Collaborative Research Center Research Articles

Recent advances in understanding the impact of infection and inflammation on hematopoietic stem and progenitor cells

Just over one decade ago, it was discovered that hematopoietic stem cells (HSCs) could directly respond to inflammatory cytokines by mounting a proliferative response thought to mediate the emergency production of mature blood cells. In the intervening years, we have gained mechanistic insight into this so-called activation process and have started to learn such a response may come at a cost in terms of ultimately resulting in HSC exhaustion and hematologic dysfunction. In this review article, we report the progress we have made in understanding the interplay between infection, inflammation and HSCs during the funding period of the Collaborative Research Center 873 “Maintenance and Differentiation of Stem Cells in Development and Disease”, and place this work within the context of recent output by others working within this field.

Oxygen‐Free Production—From Vision to Application

As oxygen negatively affects most production processes in the metalworking industry, a truly oxygen‐free production environment appears attractive in terms of the resulting material and component properties. This overview summarizes research conducted within the Collaborative Research Centre (CRC) 1368. The objectives of this CRC are twofold. First, a fundamental understanding of the mechanisms that govern the interaction between a metal surface and the environment is established. Second, it is researched how this understanding can be exploited to improve current production processes and even develop completely new ones. Herein, data obtained within the first funding period, which already demonstrate that significant effects can be realized in processes such as thermal spraying, cold rolling, compound casting, laser brazing, milling or hot stamping to name just a few examples, are presented. In addition, key aspects such as initial deoxidation of the workpieces, their transport under conditions that prevent reoxidation, and the tools needed to establish and control an oxygen‐free process environment are given, and the ramifications with respect to actual applications are discussed.

Ground-based remote sensing of aerosol properties using high-resolution infrared emission and lidar observations in the High Arctic

Abstract. Arctic amplification, the phenomenon that the Arctic is warming faster than the global mean, is still not fully understood. The Transregional Collaborative Research Centre “TRR 172: ArctiC Amplification: Climate Relevant Atmospheric and SurfaCe Processes, and Feedback Mechanisms (AC)3” program, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), contributes towards this research topic. For the purpose of measuring aerosol components, a Fourier transform infrared spectrometer (FTIR), for measuring downwelling emission (in operation since 2019), and a Raman lidar are operated at the joint Alfred Wegener Institute for Polar and Marine Research and Paul Emile Victor Institute (AWIPEV) research base in Ny-Ålesund, Spitsbergen (79∘ N, 12∘ E). To carry out aerosol retrieval using measurements from the FTS, the LBLDIS retrieval algorithm, based on a combination of the Line-by-Line Radiative Transfer Model (LBLRTM) and the DIScrete Ordinate Radiative Transfer (DISORT) algorithm, is modified for different aerosol types (dust, sea salt, black carbon, and sulfate), aerosol optical depth (AOD), and effective radius (Reff). Using lidar measurement, an aerosol and cloud classification method is developed to provide basic information about the distribution of aerosols or clouds in the atmosphere and is used as an indicator to perform aerosol or cloud retrievals with the FTS. Therefore, a two-instrument joint-observation scheme is designed and subsequently used on the data measured from 2019 to the present. In order to introduce this measurement technique in detail, an aerosol-only case study is presented using data from 10 June 2020. In the aerosol-only case, the retrieval results show that sulfate is the dominant aerosol throughout the day (τ900cm-1 = 0.007 ± 0.0027), followed by dust (τ900cm-1 = 0.0039 ± 0.0029) and black carbon (τ900cm-1 = 0.0017 ± 0.0007). Sea salt (τ900cm-1 = 0.0012 ± 0.0002), which has the weakest emission ability in the infrared wave band, shows the lowest AOD value. Such proportions of sulfate, dust, and BC also show good agreement with Modern-Era Retrospective analysis for Research and Applications version 2 (MERRA-2) reanalysis data. Additionally, comparison with a Sun photometer (AErosol RObotic NETwork – AERONET) shows the daily variation in the AOD retrieved from FTS to be similar to that retrieved by Sun photometer. Using this method, long-term observations (from April to August 2020) are retrieved and presented. We find that sulfate is often present in the Arctic; it is higher in spring and lower in summer. Similarly, BC is also frequently observed in the Arctic, with less obvious seasonal variation than sulfate. A BC outburst event is observed each spring and summer. In spring, sulfate and BC are dominant, whereas sea salt and dust are relatively low. In addition, a sea salt enhancement event is observed in summertime, which might be due to the melting of sea ice and emissions from nearby open water. From the retrieved results over a long time period, no clear correlations are found; thus, the aforementioned species can be retrieved independently of one another.

Determination of Machining Parameters for a Specific Adjustment of the Residual Stress Profile by Induction Hardening*

Abstract Within the research work of the Transregional Collaborative Research Center TRR 136, process signatures were determined for processes that generate essentially thermal loading of the component surface layer. These process signatures represent correlations between material modifications (e. g. changes of residual stress, microstructure, hardness profile, etc.) and characteristic values of the material loading. The underlying idea is that the material does not know any processes but only loads caused by processes. In particular, the same loads lead to the same material modifications regardless of the kind of process. A decisive advantage of this concept over conventional approaches is the possibility of calculating the necessary internal material loads backwards on the basis of concrete specifications for the material modifications. If there are additional correlations between internal material loads and process quantities as well as between process quantities and machining parameters, the necessary machining parameters can be determined, too. In this paper, this procedure will be introduced using the example of one-sided induction hardening of cuboidal components made of 42CrMo4. The determination of the process signature by experimental and numerical investigations is described and work for experimental verifications are presented.

“Ideology and simultaneously more than mere ideology”: On Habermas’ reflections and hypotheses on a further structural transformation of the political public sphere

“Ideology and simultaneously more than mere ideology”: On Habermas’ reflections and hypotheses on a further structural transformation of the political public sphere

Implementation of a surrogate model for a novel path‐based finite element simulation for additive manufacturing processes in construction

AbstractAdditive manufacturing in large‐scale construction is an ongoing research topic that shows significant potential to overcome the challenges in terms of efficient material usage and process automation in construction. A large challenge in deposition based additive manufacturing processes of concrete material is to ensure the structural stability while printing. Due to the weak material properties of the fresh concrete, it has to be ensured that during the printing process the not fully cured printed structure is able to carry its own weight. This requires process stabilization and a proper process control to prevent a collapse of the structure. Therefore, a numerical model of the printing process that takes into account the time dependent material behavior of the applied concrete as well as the printing path and the process parameters is necessary to support the process planning. Within the framework of project B04 of the collaborative research center TRR277 – Additive Manufacturing in Construction, a novel path‐based finite element simulation was developed in which the simulated geometry is constructed directly from the printing trajectory. Additionally, this approach allows the time‐dependent material properties of fresh concrete to be modeled directly and efficiently into the mesh of the printed structure. Since the computation of large scale printing processes with finite element simulations is quite expensive, there exists a need for a much faster computational model. In this contribution, the implementation of a surrogate model based on a neural network and its deployment to optimize the interlayer waiting time is presented.

Feasibility study on multifrequency excitation of the melt pool during ultrasonic-assisted laser beam welding

The constantly increasing demands on components and their resource-efficient production require new strategies in modern process chains. The Collaborative Research Centre (CRC) 1153 “Tailored Forming” is working on the production of hybrid solid components made from joined semi-finished products with subsequent forming. Laser beam welding with ultrasonic assistance has proven to be advantageous in the production of semi-finished products due to the active influence on the microstructure as a result of the excitation. In this work, the feasibility of extending the monofrequency excitation of the melt pool used so far during welding to a multifrequency excitation is investigated. Results from simulations and experiments show that a multi-frequency excitation of the weld pool can be effectively realised. Furthermore, it is shown that a combination of previously separately used excitation methods (positioning of the melt pool in the vibration node and in the vibration antinode, respectively) with two different frequencies is successful and leads to a combination of effects as desired, what can be seen from micrographs.

Observation of * *Supported in part by National Key R&D Program of China under Contracts Nos. Supported in part by National Key R&D Program of China (2020YFA0406300, 2020YFA0406400); National Natural Science Foundation of China (NSFC) (11975118, 11625523, 11635010, 11735014, 11822506, 11835012, 11935015, 11935016, 11935018, 11961141012, 12022510, 12025502, 12035009, 12035013, 12061131003, 12075252, 12192260, 12192261, 12192262, 12192263, 12192264, 12192265); the Natural Science

Using data taken at 29 center-of-mass energies between 4.16 and 4.70 GeV with the BESIII detector at the Beijing Electron Positron Collider corresponding to a total integrated luminosity of approximately 18.8 , the process is observed for the first time with a statistical significance of . The average Born cross sections in the energy ranges of (4.160, 4.380) GeV, (4.400, 4.600) GeV and (4.610, 4.700) GeV are measured to be fb, fb and fb, respectively, where the first uncertainties are statistical and the second are systematic. The line shapes of the and invariant mass spectra are consistent with phase space distributions, indicating that no hexaquark or di-baryon state is observed.

Situating language register across the ages, languages, modalities, and cultural aspects: Evidence from complementary methods.

In the present review paper by members of the collaborative research center "Register: Language Users' Knowledge of Situational-Functional Variation" (CRC 1412), we assess the pervasiveness of register phenomena across different time periods, languages, modalities, and cultures. We define "register" as recurring variation in language use depending on the function of language and on the social situation. Informed by rich data, we aim to better understand and model the knowledge involved in situation- and function-based use of language register. In order to achieve this goal, we are using complementary methods and measures. In the review, we start by clarifying the concept of "register", by reviewing the state of the art, and by setting out our methods and modeling goals. Against this background, we discuss three key challenges, two at the methodological level and one at the theoretical level: (1) To better uncover registers in text and spoken corpora, we propose changes to established analytical approaches. (2) To tease apart between-subject variability from the linguistic variability at issue (intra-individual situation-based register variability), we use within-subject designs and the modeling of individuals' social, language, and educational background. (3) We highlight a gap in cognitive modeling, viz. modeling the mental representations of register (processing), and present our first attempts at filling this gap. We argue that the targeted use of multiple complementary methods and measures supports investigating the pervasiveness of register phenomena and yields comprehensive insights into the cross-methodological robustness of register-related language variability. These comprehensive insights in turn provide a solid foundation for associated cognitive modeling.

Ecossistema de centro de pesquisa universitária em project studies: Um framework conceitual

Abstract Purpose: To provide a conceptual framework of the ecosystem of a collaborative research center in project studies. The ecosystem is an environment capable of articulating and integrating different actors, such as academics and practitioners from public and private organizations, non-governmental organizations, and professional associations. Furthermore, it discusses theoretical and empirical frontiers in project studies and produces knowledge and technologies directly applicable to organizations, generating impact at the individual, organizational, and social levels. Originality/value: The creation of a collaborative workspace that includes academics and practitioners in the co-production of knowledge has been highlighted as critical to driving project management forward. The framework establishes a common language among academics and practitioners to enhance the impact of the results of collaborative research on project management. Design/methodology/approach: A systematic literature review was carried out from a search on the Scopus and Web of Science databases, with 11 frameworks being evaluated from the perspective of sustainable impacts. The most appropriate framework was identified, analyzed, and enriched with an additional layer dedicated to project management. Findings: The conceptual framework proposed comprises four layers: project studies, process (resources, activities, outputs, outcomes, and impacts), supporting mechanisms and circumstances, and context. For future studies, we suggest adding empirical data to the proposed structure and evaluating the framework in a collaborative academic environment.

Ecosystem of a collaborative research center in project studies: A conceptual framework

Resumo Objetivo: Propor o framework conceitual do ecossistema de um centro de pesquisa universitária em project studies. Trata-se de um ambiente capaz de articular e integrar distintos atores, como acadêmicos e praticantes de organizações públicas e privadas, organizações não governamentais e associações de classes, com o propósito de discutir fronteiras teóricas e empíricas em project studies e produzir conhecimento e tecnologias diretamente aplicáveis às organizações, e assim gerar impacto em nível individual, das organizações e da sociedade. Originalidade/valor: A criação de espaço colaborativo, envolvendo aca-dêmicos e praticantes, para coprodução de conhecimento, tem sido apontada como crítica para impulsionar a área de gestão de projetos. O framework estabelece uma linguagem comum entre acadêmicos e praticantes para potencializar o impacto dos resultados de pesquisas colaborativas em gestão de projetos. Design/metodologia/abordagem: Foi realizada uma revisão sistemática da literatura a partir de uma busca nas bases de dados Scopus e Web of Science, e avaliaram-se 11 frameworks sob a perspectiva de impactos sustentáveis. O framework mais aderente foi identificado, analisado e enriquecido com uma camada adicional dedicada à área de gestão de projetos. Resultados: O framework conceitual proposto é composto por quatro camadas: project studies, elementos processuais (recursos, atividades, resultados diretos, indiretos e impactos), mecanismos organizacionais de suporte e circunstâncias, e contexto. Como estudos futuros, sugerem-se a agregação de dados empíricos à estrutura proposta e a avaliação do framework em um ambiente acadêmico colaborativo.

Data management strategy for a collaborative research center.

The importance of effective research data management (RDM) strategies to support the generation of Findable, Accessible, Interoperable, and Reusable (FAIR) neuroscience data grows with each advance in data acquisition techniques and research methods. To maximize the impact of diverse research strategies, multidisciplinary, large-scale neuroscience research consortia face a number of unsolved challenges in RDM. While open science principles are largely accepted, it is practically difficult for researchers to prioritize RDM over other pressing demands. The implementation of a coherent, executable RDM plan for consortia spanning animal, human, and clinical studies is becoming increasingly challenging. Here, we present an RDM strategy implemented for the Heidelberg Collaborative Research Consortium. Our consortium combines basic and clinical research in diverse populations (animals and humans) and produces highly heterogeneous and multimodal research data (e.g., neurophysiology, neuroimaging, genetics, behavior). We present a concrete strategy for initiating early-stage RDM and FAIR data generation for large-scale collaborative research consortia, with a focus on sustainable solutions that incentivize incremental RDM while respecting research-specific requirements.

Search for hidden-charm tetraquark with strangeness in * *Supported in part by National Key R&D Program of China (Grant Nos. 2020YFA0406400, 2020YFA0406300); National Natural Science Foundation of China (NSFC) (Grant Nos. 11635010, 11735014, 11805086, 11835012, 11935015, 11935016, 11935018, 11961141012, 12022510, 12025502, 12035009, 12035013, 12192260, 12192261, 12192262, 12192263, 12192264, 12192265); the Chinese Academy of Sciences (CAS) Large-Scale Scientific Facility Program; Joint

We report a search for a heavier partner of the recently observed state, denoted as , in the process , based on collision data collected at the center-of-mass energies of , 4.682 and 4.699 GeV with the BESIII detector. The is of interest as it is expected to be a candidate for a hidden-charm and open-strange tetraquark. A partial-reconstruction technique is used to isolate recoil-mass spectra, which are probed for a potential contribution from (). We find an excess of () candidates with a significance of , after considering systematic uncertainties, at a mass of . As the data set is limited in size, the upper limits are evaluated at the 90% confidence level on the product of the Born cross sections () and the branching fraction () of , under different assumptions of the mass from 4.120 to 4.140 MeV and of the width from 10 to 50 MeV at the three center-of-mass energies. The upper limits of are found to be at the level of pb at each energy. Larger data samples are needed to confirm the state and clarify its nature in the coming years.

Observation of the Y(4230) and a new structure in * *Supported in part by National Key R&D Program of China (2020YFA0406300, 2020YFA0406400); National Natural Science Foundation of China (NSFC) under Contracts Nos. (11625523, 11635010, 11735014, 11822506, 11835012, 11935015, 11935016, 11935018, 11961141012, 12022510, 12025502, 12035009, 12035013, 12061131003); the Chinese Academy of Sciences (CAS) Large-Scale Scientific Facility Program; Joint Large-Scale Scientific Facility

The cross sections of at center-of-mass energies from 4.127 to 4.600 GeV are measured based on 15.6 fb data collected with the BESIII detector operating at the BEPCII storage ring. Two resonant structures are observed in the line shape of the cross sections. The mass and width of the first structure are measured to be () MeV and () MeV, respectively. They are consistent with those of the established . The second structure is observed for the first time with a statistical significance greater than 8σ, denoted as . Its mass and width are determined to be () MeV and () MeV, respectively. The first presented uncertainties are statistical and the second ones are systematic. The product of the electronic partial width with the decay branching fraction is reported.

The novel ageing-induced long non-coding RNA MIRIAL controls endothelial cell and mitochondrial function

Abstract Vascular ageing is a key risk factor for cardiovascular diseases and is characterised by a continuous decline in endothelial cell function. Despite progress in recent years, the molecular mechanisms for this deterioration remain incompletely understood. Long non-coding RNAs (lncRNAs) are a heterogeneous class of RNAs that have been shown to regulate gene expression and protein function, however, little is known about their role in the ageing-associated dysregulation of endothelial cell (EC) function. In this study, we aimed to identify and functionally characterise a novel ageing-regulated lncRNA in ECs. Using RNA sequencing data of cardiac ECs derived from 12 weeks young and 20 months old mice, we identified Mirial as an ageing-induced lncRNA (1.32-fold, p=0.00005). Mirial is conserved between mice and humans and has no obvious coding potential. GapmeR-mediated silencing of MIRIAL in human umbilical vein ECs (HUVECs) decreased cell proliferation by 50%, migration by 24% (p=0.045) and basal angiogenic sprouting by 53% (p=0.0029), without affecting apoptosis or senescence. Additionally, silencing of MIRIAL increases mitochondrial mass (1.8-fold, p<0.01) and spare respiratory capacity (1.95-fold). Preliminary data from the hearts of Mirial knockout mice confirm the elevated mitochondrial mass after Mirial ablation (1.26-fold, p=0.05). In HUVECS, MIRIAL is mainly associated with the chromatin (80%), suggesting a role in the regulation of gene expression. Pathway analysis showed an overrepresentation of p53 target genes that were upregulated upon MIRIAL knockdown, which was validated using qRT-PCR (1.8–5.2-fold increases). Interestingly, this effect is fully dependent on the presence of p53. Moreover, p53 and phospho-p53 (Ser15) were both increased (1.8-fold, p=0.01 and 2.9-fold, p=0.02, respectively) after MIRIAL silencing. Pulldown of MIRIAL identified DDX5 and MRPL41 as direct p53 interactors and RNA immunoprecipitation revealed that MIRIAL physically interacts with p53 (3.75-fold enrichment, p<0.01). Gene set enrichment analysis of RNA sequencing data revealed that 10% of deregulated genes after MIRIAL knockdown have a binding site for Forkhead Box O (FoxO) transcription factors. In particular, FoxO1 is known as one of the key players in endothelial proliferation and regulation of angiogenesis as well as in mitochondrial biogenesis. Taken together, MIRIAL is an ageing-induced lncRNA in endothelial cells acting as a key regulator of metabolic and cellular function. MIRIAL promotes cell proliferation, migration and basal angiogenic sprouting while decreasing mitochondrial function. We hypothesise that MIRIAL influences these cellular functions by affecting the p53 pathway and mitochondrial respiration through FoxO signalling. The results from the present study suggest that modulation of cellular MIRIAL expression may be a promising strategy to prevent or even reverse ageing-induced functional decline of ECs, both in vitro and in vivo. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft - Collaborative Research Centre (SFB) 834 - Project B9Deutsche Forschungsgemeinschaft - Collaborative Research Centre/Transregio (TRR) 267 - Project B4

Dysferlin facilitates the de novo biogenesis of tubular membranes in hypertrophic remodelling

Abstract Introduction Ferlins are transmembrane proteins with multiple C2 domains that may mediate Ca2+ dependent membrane fusion and repair events. In ventricles, Dysferlin expression is dominant, and patient mutations have been associated with cardiomyopathies. Hence, we hypothesized that Dysferlin is essential for the functional integrity of the tubular endomembrane system in ventricular myocytes (VM), and may facilitate the cellular hypertrophic remodelling in pressure-overload. Results In 30 weeks old Dysferlin knockout (KO) mice, echocardiography revealed dilative cardiomyopathy with reduced left-ventricular ejection fractions (difference between means KO vs. wildtype (WT) −13.45±2.17%, p<0.001, n=16/20 mice). Asking for the subcellular relevance of Dysferlin, we investigated VM nanodomains by immunolabelling in STimulated Emission Depletion (STED) nanoscopy and visualized punctual Dysferlin clusters decorating the T-tubule system of mouse and human VM. Precisely, Dysferlin clusters localized to junctions of the tubular system and the sarcoplasmic reticulum (SR) in nanometric proximity to RyR2 Ca2+ release units. Complexome profiling (LC-MS/MS) also suggested interactions of Dysferlin with RyR2 and the SR membrane-tethering protein Junctophilin-2 (JP2) in high molecular weight complexes. In JP2-overexpressing mice, live-cell STED membrane imaging captured polyadic junctional membrane structures in VM, specifically surrounded by dense Dysferlin clusters, which proposes Dysferlin as stabilizing protein of tubule-SR junctions. Further, we studied the ultrastructural remodelling of the tubular system in a mouse model of cardiac hypertrophy and heart failure induced by transaortic constriction (TAC). Interestingly, mortality four weeks post TAC was not increased in KO mice. However, echocardiography uncovered that Dysf-KO prevents left-ventricular hypertrophy in response to pressure-overload, which was confirmed by single cell measurements (VM area: WT 3559±120 μm2 vs. KO 2671±87 μm2, n=163/158 VM, p<0.001). Thus, we assumed Dysferlin to mediate tubular network proliferation during hypertrophic remodelling. Indeed, WT VM showed an augmented Dysferlin expression post TAC (158±0,125%, p=0,005, n=7/7 mice), and immunofluorescence STED nanoscopy detected an increased Dysferlin network complexity. In detail, we visualized highly abundant Dysferlin clusters decorating newly shaped axial tubules, which were quantified by component-specific tubule network analysis. Conclusion Nanoscale imaging proposes Dysferlin as stabilizer of tubule-SR junctions, thereby promoting functional excitation-contraction coupling, and demonstrates the crucial importance of Dysferlin in pressure-overload induced hypertrophic remodelling, facilitating the de novo biogenesis of axial tubule membranes and tubule-SR junctions necessary for VM growth. Thus, Dysferlin may emerge as potential novel therapeutic rationale to control subcellular membrane remodelling in cardiac diseases. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Multiscale Bioimaging Cluster of Excellence: From Molecular Machines to Networks of Excitable Cells;German Research Foundation (DFG) - Collaborative Research Centre 1002 (SFB 1002): Modulatory Units in Heart Failure

Chronic insulin resistance deteriorates cardiac mitochondrial quality control in a mouse model of SEC-NAFLD-IR

Abstract Background Insulin resistance and nonalcoholic fatty liver disease (NAFLD) both relate to cardiovascular mortality. Using a mouse model of chronic lipid overload and secondary-NAFLD-induced insulin resistance (SEC-NAFLD-IR), we recently deciphered that SEC-NAFLD-IR already at young age provoked myocardial lipotoxicity with reduced mitochondrial efficiency and increased vulnerability to cardiac ischemia. However, long-term consequences of SEC-NAFLD-IR remain elusive. Purpose Here we aimed to elucidate the impact of long-term SEC-NAFLD-IR on multiple mitochondrial quality control (mQC) mechanisms in the heart and its consequences for cardiac function. Methods We studied 36 SEC-NAFLD-IR mice (72-week-old). For mechanistic experiments, we applied palmitate-induced insulin resistant murine HL-1 cells. Cardiac mitochondrial dynamics were measured via quantification of mitochondrial morphology and expression of mitochondrial fusion and fission factors (Opa1, Drp1, Fis1, Mfn 1 & 2). Mitophagy level was evaluated via immunofluorescence and protein expression of key mitophagy-related genes (Parkin, NIX, LC3). Mitochondrial biogenesis and mass were examined via quantitation of PGC-1α expression, mtDNA and citrate synthase activity. Results 72-week-old SEC-NAFLD-IR mice exhibited 21% (p=0.001) and 32% (p<0.001) higher body weight and heart weight compared with controls. Along with elevated oxidative stress, hepatic lipid accumulation and inflammation, 6h-fasted SEC-NAFLD-IR mice were characterized by increased plasma glucose, insulin and cholesterol. SEC-NAFLD-IR mice displayed a cardiac phenotype with 21% higher left ventricular mass (normalized to body weight, p<0.001) and 6% lower ejection fraction compared to controls (73.5% SEM 0.90 vs 69.4% SEM 1.65, p=0.04). We found several advantageous mQC mechanisms suppressed in aged SEC-NAFLD-IR mice including long form OPA1-mediated mitochondrial fusion, Parkin- and NIX-mediated mitophagy. Likewise, mitochondrial biogenesis was suppressed in the aged insulin-resistant heart, which was connected to a 65% downregulation of PGC-1α1 expression (p=0.01). Interestingly, downregulation of cardiac PGC-1α1 in aged SEC-NAFLD-IR mice coincided with upregulation of PARIS, indicating the crucial participation of the Parkin/PARIS pathway in mQC of the insulin-resistant heart. In addition, induction of insulin resistance in murine HL-1 cardiomyocytes also led to increased mitochondrial fragmentation and decreased PGC-1α1 expression. Conclusion This study demonstrated that regulation of mitochondrial network and turnover is hampered by SEC-NAFLD-IR in the hearts of aged mice, which may contribute to hypertrophy and cardiac dysfunction in insulin resistance. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Collaborative Research Centre 1116 (German Research Foundation)

Collaborative Research Centre (CRC 1451) “Key mechanisms of motor control in health and disease”

Collaborative Research Centre (CRC 1451) “Key mechanisms of motor control in health and disease”

Collaborative Research Center SFB 1528 “Cognition of Interaction”

Collaborative Research Center SFB 1528 “Cognition of Interaction”

Microplastic and dermatological care

HintergrundKunststoffe aus fossilen Rohstoffen (Plastik) werden in großer Menge hergestellt und gelangen bei unsachgemäßer Entsorgung und über weitere Eintragspfade in die Umwelt. Dies kann Auswirkungen auf Flora, Fauna und den Menschen zur Folge haben.Ziel der ArbeitDie vorliegende Arbeit soll Dermatolog*innen einen kompakten Überblick über diese komplexe Thematik und den Zusammenhang zur täglichen ärztlichen Tätigkeit bieten.Material und MethodenEs erfolgte eine selektive Literaturrecherche zu den Themen Mikroplastik und Nachhaltigkeit in der Dermatologie unter Einbezug des Sonderforschungsbereichs 1357 Mikroplastik der Universität Bayreuth.ErgebnissePrimäres und sekundäres Mikroplastik gelangt in großen Mengen in die Umwelt und akkumuliert in aquatischen und terrestrischen Ökosystemen. Dies kann zur Disruption selbiger führen und ökologische Nischen für humanpathogene Spezies schaffen. Menschen und Tiere nehmen Mikroplastik über die Atemwege und die Nahrung zu sich, die gesundheitlichen Folgen sind nicht ausreichend erforscht. Dies liegt v. a. darin begründet, dass Mikroplastik keine einheitliche Stoffgruppe ist und mögliche Effekte von vielen unterschiedlichen Eigenschaften der Partikel abhängen (z. B. Polymertyp, Größe, Form, Additivierung, Oberflächenladung). Die dermatologische Versorgung ist ressourcenintensiv und trägt auf unterschiedliche Weise zur geschilderten Gesamtproblematik bei.DiskussionKunststoffe sind aktuell in vielen Bereichen unverzichtbar. Nichtsdestoweniger haben Ärzt*innen die Verantwortung, negative Folgen für die Gesundheit der Bevölkerung abzuwenden (Vorsorgeprinzip). Es sind daher weitreichende Anstrengungen für mehr Nachhaltigkeit notwendig, dies schließt auch die ärztliche Routineversorgung mit ein.