Fibrocytes are increased in lung and peripheral blood of patients with idiopathic pulmonary fibrosis

Background: Fibrocytes are implicated in Idiopathic Pulmonary Fibrosis (IPF) pathogenesis and increased proportions in the circulation are associated with poor prognosis. Upon tissue injury, fibrocytes migrate to the affected organ. In IPF patients, circulating fibrocytes are increased especially during exacerbations, however fibrocytes in the lungs have not been examined. Therefore, we sought to evaluate if fibrocytes can be detected in IPF lungs and we compare percentages and phenotypic characteristics of lung fibrocytes with circulating fibrocytes in IPF. Methods: First we optimized flow cytometric detection circulating fibrocytes using a unique combination of intra- and extra-cellular markers to establish a solid gating strategy. Next we analyzed lung fibrocytes in single cell suspensions of explanted IPF and control lungs and compared characteristics and numbers with circulating fibrocytes of IPF. Results: Using a gating strategy for both circulating and lung fibrocytes, which excludes potentially contaminating cell populations (e.g. neutrophils and different leukocyte subsets), we show that patients with IPF have increased proportions of fibrocytes, not only in the circulation, but also in explanted end-stage IPF lungs. These lung fibrocytes have increased surface expression of HLA-DR, increased intracellular collagen-1 expression, and also altered forward and side scatter characteristics compared with their circulating counterparts. Conclusions: These findings demonstrate that lung fibrocytes in IPF patients can be quantified and characterized by flow cytometry. Lung fibrocytes have different characteristics than circulating fibrocytes and represent an intermediate cell population between circulating fibrocytes and lung fibroblast. Therefore, more insight in their phenotype might lead to specific therapeutic targeting in fibrotic lung diseases

Central role of dendritic cells in pulmonary arterial hypertension in human and mice

The pathogenesis of idiopathic pulmonary arterial hypertension (IPAH) is not fully under-stood, but evidence is accumulating tha

Molecular characteristics of carbapenemase-producing Enterobacterales in the Netherlands; results of the 2014–2018 national laboratory surveillance

Objectives: Carbapenem resistance mediated by mobile genetic elements has emerged worldwide and has become a major public health threat. To gain insight into the molecular epidemiology of carbapenem resistance in The Netherlands, Dutch medical microbiology laboratories are requested to submit suspected carbapenemase-producing Enterobacterales (CPE) to the National Institute for Public Health and the Environment as part of a national surveillance system. Methods: Meropenem MICs and species identification were confirmed by E-test and MALDI-TOF and carbapenemase production was assessed by the Carbapenem Inactivation Method. Of all submitted CPE, one species/carbapenemase gene combination per person per year was subjected to next-generation sequencing (NGS). Results: In total, 1838 unique isolates were received between 2014 and 2018, of which 892 were unique CPE isolates with NGS data available. The predominant CPE species were Klebsiella pneumoniae (n = 388, 43%), Escherichia coli (n = 264, 30%) and Enterobacter cloacae complex (n = 116, 13%). Various carbapenemase alleles of the same carbapenemase gene resulted in different susceptibilities to meropenem and this effect varied between species. Analyses of NGS data showed variation of prevalence of carbapenemase alleles over time with blaOXA-48 being predominant (38%, 336/892), followed by blaNDM-1 (16%, 145/892). For the first time in the Netherlands, blaOXA-181, blaOXA-232 and blaVIM-4 were detected. The genetic background of K. pneumoniae and E. coli isolates was highly diverse. Conclusions: The CPE population in the Netherlands is diverse, suggesting multiple introductions. The predominant carbapenemase alleles are blaOXA-48 and blaNDM-1. There was a clear association between species, carbapenemase allele and susceptibility to meropenem

Proterozoic crustal evolution in southcentral Fennoscandia

The Transscandinavian Igneous Belt (TIB) and the Eastern Segment of the Southwest Scandinavian Domain reflect advanced stages of continental growth within the Fennoscandian Shield. The relationship between the two units is not clear, mainly because N-S trending shear zones of the Protogine Zone transect the border zone. The main goal of this thesis has been to investigate rocks in the border zone and to conclude how these rocks differ from each other. In this work two volcanic sequences and 24 granitoids in the border area, near Jönköping, were examined. The thesis reports geochemical and Sm-Nd isotope data as well as U-Pb ion microprobe zircon dates for extrusive and intrusive rocks in the southwestern part of the TIB and intrusive rocks in the eastern part of the southern Eastern Segment. The TIB rocks are subdivided into TIB-0, TIB-1 and TIB-2 groups based on their ages. In this work, the Habo Volcanic Suite and the Malmbäck Formation are dated at 1795±13 Ma and 1796±7 Ma respectively, which establishes that they are part of the TIB-1 volcanic rocks. The Malmbäck Formation is situated in the southwestern part of TIB, east of the Protogine Zone, whereas the Habo Volcanic Suite is located c. 50 km northwest of the Malmbäck Formation, between shear zones of the Protogine Zone. Both suites comprise mafic to felsic components and the Malmbäck Formation includes one of the largest mafic volcanic rock units of the TIB-1. The Malmbäck Formation comprises fairly well preserved volcanic rocks, with primary textures, although mineral parageneses in some rocks suggest metamorphism at up to epidote-amphibolite facies conditions. Amphibolites facies metamorphism and deformation has largely obscured primary textures of the Habo Volcanic Suite. Dating of a Barnarp granite which intrudes the Habo Volcanic Suite gave an age of 1660±9 Ma, corresponding to TIB-2. The occurrences of Malmbäck Formation megaxenoliths within TIB-1 granitoids are explained by stoping. Geochemical signatures of the two metavolcanic rock suites suggest emplacement in an active continental margin setting. It is further suggested that the TIB regime was complex, similar to what is seen in the Andes today, with different regions characterised by subduction-related magmatism, Andinotype extension as well as local compression. Twenty-one granitoids (including the granite intruding the Habo Volcanic Suite), across and in the border zone between the TIB and the Eastern Segment, were dated by U-Pb zircon ion probe analysis. Eighteen of the granitoids yielded TIB-2 magmatic ages, ranging between 1710 and 1660 Ma. Eighteen granitoids were analyzed for geochemistry and Sm-Nd isotopes. The geochemical and isotopic signatures of the granitoids proved to be similar, supporting the theory that the TIB and the Eastern Segment originated from the same type of source and experienced the same type of emplacement mechanisms. Further, it is concluded that the TIB-2 granitoids, from both the TIB and the Eastern Segment, were derived by reworking of juvenile, pre-existing crust, in an essentially east- to northeast-directed subduction environment. The U-Pb zircon ion microprobe analyses also dated zircon rims which formed by metamorphism during the 1460-1400 Ma Hallandian-Danopolonian orogeny, in granitoids of both the southern Eastern Segment and the western TIB. Leucosome formation, for two samples was dated at 1443±9 Ma and 1437±6 Ma. An aplitic dyke, cross-cutting NW-SE to E-W folding and leucosome formation in the Eastern Segment was dated at 1383±4 Ma, which sets a minimum age for the NW-SE to E-W folding in the area. Hence, it is concluded that the leucosome formation and the NW-SE to E-W folding in the investigated part of the Eastern Segment as well as NW-SE to E-W penetrative foliation and lineation in the western TIB took place during the 1470-1400 Ma Hallandian-Danopolonian orogeny. No c. 970 Ma Sveconorwegian ages were recorded in any of the areas investigated. Nevertheless, Sveconorwegian (in addition to earlier) block movements caused uplift of the Eastern Segment relative to the TIB, revealing from west to east: (1) the highly exhumed metamorphosed southern Eastern Segment, in which the effects of both the Hallandian-Danopolonian and the Sveconorwegian orogenies can be seen, (2) the partly exhumed westernmost TIB-2 showing the effects of the Hallandian-Danopolonian orogeny only, and (3) the easternmost TIB-2 granitoids, as well as the supracrustal and shallow emplaced TIB-1 granitoid rocks in the east. The main part of TIB was apparently unaffected by the Hallandian-Danopolonian orogeny, apart from the intrusion of subordinate felsic bodies and mafic dykes. Tilting and other block movements within the Eastern Segment also occurred during the uplift, revealing lower crustal sections in the south compared to the northern part

A P. falciparum NF54 Reporter Line Expressing mCherry-Luciferase in Gametocytes, Sporozoites, and Liver-Stages

Contains fulltext : 203312.pdf (publisher's version ) (Open Access