Local genetic correlation quantifies the genetic similarity of complex traits in specific genomic regions. However, accurate estimation of local genetic correlation remains challenging, due to ...linkage disequilibrium in local genomic regions and sample overlap across studies. We introduce SUPERGNOVA, a statistical framework to estimate local genetic correlations using summary statistics from genome-wide association studies. We demonstrate that SUPERGNOVA outperforms existing methods through simulations and analyses of 30 complex traits. In particular, we show that the positive yet paradoxical genetic correlation between autism spectrum disorder and cognitive performance could be explained by two etiologically distinct genetic signatures with bidirectional local genetic correlations.
Recent advances in consortium-scale genome-wide association studies (GWAS) have highlighted the involvement of common genetic variants in autism spectrum disorder (ASD), but our understanding of ...their etiologic roles, especially the interplay with rare variants, is incomplete. In this work, we introduce an analytical framework to quantify the transmission disequilibrium of genetically regulated gene expression from parents to offspring. We applied this framework to conduct a transcriptome-wide association study (TWAS) on 7,805 ASD proband-parent trios, and replicated our findings using 35,740 independent samples. We identified 31 associations at the transcriptome-wide significance level. In particular, we identified POU3F2 (p = 2.1E-7), a transcription factor mainly expressed in developmental brain. Gene targets regulated by POU3F2 showed a 2.7-fold enrichment for known ASD genes (p = 2.0E-5) and a 2.7-fold enrichment for loss-of-function de novo mutations in ASD probands (p = 7.1E-5). These results provide a novel connection between rare and common variants, whereby ASD genes affected by very rare mutations are regulated by an unlinked transcription factor affected by common genetic variations.
Objective
This study was performed to analyze 22 cases of Mycoplasma pneumoniae pneumonia (MPP) associated with bronchial casts (BCs) in children.
Methods
We retrospectively reviewed all cases of MPP ...in children treated at our institution from November 2015 to December 2016. Demographic information, laboratory parameters, radiologic and fiberoptic bronchoscopy findings, treatment outcomes, and follow-up results were analyzed.
Results
Among 161 patients with MPP, 22 had BCs and 139 had no BCs. All BCs occurred in a segmental or subsegmental bronchus and were removed by fiberoptic bronchoscopy. Patients with BCs had a longer duration of fever after admission and higher incidence of refractory MPP. Substantially more children with than without BCs had a high M. pneumoniae load in the bronchoalveolar lavage fluid. All patients with BCs but only 55.4% without BCs were given methylprednisolone in addition to the standard antibiotic treatment. A significantly higher proportion of children with than without BCs received oxygen therapy. After discharge, complete radiological resolution took significantly longer in children with than without BCs.
Conclusions
In children with MPP, prompt removal of BCs may be necessary to prevent BC propagation. MPP with BCs is more severe than that without BCs, and treatment and recovery are more difficult.
Heterosigma akashiwo (H. akashiwo) is recognized as a harmful algal bloom (HABs) species with a global distribution, capable of posing significant threats to marine ecosystems, particularly when ...spread through ship ballast water. This investigation focused on elucidating the inactivation kinetics and underlying mechanism of H. akashiwo through a combined ultraviolet irradiation and peroxydisulfate (UV/PDS) process. The results demonstrated a strong synergistic effect within the UV/PDS system, resulting in an inactivation of 0.78-ln and 2.67-ln within 40 min of UV and UV/PDS processes. The principal agents accountable for inactivation were identified as sulfate radicals (•SO4−) and hydroxyl radical (•OH), which exhibited a synergistic effect in the UV/PDS process. Furthermore, the study observed a negatively impact of seawater pH and salinity on the efficiency of inactivation. UV/PDS caused oxidative stress on algal cells, initially involving the participation of antioxidant enzymes in counteracting cellular damage, but this protective mechanism diminished as the reaction duration extended. The UV/PDS treatment not only inflicted damage upon H. akashiwo's photosynthetic system but also caused the extracellular release of DNA and algal organic matter (AOM) due to damaged cell membranes. Transcriptome analysis provided a molecular biology perspective on the cellular inactivation process. Upregulation of genes linked to photosynthesis and oxidative phosphorylation suggested a potential elevation in energy metabolism. In contrast, genes associated with cellular and metabolic processes, including glycolysis and the tricarboxylic acid cycle (TCA cycle), exhibited downregulation. Moreover, this treatment exerted an inhibitory influence on RNA polymerase and protein synthesis, resulting in the reduced expression of genetic information.
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•Cell membrane of H. akashiwo was damaged by both •SO4− and •OH in UV/PDS.•DNA and AMO of H. akashiwo were released.•Disorder cellular metabolic processes such as TCA cycle of H. akashiwo were suppressed.•Gene expressions (RNA polymerase and protein synthesis) of H. akashiwo were disrupted.•The energy metabolism of H. akashiwo was enhanced to resist oxidative stress.
Interfacial adsorption kinetics and stabilizing emulsion behavior of lysozyme/xanthan gum nanoparticles (Ly/XG NPs) by variation of particle size and energy input. The interfacial rheology indicated ...that interfacial adsorption behavior of Ly/XG NPs displayed in a particle size manner. Increasing the particle size of Ly/XG NPs hindered its initial diffusion onto the interface. Smaller size was helpful for its fast diffusion to the interface. KP (rate constant of penetration) and KR (rate constant of penetration) of Ly/XG NPs were both affected by particle size. The KP for adsorbed Ly/XG NPs increased as the particle sizes increased. KR was considerably higher than KP, indicating the structural rearrangement of adsorbed Ly/XG NPs played an important part in interfacial film formation. The morphology of Pickering emulsion indicated its drop sizes were determined by the oil/aqueous volume fraction and prepared style. The higher energy input the size become smaller. Based on interfacial adsorption kinetics and microstructure of Pickering emulsions, the stabilization behavior was related to particle-particle associations and conformational changes of Ly/XG NPs. This work confirmed Ly/XG NPs could form Pickering emulsion by selecting different particle size and emulsification process, and offer promising prospects in stabilizing emulsion with the demands of surfactant-free.
•Interfacial adsorption kinetics of Ly/XG NPs at the interface were firstly investigated.•The stabilizing emulsion behavior of Ly/XG NPs with different particle sizes was studied.•A tentative model was established to illustrate the interfacial behavior of Ly/XG NPs.
Recent advances in large-scale genome-wide association studies (GWAS) have highlighted the involvement of common genetic variants in complex traits and diseases. Data integration efforts linking GWAS ...signals with functional annotation data have provided insights into the genetic architecture of numerous human complex traits. For example, expression quantitative trait loci (eQTL) studies in relevant biological tissues provide gene candidates for complex diseases, which can be tested as therapeutic targets. Integrating multi-omics annotation data with GWAS association data brings in orthogonal information and improves the understanding of complex trait etiology. In this dissertation, we present two approaches to link genomic annotations to genotype-phenotype associations identified through GWAS. The two approaches both associate complex traits with genetically imputed molecular traits (i.e., gene expression levels and metabolite levels), and identify regulatory and metabolic machineries underlying a variety of complex traits.We start with integrating eQTLs with autism spectrum disorder (ASD) in parent-offspring trios by quantifying the transmission disequilibrium of genetically regulated gene expression from parents to offspring and performing transcriptome-wide association studies (TWAS). We identify transcription factor POU3F2 in our analysis. POU3F2 mainly expresses in developmental brain and the gene targets regulated by POU3F2 are enriched for known risk genes for ASD and loss-of-function de novo mutations in ASD probands. TWAS suggests that ASD genes affected by very rare mutations may be regulated by an unlinked transcription factor affected by common genetic variations.Next, we extend our TWAS framework to study the regulatory roles of metabolite quantitative trait loci (mQTL). We introduce metabolome-wide association study (MWAS), which integrates metabolomics data with genetics data. We benchmarked and optimized genetic prediction models for a total of 703 metabolites from cerebrospinal fluid, plasma, and urine, and performed a biobank-wide association scan between imputed metabolite levels and 530 complex traits in UK Biobank. We found a total of 1,311 significant metabolite-trait associations after performing Bonferroni correction across all tested associations. The significant MWAS results explain the difference in human body fat mass and body fat-free mass. In summary, we perform joint analysis on eQTL/mQTL data and complex trait GWAS to identify genes or metabolites relevant to complex traits. Our approaches improve our understanding of the phenotypic outcomes of non-coding genetic variations and may contribute to novel biomarker discovery, clinical diagnosis improvement, and therapeutics development.
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•The first to investigate the Uronema marinum inactivation mechanism by omics.•The inactivation of Uronema marinum by UV/PDS in marine waters.•Contribution of reactive species on the ...inactivation of Uronema marinum.•Effect of reaction parameters on the inactivation of Uronema marinum.
Protozoa in mariculture water will cause the outbreak of seafood diseases, and there are also discharge regulations about protozoa in the ballast water of ocean ships. However, the inactivation of protozoa has not attracted attention. This study investigated the inactivation of ciliate Uronema marinum (U. marinum) as surrogate for protozoa by ultraviolet (UV)/peroxydisulfate (PDS) system. Results showed that the addition of 1 mM PDS significantly enhanced the inactivation from 0.73 log to 1.47 log by UV exposure at 3.6 mJ·cm−2. Reactive species responsible for the inactivation were identified to be •SO4− and •OH. The anions in seawater inhibited the inactivation of U. marinum in UV/PDS system. UV/PDS inactivated U. marinum by damaging the cell membrane and releasing of intracellular materials. The activities change of the antioxidant enzymes showed that oxidative species destroyed the defense function. Moreover, omics analysis proved that the radicals affected the expression of genes, proteins and metabolites of U.marinum. In authentic marine water, the inactivation of U. marinum was 1.38 log in 120 s. There was no generation of chlorate (ClO3−), bromate (BrO3−) and adsorbable organic halogens (AOX). The economic cost of UV/PDS for inactivation of U. marinum was preliminarily calculated to be 0.062 $ m−3. The results suggest that it will be beneficial to upgrade UV disinfection to •SO4− based advanced oxidation technology for inactivation of protozoa in marine water.
Sulfate radical (•SO
4
−
)–based advanced oxidation processes have attracted a great deal of attention for use in water disinfection because of their strong oxidation ability toward electron-rich ...moieties on microorganism molecules. However, a few studies have focused on the effects of •SO
4
−
on pathogenic microorganism inactivation in marine aquaculture water containing various inorganic anions. We employed the gram-negative bacteria
E. coli
and gram-positive bacteria
S. agalactiae
as representatives to evaluate the application of UV/persulfate (S
2
O
8
2−
, PDS), to the disinfection of marine aquaculture water in a comprehensive manner. Total inactivation of 4.13ˍlog of
E. coli
cells and 4.74ˍlog of
S. agalactiae
cells was reached within 120 s in the UV/PDS system. The inactivation of pathogenic bacteria in marine aquaculture water increased with the increasing PDS concentration and UV intensity. An acidic pH was beneficial for UV/PDS inactivation. Halogen-free radicals showed a strong influence on the inactivation. Anions in seawater, including Cl
−
, Br
−
, and HCO
3
−
inhibited the disinfection. The inactivation rates of pathogenic bacteria followed the order seawater < marine aquaculture water < freshwater. Pathogenic bacteria could also be effectively inactivated in actual marine aquaculture water and reservoir water. The analysis of the inactivation mechanisms showed that S
2
O
8
2−
was activated by UV to produce •SO
4
−
, which damaged the cell membranes. In addition, antioxidant enzymes, including SOD and CAT, were induced. The genomic DNA was also damaged. Inorganic disinfection byproducts such as chlorate and bromate were not formed during the disinfection of marine aquaculture water, which indicated that UV/PDS was a safe and efficient disinfection method.
Graphical abstract
Many studies have reported that hydroxyl radical (HO˙) driven advanced oxidation processes (AOPs) could degrade fluoroquinolones (FQs) antibiotics effectively. Compared with HO˙, sulfate radical (SO
...˙
) shows a similar oxidation capacity but a longer half-life. SO
˙
could cause chain reactions and resulted in the generation of halogen radicals and carbonate radicals from the main anions in sea water including Cl
, Br
and HCO
. However, few studies were focused on the degradation of FQs in marine aquaculture water and seawater, as well as the bioaccumulation of transformation products. As a typical member of FQs, flumequine (FLU) was degraded by UV/peroxodisulfate (PDS) AOPs in synthetic fresh water, marine aquaculture water and seawater. The reaction rate constants in the three water samples were 0.0348 min
, 0.0179 min
and 0.0098 min
, respectively. The reason was attributed to the inhibition of the anions as they could consume SO
˙
and initiate the quenching reaction of free radicals. When the pH value increased from 5 to 9, the reaction rate decreased from 0.0197 min
to 0.0066 min
. The energy difference between HOMO and LUMO of FLU was calculated to be 8.07 eV indicating that FLU was a stable compound. The atoms on quinolone ring of FLU with high negative charge would be more vulnerable to attack by free radicals through electrophilic reactions. Two possible degradation pathways of FLU were inferred according to the degradation products. Preliminary bioaccumulation analysis of transformation products by the EPI suite software proved that the values of log
and log BCF of the final product P100 were less than those of FLU and the intermediates.
Silver nanoparticles (Ag NPs) were green synthesized using native inulin as the reducing and capping agent with varied incubation temperatures, incubation times and Ag
concentrations. The ...biosynthesized Ag NPs were characterized using UV-visible spectroscopy, Field Emission Transmission Electron Microscopy (FE-TEM) and X-ray powder diffraction. The UV visible spectra of the Ag NPs revealed a characteristic surface plasmon resonance peak at 420 nm. FE-TEM showed that the biosynthesized Ag NPs were spherically shaped and monodispersed nanoparticles. The sizes were 18.5 ± 0.9 nm and 20.0 ± 1.2 nm for the Ag NPs synthesized at 80 °C and 100 °C for 2 h using 0.1% inulin and 2 mM Ag
. Their PDIs were 0.180 ± 0.05 and 0.282 ± 0.13, respectively. Improving the incubation temperature, incubation time and silver nitrate concentration promoted Ag NP synthesis. The prepared Ag NPs were effective in the catalytic reduction of 4-NP and in inhibiting the growth of bacteria. The inhibition zone could reach 10.21 ± 2.12 mm and 9.92 ± 0.50 mm for
and
. The kinetic rate constant (
) could reach 0.0113 s
, and the maximum inhibitory zones were 10.21 ± 2.12 mm and 9.92 ± 0.50 mm, respectively, for the two microorganisms. This biosynthesis illustrates that native inulin could be a potential candidate in the green fabrication of Ag NPs, and this is promising in catalytic and bacteriostatic fields.
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