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1.
Hollow alginate microfibers (od = 1.3 mm, id = 0.9 mm, th = 400 µm, L = 3.5 cm) comprised of 2% (w/v) medium molecular weight alginate cross-linked with 0.9 M CaCl2 were fabricated to model outward diffusion capture by 2D fluorescent microscopy. A two-fold comparison of diffusivity determination based on real-time diffusion of Fluorescein isothiocyanate molecular weight (FITC MW) markers was conducted using a proposed Fickian-based approach in conjunction with a previously established numerical model developed based on spectrophotometric data. Computed empirical/numerical (Dempiricial/Dnumerical) diffusivities characterized by small standard deviations for the 4-, 70- and 500-kDa markers expressed in m2/s are (1.06 × 10−9 ± 1.96 × 10−10)/(2.03 × 10−11), (5.89 × 10−11 ± 2.83 × 10−12)/(4.6 × 10−12) and (4.89 × 10−12 ± 3.94 × 10−13)/(1.27 × 10−12), respectively, with the discrimination between the computation techniques narrowing down as a function of MW. The use of the numerical approach is recommended for fluorescence-based measurements as the standard computational method for effective diffusivity determination until capture rates (minimum 12 fps for the 4-kDa marker) and the use of linear instead of polynomial interpolating functions to model temporal intensity gradients have been proven to minimize the extent of systematic errors associated with the proposed empirical method.  相似文献   

2.
Random mutagenesis and screening for enzymatic activity has been used to engineer horse heart myoglobin to enhance its intrinsic peroxidase activity. A chemically synthesized gene encoding horse heart myoglobin was subjected to successive cycles of PCR random mutagenesis. The mutated myoglobin gene was expressed in Escherichia coli LE392, and the variants were screened for peroxidase activity with a plate assay. Four cycles of mutagenesis and screening produced a series of single, double, triple, and quadruple variants with enhanced peroxidase activity. Steady-state kinetics analysis demonstrated that the quadruple variant T39I/K45D/F46L/I107F exhibits peroxidase activity significantly greater than that of the wild-type protein with k1 (for H2O2 oxidation of metmyoglobin) of 1.34 × 104 M−1 s−1 (≈25-fold that of wild-type myoglobin) and k3 [for reducing the substrate (2, 2′-azino-di-(3-ethyl)benzthiazoline-6-sulfonic acid] of 1.4 × 106 M−1 s−1 (1.6-fold that of wild-type myoglobin). Thermal stability of these variants as measured with circular dichroism spectroscopy demonstrated that the Tm of the quadruple variant is decreased only slightly compared with wild-type (74.1°C vs. 76.5°C). The rate constants for binding of dioxygen exhibited by the quadruple variant are identical to the those observed for wild-type myoglobin (kon, 22.2 × 10−6 M−1 s−1 vs. 22.3 × 10−6 M−1 s−1; koff, 24.3 s−1 vs. 24.2 s−1; KO2, 0.91 × 10−6 M−1 vs. 0.92 × 10−6 M−1). The affinity of the quadruple variant for CO is increased slightly (kon, 0.90 × 10−6 M−1s−1 vs. 0.51 × 10−6 M−1s−1; koff, 5.08 s−1 vs. 3.51 s−1; KCO, 1.77 × 10−7 M−1 vs. 1.45 × 10−7 M−1). All four substitutions are in the heme pocket and within 5 Å of the heme group.  相似文献   

3.
4.
The solubilization and thermodynamic analysis of isotretinoin (ITN) in eleven distinct green solvents, such as water, methyl alcohol (MeOH), ethyl alcohol (EtOH), 1-butyl alcohol (1-BuOH), 2-butyl alcohol (2-BuOH), ethane-1,2-diol (EG), propane-1,2-diol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO) was studied at several temperatures and a fixed atmospheric pressure. The equilibrium approach was used to measure the solubility of ITN, and the Apelblat, van’t Hoff, and Buchowski–Ksiazczak λh models were used to correlate the results. The overall uncertainties were less than 5.0% for all the models examined. The highest ITN mole fraction solubility was achieved as 1.01 × 10−1 in DMSO at 318.2 K; however, the least was achieved as 3.16 × 10−7 in water at 298.2 K. ITN solubility was found to be enhanced with an increase in temperature and the order in which it was soluble in several green solvents at 318.2 K was as follows: DMSO (1.01 × 10−1) > EA (1.73 × 10−2) > PEG-400 (1.66 × 10−2) > THP (1.59 × 10−2) > 2-BuOH (6.32 × 10−3) > 1-BuOH (5.88 × 10−3) > PG (4.83 × 10−3) > EtOH (3.51 × 10−3) > EG (3.49 × 10−3) > MeOH (2.10 × 10−3) > water (1.38 × 10−6). ITN–DMSO showed the strongest solute–solvent interactions when compared to the other ITN and green solvent combinations. According to thermodynamic studies, ITN dissolution was endothermic and entropy-driven in all of the green solvents tested. The obtained outcomes suggested that DMSO appears to be the best green solvent for ITN solubilization.  相似文献   

5.
A rapid Listeria detection method was developed utilizing A511 bacteriophage amplification combined with surface-enhanced Raman spectroscopy (SERS) and lateral flow immunochromatography (LFI). Anti-A511 antibodies were covalently linked to SERS nanoparticles and printed onto nitrocellulose membranes. Antibody-conjugated SERS nanoparticles were used as quantifiable reporters. In the presence of A511, phage-SERS nanoparticle complexes were arrested and concentrated as a visible test line, which was interrogated quantitatively by Raman spectroscopy. An increase in SERS intensity correlated to an increase in captured phage-reporter complexes. SERS limit of detection was 6 × 106 pfu·mL−1, offering detection below that obtainable by the naked eye (LOD 6 × 107 pfu·mL−1). Phage amplification experiments were carried out at a multiplicity of infection (MOI) of 0.1 with 4 different starting phage concentrations monitored over time using SERS-LFI and validated by spot titer assay. Detection of L. monocytogenes concentrations of 1 × 107 colony forming units (cfu)·mL−1, 5 × 106 cfu·mL−1, 5 × 105 cfu·mL−1 and 5 × 104 cfu·mL−1 was achieved in 2, 2, 6, and 8 h, respectively. Similar experiments were conducted at a constant starting phage concentration (5 × 105 pfu·mL−1) with MOIs of 1, 2.5, and 5 and were detected in 2, 4, and 5 h, respectively.  相似文献   

6.
The ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in the recent emergence of a highly divergent variant of concern (VOC) defined as Omicron or B.1.1.529. This VOC is of particular concern because it has the potential to evade most therapeutic antibodies and has undergone a sustained genetic evolution, resulting in the emergence of five distinct sub-lineages. However, the evolutionary dynamics of the initially identified Omicron BA.1 and BA.2 sub-lineages remain poorly understood. Herein, we combined Bayesian phylogenetic analysis, mutational profiling, and selection pressure analysis to track the virus’s genetic changes that drive the early evolutionary dynamics of the Omicron. Based on the Omicron dataset chosen for the improved temporal signals and sampled globally between November 2021 and January 2022, the most recent common ancestor (tMRCA) and substitution rates for BA.1 were estimated to be that of 18 September 2021 (95% highest posterior density (HPD), 4 August–22 October 2021) and 1.435 × 10−3 (95% HPD  =  1.021 × 10−3 − 1.869 × 10−3) substitution/site/year, respectively, whereas 3 November 2021 (95% highest posterior density (HPD) 26 September–28 November 2021) and 1.074 × 10−3 (95% HPD  =  6.444 × 10−4 − 1.586 × 10−3) substitution/site/year were estimated for the BA.2 sub-lineage. The findings of this study suggest that the Omicron BA.1 and BA.2 sub-lineages originated independently and evolved over time. Furthermore, we identified multiple sites in the spike protein undergoing continued diversifying selection that may alter the neutralization profile of BA.1. This study sheds light on the ongoing global genomic surveillance and Bayesian molecular dating analyses to better understand the evolutionary dynamics of the virus and, as a result, mitigate the impact of emerging variants on public health.  相似文献   

7.
A copper film modified glassy carbon electrode (CuF/GCE) and a novel copper film with carbon nanotubes modified screen-printed electrode (CuF/CN/SPE) for anodic stripping voltammetric measurement of ultratrace levels of Cd(II) are presented. During the development of the research procedure, several main parameters were investigated and optimized. The optimal electroanalytical performance of the working electrodes was achieved in electrolyte 0.1 M HCl and 2 × 10−4 M Cu(II). The copper film modified glassy carbon electrode exhibited operation in the presence of dissolved oxygen with a calculated limit of detection of 1.7 × 10−10 M and 210 s accumulation time, repeatability with RSD of 4.2% (n = 5). In the case of copper film with carbon nanotubes modified screen-printed electrode limit of detection amounted 1.3 × 10−10 M for accumulation time of 210 s and with RSD of 4.5% (n = 5). The calibration curve has a linear range in the tested concentration of 5 × 10−10–5 × 10−7 M (r = 0.999) for CuF/GCE and 3 × 10−10–3 × 10−7 M (r = 0.999) for CuF/CN/SPE with 210 s accumulation time in both cases. The used electrodes enable trace determination of cadmium in different environmental water samples containing organic matrix. The validation of the proposed procedures was carried out through analysis certified reference materials: TM-25.5, SPS-SW1, and SPS-WW1.  相似文献   

8.

Background and objectives

One hypothesis states that IgA nephropathy (IgAN) is a syndrome with an autoimmune component. Recent studies strongly support the notion of shared genetics between immune-related diseases. This study investigated single-nucleotide polymorphisms (SNPs) reported to be associated with systemic lupus erythematosus (SLE) in a Chinese cohort of patients with IgAN and in controls.

Design, setting, participants, & measurements

This study investigated whether SNP markers that had been reported to be associated with SLE were also associated with IgAN in a Chinese population. The study cohort consisted of 1194 patients with IgAN and 902 controls enrolled in Peking University First Hospital from 1997 to 2008.

Results

Ninety-six SNPs mapping to 60 SLE loci with reported P values <1×10−5 were investigated. CFH (P=8.41×10−6), HLA-DRA (P=4.91×10−6), HLA-DRB1 (P=9.46×10−9), PXK (P=3.62×10−4), BLK (P=9.32×10−3), and UBE2L3 (P=4.07×10−3) were identified as shared genes between IgAN and SLE. All associations reported herein were corroborated by associations at neighboring SNPs. Many of the alleles that are risk alleles for SLE are protective alleles for IgAN. By analyses of two open independent expression quantitative trait loci (eQTL) databases, correlations between genotypes and corresponding gene expression were observed (P<0.05 in multiple populations), suggesting a cis-eQTL effect. From gene-expression databases, differential expressions of these genes were observed in IgAN. Additive interactions between PXK rs6445961and HLA-DRA rs9501626 (P=1.51×10−2), as well as multiplicative interactions between CFH rs6677604 and HLA-DRB1 rs9271366 (P=1.77×10−2), and between HLA-DRA rs9501626 and HLA-DRB1 rs9271366 (P=3.23×10−2) were observed. Disease risk decreased with accumulation of protective alleles. Network analyses highlighted four pathways: MHC class II antigen presentation, complement regulation, signaling by the B-cell receptor, and ubiquitin/proteasome-dependent degradation.

Conclusion

From this “systems genetics” perspective, these data provide important clues for future studies on pleiotropy in IgAN and lupus nephritis.  相似文献   

9.
TiMoN coatings with different Mo contents on a SS316L substrate are deposited by using closed field unbalanced magnetron sputtering ion plating (CFUMSIP) technology to enhance the corrosion resistance and durability of stainless steel (SS) bipolar plates (BPs) in proton exchange membrane fuel cell (PEMFC) during the start-up/shut-down process. The electrochemical test results illustrate that TiMoN-4A coating has extremely good corrosion resistance compared to other coatings. The potentiostat polarization (+0.6 VSCE) tests indicate that the corrosion current density (Icorr) of TiMoN-4A coating is 5.22 × 10−7A cm−2, which meets the department of energy 2020 targets (DOE, ≤1 × 10−6 A cm−2). Otherwise, TiMoN-4A coating also exhibits the best corrosion resistance and stability in potentiostatic polarization, electrochemical impedance spectroscopy (EIS), and high potential (+1.2VSCE) polarization tests. The interfacial contact resistance (ICR) measurement results show that TiMoN-4A coating has the minimum ICR of 9.19 mΩ·cm2, which meets the DOE 2020 targets (≤10 mΩ·cm2).  相似文献   

10.
This study aimed to analyze the genetic and evolutionary characteristics of the influenza A/H3N2 viruses circulating in Myanmar from 2015 to 2019. Whole genomes from 79 virus isolates were amplified using real-time polymerase chain reaction and successfully sequenced using the Illumina iSeq100 platforms. Eight individual phylogenetic trees were retrieved for each segment along with those of the World Health Organization (WHO)-recommended Southern Hemisphere vaccine strains for the respective years. Based on the WHO clades classification, the A/H3N2 strains in Myanmar from 2015 to 2019 collectively belonged to clade 3c.2. These strains were further defined based on hemagglutinin substitutions as follows: clade 3C.2a (n = 39), 3C.2a1 (n = 2), and 3C.2a1b (n = 38). Genetic analysis revealed that the Myanmar strains differed from the Southern Hemisphere vaccine strains each year, indicating that the vaccine strains did not match the circulating strains. The highest rates of nucleotide substitution were estimated for hemagglutinin (3.37 × 10−3 substitutions/site/year) and neuraminidase (2.89 × 10−3 substitutions/site/year). The lowest rate was for non-structural protein segments (4.19 × 10−5 substitutions/site/year). The substantial genetic diversity that was revealed improved phylogenetic classification. This information will be particularly relevant for improving vaccine strain selection.  相似文献   

11.
We used intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) to explore the possibility of preoperative diagnosis of soft tissue tumors (STTs). This prospective study enrolled 23 patients. Conventional MRI and IVIM examinations were performed on a 3.0T MR imager. Eight (35%) hemangiomas, 11 (47%) benign soft tissue tumors excluding hemangiomas (BSTTEHs) and 4 soft tissue sarcomas (STSs) were assessed. The mean tumor size was about 1652.36 ± 233.66 mm2. Ten b values (0–800 s/mm2) were used to evaluate diffusion and perfusion characteristics of IVIM. IVIM parameters (ADCstandard, ADCslow, ADCfast, and f) of STTs were measured and evaluated for differentiating hemangiomas, BSTTEHs, and STSs. ADCslow and ADCfast value were different for hemangiomas, BSTTEHs, and STSs separately (P < 0.001, P < 0.001, and P = 0.001). ADCslow, cut-off value smaller than 0.93 × 10–3 mm2/s, was the best parameter to differ STSs (0.689 ± 0.173 × 10−3 mm2/s) from hemangiomas (0.933 ± 0.237 × 10−3 mm2/s) and BSTTEHs (1.156 ± 0.120 × 10−3 mm2/s) (P = 0.001). ADCslow (0.93 × 10−3 mm2/s <cut-off value <0.96 × 10−3 mm2/s) was used to distinguish hemangiomas from BSTTs. There were significant difference among hemangiomas, BSTTEHs, and STSs (P= 0.014, P= 0.036, P < 0.001). The ADCstandard, ADCfast, and f value were different (P< 0.05) for STSs (1.009 ± 0.177 × 10−3 mm2/s, 15.700 ± 1.992 × 10−3 mm2/s, 0.503 ± 0.068), hemangiomas (1.505 ± 0.226 × 10−3 mm2/s, 11.675 ± 0.456 × 10−3 mm2/s, 0.682 ± 0.060), and BSTTEHs (1.555 ± 0.176 × 10−3 mm2/s, 11.727 ± 0.686 × 10−3 mm2/s, 0.675 ± 0.054). And there was no significant difference for these 3 parameters between hemangiomas and BSTTEHs (P= 0.584, 0.907, and 0.798). IVIM may be of significant value for differential diagnosing hemangiomas, BSTTEHs, and STSs.  相似文献   

12.
In this work, an electrochemically activated screen-printed carbon electrode modified with sodium dodecyl sulfate (aSPCE/SDS) was proposed for the simultaneous determination of paracetamol (PA), diclofenac (DF), and tramadol (TR). Changes of surface morphology and electrochemical behaviour of the electrode after the electrochemical activation with H2O2 and SDS surface modification were studied by scanning electron microscopy (SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The influence of various parameters on the responses of the aSPCE/SDS such as pH and concentration of the buffer, SDS concentration, and techniques parameters were investigated. Using optimised conditions (Eacc. of −0.4 V, tacc. of 120 s, ΔEA of 150 mV, ν of 250 mV s−1, and tm of 10 ms), the aSPCE/SDS showed a good linear response in the concentration ranges of 5.0 × 10−8–2.0 × 10−5 for PA, 1.0 × 10−9–2.0 × 10−7 for DF, and 1.0 × 10−8–2.0 × 10−7 and 2.0 × 10−7–2.0 × 10−6 mol L−1 for TR. The limits of detection obtained during the simultaneous determination of PA, DF, and TR are 1.49 × 10−8 mol L−1, 2.10 × 10−10 mol L−1, and 1.71 × 10−9 mol L−1, respectively. The selectivity of the aSPCE/SDS was evaluated by examination of the impact of some inorganic and organic substances that are commonly present in environmental and biological samples on the responses of PA, DF, and TR. Finally, the differential pulse adsorptive stripping voltammetric (DPAdSV) procedure using the aSPCE/SDS was successfully applied for the determination of PA, DF, and TR in river water and serum samples as well as pharmaceuticals.  相似文献   

13.
Serological detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N), spike (S), and neutralizing antibodies (Abs) is commonly undertaken to evaluate the efficacy of vaccination. However, the relative efficiency of different SARS-CoV-2 Ab detection systems has not been extensively investigated. Here, we evaluated serological test systems in vaccinated Japanese. SARS-CoV-2 N, S, and neutralizing Abs in sera of 375 healthy subjects a mean 253 days after vaccination were assessed. The sensitivity of Elecsys Anti-SARS-CoV-2 S (Roche S) and Anti-SARS-CoV-2 S IgG (Fujirebio S) was 100% and 98.9%, respectively, with a specificity of 100% for both. The sensitivity of Anti-SARS-CoV-2 neutralizing Ab (MBL Neu) was 2.7%, and the specificity was 100%. Fujirebio S correlated with Roche S (rho = 0.9182, p = 3.97 × 10−152). Fujirebio S (rho = 0.1295, p = 0.0121) and Roche S (rho = 0.1232, p = 0.0170) correlated weakly with MBL Neu. However, Roche S did correlate with MBL Neu in patients with COVID-19 (rho = 0.8299, p = 1.01 × 10−12) and in healthy subjects more recently after vaccination (mean of 90 days, rho = 0.5306, p = 0.0003). Thus, the Fujirebio S and Roche S results were very similar, but neither correlated with neutralizing antibody titers by MBL Neu at a later time after vaccination.  相似文献   

14.
The emergence of SARS-CoV-2 in the human population and the resulting COVID-19 pandemic have led to the development of various diagnostic tests. The OraSure InteliSwab COVID-19 Rapid Test is a recently developed and FDA emergency use-authorized rapid antigen-detecting test that functions as a lateral flow device targeting the nucleocapsid protein. Due to SARS-CoV-2 evolution, there is a need to evaluate the sensitivity of rapid antigen-detecting tests for new variants, especially variants of concern such as Omicron. In this study, the sensitivity of the OraSure InteliSwab Test was investigated using cultured strains of the known variants of concern (VOCs, Alpha, Beta, Gamma, Delta, and Omicron) and the ancestral lineage (lineage A). Based on dilution series in cell culture medium, an approximate limit of detection for each variant was determined. The OraSure InteliSwab Test showed an overall comparable performance using recombinant nucleocapsid protein and different cultured variants, with recorded limits of detection ranging between 3.77 × 105 and 9.13 × 105 RNA copies/mL. Finally, the sensitivity was evaluated using oropharyngeal swabs from Syrian golden hamsters inoculated with the six VOCs. Ultimately, the OraSure InteliSwab COVID-19 Rapid Test showed no decrease in sensitivity between the ancestral SARS-CoV-2 strain and any VOCs including Omicron.  相似文献   

15.
LaBaCo2−xMoxO5+δ (LBCMx, x = 0–0.08) cathodes synthesized by a sol-gel method were evaluated for intermediate-temperature solid oxide fuel cells. The limit of the solid solubility of Mo in LBCMx was lower than 0.08. As the content of Mo increased gradually from 0 to 0.06, the thermal expansion coefficient decreased from 20.87 × 10−6 K−1 to 18.47 × 10−6 K−1. The introduction of Mo could increase the conductivity of LBCMx, which varied from 464 S cm−1 to 621 S cm−1 at 800 °C. The polarization resistance of the optimal cathode LBCM0.04 in air at 800 °C was 0.036 Ω cm2, reduced by a factor of 1.67 when compared with the undoped Mo cathode. The corresponding maximum power density of a single cell based on a YSZ electrolyte improved from 165 mW cm−2 to 248 mW cm−2 at 800 °C.  相似文献   

16.
Diesel particulates are deposited in the diesel particulate filter and removed by the regeneration process. The Printex-U (PU) particles are simulated as the diesel soot to investigate the influence of thermal aging conditions on soot combustion performance with the addition of catalysts. The comprehensive combustion index S, combustion stability index Rw and peak temperature Tp are obtained to evaluate the combustion performance. Compared with the PU/Pt mixtures of different Pt contents (2 g/ft3, 3.5 g/ft3, and 5 g/ft3), the 10 g/ft3 Pt contents improve soot combustion with the outstanding oxygen absorption ability. When the weight ratio of PU/Pt mixture is 1:1, the promoted effect achieves the maximum degree. The S and Rw increase to 8.90 × 10−8 %2min−2°C−3 and 39.11 × 105, respectively, compared with pure PU. After the thermal aging process, the PU/Pt mixture with a 350 °C aging temperature for 10 h promotes the soot combustion the best when compared to pure PU particles. It is not good as the PU/Pt mixture without aging, because the inner properties of soot and Pt/Al2O3 catalyst may have been changed. The S and Rw are 9.07 × 10−8 %2min−2°C−3 and 38.39 × 105, respectively, which are close to the no aging mixture. This work plays a crucial role in understanding the mechanism of the comprehensive effect of soot and catalyst on soot combustion after the thermal aging process.  相似文献   

17.
Testosterone (TST), despite its good properties, may be harmful to the human organism and the environment. Therefore, monitoring biological fluids and environmental samples is important. An electrochemically pretreated screen-printed carbon sensor modified with Pb nanoparticles (pSPCE/PbNPs) was successfully prepared and used for the determination of TST. The surface morphology and electrochemical properties of unmodified and modified sensors were characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning and transmission electron microscopy (SEM and TEM), and energy-dispersive X-ray spectroscopy (EDS). Selective determinations of TST at the pSPCE/PbNPs were carried out by differential pulse adsorptive stripping voltammetry (DPAdSV, EPb dep.and TST acc. of −1.1 V, t Pb dep.and TST acc. of 120 s, ΔEA of 50 mV, ν of 175 mV s−1, and tm of 5 ms) in a solution containing 0.075 mol L−1 acetate buffer of pH = 4.6 ± 0.1, and 7.5 × 10−5 mol L−1 Pb(NO3)2. The analytical signal obtained at the potential around −1.42 V (vs. silver pseudo-reference electrode) is related to the reduction process of TST adsorbed onto the electrode surface. The use of pSPCE/PbNPs allows obtaining a very low limit of TST detection (2.2 × 10−12 mol L−1) and wide linear ranges of the calibration graph (1.0 × 10−11–1.0 × 10−10, 1.0 × 10−10–2.0 × 10−9, and 2.0 × 10−9–2.0 × 10−8 mol L−1). The pSPCE/PbNPs were successfully applied for the determination of TST in reference material of human urine and wastewater purified in a sewage treatment plant without preliminary preparation.  相似文献   

18.
We have developed an online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs (TASs). Reported TASs were common [median risk allele frequency 36%, interquartile range (IQR) 21%−53%] and were associated with modest effect sizes [median odds ratio (OR) 1.33, IQR 1.20–1.61]. Among 20 genomic annotation sets, reported TASs were significantly overrepresented only in nonsynonymous sites [OR = 3.9 (2.2−7.0), p = 3.5 × 10−7] and 5kb-promoter regions [OR = 2.3 (1.5−3.6), p = 3 × 10−4] compared to SNPs randomly selected from genotyping arrays. Although 88% of TASs were intronic (45%) or intergenic (43%), TASs were not overrepresented in introns and were significantly depleted in intergenic regions [OR = 0.44 (0.34−0.58), p = 2.0 × 10−9]. Only slightly more TASs than expected by chance were predicted to be in regions under positive selection [OR = 1.3 (0.8−2.1), p = 0.2]. This new online resource, together with bioinformatic predictions of the underlying functionality at trait/disease-associated loci, is well-suited to guide future investigations of the role of common variants in complex disease etiology.  相似文献   

19.
Italy’s second wave of SARS-CoV-2 has hit hard, with more than three million cases and over 100,000 deaths, representing an almost ten-fold increase in the numbers reported by August 2020. Herein, we present an analysis of 6515 SARS-CoV-2 sequences sampled in Italy between 29 January 2020 and 1 March 2021 and show how different lineages emerged multiple times independently despite lockdown restrictions. Virus lineage B.1.177 became the dominant variant in November 2020, when cases peaked at 40,000 a day, but since January 2021 this is being replaced by the B.1.1.7 ‘variant of concern’. In addition, we report a sudden increase in another documented variant of concern—lineage P.1—from December 2020 onwards, most likely caused by a single introduction into Italy. We again highlight how international importations drive the emergence of new lineages and that genome sequencing should remain a top priority for ongoing surveillance in Italy.  相似文献   

20.
Prednisolone, at concentrations between 2·78 × 10−6 M (1 μg/ml) and 1·39 × 10−8 M (5 × 10−3 μg/ml) exerts an inhibitory effect on the phagocytosis of latex particles by normal human polymorphonuclear leucocytes in vitro as assessed by electron microscopical analysis. This inhibition appears to be receptor-mediated, as it is dependent upon RNA and protein synthesis and is glucocorticoid specific.  相似文献   

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