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During the Miocene, Hyaenidae was a highly diverse family of Carnivora that has since been severely reduced to four species: the bone-cracking spotted, striped, and brown hyenas, and the specialized insectivorous aardwolf. Previous studies investigated the evolutionary histories of the spotted and brown hyenas, but little is known about the remaining two species. Moreover, the genomic underpinnings of scavenging and insectivory, defining traits of the extant species, remain elusive. Here, we generated an aardwolf genome and analyzed it together with the remaining three species to reveal their evolutionary relationships, genomic underpinnings of their scavenging and insectivorous lifestyles, and their respective genetic diversities and demographic histories. High levels of phylogenetic discordance suggest gene flow between the aardwolf lineage and the ancestral brown/striped hyena lineage. Genes related to immunity and digestion in the bone-cracking hyenas and craniofacial development in the aardwolf showed the strongest signals of selection, suggesting putative key adaptations to carrion and termite feeding, respectively. A family-wide expansion in olfactory receptor genes suggests that an acute sense of smell was a key early adaptation. Finally, we report very low levels of genetic diversity within the brown and striped hyenas despite no signs of inbreeding, putatively linked to their similarly slow decline in effective population size over the last ∼2 million years. High levels of genetic diversity and more stable population sizes through time are seen in the spotted hyena and aardwolf. Taken together, our findings highlight how ecological specialization can impact the evolutionary history, demographics, and adaptive genetic changes of an evolutionary lineage.

Background A neuroimmune crosstalk between dendritic cells (DCs) and airway nerves in the lung has recently been reported. However, the presence of DCs in airway sensory ganglia under normal and allergic conditions has not been explored so far. Therefore, this study aims to investigate the localisation, distribution and proliferation of DCs in airway sensory ganglia under allergic airway inflammation. Methods Using the house dust mite (HDM) model for allergic airway inflammation BALB/c mice were exposed to HDM extract intranasally (25 μg/50 μl) for 5 consecutive days a week over 7 weeks. With the help of the immunohistochemistry, vagal jugular-nodose ganglia complex (JNC) sections were analysed regarding their expression of DC-markers (MHC II, CD11c, CD103), the neuronal marker PGP 9.5 and the neuropeptide calcitonin gene-related peptide (CGRP) and glutamine synthetase (GS) as a marker for satellite glia cells (SGCs). To address the original source of DCs in sensory ganglia, a proliferation experiment was also carried in this study. Results Immune cells with characteristic DC-phenotype were found to be closely located to SGCs and vagal sensory neurons under physiological conditions. The percentage of DCs in relation to neurons was significantly increased by allergic airway inflammation in comparison to the controls (HDM 51.38 ± 2.38% vs. control 28.16 ± 2.86%, p < 0.001). The present study also demonstrated that DCs were shown to proliferate in jugular-nodose ganglia, however, the proliferation rate of DCs is not significantly changed in the two treated animal groups (proliferating DCs/ total DCs: HDM 0.89 ± 0.38%, vs. control 1.19 ± 0.54%, p = 0.68). Also, increased number of CGRP-positive neurons was found in JNC after allergic sensitisation and challenge (HDM 31.16 ± 5.41% vs. control 7.16 ± 1.53%, p < 0.001). Conclusion The present findings suggest that DCs may migrate from outside into the ganglia to interact with sensory neurons enhancing or protecting the allergic airway inflammation. The increase of DCs as well as CGRP-positive neurons in airway ganglia by allergic airway inflammation indicate that intraganglionic DCs and neurons expressing CGRP may contribute to the pathogenesis of bronchial asthma. To understand this neuroimmune interaction in allergic airway inflammation further functional experiments should be carried out in future studies.

Background. Cutaneous leishmaniasis (CL) is a disfiguring but not life-threatening disease. Because antileishmanial drugs are potentially toxic, the World Health Organization (WHO) recommends simple wound care or local therapy as first-line treatment, followed or replaced by systemic therapy if local therapy fails or cannot be performed. Methods. To determine the feasibility and impact of the recommended approach, we analyzed the results of a centralized referral treatment program in 135 patients with parasitologically proven CL. Results. Infections involved 10 Leishmania species and were contracted in 29 different countries. Eighty-four of 135 patients (62%) were initially treated without systemic therapy. Of 109 patients with evaluable charts, 23 of 25 (92%) treated with simple wound care and 37 of 47 (79%) treated with local antileishmanial therapy were cured by days 42–60. In 37 patients with large or complex lesions, or preexisting morbidities, or who had not been cured with local therapy, the cure rate with systemic antileishmanial agents was 60%. Systemic adverse events were observed in 15 patients, all receiving systemic therapy. Conclusions. In this population of CL patients displaying variable degrees of complexity and severity, almost two-thirds of patients could be initially managed without systemic therapy. Of these, 60 were cured before day 60. The WHO-recommended stepwise approach favoring initial local therapy therefore resulted in at least 44% of all patients being cured without exposure to the risk of systemic adverse events. Efforts are needed to further simplify local therapy of CL and to improve the management of patients with complex lesions and/or preexisting comorbidities.

Human bone marrow‐derived mesenchymal stem/stromal cells (BM‐MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes mellitus (T2DM), but the results of autologous BM‐MSC administration in T2DM patients are contradictory. The purpose of this study was to test the hypothesis that autologous BM‐MSC administration in T2DM patient is safe and that the efficacy of the treatment is dependant on the quality of the autologous BM‐MSC population and administration routes. T2DM patients were enrolled, randomly assigned (1:1) by a computer‐based system into the intravenous and dorsal pancreatic arterial groups. The safety was assessed in all the treated patients, and the efficacy was evaluated based on the absolute changes in the hemoglobin A1c, fasting blood glucose, and C‐peptide levels throughout the 12‐month follow‐up. Our data indicated that autologous BM‐MSC administration was well tolerated in 30 T2DM patients. Short‐term therapeutic effects were observed in patients with T2DM duration of <10 years and a body mass index <23, which is in line with the phenotypic analysis of the autologous BM‐MSC population. T2DM duration directly altered the proliferation rate of BM‐MSCs, abrogated the glycolysis and mitochondria respiration of BM‐MSCs, and induced the accumulation of mitochondria DNA mutation. Our data suggest that autologous administration of BM‐MSCs in the treatment of T2DM should be performed in patients with T2DM duration <10 years and no obesity. Prior to further confirming the effects of T2DM on BM‐MSC biology, future work with a larger cohort focusing on patients with different T2DM history is needed to understand the mechanism underlying our observation. Human bone marrow‐derived mesenchymal stem/stromal cells (BM‐MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes, but the results of autologous BM‐MSC admniistration in T2DM patients are contradicted. Our data indicated that autologous BM‐MSC administration was well tolerated in 30 T2DM patients. The potential therapeutic effects of the treatments were observed in patients with less than 10 years of T2DM and a BMI<23, and this finding could be explained by reductions in autologous stem cell phenotypes, including prolonged cell proliferation, reduced metabolic functions, and alterations in mtDNA.