34 research outputs found

    Characterising the phenotypic diversity of Papilio dardanus wing patterns using an extensive museum collection

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    The history of 20th Century evolutionary biology can be followed through the study of mimetic butterflies. From the initial findings of discontinuous polymorphism through the debates regarding the evolution of mimicry and the step-size of evolutionary change, to the studies on supergene evolution and molecular characterisation of butterfly genomes, mimetic butterflies have been at the heart of evolutionary thought for over 100 years. During this time, few species have received as much attention and in-depth study as Papilio dardanus. To assist all aspects of mimicry research, we present a complete data-derived overview of the extent of polymorphism within this species. Using historical samples permanently held by the NHM London, we document the extent of phenotypic variation and characterise the diversity present in each of the subspecies and how it varies across Africa. We also demonstrate an association between “imperfect” mimetic forms and the transitional race formed in the area where Eastern and Western African populations meet around Lake Victoria. We present a novel portal for access to this collection, www.mimeticbutterflies.org, allowing remote access to this unique repository. It is hoped that this online resource can act as a nucleus for the sharing and dissemination of other collections databases and imagery connected with mimetic butterflies

    α2-Macroglobulin can crosslink multiple plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) molecules and may facilitate adhesion of parasitized erythrocytes

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    Rosetting, the adhesion of Plasmodium falciparum-infected erythrocytes to uninfected erythrocytes, involves clonal variants of the parasite protein P. falciparum erythrocyte membrane protein 1 (PfEMP1) and soluble serum factors. While rosetting is a well-known phenotypic marker of parasites associated with severe malaria, the reason for this association remains unclear, as do the molecular details of the interaction between the infected erythrocyte (IE) and the adhering erythrocytes. Here, we identify for the first time a single serum factor, the abundant serum protease inhibitor α2-macroglobulin (α2M), which is both required and sufficient for rosetting mediated by the PfEMP1 protein HB3VAR06 and some other rosette-mediating PfEMP1 proteins. We map the α2M binding site to the C terminal end of HB3VAR06, and demonstrate that α2M can bind at least four HB3VAR06 proteins, plausibly augmenting their combined avidity for host receptors. IgM has previously been identified as a rosette-facilitating soluble factor that acts in a similar way, but it cannot induce rosetting on its own. This is in contrast to α2M and probably due to the more limited cross-linking potential of IgM. Nevertheless, we show that IgM works synergistically with α2M and markedly lowers the concentration of α2M required for rosetting. Finally, HB3VAR06+ IEs share the capacity to bind α2M with subsets of genotypically distinct P. falciparum isolates forming rosettes in vitro and of patient parasite isolates ex vivo. Together, our results are evidence that P. falciparum parasites exploit α2M (and IgM) to expand the repertoire of host receptors available for PfEMP1-mediated IE adhesion, such as the erythrocyte carbohydrate moieties that lead to formation of rosettes. It is likely that this mechanism also affects IE adhesion to receptors on vascular endothelium. The study opens opportunities for broad-ranging immunological interventions targeting the α2M--(and IgM-) binding domains of PfEMP1, which would be independent of the host receptor specificity of clinically important PfEMP1 antigens

    Isolated leptomeningeal carcinomatosis and possible fungal meningitis as late sequelae of oesophageal adenocarcinoma

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    We describe a case of a 67-year-old man with known chronic obstructive pulmonary disease, type 2 diabetes mellitus, hypertension, osteoarthritis, previous history of excess alcohol intake, and oesophagectomy 3 years earlier for T3N0 adenocarcinoma, referred by his general practitioner with confusion, weight loss and several recent falls. CT of the chest, abdomen and pelvis revealed a right middle-lobe pulmonary embolism, while CT of the head revealed a communicating hydrocephalus. Lumbar puncture was performed, and empirical treatment for tuberculous and fungal meningitis was commenced. Unfortunately, he suffered a rapid neurological deterioration with markedly elevated cerebrospinal fluid (CSF) pressures, leading to an external ventricular drain. Cytological analysis of a CSF sample revealed a cellular infiltrate consistent with leptomeningeal carcinomatosis (adenocarcinoma), with the previous oesophageal malignancy the likely primary. He passed away 17 days after hospital admission. Prolonged culture of CSF later produced evidence of two distinct phaeomycotic moulds (Cladosporium sp and Exophiala sp), suggesting that fungal meningitis may also have contributed to the clinical picture

    Pathophysiology, clinical presentation, and treatment of coma and acute kidney injury complicating falciparum malaria

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    Cerebral impairment and acute kidney injury (AKI) are independent predictors of mortality in both adults and children with severe falciparum malaria. In this review, we present recent advances in understanding the pathophysiology, clinical features, and management of these complications of severe malaria, and discuss future areas of research.Cerebral malaria and AKI are serious and well recognized complications of severe malaria. Common pathophysiological pathways include impaired microcirculation, due to sequestration of parasitized erythrocytes, systemic inflammatory responses, and endothelial activation. Recent MRI studies show significant brain swelling in both adults and children with evidence of posterior reversible encephalopathy syndrome-like syndrome although targeted interventions including mannitol and dexamethasone are not beneficial. Recent work shows association of cell-free hemoglobin oxidation stress involved in the pathophysiology of AKI in both adults and children. Paracetamol protected renal function likely by inhibiting cell-free-mediated oxidative stress. It is unclear if heme-mediated endothelial activation or oxidative stress is involved in cerebral malaria.The direct causes of cerebral and kidney dysfunction remain incompletely understood. Optimal treatment involves prompt diagnosis and effective antimalarial treatment with artesunate. Renal replacement therapy reduces mortality in AKI but delayed diagnosis is an issue

    An unusual cause of a right nasal mass in a 73-year-old male

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    We report a case of a 73-year-old male presenting with a right nasal mass on a background of two years of constitutional symptoms. We outline an approach to the evaluation of nasal mass biopsies, which in this case led to the unusual diagnosis of myeloid sarcoma. This is a relatively rare neoplasm, representing an extra-medullary deposit of acute myeloid leukaemia (AML). The differential diagnosis of myeloid sarcoma is discussed, along with the clinical, histological and immunohistochemical findings that permit differentiation of this entity from more common malignancies seen at this site including carcinoma, non-Hodgkin lymphoma and melanoma

    Pathophysiology, clinical presentation, and treatment of coma and acute kidney injury complicating falciparum malaria

    No full text
    Cerebral impairment and acute kidney injury (AKI) are independent predictors of mortality in both adults and children with severe falciparum malaria. In this review, we present recent advances in understanding the pathophysiology, clinical features, and management of these complications of severe malaria, and discuss future areas of research.Cerebral malaria and AKI are serious and well recognized complications of severe malaria. Common pathophysiological pathways include impaired microcirculation, due to sequestration of parasitized erythrocytes, systemic inflammatory responses, and endothelial activation. Recent MRI studies show significant brain swelling in both adults and children with evidence of posterior reversible encephalopathy syndrome-like syndrome although targeted interventions including mannitol and dexamethasone are not beneficial. Recent work shows association of cell-free hemoglobin oxidation stress involved in the pathophysiology of AKI in both adults and children. Paracetamol protected renal function likely by inhibiting cell-free-mediated oxidative stress. It is unclear if heme-mediated endothelial activation or oxidative stress is involved in cerebral malaria.The direct causes of cerebral and kidney dysfunction remain incompletely understood. Optimal treatment involves prompt diagnosis and effective antimalarial treatment with artesunate. Renal replacement therapy reduces mortality in AKI but delayed diagnosis is an issue
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