63 research outputs found
MIA-Sig: multiplex chromatin interaction analysis by signal processing and statistical algorithms.
The single-molecule multiplex chromatin interaction data are generated by emerging 3D genome mapping technologies such as GAM, SPRITE, and ChIA-Drop. These datasets provide insights into high-dimensional chromatin organization, yet introduce new computational challenges. Thus, we developed MIA-Sig, an algorithmic solution based on signal processing and information theory. We demonstrate its ability to de-noise the multiplex data, assess the statistical significance of chromatin complexes, and identify topological domains and frequent inter-domain contacts. On chromatin immunoprecipitation (ChIP)-enriched data, MIA-Sig can clearly distinguish the protein-associated interactions from the non-specific topological domains. Together, MIA-Sig represents a novel algorithmic framework for multiplex chromatin interaction analysis
Barriers and facilitators of linkage to HIV care among HIV-infected young Chinese men who have sex with men: a qualitative study
Background: The Four Free and One Care Policy (HIV/AIDS-related free services) has been in place in China since 2004. However, linkage to human immunodeficiency virus (HIV) care is not yet achieved very well among people living with HIV. We conducted a qualitative study to explore individual and contextual factors that may influence a linkage to HIV care from the perspective of young HIV-infected men who have sex with men (MSM) in a highly centralized HIV care context of China.
Methods: Purposive sampling was used to recruit 21 HIV-infected MSM in Shandong Province, with in-depth interviews conducted between March and July 2015. Thematic content analysis was subsequently used for data analysis.
Results: Key barriers and facilitators related to a linkage to HIV care emerged from participants’ narratives. The barriers included perceived healthy status, low health literacy, and stigma associated with receiving HIV care. The facilitators included an awareness of responsibility, knowledge associated with health literacy, social support, and trusting and relying on services provided by the Center for Disease Control and Prevention (CDC) and the government. These were related to the quality of current HIV counselling and testing, service promotion, and the cost and placement of these HIV services.
Conclusions: In order to improve the MSM linkage to HIV care in China, it is imperative to improve the quality of the current on-going counselling and testing. Further critical linkage support includes increasing supportive services among local CDC systems, designated hospitals and community-based organizations (CBOs), and more financial support for HIV/ AIDS related testing, medical checkups and treatments
Chromatin topology reorganization and transcription repression by PML-RARα in acute promyeloid leukemia.
BACKGROUND: Acute promyeloid leukemia (APL) is characterized by the oncogenic fusion protein PML-RARα, a major etiological agent in APL. However, the molecular mechanisms underlying the role of PML-RARα in leukemogenesis remain largely unknown.
RESULTS: Using an inducible system, we comprehensively analyze the 3D genome organization in myeloid cells and its reorganization after PML-RARα induction and perform additional analyses in patient-derived APL cells with native PML-RARα. We discover that PML-RARα mediates extensive chromatin interactions genome-wide. Globally, it redefines the chromatin topology of the myeloid genome toward a more condensed configuration in APL cells; locally, it intrudes RNAPII-associated interaction domains, interrupts myeloid-specific transcription factors binding at enhancers and super-enhancers, and leads to transcriptional repression of genes critical for myeloid differentiation and maturation.
CONCLUSIONS: Our results not only provide novel topological insights for the roles of PML-RARα in transforming myeloid cells into leukemia cells, but further uncover a topological framework of a molecular mechanism for oncogenic fusion proteins in cancers
Altered intestinal microbiota enhances adenoid hypertrophy by disrupting the immune balance
IntroductionAdenoid hypertrophy (AH) is a common upper respiratory disorder in children. Disturbances of gut microbiota have been implicated in AH. However, the interplay of alteration of gut microbiome and enlarged adenoids remains elusive.Methods119 AH children and 100 healthy controls were recruited, and microbiome profiling of fecal samples in participants was performed using 16S rRNA gene sequencing. Fecal microbiome transplantation (FMT) was conducted to verify the effects of gut microbiota on immune response in mice.ResultsIn AH individuals, only a slight decrease of diversity in bacterial community was found, while significant changes of microbial composition were observed between these two groups. Compared with HCs, decreased abundances of Akkermansia, Oscillospiraceae and Eubacterium coprostanoligenes genera and increased abundances of Bacteroides, Faecalibacterium, Ruminococcus gnavus genera were revealed in AH patients. The abundance of Bacteroides remained stable with age in AH children. Notably, a microbial marker panel of 8 OTUs were identified, which discriminated AH from HC individuals with an area under the curve (AUC) of 0.9851 in the discovery set, and verified in the geographically different validation set, achieving an AUC of 0.9782. Furthermore, transfer of mice with fecal microbiota from AH patients dramatically reduced the proportion of Treg subsets within peripheral blood and nasal-associated lymphoid tissue (NALT) and promoted the expansion of Th2 cells in NALT.ConclusionThese findings highlight the effect of the altered gut microbiota in the AH pathogenesis
Crowdsourcing to expand HIV testing among men who have sex with men in China: A closed cohort stepped wedge cluster randomized controlled trial.
BACKGROUND: HIV testing rates are suboptimal among at-risk men. Crowdsourcing may be a useful tool for designing innovative, community-based HIV testing strategies to increase HIV testing. The purpose of this study was to use a stepped wedge cluster randomized controlled trial (RCT) to evaluate the effect of a crowdsourced HIV intervention on HIV testing uptake among men who have sex with men (MSM) in eight Chinese cities. METHODS AND FINDINGS: An HIV testing intervention was developed through a national image contest, a regional strategy designathon, and local message contests. The final intervention included a multimedia HIV testing campaign, an online HIV testing service, and local testing promotion campaigns tailored for MSM. This intervention was evaluated using a closed cohort stepped wedge cluster RCT in eight Chinese cities (Guangzhou, Shenzhen, Zhuhai, and Jiangmen in Guangdong province; Jinan, Qingdao, Yantai, and Jining in Shandong province) from August 2016 to August 2017. MSM were recruited through Blued, a social networking mobile application for MSM, from July 29 to August 21 of 2016. The primary outcome was self-reported HIV testing in the past 3 months. Secondary outcomes included HIV self-testing, facility-based HIV testing, condom use, and syphilis testing. Generalized linear mixed models (GLMMs) were used to analyze primary and secondary outcomes. We enrolled a total of 1,381 MSM. Most were ≤30 years old (82%), unmarried (86%), and had a college degree or higher (65%). The proportion of individuals receiving an HIV test during the intervention periods within a city was 8.9% (95% confidence interval [CI] 2.2-15.5) greater than during the control periods. In addition, the intention-to-treat analysis showed a higher probability of receiving an HIV test during the intervention periods as compared to the control periods (estimated risk ratio [RR] = 1.43, 95% CI 1.19-1.73). The intervention also increased HIV self-testing (RR = 1.89, 95% CI 1.50-2.38). There was no effect on facility-based HIV testing (RR = 1.00, 95% CI 0.79-1.26), condom use (RR = 1.00, 95% CI 0.86-1.17), or syphilis testing (RR = 0.92, 95% CI 0.70-1.21). A total of 48.6% (593/1,219) of participants reported that they received HIV self-testing. Among men who received two HIV tests, 32 individuals seroconverted during the 1-year study period. Study limitations include the use of self-reported HIV testing data among a subset of men and non-completion of the final survey by 23% of participants. Our study population was a young online group in urban China and the relevance of our findings to other populations will require further investigation. CONCLUSIONS: In this setting, crowdsourcing was effective for developing and strengthening community-based HIV testing services for MSM. Crowdsourced interventions may be an important tool for the scale-up of HIV testing services among MSM in low- and middle-income countries (LMIC). TRIAL REGISTRATION: ClinicalTrials.gov NCT02796963
Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation
Higher-order chromosomal organization for transcription
regulation is poorly understood in eukaryotes.
Using genome-wide Chromatin Interaction
Analysis with Paired-End-Tag sequencing (ChIAPET),
we mapped long-range chromatin interactions
associated with RNA polymerase II in human cells
and uncovered widespread promoter-centered intragenic,
extragenic, and intergenic interactions. These
interactions further aggregated into higher-order
clusters, wherein proximal and distal genes were
engaged through promoter-promoter interactions.
Most genes with promoter-promoter interactions
were active and transcribed cooperatively, and
some interacting promoters could influence each
other implying combinatorial complexity of transcriptional
controls. Comparative analyses of
different cell lines showed that cell-specific chromatin
interactions could provide structural frameworks
for cell-specific transcription, and suggested
significant enrichment of enhancer-promoter interactions
for cell-specific functions. Furthermore,
genetically-identified disease-associated noncoding
elements were found to be spatially engaged with
corresponding genes through long-range interactions.
Overall, our study provides insights into transcription
regulation by three-dimensional chromatin
interactions for both housekeeping and cell-specific
genes in human cells
Ensemble learning for impurity prediction in high-purity indium purified via vertical zone refining
The complexity of raw materials and multi-step purification processes presents considerable technical challenges in establishing universally applicable process parameters for the production of high-purity metals. Machine learning has emerged as an indispensable tool in the field of materials science, facilitating the accurate prediction of target variables and accelerating process optimization, thereby yielding substantial reductions in both experimental costs and time. This study explores the utilization of high-precision machine learning models to predict the residual impurity content in high-purity indium after vertical zone refining. A dataset comprising 82 experimental datasets was employed to determine the optimal hyperparameters for XGBoost and LightGBM models through Bayesian optimization. The XGBoost and LightGBM models demonstrated mean absolute errors (MAEs) of 0.022 and 0.023, respectively, as determined via leave-one-out cross-validation (LOOCV). Their comparable predictive performance to the previously established Ridge regression model (MAE = 0.024) prompted the exploration of fusion techniques, including mean, weighted, and stacking fusion, to further enhance accuracy. Remarkably, the weighted fusion model exhibited the most optimal predictive capabilities, supported by comprehensive evaluation metrics, including an MAE of 0.020, root mean squared error (RMSE) of 0.026, and a coefficient of determination (R2 score) of 0.830. Furthermore, the SHapley Additive exPlanations (SHAP) analysis revealed a significant correlation between lower initial arsenic (As) content and reduced total post-refining impurity levels in both the XGBoost and LightGBM models. This study underscores the precision of ensemble learning in predicting residual impurity content in vertically zone-refined indium products
Detection of metal ions in biological systems: A review
Metal ions are widely present in biological systems and participate in many critical biochemical processes such as material transportation, energy conversion, information transmission and metabolic regulation, making them indispensable substance in our body. They can cause health problems when deficiency or excess occurs. To understand various metabolic processes and facilitate diseases diagnosis, it is very important to measure the content and monitor the distribution of metal ions in individual cells, tissues and whole organisms. Among the various methods for metal ion detection, fluorescent sensors with organic dyes have attracted tremendous attention due to many advantages such as high fluorescence quantum yield, facile modification approaches and biocompatibility in addition to operation ease, high sensitivity, fast detection speed, and real-time detection. This review summarizes the recent progress on the detection and imaging of the metal ions in biological systems including Na+, K+, Ca2+, Mg2+, Fe2+/Fe3+, Zn2+, and Cu2+ provides an opinion on remaining challenges to be addressed in this field
Photoinitiated Polymerization of Cationic Acrylamide in Aqueous Solution: Synthesis, Characterization, and Sludge Dewatering Performance
A copolymer of acrylamide (AM) with acryloyloxyethyl trimethyl ammonium chloride (DAC) as the cationic monomer was synthesized under the irradiation of high-pressure mercury lamp with 2,2-azobis(2-amidinopropane) dihydrochloride (V-50) as the photoinitiator. The compositions of the photoinduced copolymer were characterized by Fourier transform infrared spectra (FTIR), ultraviolet spectra (UV), and scanning electron microscope (SEM). The effects of 6 important factors, that is, photo-initiators concentration, monomers concentration, CO(NH2)2 (urea) concentrations, pH value, mass ratio of AM to DAC, and irradiation time on the molecular weight and dissolving time, were investigated. The optimal reaction conditions were that the photo-initiators concentration was 0.3%, monomers concentration was 30 wt.%, irradiation time was 60 min, urea concentration was 0.4%, pH value was 5.0, and mass ratio of AM to DAC was 6 : 4. Its flocculation properties were evaluated with activated sludge using jar test. The zeta potential of supernatant at different cationic monomer contents was simultaneously measured. The results demonstrated the superiority of the copolymer over the commercial polyacrylamide as a flocculant
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