Copy Number Variants in the human genome and their association with quantitative traits

Copy number Variants (CNVs), which comprise deletions, insertions and inversions of genomic sequence, are a main form of genetic variation between individual genomes. CNVs are commonly present in the genomes of human and other species. However, they have not been extensively characterized as their ascertainment is challenging. I reviewed current CNV studies and CNV discovery methods, especially the algorithms which infer CNVs from whole genome Single Nucleotide Polymorphism (SNP) arrays and compared the performance of three analytical tools in order to identify the best method of CNV identification. Then I applied this method to identify CNV events in three European population isolates—the island of Vis in Croatia, the islands of Orkney in Scotland and villages in the South Tyrol in Italy - from Illumina genome-wide array data with more than 300,000 SNPs. I analyzed and compared CNV features across these three populations, including CNV frequencies, genome distribution, gene content, segmental duplication overlap and GC content. With the pedigree information for each population, I investigated the inheritance and segregation of CNVs in families. I also looked at association between CNVs and quantitative traits measured in the study samples. CNVs were widely found in study samples and reference genomes. Discrepancies were found between sets of CNVs called by different analytical tools. I detected 4016 CNVs in 1964 individuals, out of a total of 2789 participants from the three population isolates, which clustered into 743 copy number variable regions (CNVRs). Features of these CVNRs, including frequency and distribution, were compared and were shown to differ significantly between the Orcadian, South Tyrolean and Dalmatian population samples. Consistent with the inference that this indicated population-specific CNVR identity and origin, it was also demonstrated that CNV variation within each population can be used to measure genetic relatedness. Finally, I discovered that individuals who had extreme values of some metabolic traits possessed rare CNVs which overlapped with known genes more often than in individuals with moderate trait values

Identifying Expressway Accident Black Spots Based on the Secondary Division of Road Units

For the purpose of reducing the harm of expressway traffic accidents and improving the accuracy of traffic accident black spots identification, this paper proposes a method for black spots identification of expressway accidents based on road unit secondary division and empirical Bayes method. Based on the modelling ideas of expressway accident prediction models in HSM (Highway Safety Manual), an expressway accident prediction model is established as a prior distribution and combined with empirical Bayes method safety estimation to obtain a Bayes posterior estimate. The posterior estimated value is substituted into the quality control method to obtain the black spots identification threshold. Finally, combining the Xi\u27an-Baoji expressway related data and using the method proposed in this paper, a case study of Xibao Expressway is carried out, and sections 9, 19, and 25 of Xibao Expressway are identified as black spots. The results show that the method of secondary segmentation based on dynamic clustering can objectively describe the concentration and dispersion of accident spots on the expressway, and the proposed black point recognition method based on empirical Bayes method can accurately identify accident black spots. The research results of this paper can provide a basis for decision-making of expressway management departments, take targeted safety improvement measures

Chinese language teachers’ dichotomous identities when teaching ingroup and outgroup students

Research into second language teacher identity has experienced a shift in recent years from a cognitive perspective to social constructionist orientation. The existing research in Chinese language literature in relation to Foreign Language (CFL) teachers’ identity shift is principally in relation to the change of social, cultural, and institutional contexts. Built on the current literature, this research asks: “How might teachers’ self-images or self-conceptualizations be renegotiated when they are located within their own mainstream cultural and educational system, yet comprised of students from various cultural backgrounds?” The data were collected from a group of CFL teachers in a South China university. The research found that students’ backgrounds largely impacted on, and led to, the teachers’ dichotomous relational identities, but did not dramatically change the teachers’ perception on what or how much subject knowledge to be possessed to make an ideal CFL teacher. This attribute of their identity was sustained even though the teaching content was modified at a practical level in response to groups’ differences. Further, the CFL teachers’ pedagogical identity remained stable with only minor modifications when teaching “ingroups” and “outgroups” of students

miR‐155 promotes macrophage pyroptosis induced by Porphyromonas gingivalis through regulating the NLRP3 inflammasome

ObjectiveThe aim of this study is to detect pyroptosis in macrophages stimulated with Porphyromonas gingivalis and elucidate the mechanism by which P. gingivalis induces pyroptosis in macrophages.MethodsThe immortalized human monocyte cell line U937 was stimulated with P. gingivalis W83. Flow cytometry was carried out to detect pyroptosis in macrophages. The expression of miR‐155 was detected by real‐time PCR and inhibited using RNAi. Suppressor of cytokine signaling (SOCS) 1, cleaved GSDMD, caspase (CAS)‐1, caspase‐11, apoptosis‐associated speck‐like protein (ASC), and NOD‐like receptor protein 3 (NLRP3) were detected by Western blotting, and IL‐1β and IL‐18 were detected by ELISA.ResultsThe rate of pyroptosis in macrophages and the expression of miR‐155 increased upon stimulation with P. gingivalis and pyroptosis rate decreased when miR‐155 was silenced. GSDMD‐NT, CAS‐11, CAS‐1, ASC, NLRP3, IL‐1β, and IL‐18 levels increased, but SOCS1 decreased in U937 cells after stimulated with P. gingivalis. These changes were weakened in P. gingivalis‐stimulated U937 macrophages transfected with lentiviruses carrying miR‐155 shRNA compared to those transfected with non‐targeting control sequence. However, there was no significant difference in ASC expression between P. gingivalis‐stimulated shCont and shMiR‐155 cells.ConclusionsPorphyromonas gingivalis promotes pyroptosis in macrophages during early infection. miR‐155 is involved in this process through regulating the NLRP3 inflammasome.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152887/1/odi13198_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152887/2/odi13198.pd

Associated factors and global adherence of cervical cancer screening in 2019:a systematic analysis and modelling study

BACKGROUND: Cervical cancer screening is vital for its prevention. Adherence is a crucial indicator that implies the individual willingness to take cervical cancer screening. We aimed to estimate the global and regional adherence rates of cervical cancer screening in 2019 and identify its associated factors among general women. METHOD: We searched studies in PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Database, ProQuest theses database and Google Web, without a lower time limit and until 23 June, 2021. Survey studies were considered eligible if they investigated cervical cancer screening adherence among general women, with data on sample size, the number of adherent subjects, and/or adherence rate. Random-effects were used to pool the odds ratios (ORs) of associated factors of adherence. Using modelling analysis, we estimated 2019 overall and age-specific adherence rates at the global and regional levels in women aged 20–69 years. RESULTS: Eight thousand two hundred ninety records were identified, and 153 articles were included. Being married (vs not married: OR, 1.34; 95% confidence interval [CI]: 1.23–1.46), higher educational attainment (higher than high school vs less than high school: OR, 1.44; 95% CI: 1.35–1.53), having healthcare (OR, 1.64; 95% CI: 1.43–1.88), former smoking (OR, 1.20; 95% CI: 1.07–1.34), physical activity (OR, 1.19; 95% CI: 1.05–1.36), parity (OR, 1.07; 95% CI: 1.01–1.12), and chronic disease (OR, 1.17; 95% CI: 1.04–1.32) were associated with better adherence, whereas obesity (vs normal: OR, 0.85; 95% CI: 0.74–0.97) and current smoking (vs former/never: OR, 0.64; 95% CI: 0.54–0.76) were associated with worse adherence. In 2019, the adherence was at 33.66% (95% CI: 23.34–39.30%) worldwide, and was higher in high-income countries (HICs) (75.66, 95% CI: 66.74–82.81%) than in low and middle-income countries (LMICs) (24.91, 95% CI: 14.30–30.24%). It varied across regions, the highest in the European region (65.36, 95% CI: 55.40–74.19%), but the lowest in the African region (5.28, 95% CI: 3.43–8.03%). CONCLUSIONS: Cervical cancer screening adherence remained low globally, exhibiting geographical discrepancy with HICs higher than LMICs. Further implementations of screening programs should comprehensively consider the local economy, social benefits, and demographic structure to adapt delivery for vulnerable or underserved women to boost screening adherence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12992-022-00890-w

Adsorption Properties and Mechanism of Cd2+ in Water by Zr-containing Silica Residue Purification

Zirconium (Zr)-containing silica residue purification (ZSR-P) discharged from industrial production of ZrOCl2 was used as an adsorbent, and CdCl2 solution was used as the simulated wastewater containing cadmium ions (Cd2+). The properties and mechanisms of ZSR-P absorbing Cd2+ were studied. The results showed that ZSR-P had a good effect on the adsorption and removal of Cd2+ in water. The adsorption time, initial concentration of Cd2+, and pH of the solution had a significant effect on the adsorption behavior, whilst the pH value had the greatest effect amongst them. Under optimal conditions, the amount of Cd2+ adsorbed by ZSR-P was 43.1 mg/g. The isothermal adsorption conformed to the Langmuir adsorption model, and the adsorption kinetics conformed to the secondary adsorption rate model. In ZSR-P-Cd, Cd2+ was uniformly distributed on the surface of SiO2 particles and in the pores formed by the accumulation of particles. Adsorption of Cd2+ by ZSR-P was achieved through the reaction between Si-OH on the surface of SiO2 and Cd2+ hydroxyl compounds

Rational Design of a Chimeric Derivative of PcrV as a Subunit Vaccine Against Pseudomonas aeruginosa

Pseudomonas aeruginosa (PA) is a major cause of nosocomial infections, which remain an unsolved problem in the clinic despite conventional antibiotic treatment. A PA vaccine could be both an effective and economical strategy to address this issue. Many studies have shown that PcrV, a structural protein of the type 3 secretion system (T3SS) from PA, is an ideal target for immune prevention and therapy. However, difficulties in the production of high-quality PcrV likely hinder its further application in the vaccine industry. Thus, we hypothesized that an optimized PcrV derivative with a rational design could be produced. In this study, the full-length PcrV was divided into four domains with the guidance of its structure, and the Nter domain (Met1-Lys127) and H12 domain (Leu251-Ile294) were found to be immunodominant. Subsequently, Nter and H12 were combined with a flexible linker to generate an artificial PcrV derivative (PcrVNH). PcrVNH was successfully produced in E. coli and behaved as a homogenous monomer. Moreover, immunization with PcrVNH elicited a multifactorial immune response and conferred broad protection in an acute PA pneumonia model and was equally effective to full-length PcrV. In addition, passive immunization with anti-PcrVNH antibodies alone also showed significant protection, at least based on inhibition of the T3SS and mediation of opsonophagocytic killing activities. These results provide an additional example for the rational design of antigens and suggest that PcrVNH is a promising vaccine candidate for the control of PA infection

High-speed ghost imaging by an unpredictable optical phased array

Ghost imaging (GI) retrieves an image from the correlation between a sequence of illumination patterns on the object and their corresponding bucket detections. Traditionally, GI requires the precise information of the illumination patterns, which raises technology barriers on building a high-speed illumination source, limiting the scope of its application. In this study, we propose a high-speed GI system, which implements a self-correlation with a purely optical operation without determining illumination patterns. The light source is an optical phased array (OPA), built of a set of waveguide-type electro-optic phase modulators. The OPA is driven to randomly change the phases in every 200 ns, generating speckle patterns at a rate of 5 MHz. Although the speckle patterns are not predictable or post-determinable, with the help of the naked-eye GI scheme, the system in real time optically generates the images of the object at a frame rate of more than 1 kHz, which can be directly observed by eyes or using a camera. This method avoids acquiring the information of the illumination, thus providing a simple and easy way to realize high-speed GI. It also inspires a different way of applying OPAs to high-speed imaging

ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer

Purpose: ErbB2 signaling appears to be increased and may enhance AR activity in a subset of CRPC, but agents targeting ErbB2 have not been effective. This study was undertaken to assess ErbB2 activity in abiraterone-resistant prostate cancer (PCa), and determine whether it may contribute to androgen receptor (AR) signaling in these tumors. Experimental Design: AR activity and ErbB2 signaling were examined in the radical prostatectomy specimens from a neoadjuvant clinical trial of leuprolide plus abiraterone, and in the specimens from abiraterone-resistant CRPC xenograft models. The effect of ErbB2 signaling on AR activity was determined in two CRPC cell lines. Moreover, the effect of combination treatment with abiraterone and an ErbB2 inhibitor was assessed in a CRPC xenograft model. Results: We found that ErbB2 signaling was elevated in residual tumor following abiraterone treatment in a subset of patients, and was associated with higher nuclear AR expression. In xenograft models, we similarly demonstrated that ErbB2 signaling was increased and associated with AR reactivation in abiraterone-resistant tumors, while ERBB2 message level was not changed. Mechanistically, we show that ErbB2 signaling and subsequent activation of the PI3K/AKT signaling stabilizes AR protein. Inhibitors targeting ErbB2/PI3K/AKT pathway disrupt AR transcriptional activity. Furthermore, concomitantly treating CRPC xenograft with abiraterone and an ErbB2 inhibitor, lapatinib, blocked AR reactivation and suppressed tumor progression. Conclusions: ErbB2 signaling is elevated in a subset of abiraterone-resistant prostate cancer patients and stabilizes AR protein. Combination therapy with abiraterone and ErbB2 antagonists may be effective for treating the subset of CRPC with elevated ErbB2 activity

Exploring the risk factors of early sepsis after liver transplantation: development of a novel predictive model

BackgroundSepsis is a severe and common complication of liver transplantation (LT) with a high risk of mortality. However, effective tools for evaluating its risk factors are lacking. Therefore, this study identified the risk factors of early post-liver transplantation sepsis and established a nomogram.MethodsWe analyzed the risk factors of post-liver transplantation sepsis in 195 patients. Patients with infection and a systemic inflammatory response syndrome (SIRS) score ≥ 2 were diagnosed with sepsis. The predictive indicators were screened with the least absolute shrinkage and selection operator (LASSO) and collinearity analyses to develop a nomogram. The prediction performance of the new nomogram model, Sequential Organ Failure Assessment (SOFA) score, and Modified Early Warning Score (MEWS) was compared through assessment of the area under the curve (AUC), decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI).ResultsThe nomogram was based on postoperative heart rate, creatinine concentration, PaO2/FiO2 ratio < 400 mmHg, blood glucose concentration, and international normalized ratio. The AUC of the nomogram, the SOFA score, and MEWS were 0.782 (95% confidence interval CI: 0.716–0.847), 0.649 (95% CI: 0.571–0.727), and 0.541 (95% CI: 0.469–0.614), respectively. The DCA curves showed that the net benefit rate of the nomogram was higher than that of the SOFA score and MEWS. The NRI and IDI tests revealed better predictive performance for the nomogram than SOFA score and MEWS.ConclusionHeart rate, creatinine concentration, PaO2/FiO2, glucose concentration, and international normalized ratio should be monitored postoperatively for patients at risk of post-liver transplantation sepsis. The nomogram based on the aforementioned risk factors had a better predictive performance than SOFA score and MEWS