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  • 1
    Online Resource
    Online Resource
    Hindawi Limited ; 2022
    In:  Aquaculture Research Vol. 53, No. 13 ( 2022-09), p. 4767-4781
    In: Aquaculture Research, Hindawi Limited, Vol. 53, No. 13 ( 2022-09), p. 4767-4781
    Type of Medium: Online Resource
    ISSN: 1355-557X , 1365-2109
    URL: Issue
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2207423-5
    detail.hit.zdb_id: 1227359-4
    detail.hit.zdb_id: 2019895-4
    SSG: 21,3
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  • 2
    In: Journal of Molecular Medicine, Springer Science and Business Media LLC, Vol. 94, No. 1 ( 2016-1), p. 61-69
    Type of Medium: Online Resource
    ISSN: 0946-2716 , 1432-1440
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 1462132-0
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Association for Computing Machinery (ACM) ; 2023
    In:  Proceedings of the ACM on Programming Languages Vol. 7, No. ICFP ( 2023-08-30), p. 448-475
    In: Proceedings of the ACM on Programming Languages, Association for Computing Machinery (ACM), Vol. 7, No. ICFP ( 2023-08-30), p. 448-475
    Abstract: Type and effect systems have been successfully used to statically reason about effects in many different domains, including region-based memory management, exceptions, and algebraic effects and handlers. Such systems’ soundness is often stated in terms of the absence of effects. Yet, existing systems only admit indirect reasoning about the absence of effects. This is further complicated by effect polymorphism which allows function signatures to abstract over arbitrary, unknown sets of effects. We present a new type and effect system with effect polymorphism as well as union, intersection, and complement effects. The effect system allows us to express effect exclusion as a new class of effect polymorphic functions: those that permit any effects except those in a specific set. This way, we equip programmers with the means to directly reason about the absence of effects. Our type and effect system builds on the Hindley-Milner type system, supports effect polymorphism, and preserves principal types modulo Boolean equivalence. In addition, a suitable extension of Algorithm W with Boolean unification on the algebra of sets enables complete type and effect inference. We formalize these notions in the λ ∁ calculus. We prove the standard progress and preservation theorems as well as a non-standard effect safety theorem: no excluded effect is ever performed. We implement the type and effect system as an extension of the Flix programming language. We conduct a case study of open source projects identifying 59 program fragments that require effect exclusion for correctness. To demonstrate the usefulness of the proposed type and effect system, we recast these program fragments into our extension of Flix.
    Type of Medium: Online Resource
    ISSN: 2475-1421
    Language: English
    Publisher: Association for Computing Machinery (ACM)
    Publication Date: 2023
    detail.hit.zdb_id: 2924207-1
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  • 4
    Online Resource
    Online Resource
    Wiley ; 2018
    In:  Journal of Cellular and Molecular Medicine Vol. 22, No. 12 ( 2018-12), p. 5991-6001
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 22, No. 12 ( 2018-12), p. 5991-6001
    Abstract: The renin‐angiotensin system promotes oxidative stress, apoptosis, necrosis, fibrosis, and thus heart failure. Secretory renin plays a central role in these processes, initiating the generation of angiotensins. Nevertheless, alternative renin transcripts exist, which code for a cytosolically localized renin isoform (cyto‐renin) that is cardioprotective. We tested the hypothesis that the protective effects are associated with a beneficial switch of metabolic and mitochondrial functions. To assess H9c2 cell mitochondrial parameters, we used the Seahorse XF analyser. Cardiac H9c2 cells overexpressing cyto‐renin exhibited enhanced nonmitochondrial oxygen consumption, lactate accumulation, and LDH activity, reflecting a switch to more aerobic glycolysis known as Warburg effect. Additionally, mitochondrial spare capacity and cell respiratory control ratio were enhanced, indicating an increased potential to tolerate stress conditions. Renin knockdown induced opposite effects on mitochondrial functions without influencing metabolic parameters. Thus, the protective effects of cyto‐renin are associated with an altered bioenergetic profile and an enhanced stress tolerance, which are favourable under ischaemic conditions. Therefore, cyto‐renin is a promising new target for the prevention of ischaemia‐induced myocardial damage.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2076114-4
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  • 5
    In: Cells, MDPI AG, Vol. 13, No. 3 ( 2024-01-31), p. 269-
    Abstract: This study investigated how Atlantic sturgeon cells respond to elevated temperatures, shedding light on the potential impacts of climate change on fish. Atlantic sturgeon (Acipenser oxyrinchus), an IUCN (International Union for Conservation of Nature) Red List species and evolutionarily related to paleonisiform species, may have considerable physiological adaptability, suggesting that this species may be able to cope with changing climatic conditions and higher temperatures. To test this hypothesis, the AOXlar7y cell line was examined at 20 °C (control) and at elevated temperatures of 25 °C and 28 °C. Parameters including proliferation, vitality, morphology, and gene expressions related to proliferation, stemness, and stress were evaluated. Additionally, to achieve a comprehensive understanding of cellular changes, mitochondrial and metabolic activities were assessed using Seahorse XF96. AOXlar7y cells adapted to 28 °C exhibited enhanced mitochondrial adaptability, plasticity, heightened cell proliferation, and increased hsp70 expression. Increased baseline respiration indicated elevated ATP demand, which is potentially linked to higher cell proliferation and heat stress defense. Cells at 28 °C also displayed elevated reserve respiration capacity, suggesting adaptation to energy demands. At 25 °C, AOXlar7y cells showed no changes in basal respiration or mitochondrial capacity, suggesting unchanged ATP demand compared to cells cultivated at 20 °C. Proliferation and glycolytic response to energy requirements were diminished, implying a connection between glycolysis inhibition and proliferation suppression. These research results indicate sturgeon cells are capable of withstanding and adapting to an 8 °C temperature increase. This cellular analysis lays a foundation for future studies aimed at a deeper understanding of fish cell physiological adaptations, which will contribute to a better knowledge of environmental threats facing Atlantic sturgeon and fish populations amid climate change.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2024
    detail.hit.zdb_id: 2661518-6
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  • 6
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 21, No. 7 ( 2017-07), p. 1394-1410
    Abstract: The (pro)renin receptor [(P)RR, ATP6AP2] is a multifunctional transmembrane protein that activates local renin–angiotensin systems, but also interacts with Wnt pathways and vacuolar H + ‐ATPase (V‐ATPase) during organogenesis. The aim of this study was to characterize the role of ATP6AP2 in the cell cycle in more detail. ATP6AP2 down‐regulation by siRNA in renal As4.1 cells resulted in a reduction in the rate of proliferation and a G0/G1 phase cell cycle arrest. We identified a number of novel target genes downstream of ATP6AP2 knock‐down that were related to the primary cilium ( Bbs‐1, Bbs‐3, Bbs‐7, Rabl5, Ttc26, Mks‐11, Mks‐5, Mks‐2, Tctn2, Nme7 ) and the cell cycle ( Pierce1, Clock, Ppif ). Accordingly, the number of cells expressing the primary cilium was markedly increased. We found no indication that these effects were dependent of V‐ATPase activity, as ATP6AP2 knock‐down did not affect lysosomal pH and bafilomycin A neither influenced the ciliary expression pattern nor the percentage of ciliated cells. Furthermore, ATP6AP2 appears to be essential for mitosis. ATP6AP2 translocated from the endoplasmatic reticulum to mitotic spindle poles (pro‐, meta‐ and anaphase) and the central spindle bundle (telophase) and ATP6AP2 knock‐down results in markedly deformed spindles. We conclude that ATP6AP2 is necessary for cell division, cell cycle progression and mitosis. ATP6AP2 also inhibits ciliogenesis, thus promoting proliferation and preventing differentiation.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2076114-4
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  • 7
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2020
    In:  Scientific Reports Vol. 10, No. 1 ( 2020-11-12)
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-11-12)
    Abstract: The renin-angiotensin system is known to regulate blood pressure as well as water- and electrolyte balance. An activated RAS is involved in the development of hypertension and hypertension-related organ damage. Thus, inhibitors of the RAS are protective and markedly increasing the life span of patients. In contrast, renin transcripts have been discovered encoding a cytoplasmatic renin isoform, termed renin-b, which is not harmful but may be even protective. Here we demonstrate that depletion of renin-b encoding transcripts by small interference RNA decreased ATP levels and increased basal necrosis as well as apoptosis rates. Furthermore, renin-b depletion potentiated the anoxia-induced increase of necrosis rates. Vice versa, overexpression of renin-b prevented the anoxia-induced increase of caspase-mediated apoptosis rates. Besides, cells overexpressing renin-b exhibited even reduced mitochondrial mediated apoptosis rates under anoxia, when compared with normoxic conditions, as indicated by Annexin V labeling. However, whereas the protective effect of renin-b on caspase-mediated apoptosis was completely blocked by the renin inhibitor CH732, the effect on mitochondrial-mediated apoptosis was not affected by CH732 at all. From these data we conclude that renin-b overexpression mediates cardioprotective effects under anoxia with respect to mitochondrial induced apoptosis angiotensin-independently, but with respect to caspase induced apoptosis likely in an angiotensin-dependent manner.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 8
    In: Fish Physiology and Biochemistry, Springer Science and Business Media LLC
    Abstract: Pikeperch ( Sander lucioperca ) is a freshwater species and an internationally highly demanded fish in aquaculture. Despite intensive research efforts on this species, fundamental knowledge of skeletal muscle biology and structural characteristics is missing. Therefore, we conducted a comprehensive analysis of skeletal muscle parameters in adult pikeperch from two different origins, wild-caught specimens from a lake and those reared in a recirculating aquaculture system. The analyses comprised the biochemical characteristics (nucleic acid, protein content), enzyme activities (creatine kinase, lactate dehydrogenase, NADP-dependent isocitrate dehydrogenase), muscle-specific gene and protein expression (related to myofibre formation, regeneration and permanent growth, muscle structure), and muscle fibre structure. The findings reveal distinct differences between the skeletal muscle of wild and farmed pikeperch. Specifically, nucleic acid content, enzyme activity, and protein expression varied significantly. The higher enzyme activity observed in wild pikeperch suggests greater metabolically activity in their muscles. Conversely, farmed pikeperch indicated a potential for pronounced muscle growth. As the data on pikeperch skeletal muscle characteristics is sparse, the purpose of our study is to gain fundamental insights into the characteristics of adult pikeperch muscle. The presented data serve as a foundation for further research on percids’ muscle biology and have the potential to contribute to advancements and adaptations in aquaculture practices.
    Type of Medium: Online Resource
    ISSN: 0920-1742 , 1573-5168
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 2015453-7
    SSG: 21,3
    SSG: 12
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  • 9
    In: Cells, MDPI AG, Vol. 10, No. 5 ( 2021-05-14), p. 1204-
    Abstract: A stimulated renin-angiotensin system is known to promote oxidative stress, apoptosis, necrosis and fibrosis. Renin transcripts (renin-b; renin-c) encoding a cytosolic renin isoform have been discovered that may in contrast to the commonly known secretory renin (renin-a) exert protective effects Here, we analyzed the effect of renin-a and renin-b overexpression in H9c2 cardiomyoblasts on apoptosis and necrosis as well as on potential mechanisms involved in cell death processes. To mimic ischemic conditions, cells were exposed to glucose starvation, anoxia or combined oxygen–glucose deprivation (OGD) for 24 h. Under OGD, control cells exhibited markedly increased necrotic and apoptotic cell death accompanied by enhanced ROS accumulation, loss of mitochondrial membrane potential and decreased ATP levels. The effects of OGD on necrosis were exaggerated in renin-a cells, but markedly diminished in renin-b cells. However, with respect to apoptosis, the effects of OGD were almost completely abolished in renin-b cells but interestingly also moderately diminished in renin-a cells. Under glucose depletion we found opposing responses between renin-a and renin-b cells; while the rate of necrosis and apoptosis was aggravated in renin-a cells, it was attenuated in renin-b cells. Based on our results, strategies targeting the regulation of cytosolic renin-b as well as the identification of pathways involved in the protective effects of renin-b may be helpful to improve the treatment of ischemia-relevant diseases.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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  • 10
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-02-11)
    Abstract: Although the renin-angiotensin system usually promotes oxidative stress and cell death, renin transcripts have been discovered, whose transcription product may be cardioprotective. These transcripts encode a non-secretory renin isoform that is localized in the cytosol and within mitochondria. Here we tested the hypotheses that cytosolic renin [ren(2-9)] expression promotes cell survival under hypoxia and glucose depletion by preserving the mitochondrial membrane potential (∆Ψ m ) and mitigating the accumulation of ROS. To simulate ischemic insults, we exposed H9c2 cells to glucose deprivation, anoxia or to combined oxygen-glucose deprivation (OGD) for 24 hours and determined renin expression. Furthermore, H9c2 cells transfected with the empty pIRES vector (pIRES cells) or ren(2-9) cDNA-containing vector [ren(2-9) cells] were analyzed for cell death, ∆Ψ m , ATP levels, accumulation of ROS, and cytosolic Ca 2+ content. In pIRES cells, expression of ren(1A-9) was stimulated under all three ischemia-related conditions. After OGD, the cells lost their ∆Ψ m and exhibited enhanced ROS accumulation, increased cytosolic Ca 2+ levels, decreased ATP levels as well as increased cell death. In contrast, ren(2-9) cells were markedly protected from these effects. Ren(2-9) appears to represent a protective response to OGD by reducing ROS generation and preserving mitochondrial functions. Therefore, it is a promising new target for the prevention of ischemia-induced myocardial damage.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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