A molecular atlas of cell types and zonation in the brain vasculature

Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells. We also provide insight into pericyte organotypicity and define a population of perivascular fibroblast-like cells that are present on all vessel types except capillaries. Our work illustrates the power of single-cell transcriptomics to decode the higher organizational principles of a tissue and may provide the initial chapter in a molecular encyclopaedia of the mammalian vasculature.Peer reviewe

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

GAS2L1 Is a Potential Biomarker of Circulating Tumor Cells in Pancreatic Cancer

Pancreatic cancer is a malignant disease with high mortality and a dismal prognosis. Circulating tumor cell (CTC) detection and characterization have emerged as essential techniques for early detection, prognostication, and liquid biopsy in many solid malignancies. Unfortunately, due to the low EPCAM expression in pancreatic cancer CTCs, no specific marker is available to identify and isolate this rare cell population. This study analyzed single-cell RNA sequencing profiles of pancreatic CTCs from a genetically engineered mouse model (GEMM) and pancreatic cancer patients. Through dimensionality reduction analysis, murine pancreatic CTCs were grouped into three clusters with different biological functions. CLIC4 and GAS2L1 were shown to be overexpressed in pancreatic CTCs in comparison with peripheral blood mononuclear cells (PBMCs). Further analyses of PBMCs and RNA-sequencing datasets of enriched pancreatic CTCs were used to validate the overexpression of GAS2L1 in pancreatic CTCs. A combinatorial approach using both GAS2L1 and EPCAM expression leads to an increased detection rate of CTCs in PDAC in both GEMM and patient samples. GAS2L1 is thus proposed as a novel biomarker of pancreatic cancer CTCs

High-Density Lipoprotein Reduction Differentially Modulates to Classical and Nonclassical Monocyte Subpopulations in Metabolic Syndrome Patients and in LPS-Stimulated Primary Human Monocytes In Vitro

The effect of metabolic syndrome on human monocyte subpopulations has not yet been studied. Our main goal was to examine monocyte subpopulations in metabolic syndrome patients, while also identifying the risk factors that could directly influence these cells. Eighty-six subjects were divided into metabolic syndrome patients and controls. Monocyte subpopulations were quantified by flow cytometry, and interleukin- (IL-) 1β secretion levels were measured by ELISA. Primary human monocytes were cultured in low or elevated concentrations of high-density lipoprotein (HDL) and stimulated with lipopolysaccharide (LPS). The nonclassical monocyte (NCM) percentage was significantly increased in metabolic syndrome patients as compared to controls, whereas classical monocytes (CM) were reduced. Among all metabolic syndrome risk factors, HDL reduction exhibited the most important correlation with monocyte subpopulations and then was studied in vitro. Low HDL concentration reduced the CM percentage, whereas it increased the NCM percentage and IL-1β secretion in LPS-treated monocytes. The LPS effect was abolished when monocytes were cultured in elevated HDL concentrations. Concurring with in vitro results, IL-1β serum values significantly increased in metabolic syndrome patients with low HDL levels as compared to metabolic syndrome patients without HDL reduction. Our data demonstrate that HDL directly modulates monocyte subpopulations in metabolic syndrome

The cosmic dust analyser onboard cassini: ten years of discoveries

The interplanetary space probe Cassini/Huygens reached Saturn in July 2004 after 7 years of cruise phase. The German cosmic dust analyser (CDA) was developed under the leadership of the Max Planck Institute for Nuclear Physics in Heidelberg under the support of the DLR e.V. This instrument measures the interplanetary, interstellar and planetary dust in our solar system since 1999 and provided unique discoveries. In 1999, CDA detected interstellar dust in the inner solar system followed by the detection of electrical charges of interplanetary dust grains during the cruise phase between Earth and Jupiter. The instrument determined the composition of interplanetary dust and the nanometre-sized dust streams originating from Jupiter’s moon Io. During the approach to Saturn in 2004, similar streams of submicron grains with speeds in the order of 100 km/s were detected from Saturn’s inner and outer ring system and are released to the interplanetary magnetic field. Since 2004 CDA measured more than one million dust impacts characterising the dust environment of Saturn. The instrument is one of the three experiments which discovered the active ice geysers located at the south pole of Saturn’s moon Enceladus in 2005. Later, a detailed compositional analysis of the water ice grains in Saturn’s E ring system led to the discovery of large reservoirs of liquid water (oceans) below the icy crust of Enceladus. Finally, the determination of the dust-magnetosphere interaction and the discovery of the extended E ring (at least twice as large as predicted) allowed the definition of a dynamical dust model of Saturn’s E ring describing the observed properties. This paper summarizes the discoveries of a 10-year story of success based on reliable measurements with the most advanced dust detector flown in space until today. This paper focuses on cruise results and findings achieved at Saturn with a focus on flux and density measurements. CDA discoveries related to the detailed dust stream dynamics, E ring dynamics, its vertical profile and E ring compositional analysis are published elsewhere (see Hus et al. in AIP Conference Proccedings 1216:510–513, 2010; Hsu et al. in Icarus 206:653–661, 2010; Kempf et al. in Icarus 193:420, 2008; 206(2):446, 2010; Postberg et al. in Icarus 193(2):438, 2008; Nature 459:1098, 2009; Nature, 2011, doi:10.1038/nature10175)