Macrophages play an essential role in the early immune response against Toxoplasma and are the cell type preferentially infected by the parasite in vivo. Interferon gamma (IFNγ) elicits a variety of ...anti-Toxoplasma activities in macrophages. Using a genome-wide CRISPR screen we identify 353 Toxoplasma genes that determine parasite fitness in naїve or IFNγ-activated murine macrophages, seven of which are further confirmed. We show that one of these genes encodes dense granule protein GRA45, which has a chaperone-like domain, is critical for correct localization of GRAs into the PVM and secretion of GRA effectors into the host cytoplasm. Parasites lacking GRA45 are more susceptible to IFNγ-mediated growth inhibition and have reduced virulence in mice. Together, we identify and characterize an important chaperone-like GRA in Toxoplasma and provide a resource for the community to further explore the function of Toxoplasma genes that determine fitness in IFNγ-activated macrophages.
In this paper, high-performance bottom-gate thin-film transistors (TFTs) with transparent zinc oxide (ZnO) channels have been developed. The ZnO film for active channels was deposited by RF magnetron ...sputtering. The crystallinity of the ZnO film drastically improved when it was deposited on a doublelayer SiO x /SiN x gate insulator. In order to achieve a ZnO TFT back-plane for liquid-crystal display (LCD) with the required pattern accuracy, dry etching of the ZnO film in an Ar and CH 4 chemistry has been developed. The etching rate and tapered profile of the ZnO film could be controlled by the Ar content in the etching gases of Ar and CH 4 . The saturation mobility (mu sat ) of the ZnO TFT strongly depended on a gate voltage. A mu sat of 5.2 & cm 2 .(V .s) -1 at V GS = 40 V and V DS = 10 V, and an on/off-current ratio of 2.7 x 10 7 were obtained. A drain-current uniformity of plusmn7% was achieved within a radius of 20 mm from the substrate center. A 1.46 -in diagonal LCD with 61 600 pixels has been driven by the ZnO-TFT back-plane. A moving picture image was available on fabricated LCD driven by the ZnO TFTs.
Recent explosive advances in next-generation sequencing technology and computational approaches to massive data enable us to analyze a number of cancer genome profiles by whole-genome sequencing ...(WGS). To explore cancer genomic alterations and their diversity comprehensively, global and local cancer genome-sequencing projects, including ICGC and TCGA, have been analyzing many types of cancer genomes mainly by exome sequencing. However, there is limited information on somatic mutations in non-coding regions including untranslated regions, introns, regulatory elements and non-coding RNAs, and rearrangements, sometimes producing fusion genes, and pathogen detection in cancer genomes remain widely unexplored. WGS approaches can detect these unexplored mutations, as well as coding mutations and somatic copy number alterations, and help us to better understand the whole landscape of cancer genomes and elucidate functions of these unexplored genomic regions. Analysis of cancer genomes using the present WGS platforms is still primitive and there are substantial improvements to be made in sequencing technologies, informatics and computer resources. Taking account of the extreme diversity of cancer genomes and phenotype, it is also required to analyze much more WGS data and integrate these with multi-omics data, functional data and clinical-pathological data in a large number of sample sets to interpret them more fully and efficiently.
Ectopic enrichment of oral microbes in the gut is a notable alteration in gut microbial balance. These microbes are likely delivered from the oral cavity with saliva and food; however, evidence of ...oral–gut microbial transmission is insufficient and needs further investigation. In this observational study, we examined 144 pairs of saliva and stool samples collected from community-dwelling adults to verify the oral–gut microbial link and identify the relevant influencing factors on the increased abundance of oral microbes within the gut. The bacterial composition of each sample was determined using PacBio single-molecule long-read sequencing of the full-length 16S ribosomal RNA gene and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of salivary and gut microbiota were distinctly different, at least 1 ASV was shared between salivary and gut microbiota in 72.9% of subjects. Shared ASVs accounted for 0.0% to 63.1% (median 0.14%) of the gut microbiota in each subject and frequently included abundant Streptococcus salivarius and Streptococcus parasanguinis. Their total relative abundance in the gut was significantly higher in older subjects or those with dental plaque accumulation. The gut microbiota with ≥5% of shared ASVs displayed a higher abundance of Streptococcus, Lactobacillus, and Klebsiella and a lower abundance of Faecalibacterium, Blautia, Megamonas, and Parabacteroides. Our study presents evidence for the translocation of oral bacteria to the gut in community-dwelling adults and suggests that aging and dental plaque accumulation contribute to an increased abundance of oral microbes in the gut, which might be relevant to the compositional shift in the gut commensals.
Transparent and conductive Al-doped ZnO (AZO) thin films were deposited on substrates including alkali-free glass, quartz glass, Si, and SiO
2 buffer layer on alkali-free glass by using radio ...frequency magnetron sputtering. The effects of different substrates on the structural, electrical and optical properties of the AZO films were investigated. It was found that the crystal structures were remarkably influenced by the type of the substrates due to their different thermal expansion coefficients, lattice mismatch and flatness. The AZO film (100 nm in thickness) deposited on the quartz glass exhibited the best crystallinity, followed sequentially by those deposited on the Si, the SiO
2 buffer layer, and the alkali-free glass. The film deposited on the quartz glass showed the lowest resistivity of 5.14
×
10
−
4
Ω cm among all the films, a carrier concentration of 1.97
×
10
21 cm
−
3
and a Hall mobility of 6.14 cm
2/v·s. The average transmittance of this film was above 90% in the visible light spectrum range. Investigation into the thickness-dependence of the AZO films revealed that the crystallinity was improved with increasing thickness and decreasing surface roughness, accompanied with a decrease in the film resistivity.
Electrochemical immunosensors have been developed to determine the carbohydrate antigen 19-9 (CA19-9). They are based on screen-printed carbon electrodes (SPCEs) coated with layer-by-layer (LbL) ...films of carbon black (CB) and polyelectrolytes. Owing to a suitable choice of LbL film architecture, the procedures for immobilization of anti-CA19-9 antibodies on the electrode surfaces were straightforward. Mechanically flexible immunosensors were capable of detecting CA19-9 within a dynamic range of 0.01 to 40 U mL
−1
and a limit of detection of 0.07 U mL
−1
using differential pulse voltammetry. In addition to detecting CA19-9 at clinically relevant concentrations for pancreatic cancer in standard solutions, the immunosensors provide the determination of CA19-9 on cell lysate and human serum samples. Using LbL films led to immunosensors with superior performance compared to similar systems obtained by drop casting. The fabrication of this relatively simple, inexpensive platform is a demonstration that SPCEs modified with cost-effective materials are able to detect cancer biomarkers and may be adapted to other disposable immunosensors.
Graphical abstract
Schematic representation of assembly and characterization of electrochemical immunosensors for the determination of carbohydrate antigen 19-9 based on printed electrodes modified with composites of carbon black and polyelectrolyte films
A retrospective, nonrandomized, interventional case series of 8100 patients with uveal melanoma were evaluated for melanoma-related metastasis based on patient race. The patient race was Caucasian ...(n=7918, 98%), Hispanic (n=105, 1%), Asian (n=44, <1%), or African American (n=33, <1%). On the basis of race (Caucasian, Hispanic, Asian, and African American), significant differences were noted in mean age at presentation (58, 48, 44, and 52 years; P<0.001), distance of posterior tumor margin to foveola (5, 5, 6, and 4 mm; P<0.001), distance of posterior tumor margin to optic disc (5, 5, 6, and 4 mm) (P<0.001), tumor base (11, 12, 12, and 13 mm; P<0.001), tumor thickness (5.4, 7.1, 6.5, and 7.5 mm; P<0.001), intraocular hemorrhage (10, 14, 11, and 24%; P=0.02), and rupture of Bruch's membrane (20, 27, 39, and 36%; P=0.001). On the basis of multivariate analysis, the rate of metastasis increased with increasing age (P<0.001), ciliary body location (P<0.001), increasing tumor base (P<0.001), increasing tumor thickness (P<0.001), pigmented tumor (P=0.001), subretinal fluid (P=0.001), intraocular hemorrhage (P=0.045), and extraocular extension (P=0.036). Kaplan-Meier estimates of metastasis at 3, 5, and 10 were 8, 15, and 25% in Caucasians; 13, 13, and 13% in Hispanics; 4, 4, and 36% in Asians; and 8, 8, and 8% in African Americans. Compared with Caucasians, despite relative risk for metastasis of 0.31 for African Americans, 0.73 for Hispanics, and 1.42 for Asians, there was no statistical difference in metastasis, or death from uveal melanoma based on race. In summary, uveal melanoma showed similar prognosis for all races.
Although they are known to share pathophysiological processes, the relationship between periodontitis and chronic obstructive pulmonary disease (COPD) is not fully understood. The aim of the present ...study was to test the hypothesis that periodontitis is associated with a greater risk of development of COPD, when smoking is taken into account. The analysis in a 5-y follow-up population-based cohort study was based on 900 community-dwelling Japanese adults (age: 68.8 ± 6.3 mean ± SD, 46.0% male) without COPD aged 60 or older with at least 1 tooth. Participants were classified into 3 categories according to baseline periodontitis severity (no/mild, moderate, and severe). COPD was spirometrically determined by a fixed ratio of <0.7 for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and by FEV1/FVC below the lower limit of normal. Poisson regression was used to calculate the relative risk (RR) of developing COPD according to the severity of periodontitis. The population attributable fraction (PAF) was also calculated. During follow-up, 22 (2.4%) subjects developed COPD. Compared with no/mild periodontitis subjects, a significantly increased risk of COPD occurred among severe periodontitis subjects (RR = 3.55; 95% confidence interval CI, 1.18 to 10.67), but no significant differences were observed between the no/mild and moderate categories (RR = 1.48; 95% CI, 0.56 to 3.90). After adjustment for potential confounders, including smoking intensity, the relationship between severe periodontitis and risk of COPD remained significant (RR = 3.51; 95% CI, 1.15 to 10.74). Likewise, there was a positive association of periodontitis severity with risk of COPD (P for trend = 0.043). The PAF for COPD due to periodontitis was 22.6%. These data highlight the potential importance of periodontitis as a risk factor for COPD.
Abstract
Reinforced concrete structures in a salt-damaged environment are deteriorated by salt damage due to the influence of salt. As a repair measure, repair materials with salt adsorption ...performance and rebar rust prevention performance are used for inorganic materials. However, products with these added to organic materials are used for various purposes, which are used for various applications as repair materials. Unfortunately, there are few examples of its use becoming possible expected that measures against salt damage will be taken in various applications which have developed a “salt-adsorbing epoxy resin repair material” in which a salt-adsorbing agent is added to epoxy resin, which is an organic material. In addition, this research presented the salt adsorption effect and the corrosion inhibition effect on steel bars applied to each repair application.
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