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Item type: Item , A reductionist perspective on HIF-1a's role in cell proliferation under non-hypoxic conditions(2024) Dreute, Jan; Pfisterer, Maximilian; Schmitz, M. LienhardThe role of hypoxia-inducible factor (HIF)-1α in the control of proliferation under non-hypoxic conditions has been investigated in numerous studies, but does not yield a coherent picture. Therefore, we conducted this meta-analysis of existing literature to systematically evaluate the role of HIF-1α, based on a number of inclusion and exclusion criteria. Studies analyzing non-transformed, primary cells showed a largely heterogeneous distribution of pro-proliferative, anti-proliferative or absent functions for HIF-1α, which are co-determined by several parameters, including the type and age of the cell and its localization in tissues and organs. In contrast, the analyses of tumor cells showed a predominantly pro-proliferative role of HIF-1α by cell-intrinsic and cell-extrinsic molecular mechanism not yet understood.Item type: Item , Fast and sustainable planar yeast-based bioassay for endocrine disruptors in complex mixtures: Start of cell cultivation to result within one day(2024) Ronzheimer, Alisa; Ringelmann, Anne E.; Morlock, Gertrud E.High-performance thin-layer chromatography hyphenated with planar multiplex bioassays and high-resolution tandem mass spectrometry contributes to the non-target detection or even identification of active compounds in complex mixtures such as food, feed, cosmetics, commodities, and environmental samples. It can be used to discover previously unknown harmful or active substances in complex samples and to tentatively assign molecular formulas. This method is already faster than the commonly used in vitro assays along with liquid chromatographic separations, but overnight cell cultivation still prevents a planar bioassay from being performed within one day. There is also still potential for optimization in terms of sustainability. To achieve this, the planar bioassay protocols for the detection of androgen-like and estrogen-like compounds were harmonized. The successful minimization of the cell culture volume enabled accelerated cell cultivation, which allowed the bioassay to be performed within one day. This was considered a milestone achieved, as up to 23 samples per plate can now be analyzed from the start of cultivation to the biological endpoint on the same day. Doubling the substrate amount and increasing the pH of the silica gel layer led to a more sensitive and selective bioassay due to the enhanced fluorescence of the formed end-product. The faster and more sustainable bioassay protocol was applied to complex samples such as sunscreen and red wine to detect estrogen-like compounds. The developed method was validated by comparison with a standard method.Item type: Item , Liver stiffness is associated with right heart dysfunction, cardiohepatic syndrome, and prognosis in pulmonary hypertension(2024) Rako, Zvonimir A.; Yogeswaran, Athiththan; Yildiz, Selin; Weidemann, Peter; Zedler, Daniel; da Rocha, Bruno Brito; Kryvenko, Vitalii; Schäfer, Simon; Ghofrani, Hossein Ardeschir; Seeger, Werner; Kremer, Nils C.; Tello, KhodrBackground: Pulmonary hypertension (PH) can lead to congestive hepatopathy, known as cardiohepatic syndrome (CHS). Hepatic congestion is associated with increased liver stiffness, which can be quantified using shear wave elastography. We aimed to investigate whether hepatic shear wave elastography detects patients at risk in the early stages of PH. Methods: Sixty-three prospectively enrolled patients undergoing right heart catheterization (52 diagnosed with PH and 11 with invasive exclusion of PH) and 52 healthy volunteers underwent assessments including echocardiography and hepatic shear wave elastography. CHS was defined as increased levels of ≥2 of the following: gamma-glutamyl transferase, alkaline phosphatase, and bilirubin. Liver stiffness was defined as normal (≤5.0 kPa) or high (>5.0 kPa). Results: Compared with normal liver stiffness, high liver stiffness was associated with impaired right ventricular (RV) and right atrial (RA) function (median [interquartile range] RV ejection fraction: 54 [49; 57]% vs 45 [34; 51]%, p < 0.001; RA reservoir strain: 49 [41; 54]% vs 33 [22; 41]%, p < 0.001), more severe tricuspid insufficiency (p < 0.001), and higher prevalence of hepatovenous backflow (2% vs 29%, p < 0.001) and CHS (2% vs 10%, p = 0.038). In the patient subgroup with precapillary PH (n = 48), CHS and high liver stiffness were associated with increased European Society of Cardiology/European Respiratory Society 2022 risk scores (p = 0.003). Conclusions: Shear wave liver elastography yields important information regarding right heart function and may complement risk assessment in patients with (suspected) PH.Item type: Item , The distributional effects of CO2 pricing at home and at the border on German income groups(2024) Hübler, Michael; Wiese, Malin; Braun, Marius; Damster, JohannesWhile climate policy studies are widespread, fully fledged computable general equilibrium (CGE) model analyses of distributional policy effects are challenging because the required data and approaches are not directly available. To ease such distributional analyses, we provide a step-by-step “recipe” for disaggregating a country-specific representative consumer of a CGE model. Using this “recipe”, we implement German household survey data in a global CGE model by distinguishing three income groups of the German representative consumer. We find that the negative consumption effect of CO pricing is highest for the low-income group, whereas the negative income effect is highest for the high-income group and exceeds the consumption effect. The low-income group benefits most from (per capita-based redistribution of) carbon pricing revenues and receives social transfers such that poor households can be better off with such climate policies than without them. CO pricing of imports at the (EU) border slightly strengthens these distributional effects and is mainly beneficial for the low-income group. The geographic extension of emissions trading within a “climate club” leads to substantial efficiency gains that are beneficial for Germany and the EU.Item type: Item , Are ipRGCs involved in human color vision? Hints from physiology, psychophysics, and natural image statistics(2024) Barrionuevo, Pablo A.; Sandoval Salinas, María L.; Fanchini, José M.Human photoreceptors consist of cones, rods, and melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). First studied in circadian regulation and pupillary control, ipRGCs project to a variety of brain centers suggesting a broader involvement beyond non-visual functions. IpRGC responses are stable, long-lasting, and with a particular codification of photoreceptor signals. In comparison with the transient and adaptive nature of cone and rod signals, ipRGCs' signaling might provide an ecological advantage to different attributes of color vision. Previous studies have indicated melanopsin's influence on visual responses yet its contribution to color perception in humans remains debated. We summarized evidence and hypotheses (from physiology, psychophysics, and natural image statistics) about direct and indirect involvement of ipRGCs in human color vision, by first briefly assessing the current knowledge about the role of melanopsin and ipRGCs in vision and codification of spectral signals. We then approached the question about melanopsin activation eliciting a color percept, discussing studies using the silent substitution method. Finally, we explore various avenues through which ipRGCs might impact color perception indirectly, such as through involvement in peripheral color matching, post-receptoral pathways, color constancy, long-term chromatic adaptation, and chromatic induction. While there is consensus about the role of ipRGCs in brightness perception, confirming its direct contribution to human color perception requires further investigation. We proposed potential approaches for future research, emphasizing the need for empirical validation and methodological thoroughness to elucidate the exact role of ipRGCs in human color vision.