The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions

Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16–26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer

German Research FoundationWilhelm Sander-StiftungNational Health and Medical Research Council of AustraliaCancer Council QueenslandMovember FoundationProstate Cancer Foundation of Australia through a Movember Revolutionary Team AwardQueensland University of TechnologyGerman Academic Exchange Service (German-Australian Network for Personalized Medicine

Regulation of Macrophage Motility by the Water Channel Aquaporin-1: Crucial Role of M0/M2 Phenotype Switch

The water channel aquaporin-1 (AQP1) promotes migration of many cell types. Although AQP1 is expressed in macrophages, its potential role in macrophage motility, particularly in relation with phenotype polarization, remains unknown. We here addressed these issues in peritoneal macrophages isolated from AQP1-deficient mice, either undifferentiated (M0) or stimulated with LPS to orientate towards pro-inflammatory phenotype (classical macrophage activation; M1). In non-stimulated macrophages, ablation of AQP1 (like inhibition by HgCl2) increased by 2-3 fold spontaneous migration in a Src/PI3K/Rac-dependent manner. This correlated with cell elongation and formation of lamellipodia/ruffles, resulting in membrane lipid and F4/80 recruitment to the leading edge. This indicated that AQP1 normally suppresses migration of resting macrophages, as opposed to other cell types. Resting Aqp1-/- macrophages exhibited CD206 redistribution into ruffles and increased arginase activity like IL4/IL13 (alternative macrophage activation; M2), indicating a M0-M2 shift. In contrast, upon M1 orientation by LPS in vitro or peritoneal inflammation in vivo , migration of Aqp1-/- macrophages was reduced. Taken together, these data indicate that AQP1 oppositely regulates macrophage migration, depending on stimulation or not by LPS, and that macrophage phenotypic and migratory changes may be regulated independently of external cues

Fluid signature of the shear zone–controlled Veio de Quartzo ore body in the world-class BIF-hosted Cuiabá gold deposit, Archaean Rio das Velhas greenstone belt, Brazil: a fluid inclusion study

The world-class Cuiabá gold deposit of the Archaean Rio das Velhas greenstone belt in Brazil is hosted in banded iron formation containing carbonaceous matter and carbonate, within the reclined, isoclinal Cuiabá fold. Mineralised quartz veins are hosted in andesite in the stratigraphic footwall of the banded iron ores and form some of the more recently discovered ore bodies. Fluid inclusion data of the quartz vein–associated “Veio de Quartzo” ore body are obtained from four quartz types (Qz1, Qz2, Qz3, Qz5) in gold-mineralised V1 shear vein and V2 extensional veins, barren V3 extensional vein array, and V4 breccia-style veins, all developed during the Archaean D1 event. Three fluid types are distinguished: (i) aqueous fluids of low salinity (1.8–3.8 wt% NaCl equiv), homogenisation (into liquid) at 220 to 230 °C; (ii) aqueous fluids of moderate salinity (5.3–12.7 wt% NaCl equiv), and homogenisation at 250 to 290 °C; and (iii) aqueous-carbonic fluids of moderate salinity (6.0–15.1 wt% NaCl equiv), with 30–91 mol% CO2, 8–41 mol% CH4 and up to 28 mol% N2 and decrepitation (into vapour) at 280 to 310 °C. Based on an independent pressure estimate, a pressure correction was applied to aqueous fluid inclusions, resulting in minimum trapping temperatures at 360 °C for V1 veins, 330 °C for V2 veins, 300 °C for V3 veins and 270 °C for the late-stage V4 veins. Ion chromatography analyses reveal a Br/Cl ratio of 0.7 × 10−3 in Qz1-V1, from 1.4 to 1.5 × 10−3 in Qz2-V2, 0.3 to 0.4 × 10−3 in Qz3-V3 and 0.7 to 0.9 × 10−3in Qz5-V4 veins. Zinc, Pb and Cu are relatively enriched with ~ 100 to 1000 ppm in aqueous and aqueous-carbonic fluid inclusion assemblages in all vein and quartz types, which is similar to other orogenic gold deposits hosted in the Rio das Velhas greenstone belt. The fluid inclusion data are consistent with a model invoking a metamorphic origin for the mineralising fluid. A two-step model of hydrothermal fluid flow and gold enrichment is suggested to have developed during the Archaean D1 event, with an early, aqueous-carbonic fluid pulse of relatively high temperature (from V1 up to V3) and an evolved, aqueous-carbonic fluid pulse of lower temperature (V4, breccia-style veins). The Rio das Velhas greenstone belt is dominated by regionally metamorphosed metasedimentary rocks, resulting in a complex hydrothermal fluid evolution and related gold mineralisation such as the shear zone–controlled Veio de Quartzo ore body