Tissue-Resident CD169+ Macrophages Form a Crucial Front Line against Plasmodium Infection

SummaryTissue macrophages exhibit diverse functions, ranging from the maintenance of tissue homeostasis, including clearance of senescent erythrocytes and cell debris, to modulation of inflammation and immunity. Their contribution to the control of blood-stage malaria remains unclear. Here, we show that in the absence of tissue-resident CD169+ macrophages, Plasmodium berghei ANKA (PbA) infection results in significantly increased parasite sequestration, leading to vascular occlusion and leakage and augmented tissue deposition of the malarial pigment hemozoin. This leads to widespread tissue damage culminating in multiple organ inflammation. Thus, the capacity of CD169+ macrophages to contain the parasite burden and its sequestration into different tissues and to limit infection-induced inflammation is crucial to mitigating Plasmodium infection and pathogenesis

Applying ChIP and ChIA-PET to identify p300, CTCF and Lamin B binding sites in stem cells

Embryonic stem cells (ESCs) have the ability of self-renewal and differentiating into many different cell types, which makes it good choice as the cell source for stem cell therapy. And to exploit the potential of ESCs, two key pathways should be elucidated: the self-renewal process which will amplify the cells to an enough number and the differentiation process which can provide specific cell type for a cell therapy. Both of the two pathways are maintained through the interactions between chromatins and transcription regulatory networks. The group I joined investigated such interactions by chromatin immunuoprecipiation coupled with ultra-high throughput sequencing platform (ChIP-Seq) and chromatin interaction analysis by pair end tag (ChIA-PET) technologies. First, the target sequences of ESCs and neuronal progenitor cells (NPCs) of the whole genome for three different factors, p300, CTCF and Lamin B, were detected by ChIP-Seq analysis. Second, based on the binding sites information obtained, higher order chromatin structures in ESCs and NPCs involved in chromatin interactions were detected by ChIA-PET, which are mainly targeted for p300 and CTCF. The goals are to map target genes, to detect the whole genome long range chromatin interactions, their dynamic changes during differentiation and determine their associations with gene expression

Tissue macrophage complexity as seen through a novel c-kit(Cre) fate mapping mouse

In this study, I addressed two main questions: first, how does microglia maintain its population; second, ontogenic origins of other tissue macrophages. In order to study the maintenance of microglia, I utlized two new cell ablation tools in order to deplete microglia: F4/80 and CD45-DTR mouse. I also generated a novel novel c-kifMerCreMer mouse strain that allows me to fate map with a new approach macrophages/myeloid cells in various tissues at different times of ontogeny. I identified the microglia stem cells that maintain the whole population locally. In addition, my results showed that different tissues could have three pools of myeloid cells: F4/80hl macrophages, CD11bhl monocyte/macrophage/eosinophil mixtures and F4/80low neutrophils. All the CDHbhl cell mixtures and neutrophils were derived from adult BM. While four categories of F4/80hl macrophages could be defined based on the ontogenetic origins and maintenance dynamics.​Doctor of Philosophy (SBS

Experimental Investigation on Oil Enhancement Mechanism of Hot Water Injection in tight reservoirs

Aimed at enhancing the oil recovery of tight reservoirs, the mechanism of hot water flooding was studied in this paper. Experiments were conducted to investigate the influence of hot water injection on oil properties, and the interaction between rock and fluid, petrophysical property of the reservoirs. Results show that with the injected water temperature increasing, the oil/water viscosity ratio falls slightly in a tight reservoir which has little effect on oil recovery. Further it shows that the volume factor of oil increases significantly which can increase the formation energy and thus raise the formation pressure. At the same time, oil/water interfacial tension decreases slightly which has a positive effect on production though the reduction is not obvious. Meanwhile, the irreducible water saturation and the residual oil saturation are both reduced, the common percolation area of two phases is widened and the general shape of the curve improves. The threshold pressure gradient that crude oil starts to flow also decreases. It relates the power function to the temperature, which means it will be easier for oil production and water injection. Further the pore characteristics of reservoir rocks improves which leads to better water displacement. Based on the experimental results and influence of temperature on different aspects of hot water injection, the flow velocity expression of two-phase of oil and water after hot water injection in tight reservoirs is obtained

Effective Enrichment of Plasmonic Hotspots for SERS by Spinning Droplets on a Slippery Concave Dome Array

Surface-enhanced Raman scattering (SERS) detection requires dense hotspots and a uniform distribution of analytes to obtain a stable signal with good repeatability. However, due to the coffee-ring effect on the hydrophilic substrate, and the difficulty of droplet manipulation on the superhydrophobic substrate, few substrates can ensure that the analytes are evenly distributed. In this work, we develop a method that can efficiently enrich plasmonic hotspots for SERS measurement on the superhydrophobic concave dome array (SCDA). The SCDA is formed by spraying hydrophobic silica nanoparticles onto a polydimethylsiloxane (PDMS) slab with a concave dome array that can physically confine the droplets and overcome the coffee-ring effect. During droplet evaporation, the SCDA is driven by a horizontal spinner, and the droplets spin on the SCDA, enabling the plasmonic nanoparticles to become closely packed to form the SERS hotspots. The limit of detection (LOD) of the dynamic-enriched SERS hotspots for crystal violet and methylene blue can reach up to 10−11 M. Moreover, the LOD for melamine in milk can reach 5 × 10−7 M, which is lower than the safety threshold defined by the Food and Drug Administration (FDA). Based on this SERS platform, an effective, low-cost, and simple method for SERS detection in analytical chemistry and food safety is highly expected

A Discrete Subset of Monocyte-Derived Cells among Typical Conventional Type 2 Dendritic Cells Can Efficiently Cross-Present

Dendritic cells (DCs) and macrophages (Mϕs) share close developmental pathways and functional features, leading to blurring of the boundaries between these two cell lineages. However, a deeper understanding of DC and Mϕ ontogeny and more refined phenotypic and functional characterizations have helped to delineate pre-DC-derived conventional DCs (cDCs), including cDC1s and cDC2s, from monocyte-derived Mϕs. Here, we further refine DC/Mϕ cell classification and report that classically defined cDC2s contain a discrete population of monocyte-derived migratory antigen-presenting cells with Mϕ phenotype but functional DC features, including cross-presentation.MOE (Min. of Education, S’pore)Published versio