Both interchanging the positions of landmarks (transpositions) and displacing the entire landmark set along with the starting position of the ants (translations) (1) reduced the stereotypicality of the route, and (2) increased turns and meanders during travel. The ants might have used the entire panorama in view-based travel, or the distal panorama might prime the identification and use of landmarks en route. Despite the large data set, both options (not mutually exclusive) remain viable.

Ocelli contribute to the encoding of celestial compass information in the Australian desert ant Melophorus bagoti.

Many animal species, including some social hymenoptera, use the visual system for navigation. Although the insect compound eyes have been well studied, less is known about the second visual system in some insects, the ocelli. Here we demonstrate navigational functions of the ocelli in the visually guided Australian desert ant Melophorus bagoti. These ants are known to rely on both visual landmark learning and path integration. We conducted experiments to reveal the role of ocelli in the perception and use of celestial compass information and landmark guidance. Ants with directional information from their path integration system were tested with covered compound eyes and open ocelli on an unfamiliar test field where only celestial compass cues were available for homing. These full-vector ants, using only their ocelli for visual information, oriented significantly towards the fictive nest on the test field, indicating the use of celestial compass information that is presumably based on polarised skylight, the sun's position or the colour gradient of the sky. Ants without any directional information from their path-integration system (zero-vector) were tested, also with covered compound eyes and open ocelli, on a familiar training field where they have to use the surrounding panorama to home. These ants failed to orient significantly in the homeward direction. Together, our results demonstrated that M. bagoti could perceive and process celestial compass information for directional orientation with their ocelli. In contrast, the ocelli do not seem to contribute to terrestrial landmark-based navigation in M. bagoti.

Visual discrimination, sequential learning and memory retrieval in the Australian desert ant Melophorus bagoti.

Bees, wasps and ants--so-called central-place foragers--need potent homing strategies to return to their nest. Path integration and view-based landmark guidance are the key strategies for the ants' navigation. For instance, they memorise different views in a sequence (sequential memory) but also have a step counter that informs them about the covered distance during each foraging trip (odometer). The sequential memory and the odometer information can act as contextual cues during travel for retrieving the appropriate stored view. When and which cue is used at different stages and lengths of the foraging trips is still unknown. In this study, we examined how the Australian desert ant Melophorus bagoti uses sequential memory and odometric information to retrieve visual memories. Using a set-up made out of channels and two-choice boxes (Y-mazes), we demonstrate first that M. bagoti foragers are able to learn and discriminate a variety of visual stimuli in a sequence of views along the inbound trip back to the nest. We then forced the homing ants to encounter a fixed sequence of two visual patterns during their inbound trips. By manipulating the position and distance of the visual stimuli and decision boxes, we could set the two contextual cues (sequential memory and odometer) into conflict. After the short 4-m outbound distance, a preference for odometric information as a contextual cue was found, but after the long 8-m outbound distance, ants relied primarily on their sequential memory retrieval. Odometer precision deteriorates with increasing travel distance, and accordingly, our findings imply that desert ants may be relying on the most reliable contextual cue for retrieving visual memories.

A new navigational mechanism mediated by ant ocelli.

Many animals rely on path integration for navigation and desert ants are the champions. On leaving the nest, ants continuously integrate their distance and direction of travel so that they always know their current distance and direction from the nest and can take a direct path to home. Distance information originates from a step-counter and directional information is based on a celestial compass. So far, it has been assumed that the directional information obtained from ocelli contribute to a single global path integrator, together with directional information from the dorsal rim area (DRA) of the compound eyes and distance information from the step-counter. Here, we show that ocelli mediate a distinct compass from that mediated by the compound eyes. After travelling a two-leg outbound route, untreated foragers headed towards the nest direction, showing that both legs of the route had been integrated. In contrast, foragers with covered compound eyes but uncovered ocelli steered in the direction opposite to the last leg of the outbound route. Our findings suggest that, unlike the DRA, ocelli cannot by themselves mediate path integration. Instead, ocelli mediate a distinct directional system, which buffers the most recent leg of a journey.

Rapid Aversive and Memory Trace Learning during Route Navigation in Desert Ants.

The ability of bees and ants to learn long visually guided routes in complex environments is perhaps one of the most spectacular pieces of evidence for the impressive power of their small brains. Whereas flying bees can visit flowers in an optimized sequence over kilometers, walking solitary foraging ants can precisely recapitulate routes of up to 100 m in complex environments [1]. It is clear that route following depends largely on learned visual information and we have a good idea of how visual memories can guide individuals along them [2-6], as well as how this is implemented in the insect brain [7, 8]. However, little is known about the mechanisms that control route learning and development. Here we show that ants (Melophorus bagoti and Cataglyphis fortis) navigating in their natural environments can actively learn a route detour to avoid a pit trap. This adaptive flexibility depends on a mechanism of aversive learning based on memory traces of recently encountered stimuli, reflecting the laboratory paradigm of trace conditioning. The views experienced before falling into the trap become associated with the ensuing negative outcome and thus trigger salutary turns on the subsequent trip. This drives the ants to orient away from the goal direction and avoid the trap. If the pit trap is avoided, the novel views experienced during the detour become positively reinforced and the new route crystallizes. We discuss how such an interplay between appetitive and aversive memories might be implemented in insect neural circuitry.

Bringing IoT to the Lab: SiLA2 and Open-Source-Powered Gateway Module for Integrating Legacy Devices into the Digital Laboratory.

In this article a gateway module to integrate legacy laboratory devices into the network of the digital laboratory in the 21st century is introduced. The device is based on ready to buy consumer hardware that is easy to get and inexpensive. Depending on the specific requirements of the desired application (bare embedded computer, RS232 serial port connector, IP65 certified casing and connectors) the needed investment ranges from about 95 € up to 200 €. The embedded computer runs an open source Linux operating system and can in principle be used to run any kind of software needed for communicating with the laboratory device. Here the open source SiLA2 standard is used for presenting the device's functions in the network. As an example the digital integration of a magnetic stirrer is shown and can be used as a template for other applications. A method for easy remote integration of the device to ensure an easy and consistent workflow in development, testing and usage is also presented. This incorporates a method for remote installation of SiLA2 servers on the box as well as a web frontend for administration, debugging and management of those.

From dangerous branches to urban banyan: Facilitating aerial root growth of Ficus rubiginosa.

Large urban trees have many benefits. However, falling branches pose a serious hazard to both people and infrastructure. In several tree species, aerial roots grow down from branches to the ground. These roots are capable of thickening to support the branches, lessening the risk of tree failure. Unfortunately, in urban environments most aerial roots die before reaching the ground. Here, we report a new method for encouraging aerial roots to reach the ground, developed by the second-year botany class at UNSW Sydney. Our class tested three experimental treatments on aerial roots of Ficus rubiginosa Desf. ex Vent. (Port Jackson Fig)-PVC pipes filled with sphagnum moss, PVC pipes filled with potting mix, and PVC pipes filled with sphagnum moss and topped with funnels to catch extra rainwater. All three treatments significantly improved aerial root growth, with 26 of the 30 (87%) treatment roots reaching the ground after one year compared to 0 of the 10 control roots. Our method was successful for roots up to 3 m above the ground, suggesting the potential growth rate of aerial roots is substantial when conditions are favourable. Our novel approach is an attractive and cost-effective alternative to slings and other artificial supports. This project is an example of using undergraduate practical classes to teach science while simultaneously addressing important real-world problems.

Ants' navigation in an unfamiliar environment is influenced by their experience of a familiar route.

When displaced experimentally from a food source (feeder) to unfamiliar terrain, ants run off a portion of the homeward vector or its entirety, depending on species and conditions, and then search systematically, turning in loops of ever increasing size. The Australian desert ant Melophorus bagoti runs off a smaller portion of its vector if the test site is more dissimilar to its nest area. Here we manipulated familiarity with the training route between a feeder and the ants' nest to examine its effects when the ants were displaced to a distant site from the feeder. Naïve ants that arrived at an experimentally provided feeder for the first time were compared with experienced ants that had travelled the route for two days. At the unfamiliar test site, naïve ants ran off a longer portion of their vector from path integration than did experienced ants. Naïve ants also spread out in their systematic search slower than did experienced ants. We conclude that as ants learn the views encountered on their familiar route better, they identify more readily unfamiliar views. A scene distant from their nest area may not look as unfamiliar to a naïve ant as it does to an experienced ant.