Neonicotinoids (NEOs) are widely used insecticides that are ubiquitous in agricultural use. Since NEOs are found in natural waters as well as in tap water and human urine in regions where NEOs are widely used, NEOs pose a potential hazard to non-target organisms such as animals and humans. Some of the commonly detected NEOs are imidacloprid (IMD), thiamethoxam (TMX), and its metabolite clothianidin (CLO). Although previously published scientific information, including an assessment of the environmental risks, particularly for bees, had resulted in a ban on the outdoor use of these three NEOs in the EU – their use is now only permitted in closed greenhouses – these NEOs continue to be used in agriculture in many other parts of the world. Therefore, a detailed study and comparison of the effects of NEOs on the embryonic development of non-target organisms is needed to further define the risk profiles.Embryos of the South African clawed frog Xenopus laevis, a well-established aquatic model, were exposed to different concentrations of IMD, TMX, or CLO (0.1–100 mg/L) to study and compare the possible effects of a single contaminant in natural water bodies on early embryogenesis. The results included a reduced body length, a smaller orbital space, impaired cranial cartilage and nerves, and an altered heart structure and function. At the molecular level, NEO exposure partially resulted in an altered expression of tissue-specific factors, which are involved in eye, cranial placode, and heart development.Our results suggest that the NEOs studied negatively affect the embryonic development of the non-target organism X. laevis. Since pesticides, especially NEOs, pollute the environment worldwide, it is suggested that they are strictly controlled and monitored in the areas where they are used. In addition, the question arises as to whether pesticide metabolites also pose a risk to the environment and need to be investigated further so that they can be taken into account when registering ingredients.

The human impact on environmental landscapes, such as land use, climate change or pollution, is threatening global biodiversity and ecosystems maintenance. Pesticides like the herbicide glyphosate have garnered considerable attention due to their well-documented harmful effects on non-target species. During application, the active ingredient glyphosate is utilized in various formulations, each containing different additive adjuvants. However, the possible effects of these formulations on amphibians - the group with the highest decline rates among vertebrates - remain largely unknown. Therefore, the present study investigated the effects of four glyphosate formulations (Glyphosat TF, Durano TF, Helosate 450 TF, Kyleo) on the embryonic development of the model organism Xenopus laevis (South African clawed frog). Embryos at the 2-cell stage were exposed to various concentrations of glyphosate formulations (glyphosate: 0.01-100 mg/L), and mortality as well as sublethal effects on different organs and tissues were analyzed. The results indicated that the formulations had different effects, particularly on the mortality of Xenopus laevis embryos. At sublethal concentrations, the formulations altered the embryos' external appearance, leading to malformations such as reduced eye and head size. In addition, exposure to formulations impaired heart morphology and function, and the expression of heart-specific genes was altered at a molecular level. Our results confirmed that glyphosate formulations had a stronger effect on Xenopus laevis embryogenesis than pure glyphosate. Therefore, it is crucial to evaluate the active ingredient and the co-formulations independently, as well as the combined, commercially available products, during pesticide risk assessments and renewal procedures of agrochemicals. The severe global decline of amphibians, partly due to herbicide use, highlights the need for strict and efficient monitoring of environmental pesticide loads and application areas.

BACKGROUND:Glyphosate (GLY) is the most widely used herbicide in the world. Due to its mode of action as an inhibitor of the 5-enolpyruvylshikimate-3-phosphate synthase, an important step in the shikimate pathway, specifically in plants, GLY is considered to be of low toxicity to non-target organisms. However, various studies have shown the negative effects of GLY on the mortality and development of different non-target organisms, including insects, rodents, fish and amphibians. To better understand the various effects of GLY in more detail, we studied the effects of GLY without co-formulants during the embryogenesis of the aquatic model organism Xenopus laevis.RESULTS:A treatment with GLY affected various morphological endpoints in X. laevis tadpoles (body length, head width and area, eye area). Additionally, GLY interfered with the mobility as well as the neural and cardiac development of the embryos at stage 44/45. We were able to detect detailed structural changes in the cranial nerves and the heart and gained insights into the negative effects of GLY on cardiomyocyte differentiation.CONCLUSION:The application of GLY without co-formulants resulted in negative effects on several endpoints in the early embryonic development of X. laevis at concentrations that are environmentally relevant and concentrations that reflect the worst-case scenarios. This indicates that GLY could have a strong negative impact on the survival and lives of amphibians in natural waters. As a result, future GLY approvals should consider its impact on the environment.

According to the World Health Organisation, climate change poses the greatest health threat to humanity. At the same time, an environmentally friendly lifestyle has a positive impact on our health, such as a plant-based diet. In order to counter climate change, society needs to be informed about climate-friendly and health-promoting measures. Therefore, an online workshop was initiated at the Medical Faculty of Ulm. In an accompanying study, it was determined whether this leads to changes in environmental knowledge and awareness among the participants.The online workshop consisted of four 2-hour sessions. Scientific basics on climate change and possible solutions were discussed. Other focuses were on health and the health system as well as environmental psychology and climate change denial. Participants could take part in an anonymous and voluntary online survey before (pretest) and after (posttest) the workshop.86 participants took part in the workshop, of whom 24 attended all appointments and completed both surveys. While hardly any changes were observed in the subsection of environmental emotion, perception and behavior, there was a significant increase in environmental knowledge in the posttest. The workshop was evaluated very positively. Furthermore, many participants were motivated to make a personal contribution to climate protection after the workshop.The workshop serves as a good example of how medical scientific findings can be shared at a societal level. The participants already showed a high level of environmental awareness in the pretest, which is why the question remains open as to how people can be sensitized to the (health) threats posed by climate change who do not proactively sign up for such an offer themselves.

Background and objectives: According to the World Health Organization, climate change constitutes the single greatest threat to human health. However, the health care system contributes to climate change worldwide through its high CO2 emissions. In order to make future physicians more aware of this issue and to expand medical education to include climate-related aspects, the mandatory 28 academic hours elective “Climate Change and Health” for students of human medicine in the preclinical study stage was implemented at the Medical Faculty of Ulm in the 2020/21 winter semester. Our accompanying study investigated 1. in what form the topic of climate change can be successfully integrated into the study of human medicine in a manner that includes student opinions and 2. whether being required to take an elective on the topic led to changes in student environmental knowledge and awareness. Methodology: Personal individual interviews were conducted with all n=11 students after the course in a pilot that was carried out in the 2020/21 winter semester to determine course feasibility and student acceptance. The students were also able to evaluate the course using an evaluation form and were asked to complete a questionnaire on their environmental knowledge and awareness before and after the course. The course was revised on the basis of the results and offered again in the 2021 summer semester with an intervention group (n=16, participation in the mandatory elective) and a comparison group (n=25, no participation in the mandatory elective). The intervention group was asked to evaluate the course on the evaluation form. Both groups completed the environmental questionnaire at the same time. Results: The positive feedback from students for both semesters indicates a good feasibility and acceptance of the course. Student environmental knowledge was increased in both semesters. However, there were only few observable changes in student environmental awareness. Conclusion: This paper illustrates how the topic of climate change and health can be embedded into medical studies. The students considered climate change an important topic and drew added value from the course for their future work in healthcare. The study shows that knowledge transfer at the university level is an effective way to educate the young generation on climate change and its impacts.

The dynamics of cellular mechanisms can be investigated through the analysis of networks. One of the simplest but most popular modeling strategies involves logic-based models. However, these models still face exponential growth in simulation complexity compared with a linear increase in nodes. We transfer this modeling approach to quantum computing and use the upcoming technique in the field to simulate the resulting networks. Leveraging logic modeling in quantum computing has many benefits, including complexity reduction and quantum algorithms for systems biology tasks. To showcase the applicability of our approach to systems biology tasks, we implemented a model of mammalian cortical development. Here, we applied a quantum algorithm to estimate the tendency of the model to reach particular stable conditions and further revert dynamics. Results from two actual quantum processing units and a noisy simulator are presented, and current technical challenges are discussed.

BACKGROUND:The issues of climate change, environmental pollution and species extinction play an increasingly central role in the public debate. At the same time, however, there is a significant gap between environmental knowledge and sustainable action (so-called value-action gap). The education system, especially at the university level, is an important institution for imparting well-founded knowledge on this topic and, as a consequence, for deriving targeted options for action. The present study surveyed the current environmental knowledge and environmental awareness, including the everyday behavior of Generation Z students of medical study programs in comparison to science-oriented study programs.METHODS:In October/November 2021, an anonymous and voluntary online survey was conducted at the University of Ulm to evaluate the environmental knowledge and awareness of students in all semesters of the study programs Human Medicine, Dentistry, Molecular Medicine, Biology and Teaching. A total of 317 students fully completed the questionnaire.RESULTS:The results confirm the current state of studies on the environmental awareness of the German population. The value-action gap is also detectable among students. Students perceive the urgency of environmental protection measures and action on climate change and also link these with emotional feelings, but in terms of behavior personal interests (still) tend to largely take precedence over environmental protection. In addition, according to our findings, the image of stereotypes and prejudices of the various courses of study is also partially confirmed in the surveyed environmental awareness.CONCLUSION:The significant differences in environmental awareness between the compared degree programs and the gap between knowledge and action call for an individual but consistent implementation of the topics of climate change and environmental protection in the curriculum in all investigated degree courses. With the knowledge and awareness gained in this way, academics as distinguished members of society can convey climate awareness and fulfill the function as a role model.

BACKGROUND:According to the World Health Organisation, climate change poses the greatest health threat to humanity. At the same time, an environmentally friendly lifestyle has a positive impact on our health, such as a plant-based diet. In order to counter climate change, society needs to be informed about climate-friendly and health-promoting measures. Therefore, an online workshop was initiated at the Medical Faculty of Ulm. In an accompanying study, it was determined whether this leads to changes in environmental knowledge and awareness among the participants.METHODS:The online workshop consisted of four 2-hour sessions. Scientific basics on climate change and possible solutions were discussed. Other focuses were on health and the health system as well as environmental psychology and climate change denial. Participants could take part in an anonymous and voluntary online survey before (pretest) and after (posttest) the workshop.RESULTS:86 participants took part in the workshop, of whom 24 attended all appointments and completed both surveys. While hardly any changes were observed in the subsection of environmental emotion, perception and behavior, there was a significant increase in environmental knowledge in the posttest. The workshop was evaluated very positively. Furthermore, many participants were motivated to make a personal contribution to climate protection after the workshop.CONCLUSION:The workshop serves as a good example of how medical scientific findings can be shared at a societal level. The participants already showed a high level of environmental awareness in the pretest, which is why the question remains open as to how people can be sensitized to the (health) threats posed by climate change who do not proactively sign up for such an offer themselves.

Acetamiprid (ACT) is used extensively in agriculture worldwide, although data on ACT concentrations in natural water bodies and its impact on aquatic organisms are limited. To study whether ACT influences the embryo-genesis of the South African clawed frog Xenopus laevis, embryos were incubated in ACT solutions from 0.01 to 100 mg/L. The low concentrations were chosen on the basis of concentrations already found in nature. ACT treatment leads to shorter embryo lengths, intestine malformation and reduced eye areas. It also affects the cranial cartilage and cardiac development as well as the embryo's mobility. The expression of tissue-specific marker genes is affected as well. Thus, our study suggests that pesticides may lead to an increased mortality of non-target organisms and emphasizes the importance of regular testing for ACT concentrations in nature. Our study provides an overview of ACT effects and can therefore be used as a basis for an ACT risk assessment.

Background The issues of climate change, environmental pollution and species extinction play an increasingly central role in the public debate. At the same time, however, there is a significant gap between environmental knowledge and sustainable action (so-called value-action gap). The education system, especially at the university level, is an important institution for imparting well-founded knowledge on this topic and, as a consequence, for deriving targeted options for action. The present study surveyed the current environmental knowledge and environmental awareness, including the everyday behavior of Generation Z students of medical study programs in comparison to science-oriented study programs. Methods In October/November 2021, an anonymous and voluntary online survey was conducted at the University of Ulm to evaluate the environmental knowledge and awareness of students in all semesters of the study programs Human Medicine, Dentistry, Molecular Medicine, Biology and Teaching. A total of 317 students fully completed the questionnaire. Results The results confirm the current state of studies on the environmental awareness of the German population. The value-action gap is also detectable among students. Students perceive the urgency of environmental protection measures and action on climate change and also link these with emotional feelings, but in terms of behavior personal interests (still) tend to largely take precedence over environmental protection. In addition, according to our findings, the image of stereotypes and prejudices of the various courses of study is also partially confirmed in the surveyed environmental awareness. Conclusion The significant differences in environmental awareness between the compared degree programs and the gap between knowledge and action call for an individual but consistent implementation of the topics of climate change and environmental protection in the curriculum in all investigated degree courses. With the knowledge and awareness gained in this way, academics as distinguished members of society can convey climate awareness and fulfill the function as a role model.

Objective: Climate change constitutes a major challenge. The higher education sector plays an important role in regard to climate change and the adaptation to its consequences. Various approaches toward the integration of environmental subject areas to higher education teaching have already been described in other studies, but there is a lack of data supporting the effectiveness of these approaches in changing not only the environmental knowledge of students, but also their awareness. To address this, the present study tracked whether student attitudes about the environment could be changed by implicitly addressing medically relevant environmental topics as part of an online seminar. Methods: Second semester students of molecular medicine attending a mandatory 14-hour online seminar, which was required to obtain additive key qualifications and which consisted of independent study phases as well as online class meetings, were divided into two groups: the intervention group (IG, n=27, thereof 20 in the pretest and 21 in the posttest) was exposed to medically relevant environmental topics, while the comparison group (CG, n=26, thereof 22 in the pretest and 21 in the posttest) was exposed to general, non-environmental medical topics. Surveys were conducted with standardized questionnaires before and after the seminar in order to study the influence on the students' environmental knowledge, awareness and other personal attitudes. Results: While the seminar did not significantly change the environmental awareness in either group, the environmental knowledge of the IG was significantly increased by the group's exposure to environmental topics. In addition, the IG assessed its own environmental awareness regarding sustainable working methods in a laboratory as significantly higher after the seminar than the CG did, and some students of the IG had become more interested in issues relating to sustainability. Conclusion: The approach used to communicate environmental content mainly increased the environmental knowledge of students and piqued the interest of some students in climate-related and environmental topics. However, it was not possible to change deeper personal attitudes about environmental awareness, especially everyday behavior.

There is increasing concern about the health effects of pesticides that pollute natural waters. In particular, the use of neonicotinoids, such as thiacloprid (THD), is causing unease. THD is considered non-toxic to non-target vertebrates. Studies classify THD as carcinogenic, toxic to reproduction, and therefore harmful to the environ-ment. A detailed study of possible THD effects during the amphibian embryogenesis is needed because leaching can introduce THD into aquatic environments. We incubated stage 2 embryos of the South African clawed frog in various THD concentrations (0.1-100 mg/L) at 14 degrees C to study the potential effects of a one-time THD contamination of waters on the early embryogenesis. We showed that THD has, indeed, negative effects on the embryonic development of the X. laevis. A treatment with THD led to a reduced embryonic body length and mobility. Furthermore, a treatment with THD resulted in smaller cranial cartilages, eyes and brains, and the embryos had shorter cranial nerves and an impaired cardiogenesis. On a molecular basis, THD led to a reduced expression of the brain marker emx1 and the heart marker mhc alpha. Our results underly the importance of a strict and efficient monitoring of the regulatory levels and application areas of THD.

Controlling phenotypical landscapes is of vital interest to modern biology. This task becomes highly demanding because cellular decisions involve complex networks engaging in crosstalk interactions. Previous work on control theory indicates that small sets of compounds can control single phenotypes. However, a dynamic approach is missing to determine the drivers of the whole network dynamics. By analyzing 35 biologically motivated Boolean networks, we developed a method to identify small sets of compounds sufficient to decide on the entire phenotypical landscape. These compounds do not strictly prefer highly related compounds and show a smaller impact on the stability of the attractor landscape. The dynamic driver sets include many intervention targets and cellular reprogramming drivers in human networks. Finally, by using a new comprehensive model of colorectal cancer, we provide a complete workflow on how to implement our approach to shift from in silico to in vitro guided experiments.

Der anthropogene Klimawandel beruht auf der Freisetzung von Treibhausgasen in die Atmosphäre und der damit verbundenen Änderung der Zusammensetzung der Atmosphäre. Ein Anstieg der globalen Durchschnittstemperatur führt zu Änderungen der lokalen klimatischen Bedingungen. Diese Änderungen wirken zumeist negativ auf die Lebensbedingungen des Menschen, aber auch der Tiere oder Pflanzen. Die nicht-lineare Dynamik des Klimasystems äußert sich in sogenannten Kipp-Punkten oder Kipp-Elementen, an denen sich der Zustand des Erdsystems schlagartig verändern und dieses einen neuen Zustand einnehmen kann. Verschiedene Kipp-Punkte im Klimasystem könnten bereits im Temperaturbereich des Pariser Weltklimaschutzabkommens ausgelöst werden. Zudem besteht die Gefahr, dass sich die Kipp-Punkte gegenseitig beeinflussen, sodass der Mensch nach Auslösen eines Kipp-Punktes den weiteren Fortgang nicht mehr beeinflussen kann. Die Einhaltung der Pariser Klimaziele kann durch eine Begrenzung auf das noch vorhandene CO2-Restbudget aktuell noch ermöglicht werden, allerdings wird die Wahrscheinlichkeit, dies zu erreichen, aufgrund der weiter steigenden Treibhausgasemissionen immer geringer.

Ribosomal biogenesis is a fundamental process necessary for cell growth and division. Ribosomal protein L5 (Rpl5) is part of the large ribosomal subunit. Mutations in this protein have been associated with the congenital disease Diamond Blackfan anemia (DBA), a so called ribosomopathy. Despite of the ubiquitous need of ribosomes, clinical manifestations of DBA include tissue-specific symptoms, e.g., craniofacial malformations, eye abnormalities, skin pigmentation failure, cardiac defects or liver cirrhosis. Here, we made use of the vertebrate model organism Xenopus laevis and showed a specific expression of rpl5 in the developing anterior tissue correlating with tissues affected in ribosomopathies. Upon Rpl5 knockdown using an antisense-based morpholino oligonucleotide approach, we showed different phenotypes affecting anterior tissue, i.e., defective cranial cartilage, malformed eyes, and microcephaly. Hence, the observed phenotypes in Xenopus laevis resemble the clinical manifestations of DBA. Analyses of the underlying molecular basis revealed that the expression of several marker genes of neural crest, eye, and brain are decreased during induction and differentiation of the respective tissue. Furthermore, Rpl5 knockdown led to decreased cell proliferation and increased cell apoptosis during early embryogenesis. Investigating the molecular mechanisms underlying Rpl5 function revealed a more than additive effect between either loss of function of Rpl5 and loss of function of c-Myc or loss of function of Rpl5 and gain of function of Tp53, suggesting a common signaling pathway of these proteins. The co-injection of the apoptosis blocking molecule Bcl2 resulted in a partial rescue of the eye phenotype, supporting the hypothesis that apoptosis is one main reason for the phenotypes occurring upon Rpl5 knockdown. With this study, we are able to shed more light on the still poorly understood molecular background of ribosomopathies.

INTRODUCTION:Global warming is one of the major challenges faced by society. To raise students' awareness related to these issues, we embedded environmental learning goals in mandatory courses. The aim of this initiative was to determine whether the integration of environmental topics into a seminar focussing on non-environmental issues facilitates changes in the environmental knowledge and awareness of students.METHODS:Third-year molecular medicine students (intervention group, IG) were assigned short environment-related tasks in a not environment-related scientific writing seminar. Using standardized questionnaires before and after the seminar, students were assessed with a set of up to 48 questions relating to environmental affect, cognition, behavioral intention and knowledge as well as specific personal aspects. The comparison group (CG) consisted of third-year dentistry students who were assessed twice during an equivalent pre-post time period and who did not attend the seminar. The analysis was carried out with 15 students from the IG and 14 from the CG.RESULTS:Integrating environmental topics into a scientific writing seminar focussing on non-environmental issues led to a significantly increased level of awareness of the threats from climate change in the IG (p<0.05). No further significant changes in other areas of environmental awareness were observed in either group. In addition, the environmental knowledge of the IG students (p≤0.01) but not of the CG students (p=0.285) was significantly enhanced.DISCUSSION AND CONCLUSION:This study shows that factual environmental knowledge on the issues addressed can be increased by a cautious approach of environmental communication. However, more deep-seated personal attitudes and environmental awareness cannot be sustainably changed using this low intervention dose.

Block of proliferation 1 (Bop1) is a nucleolar protein known to be necessary for the assembly of the 60S subunit of ribosomes. Here, we show a specific bop1 expression in the developing anterior tissue of the South African clawed frog Xenopus laevis. Morpholino oligonucleotide-mediated knockdown approaches demonstrated that bop1 is required for proper development of the cranial cartilage, brain, and the eyes. Furthermore, we show that bop1 knockdown leads to impaired retinal lamination with disorganized cell layers. Expression of neural crest-, brain-, and eye-specific marker genes was disturbed. Apoptotic and proliferative processes, which are known to be affected during ribosomal biogenesis defects, are not hindered upon bop1 knockdown. Because early Xenopus embryos contain a large store of maternal ribosomes, we considered if Bop1 might have a role independent of de novo ribosomal biogenesis. At early embryonic stages, pax6 expression was strongly reduced in bop1 morphants and synergy experiments indicate a common signaling pathway of the two molecules, Bop1 and Pax6. Our studies imply a novel function of Bop1 independent of ribosomal biogenesis.

Inherent vulnerabilities in a cyber network’s constituent machine services can be exploited by malicious agents. As a result, the machines on any network are at risk. Security specialists seek to mitigate the risk of intrusion events through network reconfiguration and defense. When dealing with rare cyber events, high-quality risk estimates using standard simulation approaches may be unattainable, or have significant attached uncertainty, even with a large computational simulation budget. To address this issue, an efficient rare event simulation modeling and analysis technique, namely, importance sampling for cyber networks, is developed. The importance sampling method parametrically amplifies certain aspects of the network in order to cause a rare event to happen more frequently. Output collected under these amplified conditions is then scaled back into the context of the original network to provide meaningful statistical inferences. The importance sampling methodology is tailored to cyber network attacks and takes the attacker’s successes and failures as well as the attacker’s targeting choices into account. The methodology is shown to produce estimates of higher quality than standard simulation with greater computational efficiency.

Objective In medical education, biochemistry topics are usually knowledge based, and students often are unaware of their clinical relevance. To improve students' awareness of the relevance, we integrated communication skills training into biochemistry education. No studies before have examined the difference between peer and standardised patient (SP) role plays where students explain the biochemical background of a disease in patient-centred language. Therefore, we evaluated whether students' self-perceived competency in Canadian Medical Education Directives for Specialists (CanMEDS) roles and their opinion of the quality of role play differ if the layperson is played by peers or SPs. Methods We randomly assigned medical students in a preclinical semester to one of the two groups. The groups used predefined scripts to role play a physician-parent consultation with either a peer (peer group) or an SP (SP group) in the parent role. Students then assessed the activity's effects on their competency in CanMEDS roles and motivation and the relevance of the role play. To determine whether students achieved biochemistry learning goals, we evaluated results of a biochemistry exam. Results Students' self-perceived competency improved in both groups. The SP group rated their competency in the roles 'Scholar' and 'Professional' significantly higher than the peer group did. The peer group rated their competency in the role of 'Medical Expert' significantly higher if they played the role of the parent rather than physician or observer. The SP group agreed more that they were motivated by the role play and wanted to receive more role play-based teaching. The SP group perceived the role play as being realistic and rated the feedback discussion as more beneficial. The examination results were the same in both groups. Conclusion We showed that role plays in a biochemistry seminar improve students' self-perceived competency. The use of SPs has some advantages, such as being more realistic.