Highlights • The tumor microenvironment is the key determining factor to cancer development. • Exosomes are present in ovarian cancer and closely related with tumorigenesis, metastasis, and ...prognosis. • This review discusses the multifaceted and centric role of exosomes in ovarian cancer microenvironment. • This review discusses the application of exosomes as a biomarker for diagnosis and a target for treatment.
High-throughput complementary DNA sequencing technologies have advanced our understanding of transcriptome complexity and regulation. However, these methods lose information contained in biological ...RNA because the copied reads are often short and modifications are not retained. We address these limitations using a native poly(A) RNA sequencing strategy developed by Oxford Nanopore Technologies. Our study generated 9.9 million aligned sequence reads for the human cell line GM12878, using thirty MinION flow cells at six institutions. These native RNA reads had a median length of 771 bases, and a maximum aligned length of over 21,000 bases. Mitochondrial poly(A) reads provided an internal measure of read-length quality. We combined these long nanopore reads with higher accuracy short-reads and annotated GM12878 promoter regions to identify 33,984 plausible RNA isoforms. We describe strategies for assessing 3' poly(A) tail length, base modifications and transcript haplotypes.
The purpose of this paper is to investigate the research development in supply chain risk management (SCRM), which has shown an increasing global attention in recent years. Literature survey and ...citation/co-citation analysis are used to fulfil the research task. Literature survey has undertaken a thorough search of articles on selected journals relevant to supply chain operations management. Meanwhile, citation/co-citation analysis uses Web of Sciences database to disclose SCRM development between 1995 and 2009. Both the approaches show similar trends of rising publications over the past 15 years. This review has piloted us to identify and classify the potential risk associated with different flows, namely material, cash and information flows. Consequently, we identify some research gaps. Even though there is a pressing need and awareness of SCRM from industrial aspect, quantitative models in the field are relatively lacking and information flow risk has received less attention. It is also interesting to observe the evolutions and advancements of SCRM discipline. One finding is that the intellectual structure of the field made statistically significant increase during 2000–2005 and evolved from passively reacting to vague general issues of disruptions towards more proactively managing supply chain risk from system perspectives.
Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. ...Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues. In addition, we have revealed the expression of phenotypic molecules that have not been previously described for ILCs. Our analysis shows that human ILCs are highly heterogeneous cell types between individuals and tissues. It also provides a global, comprehensive, and detailed description of ILC heterogeneity in humans across patients and tissues.
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•Comprehensive profiling of human ILCs across tissues•Detailed description of previously defined ILC subsets except helper-type ILC1•ieILC1-like cells are present in several tissues and functionally similar to NK cells•Identification of markers expressed on ILCs, including functional IL-18R
Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. Simoni et al. (2016) profile human ILCs using mass cytometry across tissues. The results provide a global, comprehensive, and detailed description of ILC populations and their heterogeneity across individuals and tissues.
Myeloperoxidase (MPO) and paraoxonase 1 (PON1) are high-density lipoprotein-associated (HDL-associated) proteins mechanistically linked to inflammation, oxidant stress, and atherosclerosis. MPO is a ...source of ROS during inflammation and can oxidize apolipoprotein A1 (APOA1) of HDL, impairing its atheroprotective functions. In contrast, PON1 fosters systemic antioxidant effects and promotes some of the atheroprotective properties attributed to HDL. Here, we demonstrate that MPO, PON1, and HDL bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1. MPO oxidizes PON1 on tyrosine 71 (Tyr71), a modified residue found in human atheroma that is critical for HDL binding and PON1 function. Acute inflammation model studies with transgenic and knockout mice for either PON1 or MPO confirmed that MPO and PON1 reciprocally modulate each other's function in vivo. Further structure and function studies identified critical contact sites between APOA1 within HDL, PON1, and MPO, and proteomics studies of HDL recovered from acute coronary syndrome (ACS) subjects revealed enhanced chlorotyrosine content, site-specific PON1 methionine oxidation, and reduced PON1 activity. HDL thus serves as a scaffold upon which MPO and PON1 interact during inflammation, whereupon PON1 binding partially inhibits MPO activity, and MPO promotes site-specific oxidative modification and impairment of PON1 and APOA1 function.
Flexible metal–organic frameworks (MOFs) undergo structural transformations in response to physical and chemical stimuli. This is hard to control because of feedback between guest uptake and host ...structure change. We report a family of flexible MOFs based on derivatized amino acid linkers. Their porosity consists of a one-dimensional channel connected to three peripheral pockets. This network structure amplifies small local changes in linker conformation, which are strongly coupled to the guest packing in and the shape of the peripheral pockets, to afford large changes in the global pore geometry that can, for example, segment the pore into four isolated components. The synergy among pore volume, guest packing, and linker conformation that characterizes this family of structures can be determined by the amino acid side chain, because it is repositioned by linker torsion. The resulting control optimizes noncovalent interactions to differentiate the uptake and structure response of host–guest pairs with similar chemistries.