To investigate three-dimensional (3D) genome organization in prokaryotic and eukaryotic cells, three main strategies are employed, namely nuclear proximity ligation-based methods, imaging tools (such as fluorescence in situ hybridization (FISH) and its derivatives), and computational/visualization methods. Proximity ligation-based methods are based on digestion and re-ligation of physically proximal cross-linked chromatin fragments accompanied by massively parallel DNA sequencing to measure the relative spatial proximity between genomic loci. Imaging tools enable direct visualization and quantification of spatial distances between genomic loci, and advanced implementation of (super-resolution) microscopy helps to significantly improve the resolution of images. Computational methods are used to map global 3D genome structures at various scales driven by experimental data, and visualization methods are used to visualize genome 3D structures in virtual 3D space-based on algorithms. In this review, we focus on the introduction of novel imaging and visualization methods to study 3D genomes. First, we introduce the progress made recently in 3D genome imaging in both fixed cell and live cells based on long-probe labeling, short-probe labeling, RNA FISH, and the CRISPR system. As the fluorescence-capturing capability of a particular microscope is very important for the sensitivity of bioimaging experiments, we also introduce two novel super-resolution microscopy methods, SDOM and low-power super-resolution STED, which have potential for time-lapse super-resolution live-cell imaging of chromatin. Finally, we review some software tools developed recently to visualize proximity ligation-based data. The imaging and visualization methods are complementary to each other, and all three strategies are not mutually exclusive. These methods provide powerful tools to explore the mechanisms of gene regulation and transcription in cell nuclei.
A drop-freeze array (PeKing University Ice Nucleation Array, PKU-INA) was developed based on the cold-stage method to investigate heterogeneous ice nucleation properties of atmospheric particles in the immersion freezing mode from -30 to 0 degrees C. The instrumental details as well as characterization and performance evaluation are described in this paper. A careful temperature calibration protocol was developed in our work. The uncertainties in the reported temperatures were found to be less than 0.4 degrees C at various cooling rates after calibration. We also measured the ice nucleation activities of droplets containing different mass concentrations of illite NX, and the results obtained in our work show good agreement with those reported previously using other instruments with similar principles. Overall, we show that our newly developed PKU-INA is a robust and reliable instrument for investigation of heterogeneous ice nucleation in the immersion freezing mode.
Gaseous nitrous acid (HONO) is an important source of OH radicals in the troposphere. However, its source, especially that during daytime hours remains unclear. We present an instrument for simultaneous unambiguous measurements of HONO and NO2 with high time resolution based on incoherent broadband cavity-enhanced absorption spectroscopy (IBBCEAS). To achieve robust performance and system stability under different environment conditions, the current IBBCEAS instrument has been developed with significant improvements in terms of efficient sampling as well as resistance against vibration and temperature change, and the IBBCEAS instrument also has low power consumption and a compact design that can be easily deployed on different platforms powered by a high-capacity lithium ion battery. The effective cavity length of the IBBCEAS was determined using the absorption of O-2-O-2 to account for the "shortening" effect caused by the mirror purge flows. The wall loss for HONO was estimated to be 2.0% via a HONO standard generator. Measurement precisions (2 sigma) for HONO and NO2 are about 180 and 340 ppt in 30 s, respectively. A field inter-comparison was carried out at a rural suburban site in Wangdu, Hebei Province, China. The concentrations of HONO and NO2 measured by IBBCEAS were compared with a long optical path absorption photometer (LOPAP) and a NOx analyzer (Thermo Fisher Electron Model 42i), and the results showed very good agreement, with correlation coefficients (R-2) of HONO and NO2 being similar to 0.89 and similar to 0.95, respectively; in addition, vehicle deployments were also tested to enable mobile measurements of HONO and NO2, demonstrating the promising potential of using IBBCEAS for in situ, sensitive, accurate and fast simultaneous measurements of HONO and NO2 in the future.
Background: It is unknown whether dietary quality modifies genetic association with body mass index (BMI). Objective: This study examined whether dietary quality modifies genetic association with BMI. Design: We calculated 3 diet quality scores including the Alternative Healthy Eating Index 2010 (AHEI-2010), the Alternative Mediterranean Diet score (AMED), and the Dietary Approach to Stop Hypertension (DASH) diet score. We examined the interactions of a genetic risk score (GRS) based on 97 BMI-associated variants with the 3 diet quality scores on BMI in 30,904 participants from 3 large cohorts. Results: We found significant interactions between total GRS and all 3 diet scores on BMI assessed after 2-3 y, with an attenuated genetic effect observed in individuals with healthier diets (AHEI: P-interaction = 0.003; AMED: P = 0.001; DASH: P = 0.004). For example, the difference in BMI (kg/m2) per 10-unit increment of the GRS was smaller among participants in the highest tertile of AHEI score compared with those in the lowest tertile (0.84; 95% CI: 0.72, 0.96 compared with 1.14; 95% CI: 0.99, 1.29). Results were consistent across the 3 cohorts with no significant heterogeneity. The interactions with diet scores on BMI appeared more significant for central nervous system GRSs (P < 0.01 for 3 diet scores) than for non-central nervous system GRSs (P > 0.05 for 3 diet scores). Conclusions: A higher diet quality attenuated genetic predisposition to obesity. These findings underscore the importance of maintaining a healthful diet for the prevention of obesity, particularly for those individuals with a strong genetic predisposition to obesity. This trial was registered with the Clinical Trial Registry as NCT03577639.
Background: Emerging studies have related circulating glutamine metabolites to various chronic diseases such as cardiovascular disease and cancer; diet is the major source of nutrients involved in glutamine metabolism. However, it remains unknown whether dietary intakes of glutamine, glutamate,and their ratio are related to total and cause-specific mortality. Methods: We followed 74 082 women from the Nurses' Health Study (1984-2012) and 42 303 men from the Health Professionals Follow-up Study (1986-2012), who were free of cardiovascular disease and cancer at baseline. Diet was updated every 2 to 4 years by using validated food frequency questionnaires. The content of glutamine and glutamate in foods was calculated based on protein fractions generated from gene sequencing methods and adjusted for total energy intake. Results: We documented 30 424 deaths during 2 878 344 person-years of follow-up. After adjustment for potential confounders including lifestyle and dietary factors, higher intakes of glutamine and glutamine-to-glutamate ratio were associated with significantly lower risk of total and cause-specific mortality. Compared with people in the lowest quintile of dietary glutamine-to-glutamate ratio, the pooled hazard ratio (HR) in the highest quintile was 0.87 [95% confidence interval (CI): 0.84, 0.91; P for trend < 0.001) for total mortality, 0.81 (95% CI: 0.75, 0.88; P for trend < 0.001) for cardiovascular mortality, and 0.93 (95% CI: 0.87, 0.99; P for trend = 0.01) for cancer mortality. Conclusions: We found dietary glutamine and glutamine-to-glutamate ratio were inversely related to risk of mortality, particularly cardiovascular mortality, independent of other dietary and lifestyle factors, in US men and women.
BACKGROUND: Observational studies have demonstrated diet/lifestyle play roles in development of type 2 diabetes (T2DM); however, it remains unclear whether these relationships are causal. METHODS: A two-sample MR approach was used to examine the causal effect of diet/lifestyle upon risk of T2DM and glycemic traits. RESULTS: The protein intake-increasing allele C of FTO was significant associated with higher risk of T2DM (Beta +/- SE = 0.104 +/- 0.014, P = 4.40 x 10(- 11)), higher level of HOMA-IR (Beta +/- SE = 0.016 +/- 0.004, P = 9.55 x 10(- 5)), HOMA-B (Beta +/- SE = 0.008 +/- 0.003, P = 0.020). Using MR analyses, increased protein intake was causally associated with an increased risk of T2DM (Beta +/- SE = 0.806 +/- 0.260, P = 0.002). In addition, smoking cessation was causally associated with increased levels of glycemic traits such as HOMA-IR (Beta +/- SE = 0.165 +/- 0.072, P = 0.021), fasting insulin (Beta +/- SE = 0.132 +/- 0.066, P = 0.047) and fasting glucose (Beta +/- SE = 0.132 +/- 0.064, P = 0.039). CONCLUSIONS: These results provide evidence supporting a causal role for higher protein intake and smoking cession in T2DM. Our study provides further rationale for individuals at risk for diabetes to keep healthy lifestyle.
Plants play an important role as sinks for or indicators of semivolatile organic pollutants, however most studies have focused on terrestrial plants and insufficient information has been obtained on aquatic plants to clarify the accumulation of organic pollutants via air-to-leaf vs. water-to-leaf pathways. The presence of p, p'-dichlorodiphenyldichloroethylene (p, p'-DDE), hexachlorobenzene (HCB), 15 polycyclic aromatic hydrocarbons (PAHs), and 9 substituted PAHs (s-PAHs), including oxy-PAHs and sulfur-PAHs, in 10 submerged and emergent plants collected from Lake Dianchi was analyzed in this study. Relatively low concentrations of p, p'-DDE (ND to 2.22 ngig wet weight [ww]) and HCB (0.24-0.84 ng/g ww) and high levels of PAHs (46-244 ng/g ww) and s-PAHs (6.0-46.8 ng/g ww) were observed in the aquatic plants. Significantly higher concentrations of most of the compounds were detected in the leaves of the submerged plants than in those of the emergent plants. The percentages of concentration difference relative to the concentrations in the submerged plants were estimated at 55%, 40%, 10%-69% and 0.5% 79% for p, p'-DDE, HCB, PAHs, and s-PAHs, respectively. The percentages were found to increase significantly with an increase in log Kow, suggesting that the high level of phytoaccumulation of pollutants in aquatic plants is due to hydrophobicity-dependent diffusion via the water-to-leaf pathway and the mesophyll morphology of submerged plants. (C) 2018 Elsevier Ltd. All rights reserved.
We investigated that proteins differently expressed in Datong Yak and Chaidamu Yellow Cattle Longissimus longurum muscles and their relation to tissue water-holding capacity. Samples were classified according to breed and postmortem aging into Yakoh, Cattleoh, Yak24h and Cattle24h groups. Fifty seven differentially expressed proteins were confirmed by MALDI-TOF/TOF-MS. Twenty eight proteins could be identified and were divided into five main categories: structural proteins, metabolic enzymes, stress related proteins, transporter proteins and binding proteins. Myosin light chain (MLC), Heat Shock 27kDa (HSP 27) and Keratin 10 (KRT 10) proteins showed significant differences in expression between yak and cattle meat and may have the potential to be used as biological markers of tissue WHC. Bioinformatics analysis showed differentially these proteins included both metabolic enzymes and structural proteins. The functions of the identified proteins contribute to a more detailed molecular view of the processes behind WHC and are a valuable resource for future investigations.
Different populations may respond differently to exposure to ambient fine particulate matter, defined as particulate matter with an aerodynamic diameter less than or equal to 2.5 mum (PM2.5); however, less is known about the distribution of susceptible individuals among the entire population. We conducted a time-stratified case-crossover study to assess associations between stroke risk and exposure to PM2.5. During 2013-2015, 1,356 first-ever stroke events were derived from a large representative sample, the China National Stroke Screening Survey (CNSSS) database. Daily PM2.5 average exposures with a spatial resolution of 0.1 degrees were estimated using a data assimilation approach combining satellite measurements, air model simulations, and monitoring values. The distribution of susceptibility was derived according to individual-specific associations with PM2.5 modified by different combinations of individual-level characteristics and their joint frequencies among all of the CNSSS participants (n = 1,292,010). We found that first-ever stroke was statistically significantly associated with PM2.5 (per 10-mug/m3 increment of exposure, odds ratio = 1.049, 95% confidence interval (CI): 1.038, 1.061). This association was modified by demographic (e.g., sex), lifestyle (e.g., overweight/obesity), and medical history (e.g., diabetes) variables. The combined association with PM2.5 varied from 0.966 (95% CI: 0.920, 1.013) to 1.145 (95% CI: 1.080, 1.215) per 10-mug/m3 increment in different subpopulations. We found that most of the CNSSS participants were at increased risk of PM2.5-related stroke, while only a small proportion were highly susceptible.