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Clinical proteomics, quo vadis?
Full text linkThe field of clinical proteomics has seen enormous growth in the past 20 years, with over 40,000 scientific manuscripts published to date. At the same time, actual clinical application of the reported findings is obviously scarce. In this viewpoint article, we discuss the key issues that may be responsible for this apparent lack of success. We conclude that success must not be assessed based on the number of publications, but via the impact on patient management and treatment. We proceed with specific suggestions for potential solutions, which include keeping a strict focus on potential patient benefit. We hope this article can help shape the field, so it can in fact deliver on its realistic promise to bring significant improvement in management and care to patients
Segment specific loss of NFAT5 function in the kidneys is sufficient to induce a global kidney injury like phenotype
Full text linkNuclear factor of activated T-cells 5 (NFAT5) is a transcription factor known for its role in osmotic stress adaptation in the renal inner medulla, due to the osmotic gradient that is generated between the renal cortex and renal inner medulla. However, its broader implications in kidney injury and chronic kidney disease (CKD) are less understood. Here we used two different Cre deleter mice (Ksp1.3-Cre and Aqp2-Cre) to generate tubule segment and even cell type-specific NFAT5-deficient mice and performed extensive gene expression profiling. In both Nfat5 knockout models, we observed massive changes in gene expression pattern, with heightened inflammatory responses and renal injury, culminating in renal fibrosis. Interestingly, inflammatory responses were much more prominent in the Aqp2Cre+/−Nfat5fl/fl mice that lack NFAT5 only in the collecting duct. By analyzing gene expression in the medullary and cortical regions of the kidney separately, we confirmed that the loss of NFAT5 results in kidney injury that extends beyond hypertonic areas. Renal injury correlates with the expression level of genes involved in inflammatory response, injury severity, and cytokine signaling. Thus, NFAT5 is essential not only for adapting to osmotic stress but also for its loss of function, which induces activation of inflammatory response and cytokine signaling that might affect regions with functional NFAT5 expression
Verkehrserziehung – Mobilitätsbildung – Verkehrsbildung?! Wie viel-Perspektivität braucht Mobilitätsbildung im Sachunterricht?
Full text linkDie Genese der heute als Mobilitätsbildung bezeichneten Konzeption ist in der gängigen Literatur als Weiterentwicklung der ehemaligen Verkehrserziehung beschrieben (vgl. u.a. Spitta 2017; Schwedes et al. 2021). Positiv werden hierbei insbesondere zwei Aspekte bewertet: So stellt zum einen die Ablösung des Erziehungsbegriffs durch die Bezeichnung Mobilitätsbildung eine Orientierung an zeitgemäßen Bildungstheorien dar, wodurch sich der Fokus weg von den Lehrenden und dem Gedanken der Wissensvermittlung hin zu den Lernenden und dem Wahrnehmen von Lerngelegenheiten verschiebt. Zum anderen wird mit Blick auf die ersten Teile der Nomenkomposita Verkehr und Mobilität besonders die inhaltliche (Weiter-)Entwicklung hervorgehoben, denn der Mobilitätsbegriff umfasst weitaus mehr als der Verkehrsbegriff, der wiederum stärker nur als Bestandteil von Mobilität verstanden wird bzw. werden kann (vgl. Schwedes et al. 2021). Dadurch ergibt sich schließlich eine inhaltliche Öffnung für Bildungsangebote.„Wer wie wir heute in der fatalen Situation steht, infolge des bedingten Zweifel[s] bereits an der Möglichkeit der Wahrheit, die auch wieder geradezu die Voraussetzung unseres gewohnten verständigen/ verstandesgemäßen Gebrauchs der Wörter und Begriffe ist, nach Mitteln zu fahnden, um die Grenzen des Verstandes Überschreiten zu können, greift nach jedem Strohhalm. Und das Wort 'Widerstreit' schien mir für die Sachlage passend zu sein, da es genau in diesem Sinn als ein 'Kind' dieser Sprachnot verstanden werden kann.” (Ansgar Häußling in einem Brief an Gerold Scholz vom 1.2.2002
Botanischer Wissenstransfer in Briefen des 19. Jahrhunderts: Die Briefe des deutschen Botanikers Ernst Heinrich Friedrich Meyer (1791–1858) an Diederich Franz Leonhard von Schlechtendal (1794–1866), Zweiter Teil
Full text linkKosak, K., Heklau, H., Wagner, E. †, Tkach, N., Röser, M. 2025. Botanischer Wissenstransfer in Briefen des 19. Jahrhunderts. Die Briefe des deutschen Botanikers Ernst Heinrich Friedrich Meyer (1791–1858) an Diederich Franz Leonhard von Schlechtendal (1794–1866). Zweiter Teil. Schlechtendalia 42: 1–266.
In dieser wissenschaftshistorischen Arbeit werden weitere Originalbriefe von Ernst Heinrich Friedrich Meyer (1791–1858) an Diederich Franz Leonhard von Schlechtendal (1794–1866) vorgestellt (Teil 2), die aus den Jahren 1841 bis 1858 stammen und, wie im ersten Teil (Fischer et al., 2023, S. 3–235) transkribiert, annotiert und historisch eingeordnet wurden. Um Meyers Briefinhalte besser verstehen zu können, wurde zunächst auf seinen Wirkungsort, auf die Stadt Königsberg in Ostpreußen mit ihrer Albertus-Universität und dem Botanischen Garten, näher eingegangen. Den Mittelpunkt der Arbeit bildet der zweite Zeitabschnitt der Korrespondenz der beiden Botaniker, in dem u. a. das Versenden von Herbarbelegen, Literatur und Geldbeträgen sowie Konflikte mit anderen Fachkollegen thematisiert wurden. Zudem tauschten sich beide Botaniker über Inhalte für die Fachjournale „Linnaea“ und die „Botanische Zeitung“ aus. Darüber hinaus erhalten der Leser bzw. die Leserin einen Eindruck vom Entstehungsprozess Meyers „Geschichte der Botanik“ sowie von seinem Arbeitsalltag an der Universität in Königsberg. Zugleich werden auch historisch-politische sowie private Einblicke gewährt.Kosak, K., Heklau, H., Wagner, E. †, Tkach, N., Röser, M. 2025. Botanical science transfer in letters of the 19th century. The letters of the German botanist Ernst Heinrich Friedrich Meyer (1791–1858) to Diederich Franz Leonhard von Schlechtendal (1794–1866). Second part. Schlechtendalia 42: 1–266.
In this work on the history of science, further original letters from Ernst Heinrich Friedrich Meyer (1791–1858) to Diederich Franz Leonhard von Schlechtendal (1794–1866) are presented (Part 2), which date from the years 1841 to 1858 and have been transcribed, annotated, and historically classified as in Part 1 (Fischer et al., 2023, p. 3–235). To gain a better understanding of the content of Meyer’s letters, his place of work, the city of Königsberg in East Prussia with its Albertus University and the Botanical Garden, was first described in more detail. The focus of the work is the second period of the correspondence between the two botanists, in which, among other things, the sending of herbarium specimens, literature and sums of money, as well as conflicts with other colleagues were discussed. In addition, the two botanists exchanged ideas about the content for the journals “Linnaea” and the “Botanische Zeitung”. In addition, the reader gets an impression of the process of writing Meyer’s History of Botany as well as of his daily work at the University of Königsberg. Historical-political and private insights are also provided.Die Schlechtendalia publiziert Originalbeiträge mit Schwerpunkt Spezielle Botanik und Biodiversität, Floristik, Mykologie/Lichenologie, Wissenschaftsgeschichte und andere Themen mit Bezug zu Botanischen Gärten und Herbarien
Glucagon can increase force of contraction via glucagon receptors in the isolated human atrium
Full text linkGlucagon can increase the force of contraction (FOC) in, for example, canine hearts. Currently, whether glucagon can also increase the FOC via cAMP-increasing receptors in the human atrium is controversial discussed. Glucagon alone did not (up to 1 µM) raise the FOC in human right atrial preparations (HAP). Only in the additional presence of the phosphodiesterase (PDE) 3 inhibitor cilostamide (1 µM) or 1 nM isoprenaline did glucagon raise the FOC, starting at 1 µM. The positive inotropic effects of glucagon in HAP were attenuated by a glucagon receptor antagonist (1 µM SC203972), but not by 100 nM exendin(9-39), a glucagon-like peptide-1 receptor (GLP-1R) antagonist. Glucagon (in the presence of cilostamide) demonstrated a reduced efficacy in elevating the FOC in HAP when compared with isoprenaline. In contrast to glucagon, exenatide alone, a GLP-1R agonist, starting at 1 nM, increased the FOC and was more potent and effective than glucagon in raising the FOC in HAP. The effects of exenatide on the FOC were attenuated by exendin(9-39). Hence, glucagon and GLP-1R agonists act functionally via different receptors in the human right atrium. Clinically, these data suggest that endogenous or exogenous glucagon can stimulate glucagon receptors in the human atrium, but only in the presence of PDE inhibitors
Responsivity of two pea genotypes to the symbiosis with rhizobia and arbuscular mycorrhiza fungi : a proteomics aspect of the "efficiency of interactions with beneficial soil microorganisms" trait
Full text linkIt is well known that individual pea (Pisum sativum L.) cultivars differ in their symbiotic responsivity. This trait is typically manifested with an increase in seed weights, due to inoculation with rhizobial bacteria and arbuscular mycorrhizal fungi. The aim of this study was to characterize alterations in the root proteome of highly responsive pea genotype k-8274 plants and low responsive genotype k-3358 ones grown in non-sterile soil, which were associated with root colonization with rhizobial bacteria and arbuscular mycorrhizal fungi (in comparison to proteome shifts caused by soil supplementation with mineral nitrogen salts). Our results clearly indicate that supplementation of the soil with mineral nitrogen-containing salts switched the root proteome of both genotypes to assimilation of the available nitrogen, whereas the processes associated with nitrogen fixation were suppressed. Surprisingly, inoculation with rhizobial bacteria had only a minor effect on the root proteomes of both genotypes. The most pronounced response was observed for the highly responsive k-8274 genotype inoculated simultaneously with rhizobial bacteria and arbuscular mycorrhizal fungi. This response involved activation of the proteins related to redox metabolism and suppression of excessive nodule formation. In turn, the low responsive genotype k-3358 demonstrated a pronounced inoculation-induced suppression of protein metabolism and enhanced diverse defense reactions in pea roots under the same soil conditions. The results of the study shed light on the molecular basis of differential symbiotic responsivity in different pea cultivars. The raw data are available in the PRIDE repository under the project accession number PXD058701 and project DOI 10.6019/PXD058701
A study on sorting strategies in marshaling yards with a limited number of tracks and track capacity
No full textIn marshaling yards, freight wagons are sorted from inbound trains to outbound trains for further transport. To organize an efficient shunting process, sorting strategies are proposed in the literature. The application of sorting strategies is generally restricted by the number of classification tracks and their lengths. This can lead to difficult-to-implement or even inoperative sorting plans. To handle limited track capacity, we decompose the shunting process into a series of consecutive periods of time resembling timetables of inbound trains. A heuristic is used in every period to decide on the postponement of inbound trains when track capacity is scarce. This way, sorting strategies become applicable on a rolling time basis. A strategy is said to solve a shunting task when it enables building all outbound trains within a given time horizon. We examine the performance of five well-known sorting strategies for a large set of shunting tasks within a computational study. The simulation results indicate that the sorting strategies perform differently when numbers and lengths of classification tracks vary. In conclusion, we are able to determine the most reliable strategy among the set of considered sorting strategies for a marshaling yard of a certain size
Exploring the effect of an 8-week AI-composed exercise program on pain intensity and well-being in patients with Spinal pain : Retrospective cohort analysis
Full text linkBackground: Spinal pain, one of the most common musculoskeletal disorders (MSDs), significantly impacts the quality of life due to chronic pain and disability. Physical activity has shown promise in managing spinal pain, although optimizing adherence to exercise remains a challenge. The digital development of artificial intelligence (AI)-driven applications offers a possibility for guiding and supporting patients with MSDs in their daily lives.
Objective: The trial aimed to investigate the effect of an 8-week AI-composed exercise program on pain intensity and well-being in patients with spinal pain. It also examined the relationship between exercise frequency, pain intensity, and well-being. In addition, app usage frequency was examined as a proxy for app engagement.
Methods: Data from users who met the inclusion criteria were collected retrospectively from the medicalmotion app between January 1, 2020, and June 30, 2023. The intervention involved the use of the medicalmotion app, which provides 3‐5 personalized exercises for each session based on individual user data. The primary outcomes assessed pain intensity and well-being using the numeric rating scale (NRS) and the Likert scale. Data were collected at baseline (t0), 4 weeks (t1), and 8 weeks (t2). The correlation between exercise frequency, pain intensity, and well-being was analyzed as a secondary outcome. In addition, average session length and frequency were measured to determine app engagement. Statistical analysis included ANOVA and Spearman correlation analysis.
Results: The study included 379 participants with a mean age of 50.96 (SD 12.22) years. At t2, there was a significant reduction of 1.78 points on the NRS (P<.001). The score on the Likert scale for well-being improved by 3.11 points after 8 weeks. Pain intensity showed a negative correlation with the number of daily exercises performed at t1 and t2. Well-being had a small negative correlation with the average number of exercises performed per day. The average number of exercises performed per day was 3.58. The average session length was approximately 10 minutes, and the average interaction with the app was 49.2% (n=27.6 days) of the 56 available days.
Conclusions: Overall, the study demonstrates that an app-based intervention program can substantially reduce pain intensity and increase well-being in patients with spinal pain. This retrospective study showed that an app that digitizes multidisciplinary rehabilitation for the self-management of spinal pain significantly reduced user-reported pain intensity in a preselected population of app users
A precise and efficient exceedance-set algorithm for detecting environmental extremes
Full text linkInference for predicted exceedance sets is important for various environmental issues such as detecting environmental anomalies and emergencies with high confidence. A critical part is to construct inner and outer predicted exceedance sets using an algorithm that samples from the predictive distribution. The simple currently used sampling procedure can lead to misleading conclusions for some locations due to relatively large standard errors when proportions are estimated from independent observations. Instead we propose an algorithm that calculates probabilities numerically using the Genz–Bretz algorithm, which is based on quasi-random numbers leading to more accurate inner and outer sets, as illustrated on rainfall data in the state of Paraná, Brazil
On the localization of reward effects in overlapping dual tasks
Full text linkIn dual-task (DT) situations, performance deteriorates compared with single-task situations. Such performance decrements are frequently explained with the serial scheduling of the response selection stages constituting a bottleneck. Proof of this assumption stems from the observation that response times for the second task (task 2; RT 2) increase with decreasing stimulus-onset asynchrony (SOA).
In this study, we investigated how the reward prospect for task 1 performance affects task 1 and task 2 processing. For that purpose, we relied on the psychological refractory period paradigm (PRP) as a chronometric tool, to determine the locus of the reward effect in the processing chain of both tasks.
We obtained improved task 1 and task 2 performance; as indicated by reduced RTs in the reward compared to the no reward condition of task 1 and task 2. Furthermore, the reward effect propagated at short SOA from task 1 onto task 2, suggesting that the locus of the reward effect can be pinpointed before or at the bottleneck of task 1. Importantly, the mean reward effect on task 1 was increased compared to task 2, thus indicating that parts of the reward effect were not propagated onto task 2, therefore affecting task 1 motor processes.
In Experiment 2, we tested for the locus of the effect propagation to task 2. Therefore, we implemented a difficulty manipulation of the response selection of task 2. The results indicate that the reward effect is propagated from task 1 onto the response selection stage of task 2