Rapid radiation of treponema pallidum pertenue in wild non-human primates

Bacteria of the species Treponema pallidum are causative agents of venereal syphilis (Treponema pallidum pallidum), Bejel (T. p. endemicum), and yaws (T. p. pertenue) in humans. We documented Treponema pallidum infections associated with disease in wild sooty mangabeys (Cercocebus atys) in Taï National Park, Côte d’Ivoire, and green monkeys (Chlorocebus sabaeus) from Bijilo Forest Park, Gambia and Niokolo-Koba National Park, Senegal. To examine the evolutionary relatedness of these treponemes to those responsible for diseases in humans and for previously documented infections in baboons (Papio papio), we conducted a hybridization capture experiment to enrich Treponema pallidum DNA from samples collected from symptomatic individuals. This approach allowed us to sequence the full genomes of Treponema pallidum strains infecting sooty mangabeys (n = 2) and green monkeys (n = 4). Phylogenomic analyses revealed that all Treponema pallidum strains infecting non-human primates are most closely related to the sub-species T. p. pertenue. Strains infecting humans and non-human primates do not appear to be reciprocally monophyletic. The star-like phylogenetic branching pattern of the T. p. pertenue clade, with short basal branches receiving low statistical support, suggests a rapid initial radiation across humans and non-human primates. These results greatly broaden the known host range of T.p. pertenue and suggest the existence of a vast zoonotic reservoir that could possibly contribute to the failure of global eradication efforts

Circulating pancreatic cancer exosomal RNAs for detection of pancreatic cancer

Diagnostic biomarkers for the early diagnosis of pancreatic cancer are needed to improve prognosis for this disease. The aim of this study was to investigate differences in the expression of four messenger RNAs (mRNAs: CCDC88A, ARF6, Vav3, and WASF2) and five small nucleolar RNAs (snoRNAs: SNORA14B, SNORA18, SNORA25, SNORA74A, and SNORD22) in serum of patients with pancreatic cancer and control participants for use in the diagnosis of pancreatic cancer. Results were compared with the expression of sialylated Lewis (a) blood group antigen CA19‐9, the standard clinical tumor biomarker. Reverse transcription quantitative real‐time PCR showed that all of the mRNAs and snoRNAs, except CCDC88A, were encapsulated in exosomes and secreted from cultured pancreatic cancer cells, and present in cell culture medium. In a discovery‐stage clinical study involving 27 pancreatic cancer patients and 13 controls, the area under the receiver operating characteristic curve (AUC) of two mRNAs (WASF2 and ARF6) and two snoRNAs (SNORA74A and SNORA25) was > 0.9 for distinguishing pancreatic cancer patients from controls; the AUC of CA19‐9 was 0.897. Comparing serum levels of WASF2, ARF6, SNORA74A, SNORA25, and CA19‐9 revealed that levels of WASF2 were the most highly correlated with the risk of pancreatic cancer. The AUCs of WASF2, ARF6, SNORA74A, and SNORA25 in serum from patients in the early stages of pancreatic cancer (stages 0, I, and IIA) were > 0.9, compared with an AUC of 0.93 for the level of CA19‐9. The results of this study suggest that WASF2, ARF6, SNORA74A, and SNORA25 may be useful tools for the early detection of pancreatic cancer. Monitoring serum levels of WASF2 mRNA may be particularly useful, as it was the most highly correlated with pancreatic cancer risk

Additional file 1: Figure S1. of CCDC88A, a prognostic factor for human pancreatic cancers, promotes the motility and invasiveness of pancreatic cancer cells

Roles of CCDC88A in the formation of cell protrusions in PANC-1 cells. a. Confocal Z stack images of PANC-1 cells that were transiently transfected with scrambled control-siRNA (Scr) or CCDC88A-siRNA (siCCDC88A). The transfected cells were incubated on fibronectin, and were subsequently stained with anti-CCDC88A antibody (green) and phalloidin (red). The lower and right panels in the confocal Z stack show a vertical cross-section (yellow lines) through the cells. Arrows, peripheral actin structures in cell protrusions of control-siRNA transfected cells. Blue, nuclear DAPI staining. Bars, 10 μm. b. Quantification of the data shown in Figure S1a. Columns, mean; bars, SD. *p < 0.001 compared with Scr-transfected controls (Student’s t-test). c. Confocal immunofluorescence microscopic images of PANC-1 cells that had been transfected with CCDC88A-siRNA and were subsequently transfected with a myc-tagged CCDC88A-rescue construct. After 48 h, the cells were incubated on fibronectin. Cells were stained with anti-myc antibody (green), anti-CCDC88A antibody (red) and phalloidin (violet). Arrows, cell protrusions reproduced by myc-tagged CCDC88A in CCDC88A-siRNA transfected cells. Bars, 10 μm. d. Quantification of the data shown in Figure S1c; the values represent the number of cells with fibronectin-mediated cell protrusions in which peripheral actin structures were increased. All cells in four fields per group were scored. Data are derived from three independent experiments. Columns, mean; bars, SD. *p < 0.001 compared with corresponding CCDC88A-siRNA transfected PANC-1 cells that were transfected with mock vector (Student’s t-test). e. Confocal Z stack images showing nuclear DAPI staining (blue) and the accumulation of myc-tagged CCDC88A (green) in fibronectin-stimulated CCDC88A-siRNA transfected PANC-1 cells transfected with the myc-tagged CCDC88A-rescue construct. Arrows, myc-tagged CCDC88A accumulated in cell protrusions. The lower and right panels of the confocal Z stack show a vertical cross-section (yellow lines) through the cells. Bar, 10 μm. (DOCX 1733 kb