TY - JOUR A1 - Ogunkola, Moses Olalekan A1 - Guiraudie-Capraz, Gaelle A1 - Féron, François A1 - Leimkühler, Silke T1 - The Human Mercaptopyruvate Sulfurtransferase TUM1 Is Involved in Moco Biosynthesis, Cytosolic tRNA Thiolation and Cellular Bioenergetics in Human Embryonic Kidney Cells JF - Biomolecules N2 - Sulfur is an important element that is incorporated into many biomolecules in humans. The incorporation and transfer of sulfur into biomolecules is, however, facilitated by a series of different sulfurtransferases. Among these sulfurtransferases is the human mercaptopyruvate sulfurtransferase (MPST) also designated as tRNA thiouridine modification protein (TUM1). The role of the human TUM1 protein has been suggested in a wide range of physiological processes in the cell among which are but not limited to involvement in Molybdenum cofactor (Moco) biosynthesis, cytosolic tRNA thiolation and generation of H2S as signaling molecule both in mitochondria and the cytosol. Previous interaction studies showed that TUM1 interacts with the L-cysteine desulfurase NFS1 and the Molybdenum cofactor biosynthesis protein 3 (MOCS3). Here, we show the roles of TUM1 in human cells using CRISPR/Cas9 genetically modified Human Embryonic Kidney cells. Here, we show that TUM1 is involved in the sulfur transfer for Molybdenum cofactor synthesis and tRNA thiomodification by spectrophotometric measurement of the activity of sulfite oxidase and liquid chromatography quantification of the level of sulfur-modified tRNA. Further, we show that TUM1 has a role in hydrogen sulfide production and cellular bioenergetics. KW - Moco biosynthesis KW - sulfite oxidase KW - cytosolic tRNA thiolation KW - 5-methoxycarbonylmethyl-2-thiouridine KW - H2S biosynthesis KW - cellular bioenergetics Y1 - 2023 U6 - https://doi.org/10.3390/biom13010144 SN - 2218-273X VL - 13 SP - 1 EP - 23 PB - MDPI CY - Basel, Schweiz ET - 1 ER - TY - JOUR A1 - Marggraf, Lara Christin A1 - Lindecke, Oliver A1 - Voigt, Christian C. A1 - Pētersons, Gunārs A1 - Voigt-Heucke, Silke Luise T1 - Nathusius’ bats, Pipistrellus nathusii, bypass mating opportunities of their own species, but respond to foraging heterospecifics on migratory transit flights JF - Frontiers in Ecology and Evolution N2 - In late summer, migratory bats of the temperate zone face the challenge of accomplishing two energy-demanding tasks almost at the same time: migration and mating. Both require information and involve search efforts, such as localizing prey or finding potential mates. In non-migrating bat species, playback studies showed that listening to vocalizations of other bats, both con-and heterospecifics, may help a recipient bat to find foraging patches and mating sites. However, we are still unaware of the degree to which migrating bats depend on con-or heterospecific vocalizations for identifying potential feeding or mating opportunities during nightly transit flights. Here, we investigated the vocal responses of Nathusius’ pipistrelle bats, Pipistrellus nathusii, to simulated feeding and courtship aggregations at a coastal migration corridor. We presented migrating bats either feeding buzzes or courtship calls of their own or a heterospecific migratory species, the common noctule, Nyctalus noctula. We expected that during migratory transit flights, simulated feeding opportunities would be particularly attractive to bats, as well as simulated mating opportunities which may indicate suitable roosts for a stopover. However, we found that when compared to the natural silence of both pre-and post-playback phases, bats called indifferently during the playback of conspecific feeding sounds, whereas P. nathusii echolocation call activity increased during simulated feeding of N. noctula. In contrast, the call activity of P. nathusii decreased during the playback of conspecific courtship calls, while no response could be detected when heterospecific call types were broadcasted. Our results suggest that while on migratory transits, P. nathusii circumnavigate conspecific mating aggregations, possibly to save time or to reduce the risks associated with social interactions where aggression due to territoriality might be expected. This avoidance behavior could be a result of optimization strategies by P. nathusii when performing long-distance migratory flights, and it could also explain the lack of a response to simulated conspecific feeding. However, the observed increase of activity in response to simulated feeding of N. noctula, suggests that P. nathusii individuals may be eavesdropping on other aerial hawking insectivorous species during migration, especially if these occupy a slightly different foraging niche. KW - playback KW - phonotaxis KW - bats KW - acoustic communication KW - animal migration KW - eavesdropping KW - echolocation KW - Pipistrellus nathusii Y1 - 2023 U6 - https://doi.org/10.3389/fevo.2022.908560 SN - 2296-701X SP - 1 EP - 10 PB - Frontiers CY - Lausanne, Schweiz ER - TY - JOUR A1 - Taguchi, Mioko A1 - Goto, Mutsuo A1 - Matsuoka, Koji A1 - Tiedemann, Ralph A1 - Pastene, Luis A. T1 - Population genetic structure of Bryde's whales (Balaenoptera brydei) on the central and western North Pacific feeding grounds JF - Canadian Journal of Fisheries and Aquatic Sciences N2 - The genetic structure of Bryde's whale (Balaenoptera brydei) on the central and western North Pacific feeding grounds was investigated using a total of 1195 mitochondrial control region sequences and 1182 microsatellite genotypes at 17 loci in specimens collected from three longitudinal areas, 1W (135 degrees E-165 degrees E), 1E (165 degrees E-180 degrees), and 2 (180 degrees-155 degrees W). Genetic diversities were similar among areas and a haplotype network did not show any geographic structure, while an analysis of molecular variance found evidence of genetic structure in this species. Pairwise FST and G'ST estimates and heterogeneity tests attributed this structure to weak but significant differentiation between areas 1W/1E and 2. A Mantel test and a high-resolution analysis of genetic diversity statistics showed a weak spatial cline of genetic differentiation. These findings could be reconciled by two possible stock structure scenarios: (1) a single population with kin-association affecting feeding ground preference and (2) two populations with feeding ground preference for either area 1W or area 2. An estimated dispersal rate between areas 1W and 2 indicates that both scenarios should be considered as a precautionary principle in stock assessments. KW - stock structure KW - stock assessment KW - fisheries management KW - conservation KW - cetacean Y1 - 2023 U6 - https://doi.org/10.1139/cjfas-2022-0005 SN - 0706-652X SN - 1205-7533 VL - 80 IS - 1 SP - 142 EP - 155 PB - Canadian science publishing CY - Ottawa ER - TY - JOUR A1 - Pandey, Yogesh T1 - Enriched cell-free and cell-based native membrane derived vesicles (nMV) enabling rapid in-vitro electrophysiological analysis of the voltage-gated sodium channel 1.5. JF - Biochimica et Biophysica Acta (BBA) - Biomembranes N2 - Here, we demonstrate the utility of native membrane derived vesicles (nMVs) as tools for expeditious electrophysiological analysis of membrane proteins. We used a cell-free (CF) and a cell-based (CB) approach for preparing protein-enriched nMVs. We utilized the Chinese Hamster Ovary (CHO) lysate-based cell-free protein synthesis (CFPS) system to enrich ER-derived microsomes in the lysate with the primary human cardiac voltage-gated sodium channel 1.5 (hNaV1.5; SCN5A) in 3 h. Subsequently, CB-nMVs were isolated from fractions of nitrogen-cavitated CHO cells overexpressing the hNaV1.5. In an integrative approach, nMVs were micro-transplanted into Xenopus laevis oocytes. CB-nMVs expressed native lidocaine-sensitive hNaV1.5 currents within 24 h; CF-nMVs did not elicit any response. Both the CB- and CF-nMV preparations evoked single-channel activity on the planar lipid bilayer while retaining sensitivity to lidocaine application. Our findings suggest a high usability of the quick-synthesis CF-nMVs and maintenance-free CB-nMVs as ready-to-use tools for in-vitro analysis of electrogenic membrane proteins and large, voltage-gated ion channels. KW - Cell-free protein synthesis KW - Electrophysiology KW - Membrane proteins KW - Micro-translantation KW - Protein expression Y1 - 2023 U6 - https://doi.org/10.1016/j.bbamem.2023.184144 SN - 1879-2642 SN - 0005-2736 VL - 1865 IS - 5 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Glowinski, Ingrid A1 - Autenrieth, Marijke T1 - Eigene Forschung im Labor, um naturwissenschaftliche Erkenntnisgewinnung kompetent unterrichten zu können? BT - Konzeption und Evaluation eines forschungsorientierten Seminars und Praktikums für Lehramtsstudierende im Fach Biologie JF - PSI-Potsdam: Ergebnisbericht zu den Aktivitäten im Rahmen der Qualitätsoffensive Lehrerbildung (2019-2023) (Potsdamer Beiträge zur Lehrerbildung und Bildungsforschung ; 3) N2 - Im Rahmen des PSI-Projekts wurde eine Lehrveranstaltung konzipiert, die Lehramtsstudierenden einen vertieften Einblick sowohl in den Ablauf von Forschung als auch eine Bearbeitung einer eigenen experimentellen Forschungsaufgabe ermöglichen soll. Anlass waren die Berücksichtigung eines „Wissens über Erkenntnisgewinnung in der Disziplin“ im Modell des „Erweiterten Fachwissens für den schulischen Kontext“ (PSI) sowie Erkenntnisse empirischer Studien, die die Relevanz eigener Forschungserfahrung für das Unterrichten naturwissenschaftlicher Erkenntnisgewinnungsprozesse zeigen. Hier stellen wir eine neue Lehrveranstaltung (4 SWS) vor, die den angehenden Lehrkräften Forschungserfahrung ermöglicht (Seminar und Praktikum). Die Lehrveranstaltung vermittelt Einblicke in Forschung und die „Natur der Naturwissenschaften“, ermöglicht das Durchführen eigener wissenschaftlicher und schulrelevanter Experimente und bietet eine angemessene Reflexion über die verschiedenen Kurselemente. Die Evaluationsergebnisse sind überwiegend positiv, zeigen aber auch, dass für die Studierenden die wahrgenommene Schulrelevanz und die fachdidaktischen Aspekte ein wichtiges Kriterium für die positive Bewertung sind. N2 - As part of the PSI project, a new course was designed to give pre-service science teachers an in-depth insight into scientific research and to enable them to design their own scientific research experiment. Motivated by the consideration of “knowledge of scientific research processes” in the model of “extended content knowledge for the school context” (PSI) as well as by findings of empirical studies showing the relevance of own scientific research experiences for the competencies of pre-service science teachers concerning teaching about “Nature of Science” and “scientific inquiry” processes. Here we present a new course (4 hours/week) that provides pre-service science teachers with research experiences and knowledge about scientific research, integrated with aspects of pedagogical content knowledge (seminar and laboratory course). The course provides insights into scientific research and the “Nature of Science”, allows pre-service teachers to conduct their own scientific and school-relevant experiments, and provides appropriate reflection on the various course elements. The evaluation results are predominantly positive, but also show that for the pre-service science teachers the perceived school relevance and the aspects of pedagogical content knowledge are an important criterion for the positive evaluation. KW - Professionswissen KW - Erkenntnisgewinnung KW - Forschungsorientierung KW - Lehramtsstudium Biologie KW - „Natur der Naturwissenschaften“ KW - pre-service teacher KW - professional knowledge KW - inquiry KW - nature of science KW - biology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-617922 SN - 978-3-86956-568-2 SN - 2626-3556 SN - 2626-4722 IS - 3 SP - 273 EP - 293 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Hermanussen, Michael A1 - Scheffler, Christiane A1 - Pulungan, Aman B. A1 - Bandyopadhyay, Arup Ratan A1 - Ghosh, Jyoti Ratan A1 - Özdemir, Ayşegül A1 - Koca Özer, Başak A1 - Musalek, Martin A1 - Lebedeva, Lidia A1 - Godina, Elena A1 - Bogin, Barry A1 - Tutkuviene, Janina A1 - Budrytė, Milda A1 - Gervickaite, Simona A1 - Limony, Yehuda A1 - Kirchengast, Sylvia A1 - Buston, Peter A1 - Groth, Detlef A1 - Rösler, Antonia A1 - Gasparatos, Nikolaos A1 - Erofeev, Sergei A1 - Novine, Masiar A1 - Navazo, Bárbara A1 - Dahinten, Silvia A1 - Gomuła, Aleksandra A1 - Nowak-Szczepańska, Natalia A1 - Kozieł, Sławomir T1 - Environment, social behavior, and growth BT - Proceedings of the 30th Aschauer Soiree, held at Krobielowice, Poland, June 18th 2022 JF - Human biology and public health N2 - Twenty-four scientists met for the annual Auxological conference held at Krobielowice castle, Poland, to discuss the diverse influences of the environment and of social behavior on growth following last year’s focus on growth and public health concerns (Hermanussen et al., 2022b). Growth and final body size exhibit marked plastic responses to ecological conditions. Among the shortest are the pygmoid people of Rampasasa, Flores, Indonesia, who still live under most secluded insular conditions. Genetics and nutrition are usually considered responsible for the poor growth in many parts of this world, but evidence is accumulating on the prominent impact of social embedding on child growth. Secular trends not only in the growth of height, but also in body proportions, accompany the secular changes in the social, economic and political conditions, with major influences on the emotional and educational circumstances under which the children grow up (Bogin, 2021). Aspects of developmental tempo and aspects of sports were discussed, and the impact of migration by the example of women from Bangladesh who grew up in the UK. Child growth was considered in particular from the point of view of strategic adjustments of individual size within the network of its social group. Theoretical considerations on network characteristics were presented and related to the evolutionary conservation of growth regulating hypothalamic neuropeptides that have been shown to link behavior and physical growth in the vertebrate species. New statistical approaches were presented for the evaluation of short term growth measurements that permit monitoring child growth at intervals of a few days and weeks. KW - St. Nicolas House Analysis KW - child growth KW - body proportions KW - social network KW - public health KW - migration Y1 - 2023 U6 - https://doi.org/10.52905/hbph2023.1.59 SN - 2748-9957 VL - 1 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Gasparatos, Nikolaos A1 - Scheffler, Christiane A1 - Hermanussen, Michael T1 - Assessing the applicability of changepoint analysis to analyse short-term growth JF - Human biology and public health N2 - Background: Assessing short-term growth in humans is still fraught with difficulties. Especially when looking for small variations and increments, such as mini growth spurts, high precision instruments or frequent measurements are necessary. Daily measurements however require a lot of effort, both for anthropologists and for the subjects. Therefore, new sophisticated approaches are needed that reduce fluctuations and reveal underlying patterns. Objectives: Changepoints are abrupt variations in the properties of time series data. In the context of growth, such variations could be variation in mean height. By adjusting the variance and using different growth models, we assessed the ability of changepoint analysis to analyse short-term growth and detect mini growth spurts. Sample and Methods: We performed Bayesian changepoint analysis on simulated growth data using the bcp package in R. Simulated growth patterns included stasis, linear growth, catch-up growth, and mini growth spurts. Specificity and a normalised variant of the Matthews correlation coefficient (MCC) were used to assess the algorithm’s performance. Welch’s t-test was used to compare differences of the mean. Results: First results show that changepoint analysis can detect mini growth spurts. However, the ability to detect mini growth spurts is highly dependent on measurement error. Data preparation, such as ranking and rotating time series data, showed negligible improvements. Missing data was an issue and may affect the prediction quality of the classification metrics. Conclusion: Changepoint analysis is a promising tool to analyse short-term growth. However, further optimisation and analysis of real growth data is needed to make broader generalisations. KW - changepoint analysis KW - changepoint detection KW - performance evaluation KW - mini growth spurt KW - short-term growth Y1 - 2023 U6 - https://doi.org/10.52905/hbph2023.1.62 SN - 2748-9957 VL - 1 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Groth, Detlef A1 - Scheffler, Christiane A1 - Hermanussen, Michael T1 - Human growth data analysis and statistics – the 5th Gülpe International Student Summer School JF - Human biology and public health N2 - The Summer School in Gülpe (Ecological Station of the University of Potsdam) offers an exceptional learning opportunity for students to apply their knowledge and skills to real-world problems. With the guidance of experienced human biologists, statisticians, and programmers, students have the unique chance to analyze their own data and gain valuable insights. This interdisciplinary setting not only bridges different research areas but also leads to highly valuable outputs. The progress of students within just a few days is truly remarkable, especially when they are motivated and receive immediate feedback on their questions, problems, and results. The Summer School covers a wide range of topics, with this year’s focus mainly on two areas: understanding the impact of socioeconomic and physiological factors on human development and mastering statistical techniques for analyzing data such as changepoint analysis and the St. Nicolas House Analysis (SNHA) to visualize interacting variables. The latter technique, born out of the Summer School’s emphasis on gaining comprehensive data insights and understanding major relationships, has proven to be a valuable tool for researchers in the field. The articles in this special issue demonstrate that the Summer School in Gülpe stands as a testament to the power of practical learning and collaboration. Students who attend not only gain hands-on experience but also benefit from the expertise of professionals and the opportunity to engage with peers from diverse disciplines. KW - Summer Schools KW - Statistical Exercise KW - Repetition Y1 - 2023 U6 - https://doi.org/10.52905/hbph2023.1.70 SN - 2748-9957 VL - 1 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Rösler, Antonia A1 - Scheffler, Christiane A1 - Hermanussen, Michael T1 - No evidence of growth impairment after forced migration in Polish school children after World War II JF - Human biology and public health N2 - Background: Migration is omnipresent. It can come hand in hand with emotional stress which is known to influence the growth of children. Objective: The aim of this study was to analyse whether type of migration (forced or voluntary) and the geographic direction had influenced the growth of Polish children after World War II. Sample and Methods: A sub dataset of 2,208 individuals between the ages of 2-20, created from data of the 2nd Polish Anthropological Survey carried out in 1966–1969, including anthropometrical data and social and demographic information based on questionnaire, was used to analyse migration effects. Results: No association could be found between the direction of migration and the height of the children. The confidence intervals of the means of all classified migration categories overlap significantly and the effect size of the influence of migration category on height is ds=.140, which is too low to see any effects, even if there were one. Conclusion: Neither forced nor voluntary migration in Poland after World War II led to a change in height in children of migrating families. KW - nutrition KW - stunting KW - socioeconomy KW - education KW - secular changes KW - pubertal timing Y1 - 2023 U6 - https://doi.org/10.52905/hbph2023.1.68 SN - 2748-9957 VL - 1 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Hermanussen, Michael A1 - Scheffler, Christiane T1 - Nutrition, size, and tempo JF - Human biology and public health N2 - Nutrition is a prerequisite, but not a regulator of growth. Growth is defined as increase in size over time. The understanding of growth includes an understanding of the binary concept of physical time and individual tempo. Excess food causes tempo acceleration. Food restriction delays tempo. Tempo reflects the pace of life. It is a dynamic physical response to a broad spectrum of social, economic, political, and emotional (SEPE) factors and can affect life expectancy. Variations in tempo create distortions of the z-score patterns of height and weight. Illness or intermediate food shortage lead to intermediate halts in development and create short dips in the z-score patterns. Children who develop throughout life at delayed pace usually run at lower z-scores for height and weight, and show a characteristic adolescent trough; children who develop throughout life at faster than average pace usually run at higher z-scores and show a characteristic adolescent peak in their z-score patterns. During adolescence, almost half of the height variance is due to tempo variation. There is not one tempo for the whole body. Different organ systems grow and mature at different pace. KW - food access KW - physical time KW - SEPS factors KW - pace of life KW - catch-up-growth Y1 - 2023 U6 - https://doi.org/10.52905/hbph2022.3.37 SN - 2748-9957 VL - 2022 IS - 3 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Scheffler, Christiane A1 - Hermanussen, Michael T1 - What does stunting tell us? JF - Human biology and public health N2 - Stunting is commonly linked with undernutrition. Yet, already after World War I, German pediatricians questioned this link and stated that no association exists between nutrition and height. Recent analyses within different populations of Low- and middle-income countries with high rates of stunted children failed to support the assumption that stunted children have a low BMI and skinfold sickness as signs of severe caloric deficiency. So, stunting is not a synonym of malnutrition. Parental education level has a positive influence on body height in stunted populations, e.g., in India and in Indonesia. Socially disadvantaged children tend to be shorter and lighter than children from affluent families. Humans are social mammals; they regulate growth similar to other social mammals. Also in humans, body height is strongly associated with the position within the social hierarchy, reflecting the personal and group-specific social, economic, political, and emotional environment. These non-nutritional impact factors on growth are summarized by the concept of SEPE (Social-Economic-Political-Emotional) factors. SEPE reflects on prestige, dominance-subordination, social identity, and ego motivation of individuals and social groups. KW - SEPE Factors KW - physical fitness KW - height in history KW - malnutrition Y1 - 2023 U6 - https://doi.org/10.52905/hbph2022.3.36 SN - 2748-9957 VL - 2022 IS - 3 SP - 1 EP - 15 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Hake, Tim A1 - Bodenberger, Bernhard A1 - Groth, Detlef T1 - In Python available: St. Nicolas House Algorithm (SNHA) with bootstrap support for improved performance in dense networks JF - Human biology and public health N2 - The St. Nicolas House Algorithm (SNHA) finds association chains of direct dependent variables in a data set. The dependency is based on the correlation coefficient, which is visualized as an undirected graph. The network prediction is improved by a bootstrap routine. It enables the computation of the empirical p-value, which is used to evaluate the significance of the predicted edges. Synthetic data generated with the Monte Carlo method were used to firstly compare the Python package with the original R package, and secondly to evaluate the predicted network using the sensitivity, specificity, balanced classification rate and the Matthew's correlation coefficient (MCC). The Python implementation yields the same results as the R package. Hence, the algorithm was correctly ported into Python. The SNHA scores high specificity values for all tested graphs. For graphs with high edge densities, the other evaluation metrics decrease due to lower sensitivity, which could be partially improved by using bootstrap,while for graphs with low edge densities the algorithm achieves high evaluation scores. The empirical p-values indicated that the predicted edges indeed are significant. KW - Python KW - correlation KW - network reconstruction KW - bootstrap KW - St. Nicolas House Algorithm Y1 - 2023 U6 - https://doi.org/10.52905/hbph2023.1.63 SN - 2748-9957 VL - 1 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Petrich, Annett A1 - Aji, Amit Koikkarah A1 - Dunsing, Valentin A1 - Chiantia, Salvatore T1 - Benchmarking of novel green fluorescent proteins for the quantification of protein oligomerization in living cells JF - PLoS one N2 - Protein-protein-interactions play an important role in many cellular functions. Quantitative non-invasive techniques are applied in living cells to evaluate such interactions, thereby providing a broader understanding of complex biological processes. Fluorescence fluctuation spectroscopy describes a group of quantitative microscopy approaches for the characterization of molecular interactions at single cell resolution. Through the obtained molecular brightness, it is possible to determine the oligomeric state of proteins. This is usually achieved by fusing fluorescent proteins (FPs) to the protein of interest. Recently, the number of novel green FPs has increased, with consequent improvements to the quality of fluctuation-based measurements. The photophysical behavior of FPs is influenced by multiple factors (including photobleaching, protonation-induced "blinking" and long-lived dark states). Assessing these factors is critical for selecting the appropriate fluorescent tag for live cell imaging applications. In this work, we focus on novel green FPs that are extensively used in live cell imaging. A systematic performance comparison of several green FPs in living cells under different pH conditions using Number & Brightness (N & B) analysis and scanning fluorescence correlation spectroscopy was performed. Our results show that the new FP Gamillus exhibits higher brightness at the cost of lower photostability and fluorescence probability (pf), especially at lower pH. mGreenLantern, on the other hand, thanks to a very high pf, is best suited for multimerization quantification at neutral pH. At lower pH, mEGFP remains apparently the best choice for multimerization investigation. These guidelines provide the information needed to plan quantitative fluorescence microscopy involving these FPs, both for general imaging or for protein-protein-interactions quantification via fluorescence fluctuation-based methods. Y1 - 2023 U6 - https://doi.org/10.1371/journal.pone.0285486 SN - 1932-6203 VL - 18 IS - 8 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Kappel, Christian A1 - Friedrich, Thomas A1 - Oberkofler, Vicky A1 - Jiang, Li A1 - Crawford, Tim A1 - Lenhard, Michael A1 - Bäurle, Isabel T1 - Genomic and epigenomic determinants of heat stress-induced transcriptional memory in Arabidopsis JF - Genome biology : biology for the post-genomic era N2 - Background Transcriptional regulation is a key aspect of environmental stress responses. Heat stress induces transcriptional memory, i.e., sustained induction or enhanced re-induction of transcription, that allows plants to respond more efficiently to a recurrent HS. In light of more frequent temperature extremes due to climate change, improving heat tolerance in crop plants is an important breeding goal. However, not all heat stress-inducible genes show transcriptional memory, and it is unclear what distinguishes memory from non-memory genes. To address this issue and understand the genome and epigenome architecture of transcriptional memory after heat stress, we identify the global target genes of two key memory heat shock transcription factors, HSFA2 and HSFA3, using time course ChIP-seq. Results HSFA2 and HSFA3 show near identical binding patterns. In vitro and in vivo binding strength is highly correlated, indicating the importance of DNA sequence elements. In particular, genes with transcriptional memory are strongly enriched for a tripartite heat shock element, and are hallmarked by several features: low expression levels in the absence of heat stress, accessible chromatin environment, and heat stress-induced enrichment of H3K4 trimethylation. These results are confirmed by an orthogonal transcriptomic data set using both de novo clustering and an established definition of memory genes. Conclusions Our findings provide an integrated view of HSF-dependent transcriptional memory and shed light on its sequence and chromatin determinants, enabling the prediction and engineering of genes with transcriptional memory behavior. KW - Transcriptional memory KW - Priming KW - Heat stress KW - HSFA2 KW - HSFA3 KW - Arabidopsis thaliana KW - Histone H3K4 trimethylation KW - ChIP-seq Y1 - 2023 U6 - https://doi.org/10.1186/s13059-023-02970-5 SN - 1474-760X VL - 24 IS - 1 PB - BioMed Central CY - London ER - TY - JOUR A1 - Ferreira, Clara Mendes A1 - Dammhahn, Melanie A1 - Eccard, Jana T1 - So many choices, so little time BT - food preference and movement vary with the landscape of fear JF - Ecology and evolution N2 - Spatial and temporal variation in perceived predation risk is an important determinant of movement and foraging activity of animals. Foraging in this landscape of fear, individuals need to decide where and when to move, and what resources to choose. Foraging theory predicts the outcome of these decisions based on energetic trade-offs, but complex interactions between perceived predation risk and preferences of foragers for certain functional traits of their resources are rarely considered. Here, we studied the interactive effects of perceived predation risk on food trait preferences and foraging behavior in bank voles (Myodes glareolus) in experimental landscapes. Individuals (n = 19) were subjected for periods of 24 h to two extreme, risk-uniform landscapes (either risky or safe), containing 25 discrete food patches, filled with seeds of four plant species in even amounts. Seeds varied in functional traits: size, nutrients, and shape. We evaluated whether and how risk modifies forager preference for functional traits. We also investigated whether perceived risk and distance from shelter affected giving-up density (GUD), time in patches, and number of patch visits. In safe landscapes, individuals increased time spent in patches, lowered GUD and visited distant patches more often compared to risky landscapes. Individuals preferred bigger seeds independent of risk, but in the safe treatment they preferred fat-rich over carb-rich seeds. Thus, higher densities of resource levels remained in risky landscapes, while in safe landscapes resource density was lower and less diverse due to selective foraging. Our results suggest that the interaction of perceived risk and dietary preference adds an additional layer to the cascading effects of a landscape of fear which affects biodiversity at resource level. KW - foraging behavior KW - functional traits KW - giving-up density KW - myodes glareolus KW - perceived predation risk KW - seed ecology Y1 - 2023 U6 - https://doi.org/10.1002/ece3.10330 SN - 2045-7758 VL - 13 IS - 7 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Apriyanto, Ardha A1 - Compart, Julia A1 - Fettke, Jörg T1 - Transcriptomic analysis of mesocarp tissue during fruit development of the oil palm revealed specific isozymes related to starch metabolism that control oil yield JF - Frontiers in plant science N2 - The oil palm (Elaeis guineensis Jacq.) produces a large amount of oil from the fruit. However, increasing the oil production in this fruit is still challenging. A recent study has shown that starch metabolism is essential for oil synthesis in fruit-producing species. Therefore, the transcriptomic analysis by RNA-seq was performed to observe gene expression alteration related to starch metabolism genes throughout the maturity stages of oil palm fruit with different oil yields. Gene expression profiles were examined with three different oil yields group (low, medium, and high) at six fruit development phases (4, 8, 12, 16, 20, and 22 weeks after pollination). We successfully identified and analyzed differentially expressed genes in oil palm mesocarps during development. The results showed that the transcriptome profile for each developmental phase was unique. Sucrose flux to the mesocarp tissue, rapid starch turnover, and high glycolytic activity have been identified as critical factors for oil production in oil palms. For starch metabolism and the glycolytic pathway, we identified specific gene expressions of enzyme isoforms (isozymes) that correlated with oil production, which may determine the oil content. This study provides valuable information for creating new high-oil-yielding palm varieties via breeding programs or genome editing approaches. KW - starch KW - oil yield KW - fruit development KW - gene expression KW - RNA-seq KW - and palm KW - oil KW - Elaeis guineensis Jacq Y1 - 2023 U6 - https://doi.org/10.3389/fpls.2023.1220237 SN - 1664-462X VL - 14 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Compart, Julia A1 - Singh, Aakanksha A1 - Fettke, Jörg A1 - Apriyanto, Ardha T1 - Customizing starch properties BT - a review of starch modifications and their applications JF - Polymers N2 - Starch has been a convenient, economically important polymer with substantial applications in the food and processing industry. However, native starches present restricted applications, which hinder their industrial usage. Therefore, modification of starch is carried out to augment the positive characteristics and eliminate the limitations of the native starches. Modifications of starch can result in generating novel polymers with numerous functional and value-added properties that suit the needs of the industry. Here, we summarize the possible starch modifications in planta and outside the plant system (physical, chemical, and enzymatic) and their corresponding applications. In addition, this review will highlight the implications of each starch property adjustment. KW - starch KW - starch modification KW - in planta modification KW - physical modification KW - chemical modification KW - enzymatic modification KW - starch application Y1 - 2023 U6 - https://doi.org/10.3390/polym15163491 SN - 2073-4360 VL - 15 IS - 16 PB - MDPI CY - Basel ER - TY - JOUR A1 - Berry, Paul E. A1 - Dammhahn, Melanie A1 - Blaum, Niels T1 - Keeping cool on hot days BT - activity responses of African antelope to heat extremes JF - Frontiers in ecology and evolution N2 - Long-lived organisms are likely to respond to a rapidly changing climate with behavioral flexibility. Animals inhabiting the arid parts of southern Africa face a particularly rapid rise in temperature which in combination with food and water scarcity places substantial constraints on the ability of animals to tolerate heat. We investigated how three species of African antelope-springbok Antidorcas marsupialis, kudu Tragelaphus strepsiceros and eland T. oryx-differing in body size, habitat preference and movement ecology, change their activity in response to extreme heat in an arid savanna. Serving as a proxy for activity, dynamic body acceleration data recorded every five minutes were analyzed for seven to eight individuals per species for the three hottest months of the year. Activity responses to heat during the hottest time of day (the afternoons) were investigated and diel activity patterns were compared between hot and cool days. Springbok, which prefer open habitat, are highly mobile and the smallest of the species studied, showed the greatest decrease in activity with rising temperature. Furthermore, springbok showed reduced mean activity over the 24 h cycle on hot days compared to cool days. Large-bodied eland seemed less affected by afternoon heat than springbok. While eland also reduced diurnal activity on hot days compared to cool days, they compensated for this by increasing nocturnal activity, possibly because their predation risk is lower. Kudu, which are comparatively sedentary and typically occupy shady habitat, seemed least affected during the hottest time of day and showed no appreciable difference in diel activity patterns between hot and cool days. The interplay between habitat preference, body size, movement patterns, and other factors seems complex and even sub-lethal levels of heat stress have been shown to impact an animal's long-term survival and reproduction. Thus, differing heat tolerances among species could result in a shift in the composition of African herbivore communities as temperatures continue to rise, with significant implications for economically important wildlife-based land use and conservation. KW - springbok KW - kudu KW - eland KW - dynamic body acceleration KW - tri-axial accelerometers KW - behavioral flexibility KW - climate change KW - savanna ecology Y1 - 2023 U6 - https://doi.org/10.3389/fevo.2023.1172303 SN - 2296-701X VL - 11 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Stiegler, Jonas A1 - Pahl, Janice A1 - Guillen, Rafael Arce A1 - Ullmann, Wiebke A1 - Blaum, Niels T1 - The heat is on BT - impacts of rising temperature on the activity of a common European mammal JF - Frontiers in Ecology and Evolution N2 - Climate conditions severely impact the activity and, consequently, the fitness of wildlife species across the globe. Wildlife can respond to new climatic conditions, but the pace of human-induced change limits opportunities for adaptation or migration. Thus, how these changes affect behavior, movement patterns, and activity levels remains unclear. In this study, we investigate how extreme weather conditions affect the activity of European hares (Lepus europaeus) during their peak reproduction period. When hares must additionally invest energy in mating, prevailing against competitors, or lactating, we investigated their sensitivities to rising temperatures, wind speed, and humidity. To quantify their activity, we used the overall dynamic body acceleration (ODBA) calculated from tri-axial acceleration measurements of 33 GPS-collared hares. Our analysis revealed that temperature, humidity, and wind speed are important in explaining changes in activity, with a strong response for high temperatures above 25 & DEG;C and the highest change in activity during temperature extremes of over 35 & DEG;C during their inactive period. Further, we found a non-linear relationship between temperature and activity and an interaction of activity changes between day and night. Activity increased at higher temperatures during the inactive period (day) and decreased during the active period (night). This decrease was strongest during hot tropical nights. At a stage of life when mammals such as hares must substantially invest in reproduction, the sensitivity of females to extreme temperatures was particularly pronounced. Similarly, both sexes increased their activity at high humidity levels during the day and low wind speeds, irrespective of the time of day, while the effect of humidity was stronger for males. Our findings highlight the importance of understanding the complex relationships between extreme weather conditions and mammal behavior, critical for conservation and management. With ongoing climate change, extreme weather events such as heat waves and heavy rainfall are predicted to occur more often and last longer. These events will directly impact the fitness of hares and other wildlife species and hence the population dynamics of already declining populations across Europe. KW - activity KW - ODBA KW - animal tracking KW - European hare KW - extreme weather events KW - climate change Y1 - 2023 U6 - https://doi.org/10.3389/fevo.2023.1193861 SN - 2296-701X VL - 11 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Agarwal, Saloni A1 - Hamidizadeh, Mojdeh A1 - Bier, Frank Fabian T1 - Detection of reverse transcriptase LAMP-amplified nucleic acid from oropharyngeal viral swab samples using biotinylated DNA probes through a lateral flow assay JF - Biosensors : open access journal N2 - This study focuses on three key aspects: (a) crude throat swab samples in a viral transport medium (VTM) as templates for RT-LAMP reactions; (b) a biotinylated DNA probe with enhanced specificity for LFA readouts; and (c) a digital semi-quantification of LFA readouts. Throat swab samples from SARS-CoV-2 positive and negative patients were used in their crude (no cleaning or pre-treatment) forms for the RT-LAMP reaction. The samples were heat-inactivated but not treated for any kind of nucleic acid extraction or purification. The RT-LAMP (20 min processing time) product was read out by an LFA approach using two labels: FITC and biotin. FITC was enzymatically incorporated into the RT-LAMP amplicon with the LF-LAMP primer, and biotin was introduced using biotinylated DNA probes, specifically for the amplicon region after RT-LAMP amplification. This assay setup with biotinylated DNA probe-based LFA readouts of the RT-LAMP amplicon was 98.11% sensitive and 96.15% specific. The LFA result was further analysed by a smartphone-based IVD device, wherein the T-line intensity was recorded. The LFA T-line intensity was then correlated with the qRT-PCR Ct value of the positive swab samples. A digital semi-quantification of RT-LAMP-LFA was reported with a correlation coefficient of R2 = 0.702. The overall RT-LAMP-LFA assay time was recorded to be 35 min with a LoD of three RNA copies/µL (Ct-33). With these three advancements, the nucleic acid testing-point of care technique (NAT-POCT) is exemplified as a versatile biosensor platform with great potential and applicability for the detection of pathogens without the need for sample storage, transportation, or pre-processing. KW - RT-LAMP KW - LFA KW - NAAT-LFA KW - semi-quantitative KW - surveillance-based diagnostics Y1 - 2023 U6 - https://doi.org/10.3390/bios13110988 SN - 2079-6374 VL - 13 IS - 11 PB - MDPI CY - Basel ER - TY - JOUR A1 - Cheng, Feng A1 - Dennis, Alice B. A1 - Osuoha, Josephine Ijeoma A1 - Canitz, Julia A1 - Kirschbaum, Frank A1 - Tiedemann, Ralph T1 - A new genome assembly of an African weakly electric fish (Campylomormyrus compressirostris, Mormyridae) indicates rapid gene family evolution in Osteoglossomorpha JF - BMC genomics N2 - Background Teleost fishes comprise more than half of the vertebrate species. Within teleosts, most phylogenies consider the split between Osteoglossomorpha and Euteleosteomorpha/Otomorpha as basal, preceded only by the derivation of the most primitive group of teleosts, the Elopomorpha. While Osteoglossomorpha are generally species poor, the taxon contains the African weakly electric fish (Mormyroidei), which have radiated into numerous species. Within the mormyrids, the genus Campylomormyrus is mostly endemic to the Congo Basin. Campylomormyrus serves as a model to understand mechanisms of adaptive radiation and ecological speciation, especially with regard to its highly diverse species-specific electric organ discharges (EOD). Currently, there are few well-annotated genomes available for electric fish in general and mormyrids in particular. Our study aims at producing a high-quality genome assembly and to use this to examine genome evolution in relation to other teleosts. This will facilitate further understanding of the evolution of the osteoglossomorpha fish in general and of electric fish in particular. Results A high-quality weakly electric fish (C. compressirostris) genome was produced from a single individual with a genome size of 862 Mb, consisting of 1,497 contigs with an N50 of 1,399 kb and a GC-content of 43.69%. Gene predictions identified 34,492 protein-coding genes, which is a higher number than in the two other available Osteoglossomorpha genomes of Paramormyrops kingsleyae and Scleropages formosus. A Computational Analysis of gene Family Evolution (CAFE5) comparing 33 teleost fish genomes suggests an overall faster gene family turnover rate in Osteoglossomorpha than in Otomorpha and Euteleosteomorpha. Moreover, the ratios of expanded/contracted gene family numbers in Osteoglossomorpha are significantly higher than in the other two taxa, except for species that had undergone an additional genome duplication (Cyprinus carpio and Oncorhynchus mykiss). As potassium channel proteins are hypothesized to play a key role in EOD diversity among species, we put a special focus on them, and manually curated 16 Kv1 genes. We identified a tandem duplication in the KCNA7a gene in the genome of C. compressirostris. Conclusions We present the fourth genome of an electric fish and the third well-annotated genome for Osteoglossomorpha, enabling us to compare gene family evolution among major teleost lineages. Osteoglossomorpha appear to exhibit rapid gene family evolution, with more gene family expansions than contractions. The curated Kv1 gene family showed seven gene clusters, which is more than in other analyzed fish genomes outside Osteoglossomorpha. The KCNA7a, encoding for a potassium channel central for EOD production and modulation, is tandemly duplicated which may related to the diverse EOD observed among Campylomormyrus species. KW - Campylomormyrus KW - Pacbio sequencing KW - Gene family KW - Osteoglossomorpha KW - Kv1 Y1 - 2023 U6 - https://doi.org/10.1186/s12864-023-09196-6 SN - 1471-2164 VL - 24 IS - 1 PB - BMC CY - London ER - TY - JOUR A1 - Córdoba, Sandra Correa A1 - Tong, Hao A1 - Burgos, Asdrubal A1 - Zhu, Feng A1 - Alseekh, Saleh A1 - Fernie, Alisdair R. A1 - Nikoloski, Zoran T1 - Identification of gene function based on models capturing natural variability of Arabidopsis thaliana lipid metabolism JF - Nature Communications N2 - The use of automated tools to reconstruct lipid metabolic pathways is not warranted in plants. Here, the authors construct Plant Lipid Module for Arabidopsis rosette using constraint-based modeling, demonstrate its integration in other plant metabolic models, and use it to dissect the genetic architecture of lipid metabolism. Lipids play fundamental roles in regulating agronomically important traits. Advances in plant lipid metabolism have until recently largely been based on reductionist approaches, although modulation of its components can have system-wide effects. However, existing models of plant lipid metabolism provide lumped representations, hindering detailed study of component modulation. Here, we present the Plant Lipid Module (PLM) which provides a mechanistic description of lipid metabolism in the Arabidopsis thaliana rosette. We demonstrate that the PLM can be readily integrated in models of A. thaliana Col-0 metabolism, yielding accurate predictions (83%) of single lethal knock-outs and 75% concordance between measured transcript and predicted flux changes under extended darkness. Genome-wide associations with fluxes obtained by integrating the PLM in diel condition- and accession-specific models identify up to 65 candidate genes modulating A. thaliana lipid metabolism. Using mutant lines, we validate up to 40% of the candidates, paving the way for identification of metabolic gene function based on models capturing natural variability in metabolism. KW - Biochemical networks KW - Biochemical reaction networks KW - Genetic models KW - Plant molecular biology Y1 - 2023 U6 - https://doi.org/10.1038/s41467-023-40644-9 SN - 2041-1723 VL - 14 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Tomowski, Maxi A1 - Lozada-Gobilard, Sissi Donna A1 - Jeltsch, Florian A1 - Tiedemann, Ralph T1 - Recruitment and migration patterns reveal a key role for seed banks in the meta-population dynamics of an aquatic plant JF - Scientific reports N2 - Progressive habitat fragmentation threatens plant species with narrow habitat requirements. While local environmental conditions define population growth rates and recruitment success at the patch level, dispersal is critical for population viability at the landscape scale. Identifying the dynamics of plant meta-populations is often confounded by the uncertainty about soil-stored population compartments. We combined a landscape-scale assessment of an amphibious plant's population structure with measurements of dispersal complexity in time to track dispersal and putative shifts in functional connectivity. Using 13 microsatellite markers, we analyzed the genetic structure of extant Oenanthe aquatica populations and their soil seed banks in a kettle hole system to uncover hidden connectivity among populations in time and space. Considerable spatial genetic structure and isolation-by-distance suggest limited gene flow between sites. Spatial isolation and patch size showed minor effects on genetic diversity. Genetic similarity found among extant populations and their seed banks suggests increased local recruitment, despite some evidence of migration and recent colonization. Results indicate stepping-stone dispersal across adjacent populations. Among permanent and ephemeral demes the resulting meta-population demography could be determined by source-sink dynamics. Overall, these spatiotemporal connectivity patterns support mainland-island dynamics in our system, highlighting the importance of persistent seed banks as enduring sources of genetic diversity. Y1 - 2023 U6 - https://doi.org/10.1038/s41598-023-37974-5 SN - 2045-2322 VL - 13 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Arend, Marius A1 - Zimmer, David A1 - Xu, Rudan A1 - Sommer, Frederik A1 - Mühlhaus, Timo A1 - Nikoloski, Zoran T1 - Proteomics and constraint-based modelling reveal enzyme kinetic properties of Chlamydomonas reinhardtii on a genome scale JF - Nature Communications N2 - Metabolic engineering of microalgae offers a promising solution for sustainable biofuel production, and rational design of engineering strategies can be improved by employing metabolic models that integrate enzyme turnover numbers. However, the coverage of turnover numbers for Chlamydomonas reinhardtii, a model eukaryotic microalga accessible to metabolic engineering, is 17-fold smaller compared to the heterotrophic cell factory Saccharomyces cerevisiae. Here we generate quantitative protein abundance data of Chlamydomonas covering 2337 to 3708 proteins in various growth conditions to estimate in vivo maximum apparent turnover numbers. Using constrained-based modeling we provide proxies for in vivo turnover numbers of 568 reactions, representing a 10-fold increase over the in vitro data for Chlamydomonas. Integration of the in vivo estimates instead of in vitro values in a metabolic model of Chlamydomonas improved the accuracy of enzyme usage predictions. Our results help in extending the knowledge on uncharacterized enzymes and improve biotechnological applications of Chlamydomonas. KW - Computational models KW - Enzymes KW - Proteomics Y1 - 2023 U6 - https://doi.org/10.1038/s41467-023-40498-1 SN - 2041-1723 VL - 14 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Zavorka, Libor A1 - Blanco, Andreu A1 - Chaguaceda, Fernando A1 - Cucherousset, Julien A1 - Killen, Shaun S. A1 - Lienart, Camilla A1 - Mathieu-Resuge, Margaux A1 - Nemec, Pavel A1 - Pilecky, Matthias A1 - Scharnweber, Inga Kristin A1 - Twining, Cornelia W. A1 - Kainz, Martin J. T1 - The role of vital dietary biomolecules in eco-evo-devo dynamics JF - Trends in ecology and evolution N2 - The physiological dependence of animals on dietary intake of vitamins, amino acids, and fatty acids is ubiquitous. Sharp differences in the availability of these vital dietary biomolecules among different resources mean that consumers must adopt a range of strategies to meet their physiological needs. We review the emerging work on omega-3 long-chain polyunsaturated fatty acids, focusing predominantly on predator-prey interactions, to illustrate that trade-off between capacities to consume resources rich in vital biomolecules and internal synthesis capacity drives differences in phenotype and fitness of consumers. This can then feedback to impact ecosystem functioning. We outline how focus on vital dietary biomolecules in eco-eco-devo dynamics can improve our understanding of anthropogenic changes across multiple levels of biological organization. Y1 - 2023 U6 - https://doi.org/10.1016/j.tree.2022.08.010 SN - 0169-5347 SN - 1872-8383 VL - 38 IS - 1 SP - 72 EP - 84 PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Grdseloff, Nastasja A1 - Boulday, Gwenola A1 - Roedel, Claudia J. A1 - Otten, Cecile A1 - Vannier, Daphne Raphaelle A1 - Cardoso, Cecile A1 - Faurobert, Eva A1 - Dogra, Deepika A1 - Tournier-Lasserve, Elisabeth A1 - Abdelilah-Seyfried, Salim T1 - Impaired retinoic acid signaling in cerebral cavernous malformations JF - Scientific reports N2 - The capillary-venous pathology cerebral cavernous malformation (CCM) is caused by loss of CCM1/Krev interaction trapped protein 1 (KRIT1), CCM2/MGC4607, or CCM3/PDCD10 in some endothelial cells. Mutations of CCM genes within the brain vasculature can lead to recurrent cerebral hemorrhages. Pharmacological treatment options are urgently needed when lesions are located in deeply-seated and in-operable regions of the central nervous system. Previous pharmacological suppression screens in disease models of CCM led to the discovery that treatment with retinoic acid improved CCM phenotypes. This finding raised a need to investigate the involvement of retinoic acid in CCM and test whether it has a curative effect in preclinical mouse models. Here, we show that components of the retinoic acid synthesis and degradation pathway are transcriptionally misregulated across disease models of CCM. We complemented this analysis by pharmacologically modifying retinoic acid levels in zebrafish and human endothelial cell models of CCM, and in acute and chronic mouse models of CCM. Our pharmacological intervention studies in CCM2-depleted human umbilical vein endothelial cells (HUVECs) and krit1 mutant zebrafish showed positive effects when retinoic acid levels were increased. However, therapeutic approaches to prevent the development of vascular lesions in adult chronic murine models of CCM were drug regiment-sensitive, possibly due to adverse developmental effects of this hormone. A treatment with high doses of retinoic acid even worsened CCM lesions in an adult chronic murine model of CCM. This study provides evidence that retinoic acid signaling is impaired in the CCM pathophysiology and suggests that modification of retinoic acid levels can alleviate CCM phenotypes. KW - Developmental biology KW - Molecular medicine Y1 - 2023 U6 - https://doi.org/10.1038/s41598-023-31905-0 SN - 2045-2322 VL - 13 IS - 1 PB - Nature Portfolio CY - Berlin ER - TY - JOUR A1 - Stübler, Sabine A1 - Kloft, Charlotte A1 - Huisinga, Wilhelm T1 - Cell-level systems biology model to study inflammatory bowel diseases and their treatment options JF - CPT: pharmacometrics & systems pharmacology N2 - To help understand the complex and therapeutically challenging inflammatory bowel diseases (IBDs), we developed a systems biology model of the intestinal immune system that is able to describe main aspects of IBD and different treatment modalities thereof. The model, including key cell types and processes of the mucosal immune response, compiles a large amount of isolated experimental findings from literature into a larger context and allows for simulations of different inflammation scenarios based on the underlying data and assumptions. In the context of a large and diverse virtual IBD population, we characterized the patients based on their phenotype (in contrast to healthy individuals, they developed persistent inflammation after a trigger event) rather than on a priori assumptions on parameter differences to a healthy individual. This allowed to reproduce the enormous diversity of predispositions known to lead to IBD. Analyzing different treatment effects, the model provides insight into characteristics of individual drug therapy. We illustrate for anti-TNF-alpha therapy, how the model can be used (i) to decide for alternative treatments with best prospects in the case of nonresponse, and (ii) to identify promising combination therapies with other available treatment options. Y1 - 2023 U6 - https://doi.org/10.1002/psp4.12932 SN - 2163-8306 VL - 12 IS - 5 SP - 690 EP - 705 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Nendel, Claas A1 - Reckling, Moritz A1 - Debaeke, Philippe A1 - Schulz, Susanne A1 - Berg-Mohnicke, Michael A1 - Constantin, Julie A1 - Fronzek, Stefan A1 - Hoffmann, Munir A1 - Jakšić, Snežana A1 - Kersebaum, Kurt-Christian A1 - Klimek-Kopyra, Agnieszka A1 - Raynal, Hélène A1 - Schoving, Céline A1 - Stella, Tommaso A1 - Battisti, Rafael T1 - Future area expansion outweighs increasing drought risk for soybean in Europe JF - Global change biology N2 - The European Union is highly dependent on soybean imports from overseas to meet its protein demands. Individual Member States have been quick to declare self-sufficiency targets for plant-based proteins, but detailed strategies are still lacking. Rising global temperatures have painted an image of a bright future for soybean production in Europe, but emerging climatic risks such as drought have so far not been included in any of those outlooks. Here, we present simulations of future soybean production and the most prominent risk factors across Europe using an ensemble of climate and soybean growth models. Projections suggest a substantial increase in potential soybean production area and productivity in Central Europe, while southern European production would become increasingly dependent on supplementary irrigation. Average productivity would rise by 8.3% (RCP 4.5) to 8.7% (RCP 8.5) as a result of improved growing conditions (plant physiology benefiting from rising temperature and CO2 levels) and farmers adapting to them by using cultivars with longer phenological cycles. Suitable production area would rise by 31.4% (RCP 4.5) to 37.7% (RCP 8.5) by the mid-century, contributing considerably more than productivity increase to the production potential for closing the protein gap in Europe. While wet conditions at harvest and incidental cold spells are the current key challenges for extending soybean production, the models and climate data analysis anticipate that drought and heat will become the dominant limitations in the future. Breeding for heat-tolerant and water-efficient genotypes is needed to further improve soybean adaptation to changing climatic conditions. KW - genotypes KW - legumes KW - maturity groups KW - protein crops KW - protein transition KW - resilience Y1 - 2022 U6 - https://doi.org/10.1111/gcb.16562 SN - 1354-1013 SN - 1365-2486 VL - 29 IS - 5 SP - 1340 EP - 1358 PB - Wiley-Blackwell CY - Ocford [u.a] ER - TY - JOUR A1 - Küken, Anika A1 - Treves, Haim A1 - Nikoloski, Zoran T1 - A simulation-free constrained regression approach for flux estimation in isotopically nonstationary metabolic flux analysis with applications in microalgae JF - Frontiers in plant science : FPLS N2 - Introduction Flux phenotypes from different organisms and growth conditions allow better understanding of differential metabolic networks functions. Fluxes of metabolic reactions represent the integrated outcome of transcription, translation, and post-translational modifications, and directly affect growth and fitness. However, fluxes of intracellular metabolic reactions cannot be directly measured, but are estimated via metabolic flux analysis (MFA) that integrates data on isotope labeling patterns of metabolites with metabolic models. While the application of metabolomics technologies in photosynthetic organisms have resulted in unprecedented data from 13CO2-labeling experiments, the bottleneck in flux estimation remains the application of isotopically nonstationary MFA (INST-MFA). INST-MFA entails fitting a (large) system of coupled ordinary differential equations, with metabolite pools and reaction fluxes as parameters. Here, we focus on the Calvin-Benson cycle (CBC) as a key pathway for carbon fixation in photosynthesizing organisms and ask if approaches other than classical INST-MFA can provide reliable estimation of fluxes for reactions comprising this pathway. Methods First, we show that flux estimation with the labeling patterns of all CBC intermediates can be formulated as a single constrained regression problem, avoiding the need for repeated simulation of time-resolved labeling patterns. Results We then compare the flux estimates of the simulation-free constrained regression approach with those obtained from the classical INST-MFA based on labeling patterns of metabolites from the microalgae Chlamydomonas reinhardtii, Chlorella sorokiniana and Chlorella ohadii under different growth conditions. Discussion Our findings indicate that, in data-rich scenarios, simulation-free regression-based approaches provide a suitable alternative for flux estimation from classical INST-MFA since we observe a high qualitative agreement (rs=0.89) to predictions obtained from INCA, a state-of-the-art tool for INST-MFA. KW - metabolic flux analysis KW - INST-MFA KW - regression KW - 13C labeling KW - algae Y1 - 2023 U6 - https://doi.org/10.3389/fpls.2023.1140829 SN - 1664-462X VL - 14 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Langary, Damoun A1 - Küken, Anika A1 - Nikoloski, Zoran T1 - The effective deficiency of biochemical networks JF - Scientific reports N2 - The deficiency of a (bio)chemical reaction network can be conceptually interpreted as a measure of its ability to support exotic dynamical behavior and/or multistationarity. The classical definition of deficiency relates to the capacity of a network to permit variations of the complex formation rate vector at steady state, irrespective of the network kinetics. However, the deficiency is by definition completely insensitive to the fine details of the directionality of reactions as well as bounds on reaction fluxes. While the classical definition of deficiency can be readily applied in the analysis of unconstrained, weakly reversible networks, it only provides an upper bound in the cases where relevant constraints on reaction fluxes are imposed. Here we propose the concept of effective deficiency, which provides a more accurate assessment of the network’s capacity to permit steady state variations at the complex level for constrained networks of any reversibility patterns. The effective deficiency relies on the concept of nonstoichiometric balanced complexes, which we have already shown to be present in real-world biochemical networks operating under flux constraints. Our results demonstrate that the effective deficiency of real-world biochemical networks is smaller than the classical deficiency, indicating the effects of reaction directionality and flux bounds on the variation of the complex formation rate vector at steady state. Y1 - 2023 U6 - https://doi.org/10.1038/s41598-023-41767-1 SN - 2045-2322 VL - 13 PB - Springer Nature CY - London ER -