Project description:Approximately 20% of sleeping sickness patients exhibit respiratory complications which are commonly attributed to secondary bacterial infections, with an unknown role of the parasite. Using a Glossina morsitans tsetse fly initiated Trypansoma brucei infection in mice we found that parasites rapidly and permanently colonize the lungs, representing one of the major target organs next to the adipose tissue. Trypanosomes were found by immunofluorescence staining and scanning electron microscopy to occupy the extravascular spaces surrounding the blood vessels of the alveoli and bronchi. Parasites were even found in the lung cartilage. Trypanosomes were often observed as nests of multiplying parasites exhibiting close interactions with collagen and highly active secretion of extracellular vesicles that are engaged in intercellular communication. The local immune response was analysed by flow cytometry after 10 and 21 days of infection and was characterized by a substantial increase of CD11b+ Ly6C+ monocytes, CD11b+ Ly6C+ F4/80+ macrophages and CD11b+ CD11c+ dendritic cells. CD11b+ Ly6G+ neutrophils only accumulated prominently at the late infection time point. Interestingly, parasite presence resulted in a significant reduction of B220+ IgM+ B cells, CD11b+ CD11clo/- SiglecF+ eosinophils and TcR-β- NK1.1+ natural killer cells. Digital transcriptomics revealed infection-induced upregulation of Il-10, IFN-ɣ- and IFN-α-responses, IL-2-, IL-6- and TNF-signalling, a Th1 pro-inflammatory signature, negative immune checkpoint regulators and a predominant M1 macrophage polarization. Il12a and genes associated with complement and the B cell receptor were downregulated. No infection-associated pulmonary dysfunction could be detected by in vivo lung function measurements, mirroring the limited pulmonary complications during sleeping sickness. However, the substantial reduction of eosinophils, B cells and NK cells may render individuals more susceptible to opportunistic infections. Collectively, these observations provide essential insights in the peculiar parasite biology, immunological reactions and physiological function of a largely overlooked target organ which may trigger new diagnostic approaches for sleeping sickness.
Project description:BACKGROUND:Certainty of paternity is considered an important factor in the evolution of paternal care. Several meta-analyses across birds support this idea, particularly for species with altricial young. However, the role of certainty of paternity in the evolution and maintenance of exclusive paternal care in the black coucal (Centropus grillii), which is the only known altricial bird species with male-only care, is not well understood. Here we investigated whether the differences in levels of paternal care in the black coucal and its sympatric congener, the bi-parental white-browed coucal (Centropus superciliosus), are shaped by extra-pair paternity. RESULTS:We found that male black coucals experienced a substantially higher loss of paternity than white-browed coucals. Further, unlike any previously reported bird species, extra-pair offspring in black coucals represented mainly the last hatchlings of the broods, and these last hatchlings were more likely to disappear during partial-brood loss. CONCLUSION:The results suggest that exclusive paternal care in black coucals is not maintained by male certainty of parentage, and extra-pair fertilizations are unlikely to be a female strategy for seeking 'good genes'. Extra-pair paternity in black coucals may reflect the inability of males to guard and copulate with the female after the onset of incubation, and a female strategy to demonstrate her commitment to other males of her social group.
Project description:Some South American poison frogs (Dendrobatidae) are chemically defended and use bright aposematic colors to warn potential predators of their unpalatability. Aposematic signals are often frequency-dependent where individuals deviating from a local model are at a higher risk of predation. However, extreme diversity in the aposematic signal has been documented in poison frogs, especially in Oophaga. Here, we explore the phylogeographic pattern among color-divergent populations of the Little Devil poison frog Oophaga sylvatica by analyzing population structure and genetic differentiation to evaluate which processes could account for color diversity within and among populations. With a combination of PCR amplicons (three mitochondrial and three nuclear markers) and genome-wide markers from a double-digested RAD (ddRAD) approach, we characterized the phylogenetic and genetic structure of 199 individuals from 13 populations (12 monomorphic and 1 polymorphic) across the O. sylvatica distribution. Individuals segregated into two main lineages by their northern or southern latitudinal distribution. A high level of genetic and phenotypic polymorphism within the northern lineage suggests ongoing gene flow. In contrast, low levels of genetic differentiation were detected among the southern lineage populations and support recent range expansions from populations in the northern lineage. We propose that a combination of climatic gradients and structured landscapes might be promoting gene flow and phylogenetic diversification. Alternatively, we cannot rule out that the observed phenotypic and genomic variations are the result of genetic drift on near or neutral alleles in a small number of genes.
Project description:An air embolism (AE) is a rare but dreaded complication during endovascular procedures. Current guidance recommends hyperbaric oxygen therapy and aspiration for the management of a venous AE. However, the management of an arterial AE is much less described. We report a case of a 79-year-old man with symptomatic mitral regurgitation who underwent a MitraClip procedure. During the intervention, a massive AE was detected in the ascending aorta on transesophageal echocardiography. The AE was successfully aspirated while the patient remained hemodynamically stable. This report demonstrates the efficacy of an arterial AE's aspiration with a real-time echocardiography recording of the technique.
Project description:The Tasmanian devil (Sarcophilus harrisii) is endangered due to the spread of Devil Facial Tumour Disease (DFTD), a contagious cancer with no current treatment options. Here we test whether seven recently characterized Tasmanian devil cathelicidins are involved in cancer regulation. We measured DFTD cell viability in vitro following incubation with each of the seven peptides and describe the effect of each on gene expression in treated cells. Four cathelicidins (Saha-CATH3, 4, 5 and 6) were toxic to DFTD cells and caused general signs of cellular stress. The most toxic peptide (Saha-CATH5) also suppressed the ERBB and YAP1/TAZ signaling pathways, both of which have been identified as important drivers of cancer proliferation. Three cathelicidins induced inflammatory pathways in DFTD cells that may potentially recruit immune cells in vivo. This study suggests that devil cathelicidins have some anti-cancer and inflammatory functions and should be explored further to determine whether they have potential as treatment leads.
Project description:The Tasmanian devil (Sarcophilus harrisii) was widespread in Australia during the Late Pleistocene but is now endemic to the island of Tasmania. Low genetic diversity combined with the spread of devil facial tumour disease have raised concerns for the species' long-term survival. Here, we investigate the origin of low genetic diversity by inferring the species' demographic history using temporal sampling with summary statistics, full-likelihood and approximate Bayesian computation methods. Our results show extensive population declines across Tasmania correlating with environmental changes around the last glacial maximum and following unstable climate related to increased 'El Niño-Southern Oscillation' activity.
Project description:The ability to recognize and respond to universal molecular patterns on invading microorganisms allows our immune system to stay on high alert, sensing danger to our self-integrity. Our own damaged cells and tissues in pathological situations activate similar warning systems as microbes. In this way, the body is able to mount a response that is appropriate to the danger. Toll-like receptors are at the heart of this pattern recognition system that initiates innate pro-oxidant, pro-inflammatory signaling cascades and ultimately bridges recognition of danger to adaptive immunity. The acute inflammatory lesions that are formed segue into resolution of inflammation, repair and healing or, more dysfunctionally, into chronic inflammation, autoimmunity, excessive tissue damage and carcinogenesis. Redox is at the nexus of this decision making process and is the point at which ionizing radiation initially intercepts to trigger similar responses to self-damage. In this review we discuss our current understanding of how radiation-damaged cells interact with Toll-like receptors and how the immune systems interprets these radiation-induced danger signals in the context of whole-body exposures and during local tumor irradiation.
Project description:Recent findings suggest that sleep might serve a role in emotional coping. However, most findings are based on subjective reports of sleep quality, while the relation with underlying sleep physiology is still largely unknown. In this study, the impact of an emotionally distressing experience on the EEG correlates of sleep was assessed. In addition, the association between sleep physiological parameters and the extent of emotional attenuation over sleep was determined. The experimental set up involved presentation of an emotionally neutral or distressing film fragment in the evening, followed by polysomnographic registration of undisturbed, whole-night sleep and assessment of emotional reactivity to film cues on the next evening. We found that emotional distress induced mild sleep deterioration, but also an increase in the proportion of slow wave sleep (SWS) and altered patterning of rapid eye movement (REM) sleep. Indeed, while REM sleep occurrence normally increases over the course of the night, emotional distress flattened this distribution and correlated with an increased number of REM periods. While sleep deterioration was negatively associated to emotional attenuation over sleep, the SWS response was positively related to such attenuation and may form part of a compensatory response to the stressor. Interestingly, trait-like SWS characteristics also correlated positively with the extent of emotion attenuation over sleep. The combined results provide strong evidence for an intimate reciprocal relation between sleep physiology and emotional processing. Moreover, individual differences in subjects' emotional and sleep responses suggest there may be a coupling of certain emotion and sleep traits into distinct emotional sleep types.