524 research outputs found

    Decreased Innate Migration of Pro-Inflammatory M1 Macrophages through the Mesothelial Membrane Is Affected by Ceramide Kinase and Ceramide 1-P

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    The retrograde flow of endometrial tissues deposited into the peritoneal cavity occurs in women during menstruation. Classically (M1) or alternatively (M2) activated macrophages partake in the removal of regurgitated menstrual tissue. The failure of macrophage egress from the peritoneal cavity through the mesothelium leads to chronic inflammation in endometriosis. To study the migration differences of macrophage phenotypes across mesothelial cells, an in vitro model of macrophage egress across a peritoneal mesothelial cell monolayer membrane was developed. M1 macrophages were more sessile, emigrating 2.9-fold less than M2 macrophages. The M1 macrophages displayed a pro-inflammatory cytokine signature, including IL-1α, IL-1β, TNF-α, TNF-β, and IL-12p70. Mass spectrometry sphingolipidomics revealed decreased levels of ceramide-1-phosphate (C1P), an inducer of migration in M1 macrophages, which correlated with its poor migration behavior. C1P is generated by ceramide kinase (CERK) from ceramide, and blocking C1P synthesis via the action of NVP231, a specific CERK chemical inhibitor, prohibited the emigration of M1 and M2 macrophages up to 6.7-fold. Incubation with exogenously added C1P rescued this effect. These results suggest that M1 macrophages are less mobile and have higher retention in the peritoneum due to lower C1P levels, which contributes to an altered peritoneal environment in endometriosis by generating a predominant pro-inflammatory cytokine environment

    3,4-Dihydroxy­benzaldehyde thio­semi­carbazone

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    The asymmetric unit of the title compound, C8H9N3O2S, contains three independent mol­ecules which are stacked approximately over each other. In the crystal structure, centrosymmetric pairs of mol­ecules are formed through inter­molecular hydr­oxy–hydr­oxy O—H⋯O and hydr­oxy–sulfur O—H⋯S hydrogen bonds which are, in turn, linked into a two-dimensional network by N—H⋯O(hydr­oxy) hydrogen bonds

    Ultra-fast charging in aluminum-ion batteries: electric double layers on active anode

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    With the rapid iteration of portable electronics and electric vehicles, developing high-capacity batteries with ultra-fast charging capability has become a holy grail. Here we report rechargeable aluminum-ion batteries capable of reaching a high specific capacity of 200 mAh g−1. When liquid metal is further used to lower the energy barrier from the anode, fastest charging rate of 104 C (duration of 0.35 s to reach a full capacity) and 500% more specific capacity under high-rate conditions are achieved. Phase boundaries from the active anode are believed to encourage a high-flux charge transfer through the electric double layers. As a result, cationic layers inside the electric double layers responded with a swift change in molecular conformation, but anionic layers adopted a polymer-like configuration to facilitate the change in composition

    3,4-Dihydroxy­benzaldehyde 4-phenyl­thio­semicarbazone

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    Mol­ecules of the title compound, C14H13N3O2S, are linked by inter­molecular O—H⋯O hydrogen bonds into centrosymmetric dimers forming R 2 2(4) rings which are further linked by O—H⋯S hydrogen bonds and weaker N—H⋯S and N—H⋯O hydrogen bonds to form a three-dimensional network

    AluScan: a method for genome-wide scanning of sequence and structure variations in the human genome

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    <p>Abstract</p> <p>Background</p> <p>To complement next-generation sequencing technologies, there is a pressing need for efficient pre-sequencing capture methods with reduced costs and DNA requirement. The Alu family of short interspersed nucleotide elements is the most abundant type of transposable elements in the human genome and a recognized source of genome instability. With over one million Alu elements distributed throughout the genome, they are well positioned to facilitate genome-wide sequence amplification and capture of regions likely to harbor genetic variation hotspots of biological relevance.</p> <p>Results</p> <p>Here we report on the use of inter-Alu PCR with an enhanced range of amplicons in conjunction with next-generation sequencing to generate an Alu-anchored scan, or 'AluScan', of DNA sequences between Alu transposons, where Alu consensus sequence-based 'H-type' PCR primers that elongate outward from the head of an Alu element are combined with 'T-type' primers elongating from the poly-A containing tail to achieve huge amplicon range. To illustrate the method, glioma DNA was compared with white blood cell control DNA of the same patient by means of AluScan. The over 10 Mb sequences obtained, derived from more than 8,000 genes spread over all the chromosomes, revealed a highly reproducible capture of genomic sequences enriched in genic sequences and cancer candidate gene regions. Requiring only sub-micrograms of sample DNA, the power of AluScan as a discovery tool for genetic variations was demonstrated by the identification of 357 instances of loss of heterozygosity, 341 somatic indels, 274 somatic SNVs, and seven potential somatic SNV hotspots between control and glioma DNA.</p> <p>Conclusions</p> <p>AluScan, implemented with just a small number of H-type and T-type inter-Alu PCR primers, provides an effective capture of a diversity of genome-wide sequences for analysis. The method, by enabling an examination of gene-enriched regions containing exons, introns, and intergenic sequences with modest capture and sequencing costs, computation workload and DNA sample requirement is particularly well suited for accelerating the discovery of somatic mutations, as well as analysis of disease-predisposing germline polymorphisms, by making possible the comparative genome-wide scanning of DNA sequences from large human cohorts.</p
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