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  • 1
    Online Resource
    Online Resource
    Wiley ; 2021
    In:  The FEBS Journal Vol. 288, No. 4 ( 2021-02), p. 1387-1406
    In: The FEBS Journal, Wiley, Vol. 288, No. 4 ( 2021-02), p. 1387-1406
    Abstract: After 300 million years of evolution, the first land‐living mammals reentered the marine environment some 50 million years ago. The driving forces for this dramatic lifestyle change are still a matter of discussion but the struggle for food resources and the opportunity to escape predators probably contributed. Reentering the oceans requires metabolic adaption putting evolutionary pressure on a number of genes. To explore whether eicosanoid signaling has been part of this adaptive response, we first explored whether the genomes of marine mammals involve functional genes encoding for key enzymes of eicosanoid biosynthesis. Cyclooxygenase (COX) and lipoxygenase (ALOX) genes are present in the genome of all marine mammals tested. Interestingly, ALOX12B, which has been implicated in skin development of land‐living mammals, is lacking in whales and dolphins and genes encoding for its sister enzyme (ALOXE3) involve premature stop codons and/or frameshifting point mutations, which interrupt the open reading frames. ALOX15 orthologs have been detected in all marine mammals, and the recombinant enzymes exhibit similar catalytic properties as those of land‐living species. All marine mammals express arachidonic acid 12‐lipoxygenating ALOX15 orthologs, and these data are consistent with the Evolutionary Hypothesis of ALOX15 specificity. These enzymes exhibit membrane oxygenase activity and introduction of big amino acids at the triad positions altered the reaction specificity in favor of arachidonic acid 15‐lipoxygenation. Thus, the ALOX15 orthologs of marine mammals follow the Triad concept explaining their catalytic specificity.
    Type of Medium: Online Resource
    ISSN: 1742-464X , 1742-4658
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2172518-4
    SSG: 12
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  • 2
    In: Nordic Journal of Botany, Wiley, Vol. 25, No. 5-6 ( 2007-12), p. 366-371
    Abstract: In a pilot study presented here, the genetic diversity of Dryopteris dilatata in relation to the history of forest stands in the Western Bavarian Forest, Germany, was investigated using random amplified polymorphic DNA (RAPD) analysis. We selected three ancient and three recent sites, which were classified for age considering historical maps, stand age, vegetation composition and charcoal analysis. RAPD analysis of 118 individuals with ten primers resulted in 81 fragments. Mean genetic diversity, measured as percentage of polymorphic bands and Nei's gene diversity, was higher in ancient than in recent forests. Furthermore, we detected a higher total number of genotypes and more unique genotypes in ancient than in recent forests. An analysis of molecular variance (AMOVA) revealed significant genetic variation between the populations in the differently aged forests (6%), the populations within the forests (9%) and a high variation (85%) within populations. Populations from ancient forests were clearly differentiated from each other (14%), while populations from recent forests exhibited no significant differences (0%). Thus, forest history seems to have an impact both on genetic differentiation between and on diversity within populations of forest plants. In conclusion, the combination of population genetics and palaeoecology is a promising approach to analyse the impact of historical events on the genetic structure of plant populations.
    Type of Medium: Online Resource
    ISSN: 0107-055X , 1756-1051
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2007
    detail.hit.zdb_id: 2406507-9
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Wiley ; 2021
    In:  Diversity and Distributions Vol. 27, No. 3 ( 2021-03), p. 392-401
    In: Diversity and Distributions, Wiley, Vol. 27, No. 3 ( 2021-03), p. 392-401
    Abstract: Empirical studies have often reported parallel patterns of genetic and species diversity, but the strength and generality of this association, as well as its origin, are still debated. Particularly in human‐dominated landscapes with complex histories of land use histories, more complicated and partly diverging patterns have been observed. In this study, we examine whether species and genetic diversity correlate across grasslands with different levels of land use pressure and spatial differentiation in habitat quality and heterogeneity. Location We selected eight extensively used (grazed, unfertilized) dry grasslands and eight intensively used (mown, fertilized) hay meadows in southeastern Germany. Methods We used vegetation surveys and molecular markers of six widespread dry grassland and six hay meadow plant species to compare species and genetic alpha and beta diversity between the two grassland types. Results Species diversity patterns expectedly showed higher alpha diversity, stronger spatial structure and less turnover in dry grasslands than in hay meadows. Neither of the corresponding genetic diversity patterns showed the same significant trends. Main conclusion Our results question the idea that species and genetic diversity patterns will always show similar patterns. Likely, genetic and species diversity emerge partly from shared, partly from different processes, including the regional species pool, environmental heterogeneity, fragmentation and land use history. The practical conservation implication is that species and genetic diversity are not generally interchangeable. Looking at species and genetic patterns together, however, may eventually lead to a better understanding of the complex processes that shape the structure and dynamics of ecological communities.
    Type of Medium: Online Resource
    ISSN: 1366-9516 , 1472-4642
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2020139-4
    detail.hit.zdb_id: 1443181-6
    SSG: 12
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  • 4
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 9 ( 2018-10-26)
    Type of Medium: Online Resource
    ISSN: 1664-0640
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2564218-2
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  • 5
    In: Endocrine Abstracts, Bioscientifica, ( 2021-05-15)
    Type of Medium: Online Resource
    ISSN: 1479-6848
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2021
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  • 6
    In: Endocrine Abstracts, Bioscientifica, ( 2023-05-02)
    Type of Medium: Online Resource
    ISSN: 1479-6848
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2023
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  • 7
    In: Biomedicines, MDPI AG, Vol. 10, No. 6 ( 2022-06-10), p. 1379-
    Abstract: Mammalian arachidonic acid lipoxygenases (ALOXs) have been implicated in cell differentiation and in the pathogenesis of inflammation. The mouse genome involves seven functional Alox genes and the encoded enzymes share a high degree of amino acid conservation with their human orthologs. There are, however, functional differences between mouse and human ALOX orthologs. Human ALOX15B oxygenates arachidonic acid exclusively to its 15-hydroperoxy derivative (15S-HpETE), whereas 8S-HpETE is dominantly formed by mouse Alox15b. The structural basis for this functional difference has been explored and in vitro mutagenesis humanized the reaction specificity of the mouse enzyme. To explore whether this mutagenesis strategy may also humanize the reaction specificity of mouse Alox15b in vivo, we created Alox15b knock-in mice expressing the arachidonic acid 15-lipoxygenating Tyr603Asp+His604Val double mutant instead of the 8-lipoxygenating wildtype enzyme. These mice are fertile, display slightly modified plasma oxylipidomes and develop normally up to an age of 24 weeks. At later developmental stages, male Alox15b-KI mice gain significantly less body weight than outbred wildtype controls, but this effect was not observed for female individuals. To explore the possible reasons for the observed gender-specific growth arrest, we determined the basic hematological parameters and found that aged male Alox15b-KI mice exhibited significantly attenuated red blood cell parameters (erythrocyte counts, hematocrit, hemoglobin). Here again, these differences were not observed in female individuals. These data suggest that humanization of the reaction specificity of mouse Alox15b impairs the functionality of the hematopoietic system in males, which is paralleled by a premature growth arrest.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-4-21)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-4-21)
    Abstract: Arachidonic acid lipoxygenases (ALOXs) have been implicated in the immune response of mammals. The reaction specificity of these enzymes is decisive for their biological functions and ALOX classification is based on this enzyme property. Comparing the amino acid sequences and the functional properties of selected mammalian ALOX15 orthologs we previously hypothesized that the reaction specificity of these enzymes can be predicted based on their amino acid sequences (Triad Concept) and that mammals, which are ranked in evolution below gibbons, express arachidonic acid 12-lipoxygenating ALOX15 orthologs. In contrast, Hominidae involving the great apes and humans possess 15-lipoxygenating enzymes (Evolutionary Hypothesis). These two hypotheses were based on sequence data of some 60 mammalian ALOX15 orthologs and about half of them were functionally characterized. Here, we compared the ALOX15 sequences of 152 mammals representing all major mammalian subclades expressed 44 novel ALOX15 orthologs and performed extensive mutagenesis studies of their triad determinants. We found that ALOX15 genes are absent in extant Prototheria but that corresponding enzymes frequently occur in Metatheria and Eutheria . More than 90% of them catalyze arachidonic acid 12-lipoxygenation and the Triad Concept is applicable to all of them. Mammals ranked in evolution above gibbons express arachidonic acid 15-lipoxygenating ALOX15 orthologs but enzymes with similar specificity are only present in less than 5% of mammals ranked below gibbons. This data suggests that ALOX15 orthologs have been introduced during Prototheria - Metatheria transition and put the Triad Concept and the Evolutionary Hypothesis on a much broader and more reliable experimental basis.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2018
    In:  Biodiversity and Conservation Vol. 27, No. 8 ( 2018-7), p. 2021-2028
    In: Biodiversity and Conservation, Springer Science and Business Media LLC, Vol. 27, No. 8 ( 2018-7), p. 2021-2028
    Type of Medium: Online Resource
    ISSN: 0960-3115 , 1572-9710
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2000787-5
    SSG: 12
    SSG: 23
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  • 10
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: A. Huebner: None. S. Thirumalasetty: None. T. Schubert: None. R. Naumann: None. I. Reichardt: None. M. Rohm: None. D. Landgraf: None. F. Gembardt: None. M.F. Hartmann: None. S.A. Wudy: None. M. Peitzsch: None. N. Reisch: None. K. Koehler, PhD: None. 21-hydroxylase deficiency (21OHD) is the most common form of congenital adrenal hyperplasia (CAH) and is caused by mutations in the CYP21A2 gene. 21OHD causes a wide array of clinical symptoms that result from gluco- and mineralocorticoid deficiency and adrenal androgen excess. Treatment firstly aims to substitute lacking steroid hormones, and secondly to restore negative feedback towards CRH and pituitary ACTH secretion to diminish adrenal androgen overproduction. In most cases supra-physiological glucocorticoid doses are necessary which may cause short stature, obesity, hypertension, and cardiovascular and metabolic co-morbidity with reduced quality of life. Hence, current steroid substitution regimens have significant limitations, so novel therapeutic strategies are required. In recent years new therapeutic approaches have emerged including new non-glucocorticoid substances interfering with the HPA axis to minimize adrenal androgen production and to lower external glucocorticoid substitution to physiological levels. However, valuable in-vivo models for pre-clinical testing of such drugs are lacking. Here we present the first viable and humanized mouse model in which the mouse gene Cyp21a1 is replaced by the human orthologue CYP21A2 in which the human point mutation R484Q is integrated. Twenty-weeks-old homozygous mice show marked adrenal hyperplasia, enhanced expression of the CYP21A2 gene and a weak increase of Cyp11a1 and Cyp11b2 gene expression. Tandem mass spectrometry measurements of the mice plasma at 20 weeks show decreased corticosterone and 11-deoxycorticosterone levels in the presence of increased ACTH levels in both male and female homozygous animals. Progesterone levels in homozygous mice are significantly higher (p & lt;0.01) than in wildtype mice. We also observed increased aldosterone levels in female mutants whereas blood pressure does not differ between wildtype and mutant mice strains. Histologically, mutants exhibit adrenocortical hyperplasia. While mutant male mice are fertile with normal appearing testes, females are infertile, remain in the diestrus phase and present with a reduced number of ovarian follicles. In parallel, a second mouse strain bearing the I173N mutation was developed. This mutation is frequent in human patients causing simple virilizing or rarely salt wasting CAH. Homozygous mice require dexamethasone treatment during pregnancy and until weaning but are viable without treatment afterwards. Preliminary results show adrenal hyperplasia and alteration in steroidogenic gene expression and steroid profiles. In conclusion, we demonstrate that the humanized mutant CYP21A2 mice may represent an excellent animal CAH model to test novel treatment strategies for CAH patients. We believe that this model(s) will facilitate the transition from basic research into clinical application. Presentation: Saturday, June 17, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2881023-5
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