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For the past 20 years, reintroduction efforts have been underway to re-establish a migratory population of Northern Bald Ibises (Geronticus eremita) in Central Europe, which now consists of more than 250 birds. They breed both north and south of the Alps and migrate to a common wintering ground in Tuscany. Recently, the start of autumn migration has been increasingly delayed, which correlates with extended warm periods in autumn. Later in the year, however, the birds no longer find sufficient thermals to cross the Alps and remain in the northern Alpine foothills. In order to save their lives, we had to capture the affected birds before the onset of winter, which is not a sustainable solution. A new approach to solving the problem is the establishment of a second migration route to a wintering area in Andalusia, Spain, connecting our population with a sedentary population there. The new migration route bypasses mountain barriers and also allows the birds to reach the wintering grounds later in the year. The modelling of a pan-European population will provide the birds with high ecological and spatial flexibility. Our project exemplifies the consequences of advancing global warming for animal populations and the associated challenges for conservation projects.

The northern bald ibis Geronticus eremita disappeared from Europe in the Middle Ages. Since 2003 a migratory population has been reintroduced in Central Europe. We conducted demographic analyses of the survival and reproduction of 384 northern bald ibises over a period of 12 years (2008–2019). These data also formed the basis for a population viability analysis simulating the possible future development of the northern bald ibis population under different scenarios. We analysed life stage-specific survival rates, rearing protocols and colonies, and the influence of stochastic catastrophic events and reinforcement translocations on population growth. Life stage-specific survival probabilities were 0.64–0.78. Forty-five per cent of the mature females reproduced, with a mean fecundity of 2.15 fledglings per nest. The complementary population viability analysis indicated that the Waldrappteam population is close to self-sustainability, with an estimated population growth rate of 0.95 and a 24% extinction probability within 50 years. Of the 326 future scenarios tested, 94% reached the criteria of extinction probabilities < 5% and population growth rates > 1. Stochastic catastrophic events had only a limited effect. Despite comparatively high survival and fecundity rates the population viability analysis indicated that to achieve self-sustainability the Waldrappteam population needs further translocations to support population growth and the implementation of effective measures against major mortality threats: illegal hunting in Italy and electrocution on unsecured power poles. The findings of this study are to be implemented as part of a second European LIFE project.

Abstract Background The impact of biologging devices on the aerodynamics or hydrodynamics of animals is still poorly understood. This stands in marked contrast to the ever more extensive use of such technologies in wild-living animals. Recently, increasing concerns have been raised about the impairing effects of these devices on the animals concerned. In the early days of biotelemetry, attention was focused solely on reducing weight, but now aerodynamic effects are also increasingly being considered. To investigate these effects, we trained Northern Bald Ibises to fly in a wind tunnel in which we measured heart rate and dynamic body acceleration (VeDBA) as proxies for energy expenditure in relation to different logger shapes and wind flow directions. Results Our data provide evidence that the position of biologging devices significantly influence the flight distances, and the shape of biologging devices has a considerable effect on heart rate and VeDBA, both of which have been used as proxies for energy expenditure. Unfavorable shape and positioning go beyond merely affecting the effort required during flapping flight. The energetically probably more important effect is that the devices impair the bird’s ability to glide or soar and thus force them to perform the energetically much more demanding flapping flight more frequently. This effect was more pronounced in rising air than in horizontal airflow. A complementary study with wild Northern Bald Ibises during spring migration provides evidence that the position of the devices on the bird’s back affects the length of the flight stages. Birds carrying the devices on the upper back, fixed by wing-loop harnesses, had significantly shorter flight stages compared to birds with a more caudally positioned device, fixed by leg-loop harnesses. Conclusion The attachment of biologging devices on birds affects their performance and behavior and thus may influence their fitness and mortality. Our results show that detrimental effects can be reduced with relatively little effort, in particular through a strictly aerodynamic design of the housing and increased consideration of aerodynamics when attaching the device to the body. In birds, the attachment of biologging devices via leg loops to the lower back is clearly preferable to the common attachment via wing loops on the upper back, even if this affects the efficiency of the solar panels. Nevertheless, the importance of drag reduction may vary between systems, as the benefits of having a biologging devices close to the center of gravity may outweigh the increase in drag that this involves. Overall, more research is required in this field. This is both in the interest of animal welfare and of avoiding biasing the quality of the collected data.

Commercial activity and regulatory oversight of the digital economy are growing apace. This essay argues that regulatory heterogeneity can deter digital trade without discrimination. Domestic policies that are not discriminatory can still result in fragmentation of the global digital economy, if sufficiently heterogeneous. We find that rules at the World Trade Organization (WTO) and in digital trade agreements offer important directions but insufficiently mitigate heterogeneity. We suggest that heterogeneity should be addressed through the progressive expansion of international trade law. We emphasize the importance of encouraging regulatory coherence and pre-empting the formation of digital blocks.

Abstract Background In this paper, we present evidence that biologging is strongly correlated with eye irritation, with sometimes severely impairing effects. A migratory population of the Northern Bald Ibis (Geronticus eremita, NBI) is reintroduced in Europe, in course of a LIFE + project. Since 2014, all individuals have been equipped with GPS-devices. Remote monitoring allows the implementation of focussed measures against major mortality causes. Methods Initially all birds carried battery-powered devices, fixed on the lower back of the birds. Since 2016 an increasing amount of birds has been equipped with solar-powered devices, fixed on the upper back, the more sun-exposed position. In 2016, we observed opacity in the cornea of one eye (unilateral corneal opacity; UCO) during a regular health monitoring for the first time. Results By 2018, a total of 25 birds were affected by UCO, with varying intensity up to blindness. Clinical examination of the birds revealed no clear cause for the symptoms. However, only birds carrying a device on the upper back were affected (2017 up to 70% of this group). In contrast, none of the birds carrying devices on the lower back ever showed UCO symptoms. This unexpected relationship between tagging and UCO was discovered in 2017. After we took countermeasures by removing the device or repositioning it on the lower back, we observed an immediate reduction of the incidence rate without any new cases reported since January 2019. NBI roost with their head on the back, one eye closely placed to the device if it was positioned on the upper back. Thus, we conclude that the most parsimonious explanation for the symptomatology is either a repetitive slight temperature rise in the corneal tissue due to electromagnetic radiation by the GSM module of the device or a repetitive slight mechanical irritation of the corneal surface. Concrete evidence is missing so far. Meanwhile, cases of UCO were found in another NBI population. Conclusion Our observations indicate that further research in the fast-growing field of biologging is urgently needed. The findings question the positioning of devices on the upper back in birds roosting with the head on the back.

Birds face exceptionally high energy demands during their flight. One visible feature of some species is alternating between flapping and gliding, which should allow them to save energy. To date, there is no empirical evidence of an energetic benefit to this. To understand the physiology behind the strategy, we equipped hand-raised Northern Bald Ibises (Geronticus eremita) with data loggers during human-guided migration. We monitored the position of the birds, wingbeats, overall dynamic body acceleration (ODBA), and heart rates as a proxy for energy expenditure. The energy expenditure was significantly affected by the length of flapping and gliding bouts. A pronounced decrease in heart rate was measured after already 1 s of gliding. Additionally, the heart rate at flapping bouts up to 30 s increased steadily but stabilized thereafter. The gilding proportion during intermittent flight affected the energy saving compared to continuous flapping. At a gliding proportion of about 20%, we measured a maximum of 11% saving based on heart rate measurement. At higher gliding proportions, the additional energy saving was negligible. Furthermore, as during flight, not all energy is used for mechanical work, we found a greater decrease rate of ODBA at different gliding proportions compared to heart rate. Nevertheless, the combination of the two methods is essential to determine birds’ movement and energy expenditure. This study provides empirical evidence that intermittent flight is energetically beneficial and can reduce the high costs of flights.

We trace the history of the endangered Northern Bald Ibis through different epochs to the present. A particular focus is placed on its life in and disappearance from ancient Egypt, where the bird attained great cultural and religious significance, and on the modern endeavour to re-wild the species. Due to the characteristic appearance, behaviour and habitat of the species as well as its need for open foraging areas, a close mutualistic relationship between humans and the birds was formed in ancient Egypt, as in other cultures. A clear benefit for the Northern Bald Ibis was the availability of feeding habitats, which were cleared by humans for farming or grazing. The benefit to people was rather cultural because the bird attracted religious veneration or symbolic meanings from ancient Egypt to medieval Europe. The proximity to humans, however, carried a high risk as well. We discuss various types of impact (including human impacts as well as climate change) as triggers for the extinction of the species. The evidence for a triple disappearance of the Northern Bald Ibis (around 2000 BCE, around 1600 CE and in modern time) represents a unique basis for studying both the bird’s habitat preferences and its vulnerability. This is because different, mainly anthropogenic, causes stood behind these three historical disappearances, although the disappearances in all three epochs occurred during a period of climate change.

The Northern Bald Ibis (Geronticus eremita, NBI) is an endangered migratory species, which went extinct in Europe in the 17th century. Currently, a translocation project in the frame of the European LIFE program is carried out, to reintroduce a migratory population with breeding colonies in the northern and southern Alpine foothills and a common wintering area in southern Tuscany. The population meanwhile consists of about 200 individuals, with about 90% of them carrying a GPS device on their back. We used biologging data from 2021 to model the habitat suitability for the species in the northern Alpine foothills. To set up a species distribution model, indices describing environmental conditions were calculated from satellite images of Landsat-8, and in addition to the well-proven use of optical remote sensing data, we also included Sentinel-1 actively sensed observation data, as well as climate and urbanization data. A random forest model was fitted on NBI GPS positions, which we used to identify regions with high predicted foraging suitability within the northern Alpine foothills. The model resulted in 84.5% overall accuracy. Elevation and slope had the highest predictive power, followed by grass cover and VV intensity of Sentinel-1 radar data. The map resulting from the model predicts the highest foraging suitability for valley floors, especially of Inn, Rhine, and Salzach-Valley as well as flatlands, like the Swiss Plateau and the agricultural areas surrounding Lake Constance. Areas with a high suitability index largely overlap with known historic breeding sites. This is particularly noteworthy because the model only refers to foraging habitats without considering the availability of suitable breeding cliffs. Detailed analyses identify the transition zone from extensive grassland management to intensive arable farming as the northern range limit. The modeling outcome allows for defining suitable areas for further translocation and management measures in the frame of the European NBI reintroduction program. Although required in the international IUCN translocation guidelines, the use of models in the context of translocation projects is still not common and in the case of the Northern Bald Ibis not considered in the present Single Species Action Plan of the African-Eurasian Migratory Water bird Agreement. Our species distribution model represents a contemporary snapshot, but sustainability is essential for conservation planning, especially in times of climate change. In this regard, a further model could be optimized by investigating sustainable land use, temporal dynamics, and climate change scenarios.

[This corrects the article DOI: 10.1371/journal.pone.0195255.].

The critically endangered Northern bald ibis (Geronticus eremita) is a migratory bird that became extinct in Europe centuries ago. Since 2014, the Northern bald ibis is subject to an intensive rehabilitation and conservation regime aiming to reintroduce the bird in its original distribution range in Central Europe and concurrently to maintain bird health and increase population size. Hitherto, virtually nothing is known about the microbial communities associated with the ibis species; an information pivotal for the veterinary management of these birds. Hence, the present study was conducted to provide a baseline description of the cultivable microbiota residing in the Northern bald ibis. Samples derived from the choana, trachea, crop and cloaca were examined employing a culturomic approach in order to identify microbes at each sampling site and to compare their frequency among age classes, seasonal appearances and rearing types. In total, 94 microbial species including 14 potentially new bacterial taxa were cultivated from the Northern bald ibis with 36, 58 and 59 bacterial species isolated from the choana, crop and cloaca, respectively. The microbiota of the Northern bald ibis was dominated by members of the phylum Firmicutes, followed by Proteobacteria, Actinobacteria, Bacteroidetes and Fusobacteria, altogether phylotypes commonly observed within avian gut environments. Differences in relative abundances of various microbial taxa were evident among sample types indicating mucosa-specific colonisation properties and tissue tropism. Besides, results of the present study indicate that the composition of microbiota was also affected by age, season (environment) and rearing type. While the prevalence of traditional pathogenic microbial species was extremely low, several opportunists including Clostridium perfringens toxotype A were frequently present in samples indicating that the Northern bald ibis may represent an important animal reservoir for these pathogens. In summary, the presented study provides a first inventory of the cultivable microbiota residing in the critically endangered Northern bald ibis and represents a first step in a wider investigation of the ibis microbiome with the ultimate goal to contribute to the management and survival of this critically endangered bird.

Many migrating birds undertake extraordinary long flights. How birds are able to perform such endurance flights of over 100-hour durations is still poorly understood. We examined energy expenditure and physiological changes in Northern Bald Ibis Geronticus eremite during natural flights using birds trained to follow an ultra-light aircraft. Because these birds were tame, with foster parents, we were able to bleed them immediately prior to and after each flight. Flight duration was experimentally designed ranging between one and almost four hours continuous flights. Energy expenditure during flight was estimated using doubly-labelled-water while physiological properties were assessed through blood chemistry including plasma metabolites, enzymes, electrolytes, blood gases, and reactive oxygen compounds. Instantaneous energy expenditure decreased with flight duration, and the birds appeared to balance aerobic and anaerobic metabolism, using fat, carbohydrate and protein as fuel. This made flight both economic and tolerable. The observed effects resemble classical exercise adaptations that can limit duration of exercise while reducing energetic output. There were also in-flight benefits that enable power output variation from cruising to manoeuvring. These adaptations share characteristics with physiological processes that have facilitated other athletic feats in nature and might enable the extraordinary long flights of migratory birds as well.

Abstract Background Colorectal cancer stands as a prevalent cause of cancer-related mortality, necessitating effective treatment strategies. Acute colonic obstruction occurs in approximately 20% of patients and represents a surgical emergency with substantial morbidity and mortality. The optimal approach for managing left-sided colon cancer with acute colonic obstruction remains debatable, with no consensus on whether emergency resection or bridge-to-surgery, involving initial decompressing stoma and subsequent elective resection after recovery, should be employed. Current studies show a decrease in morbidity and short-term mortality for the bridge-to-surgery approach, yet it remains unclear if the long-term oncological outcome is equivalent to emergency resection. Methods This prospective, randomized, multicenter trial aims to investigate the management of obstructive left-sided colon cancer in a comprehensive manner. The study will be conducted across 26 university hospitals and 40 academic hospitals in Germany. A total of 468 patients will be enrolled, providing a cohort of 420 evaluable patients, with an equal distribution of 210 patients in each treatment arm. Patients with left-sided colon cancer, defined as cancer between the left splenic flexure and > 12 cm ab ano and obstruction confirmed by X-ray or CT scan, are eligible. Randomization will be performed in a 1:1 ratio, assigning patients either to the oncological emergency resection group or the bridge-to-surgery group, wherein patients will undergo diverting stoma and subsequent elective oncological resection after recovery. The primary endpoint of this trial will be 120-day mortality, allowing for consideration of the time interval between diverting stoma and resection. Discussion The findings derived from this trial possess the potential to reshape the current clinical approach of emergency resection for obstructive left-sided colon cancer by favoring the bridge-to-surgery practice, provided that a reduction in morbidity can be achieved without compromising the oncological long-term outcome. Trial registration German Clinical Trials Register (DRKS) under the identifier DRKS00031827. Registered on May 15, 2023. Protocol: 28.04.2023, protocol version 2.0F.

Coordinated and efficient operation in large, complex systems requires the synchronization of the rhythms of spatially distributed components. Such systems are the basis for critical infrastructure such as satellite navigation, mobile communications, and services like the precision time protocol and Universal Coordinated Time. Different concepts for the synchronization of oscillator networks have been proposed, in particular mutual synchronization without and hierarchical synchronization from a reference clock. Established network synchronization models in electrical engineering address the role of inevitable cross-coupling time delays for network synchronization. Mutual synchronization has been studied using linear approximations of the coupling functions of these models. We review previous work and present a general model in which we study synchronization taking into account nonlinearities and finite time delays. As a result, dynamical phenomena in networks of coupled electronic oscillators induced by time delays, such as the multistability and stabilization of synchronized states can be predicted and observed. We study the linear stability of nonlinear states and predict for which system parameters synchronized states can be stable. We use these results to discuss the implementation of mutual synchronization for complex system architectures. A key finding is that mutual synchronization can result in stable in- and anti-phase synchronized states in the presence of large time delays. We provide the condition for which such synchronized states are guaranteed to be stable.

Introduction: During the first wave of the COVID-19 pandemic in 2020, the German government implemented legal restrictions to avoid the overloading of intensive care units by patients with COVID-19. The influence of these effects on diagnosis and treatment of cancer in Germany is largely unknown.Methods: To evaluate the effect of the first wave of the COVID-19 pandemic on tumor board presentations in a high-volume tertiary referral center (the German Comprehensive Cancer Center NCT/UCC Dresden), we compared the number of presentations of gastrointestinal tumors stratified by tumor entity, tumor stage, and treatment intention during the pandemic to the respective data from previous years.Results: The number of presentations decreased by 3.2% (95% CI −8.8, 2.7) during the COVID year 2020 compared with the pre-COVID year 2019. During the first shutdown, March–May 2020, the total number of presentations was 9.4% (−18.7, 1) less than during March–May 2019. This decrease was significant for curable cases of esophageal cancer [N = 37, 25.5% (−41.8, −4.4)] and colon cancer [N = 36, 17.5% (−32.6, 1.1)] as well as for all cases of biliary tract cancer [N = 26, 50% (−69.9, −15)] during the first shutdown from March 2020 to May 2020.Conclusion: The impact of the COVID-19 pandemic on the presentation of oncological patients in a CCC in Germany was considerable and should be taken into account when making decisions regarding future pandemics.

Abstract Background Epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSC) contribute to tumour progression and metastasis. Assessment of transcription factors involved in these two mechanisms can help to identify new targets for an oncological therapy. In this study, we focused on the evaluation of the transcription factor Six1 (Sine oculis 1). This protein is involved in embryologic development and its contribution to carcinogenesis has been described in several studies. Methods Immunohistochemistry against Six1 was performed on a tissue microarray containing specimens of primary pancreatic ductal adenocarcinomas (PDAC) of 139 patients. Nuclear and cytoplasmic expression was evaluated and correlated to histopathological parameters. Expression of Six1 was inhibited transiently by siRNA in Panc1 and BxPc3 cells and stably by shRNA in Panc1 cells. Expression analysis of CDH1 and Vimentin mRNA was performed and cell motility was tested in a migration assay. Panc1 cells transfected with Six1 shRNA or scrambled shRNA were injected subcutaneously into nude mice. Tumour growth was observed for four weeks. Afterwards, tumours were stained against Six1, CD24 and CD44. Results Six1 was overexpressed in the cytoplasm and cellular nuclei in malignant tissues (p

Considering the representation of the atmosphere, the current generation of Earth-System Models (ESMs) differs mainly in the representation of the stratospheric ozone layer and its variability and changes. So-called high-top models have a well resolved stratosphere and typically calculate ozone chemistry interactively, low-top models on the other hand rely on parameterized ozone chemistry or prescribed climatological ozone fields and have a model top below the stratopause. Here we investigate whether interactive ozone chemistry is important for representing temperature variability and extremes in the Arctic polar stratosphere. To this end we analyze a suite of two 200 year sensitivity simulations, one with interactive ozone chemistry and one without, performed with the Whole Atmosphere Community Climate Model version 4 (WACCM4), a stratosphere-resolving version of the National Center for Atmospheric Research Community Earth-System Model. We find a tight coupling between ozone and temperatures over the Arctic polar cap, manifesting in increased variability in stratospheric spring-time temperatures in simulations with interactive chemistry compared to simulations imposing climatological mean ozone abundances. Our results indicate that stratospheric temperature extremes regularly occurring in simulations with interactive chemistry are absent in uncoupled model simulations.

In tumor cells, stepwise oncogenic deregulation of signaling cascades induces alterations of cellular morphology and promotes the acquisition of malignant traits. Here, we identified a set of 21 genes, including FGF9, as determinants of tumor cell morphology by an RNA interference phenotypic screen in SW480 colon cancer cells. Using a panel of small molecular inhibitors, we subsequently established phenotypic effects, downstream signaling cascades, and associated gene expression signatures of FGF receptor signals. We found that inhibition of FGF signals induces epithelial cell adhesion and loss of motility in colon cancer cells. These effects are mediated via the mitogen-activated protein kinase (MAPK) and Rho GTPase cascades. In agreement with these findings, inhibition of the MEK1/2 or JNK cascades, but not of the PI3K-AKT signaling axis also induced epithelial cell morphology. Finally, we found that expression of FGF9 was strong in a subset of advanced colon cancers, and overexpression negatively correlated with patients' survival. Our functional and expression analyses suggest that FGF receptor signals can contribute to colon cancer progression.

Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties.