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  • 2015-2019  (47)
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  • 1
    Publication Date: 2018-04-14
    Description: Objective To completely and quantifiably determine the effect of systemic lupus erythematosus (SLE) on pregnancy outcomes in a Chinese cohort. Design A retrospective cohort study. Setting Data were collected at a tertiary medical centre located in Shanghai, China, from September 2011 to May 2017. Participants We assigned 338 pregnant women with SLE to the study cohort and 1014 randomly selected pregnant women without SLE (three for every woman with SLE) to a comparison cohort. The relevant medical records of all pregnant women were retrospectively reviewed. Cases of multiple pregnancy and cases in which an artificial abortion was performed for personal reasons were excluded. Primary and secondary outcome measures Maternal and fetal outcomes were primary outcomes, and management of antenatal care was the secondary outcome. Results The risks of pregnancy-induced hypertension (OR 2.68, 95% CI 1.75 to 4.09), pre-eclampsia (OR 3.13, 95% CI 1.95 to 5.03) and premature rupture of membranes (OR 2.53, 95% CI 1.46 to 4.40) were significantly different between women with and without SLE. Gestational diabetes was negatively associated with SLE in pregnant women (OR 0.49, 95% CI 0.28 to 0.85). Pregnant women with SLE displayed significantly higher rates of fetal loss (OR 10.23, 95% CI 5.08 to 20.59), including spontaneous abortion (OR 4.42, 95% CI 1.52 to 12.80), therapeutic abortion (OR 16.57, 95% CI 5.80 to 47.35) and stillbirth (OR 13.25, 95% CI 1.49 to 118.11), and a higher risk of preterm birth (OR 3.15, 95% CI 2.21 to 4.50), intrauterine growth restriction (OR 2.20, 95% CI 1.35 to 3.58), a child who was small for the gestational age (OR 1.86, 95% CI 1.11 to 3.13), a caesarean section (OR 4.73, 95% CI 3.30 to 6.80) or a neonatal intensive care unit admission (OR 3.48, 95% CI 2.21 to 5.48) than women in the non-SLE population after adjusting for confounding factors. Conclusions In this study, SLE significantly increased the risk of adverse pregnancy outcomes. Therefore, a preconception assessment and close antenatal monitoring by both rheumatologists and obstetricians should be performed in pregnant women with SLE.
    Keywords: Open access
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 2
    Publication Date: 2018-03-06
    Description: Spike density and processing quality are important traits in modern wheat production and are controlled by multiple gene loci. The associated genes have been intensively studied and new discoveries have been constantly reported during the past few decades. However, no gene playing a significant role in the development of these two traits has been identified. In the current study, a common wheat mutant with extremely compact spikes and good processing quality was isolated and characterized. A new allele ( Q c1 ) of the Q gene (an important domestication gene) responsible for the mutant phenotype was cloned, and the molecular mechanism for the mutant phenotype was studied. Results revealed that Q c1 originated from a point mutation that interferes with the miRNA172-directed cleavage of Q transcripts, leading to its overexpression. It also reduces the longitudinal cell size of rachises, resulting in an increased spike density. Furthermore, Q c1 increases the number of vascular bundles, which suggests a higher efficiency in the transportation of assimilates in the spikes of the mutant than that of wild type. This accounts for the improved processing quality. The effects of Q c1 on spike density and wheat processing quality were confirmed by analyzing nine common wheat mutants possessing four different Q c alleles. These results deepen our understanding of the key roles of Q gene, and provide new insights for the potential application of Q c alleles in wheat quality breeding.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 3
    Publication Date: 2018-06-22
    Description: Streptococcus suis has received increasing attention for its involvement in severe human infections worldwide as well as in multidrug resistance. Two-component signaling systems (TCSSs) play important roles in bacterial adaptation to various environmental stimuli. In this study, we identified a novel TCSS located in S. suis serotype 2 (SS2), designated VraSR SS , which is involved in bacterial pathogenicity and susceptibility to antimicrobials. Our data demonstrated that the yvqF SS gene, located upstream of vraSR SS , shared the same promoter with the TCSS genes, which was directly regulated by VraSR SS , as shown in electrophoretic mobility shift assays. Notably, YvqF SS and VraSR SS constitute a novel multidrug resistance module of SS2 that participates in resistance to certain groups of antimicrobials. Further analyses showed that VraSR SS inactivation significantly attenuated bacterial virulence in animal models, which, coupled with the significant activation of VraSR SS expression observed in host blood, strongly suggested that VraSR SS is an important regulator of SS2 pathogenicity. Indeed, RNA-sequencing analyses identified 106 genes that were differentially expressed between the wild-type and vraSR SS strains, including genes involved in capsular polysaccharide (CPS) biosynthesis. Subsequent studies confirmed that VraSR SS indirectly regulated the transcription of CPS gene clusters and, thus, controlled the CPS thickness shown by transmission electron microscopy. Decreased CPS biosynthesis caused by vraSR SS deletion subsequently increased bacterial adhesion to epithelial cells and attenuated antiphagocytosis against macrophages, which partially clarified the pathogenic mechanism mediated by VraSR SS . Taken together, our data suggest that the novel TCSS, VraSR SS , plays critical roles for multidrug resistance and full virulence in SS2.
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
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  • 4
    Publication Date: 2018-09-13
    Description: Targeting fibroblast-like synoviocyte (FLS) migration and invasion-mediated bone erosion is a promising clinical strategy for the treatment of rheumatoid arthritis (RA). Drug sensitivity testing is fundamental to this scheme. We designed a microfluidic chip-based, cell co-cultured platform to mimic RA FLS-mediated bone erosion and perform drug-sensitive assay. Human synovium SW982 cells were cultured in the central channel and migrated to flow through matrigel-coated side channels towards cell culture chamber where RANKL-stimulated osteoclastic RAW264.7 and osteogenic medium (OS)-stimulated bone marrow mesenchymal stem cells (BMSC) were cultured in the microfluidic chip device, mimicking FLS migration and invasion-mediated bone erosion in RA. These SW982 cells showed different migration potentials to osteoclasts and BMSC. The migration of SW982 cells with high expression of cadherin-11 was more potent when SW982 cells were connected with the co-culture of RAW264.7 and BMSC. Simultaneously, in the co-cultured chamber, tartrate-resistant acid phosphatase (TRAP) activity of RANKL-stimulated RAW264.7 cells was enhanced, but alkaline phosphatase (ALP) activity was decreased in comparison with mono-cultured chamber. Furthermore, it was confirmed that celastrol, a positive drug for the treatment of RA, inhibited SW982 cell migration as well as TRAP activity in the cell-cultured microfluidic chips. Thus, the migration and invasion to bone-related cells was reconstituted on the microfluidic model. It may provide an effective anti-RA drug screen model for targeting FLS migration-mediated bone erosion.
    Keywords: biochemistry, health and disease and epidemiology
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 5
    Publication Date: 2018-10-03
    Description: Obesity is associated with cancer risk and its link with liver cancer is particularly strong. Obesity causes non-alcoholic fatty liver disease (NAFLD) that could progress to hepatocellular carcinoma (HCC). Chronic inflammation likely plays a key role. We carried out a bioassay in the high-fat diet (HFD)-fed C57BL/6J mice to provide insight into the mechanisms of obesity-related HCC by studying -OHPdG, a mutagenic DNA adduct derived from lipid peroxidation. In an 80-week bioassay, mice received a low-fat diet (LFD), high-fat diet (HFD), and HFD with 2% Theaphenon E (TE) (HFD+TE). HFD mice developed a 42% incidence of HCC and LFD mice a 16%. Remarkably, TE, a standardized green tea extract formulation, completely blocked HCC in HFD mice with a 0% incidence. -OHPdG measured in the hepatic DNA of mice fed HFD and HFD+TE showed its levels increased during the early stages of NAFLD in HFD mice and the increases were significantly suppressed by TE, correlating with the tumor data. Whole-exome sequencing showed an increased mutation load in the liver tumors of HFD mice with G〉A and G〉T as the predominant mutations, consistent with the report that -OHPdG induces G〉A and G〉T. Furthermore, the mutation loads were significantly reduced in HFD+TE mice, particularly G〉T, the most common mutation in human HCC. These results demonstrate in a relevant model of obesity-induced HCC that -OHPdG formation during fatty liver disease may be an initiating event for accumulated mutations that leads to HCC and this process can be effectively inhibited by TE. Cancer Prev Res; 11(10); 665–76. ©2018 AACR .
    Print ISSN: 1940-6207
    Electronic ISSN: 1940-6215
    Topics: Medicine
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  • 6
    Publication Date: 2018-06-29
    Description: Chiral amines are widely used as catalysts in asymmetric synthesis to activate carbonyl groups for α-functionalization. Carbonyl catalysis reverses that strategy by using a carbonyl group to activate a primary amine. Inspired by biological carbonyl catalysis, which is exemplified by reactions of pyridoxal-dependent enzymes, we developed an N-quaternized pyridoxal catalyst for the asymmetric Mannich reaction of glycinate with aryl N -diphenylphosphinyl imines. The catalyst exhibits high activity and stereoselectivity, likely enabled by enzyme-like cooperative bifunctional activation of the substrates. Our work demonstrates the catalytic utility of the pyridoxal moiety in asymmetric catalysis.
    Keywords: Chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2018-08-24
    Keywords: Lymphoid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 8
    Publication Date: 2018-08-24
    Description: Projectors are a simple but powerful tool for manipulating and probing quantum systems. For instance, projecting two-qubit systems onto maximally entangled states can enable quantum teleportation. While such projectors have been extensively studied, partially-entangling projectors have been largely overlooked, especially experimentally, despite their important role in quantum foundations and quantum information. Here, we propose a way to project two polarized photons onto any state with a single experimental setup. Our scheme does not require optical nonlinearities or additional photons. Instead, the entangling operation is provided by Hong–Ou–Mandel interference and post-selection. The efficiency of the scheme is between 50% and 100%, depending on the projector. We perform an experimental demonstration and reconstruct the operator describing our measurement using detector tomography. Finally, we flip the usual role of measurement and state in Hardy’s test by performing a partia...
    Electronic ISSN: 1367-2630
    Topics: Physics
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  • 9
    Publication Date: 2018-09-07
    Description: Galaxies grow inefficiently, with only a small percentage of the available gas converted into stars each free-fall time. Feedback processes, such as outflowing winds driven by radiation pressure, supernovae, or supermassive black hole accretion, can act to halt star formation if they heat or expel the gas supply. We report a molecular outflow launched from a dust-rich star-forming galaxy at redshift 5.3, 1 billion years after the Big Bang. The outflow reaches velocities up to 800 kilometers per second relative to the galaxy, is resolved into multiple clumps, and carries mass at a rate within a factor of 2 of the star formation rate. Our results show that molecular outflows can remove a large fraction of the gas available for star formation from galaxies at high redshift.
    Keywords: Astronomy
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2018-10-16
    Description: Purpose: Small cell lung cancer (SCLC) is an aggressive malignancy with a critical need for novel therapies. Our goal was to determine whether PARP inhibition could sensitize SCLC cells to ionizing radiation (IR) and if so, to determine the contribution of PARP trapping to radiosensitization. Experimental Design: Short-term viability assays and clonogenic survival assays (CSA) were used to assess radiosensitization in 6 SCLC cell lines. Doses of veliparib and talazoparib with equivalent enzymatic inhibitory activity but differing PARP trapping activity were identified and compared in CSAs. Talazoparib, IR, and their combination were tested in three patient-derived xenograft (PDX) models. Results: Talazoparib radiosensitized 5 of 6 SCLC cell lines in short-term viability assays and confirmed in 3 of 3 cell lines by CSAs. Concentrations of 200 nmol/L talazoparib and 1,600 nmol/L veliparib similarly inhibited PAR polymerization; however, talazoparib exhibited greater PARP trapping activity that was associated with superior radiosensitization. This observation further correlated with an increased number of double-stranded DNA breaks induced by talazoparib as compared with veliparib. Finally, a dose of 0.2 mg/kg talazoparib in vivo caused tumor growth inhibition in combination with IR but not as a single agent in 3 SCLC PDX models. Conclusions: PARP inhibition effectively sensitizes SCLC cell lines and PDXs to IR, and PARP trapping activity enhances this effect. PARP inhibitors, especially those with high PARP trapping activity, may provide a powerful tool to improve the efficacy of radiotherapy in SCLC. Clin Cancer Res; 24(20); 5143–52. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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