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Intensified exploration of sub-Saharan Africa during the 18th and 19th centuries led to many newly described giraffe subspecies. Several populations described at that time are now extinct, which is problematic for a full understanding of giraffe taxonomy. In this study, we provide mitochondrial sequences for 41 giraffes, including 19 museum specimens of high importance to resolve giraffe taxonomy, such as Zarafa from Sennar and two giraffes from Abyssinia (subspecies camelopardalis), three of the first southern individuals collected by Levaillant and Delalande (subspecies capensis), topotypes of the former subspecies congoensis and cottoni, and giraffes from an extinct population in Senegal. Our phylogeographic analysis shows that no representative of the nominate subspecies camelopardalis was included in previous molecular studies, as Zarafa and two other specimens assigned to this taxon are characterized by a divergent haplogroup, that the former subspecies congoensis and cottoni should be treated as synonyms of antiquorum, and that the subspecies angolensis and capensis should be synonymized with giraffa, whereas the subspecies wardi should be rehabilitated. In addition, we found evidence for the existence of a previously unknown subspecies from Senegal (newly described in this study), which is now extinct. Based on these results, we propose a new classification of giraffes recognizing three species and 10 subspecies. According to our molecular dating estimates, the divergence among these taxa has been promoted by Pleistocene climatic changes resulting in either savannah expansion or the development of hydrographical networks (Zambezi, Nile, Lake Chad, Lake Victoria).
The present corrigendum corrects errors that occurred in: Petzold A., Magnant A.-S., Edderai D., Chardonnet B., Rigoulet J., Saint-Jalme M. & Hassanin A. 2020. First insights into past biodiversity of giraffes based on mitochondrial sequences from museum specimens. European Journal of Taxonomy 703: 1–33. https://doi.org/10.5852/ejt.2020.703
Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB. Methods: A total of 178 patients with metastatic UM treated with ICB were included in this analysis. Patients were recruited from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of hepatic metastasis, two cohorts were compared: patients with liver metastasis only (cohort A, n = 55) versus those with both liver and extra-hepatic metastasis (cohort B, n = 123). Data were analyzed in both cohorts for response to treatment, progression-free survival (PFS), and overall survival (OS). The survival and progression probabilities were calculated with the Kaplan–Meier method. Log-rank tests, χ2 tests, and t-tests were performed to detect significant differences between both cohorts. Results: The median OS of the overall population was 16 months (95% CI 13.4–23.7) and the median PFS, 2.8 months (95% CI 2.5–3.0). The median OS was longer in cohort B than in cohort A (18.2 vs. 6.1 months; p = 0.071). The best objective response rate to dual ICB was 13.8% and to anti-PD-1 monotherapy 8.9% in the entire population. Patients with liver metastases only had a lower response to dual ICB, yet without significance (cohort A 8.7% vs. cohort B 16.7%; p = 0.45). Adverse events (AE) occurred in 41.6%. Severe AE were observed in 26.3% and evenly distributed between both cohorts. Conclusion: The survival of this large cohort of patients with advanced UM was more favorable than reported in previous benchmark studies. Patients with both hepatic and extrahepatic metastasis showed more favorable survival and higher response to dual ICB than those with hepatic metastasis only.
Patients with type 2 diabetes (T2D) are threatened by excessive cardiovascular morbidity and mortality. While accelerated arterial stiffening may represent a critical mechanistic factor driving cardiovascular risk in T2D, specific therapies to contain the underlying diabetic arterial remodeling have been elusive. The present translational study investigates the role of microRNA-29b (miR-29b) as a driver and therapeutic target of diabetic aortic remodeling and stiffening. Using a murine model (db/db mice), as well as human aortic tissue samples, we find that diabetic aortic remodeling and stiffening is associated with medial fibrosis, as well as fragmentation of aortic elastic layers. miR-29b is significantly downregulated in T2D and miR-29b repression is sufficient to induce both aortic medial fibrosis and elastin breakdown through upregulation of its direct target genes COL1A1 and MMP2 thereby increasing aortic stiffness. Moreover, antioxidant treatment restores aortic miR-29b levels and counteracts diabetic aortic remodeling. Concluding, we identify miR-29b as a comprehensive—and therefore powerful—regulator of aortic remodeling and stiffening in T2D that moreover qualifies as a (redox-sensitive) target for therapeutic intervention.