Search

Somatic mutations accumulated in normal tissues are associated with aging and disease. Here, we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies (~ 600 cells each), mostly from the epithelia, of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although with variable extent, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for tissues from esophagus and cardia. Endogenous mutational processes like SBS1 and SBS5 are ubiquitous among normal tissues though exhibiting different relative activities. Exogenous mutational processes like SBS22 were found in different tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In epithelial tissues from esophagus and cardia, macroscopic somatic clones expanded to several millimeters were frequently seen, whereas in tissues from colon, rectum, and duodenum somatic clones were microscopic in size and evolved independently. Our study depicted a body map of somatic mutations and clonal expansions from the same individuals, and it revealed that the degree of somatic clonal expansion and enrichment of driver mutations are highly organ specific.

Genetic profiles of the bladder Depending on the environment of the individual, the human bladder can be exposed to carcinogens as they are flushed through the body. Lawson et al. and Li et al. examined the genetic composition of laser-dissected microbiopsies from normal and cancer cells collected from the urothelium, a specialized epithelium lining the lower urinary tract (see the Perspective by Rozen). These complementary studies identified the mutational landscape of bladder urothelium through various sequencing strategies and identified high mutational heterogeneity within and between individuals and tumors. Both studies identified mutational profiles related to specific carcinogens such as aristolochic acid and the molecules found in tobacco. These studies present a comprehensive description of the diverse mutational landscape of the human bladder in health and disease, unraveling positive selection for cancer-causing mutations, a diversity of mutational processes, and large differences across individuals. Science , this issue p. 75 , p. 82 ; see also p. 34

Polycyclic aromatic hydrocarbons (PAHs) are one of the most prevalent classes of environmental pollutants resulting from the incomplete combustion of hydrocarbons. Exposure to PAHs is implicated in the pathogenesis of the cardiovascular disease, pulmonary disease, and even cancer. However, little is known about organ- and tissue-specific distribution patterns of PAHs in animals at macro-tissue and microscopic levels. Here, by combining GC-MS and single-molecule fluorescence microscopy (SMFM), we revealed the distribution characteristics of four different PAHs (phenanthrene (Phe), pyrene (Pyr), perylene (Per), and benzo[a]pyrene (BaP)) in atherosclerosis model mice (ApoE-KO mice) at macro-tissue and micro-region level after long-term oral exposure. Average PAH concentrations detected by GC-MS in seven tissues ranged from 6.44 to 441 ng/g. The gastrointestinal tract, epididymal fat pat, and lung accumulated higher levels of PAHs, whereas relatively lower PAH residuals were found in the liver, brain, and kidney. Correlation analysis showed that PAHs with higher molecular weight (r: −0.972 to −0.746), Log Kow (r: −0.984 to −0.746) and lower water solubility (r: 0.720 to 0.994) were less prone to bioaccumulate. For the first time, SMFM demonstrated a distinct heterogeneous distribution of Per in the tissue slices. More interestingly, we observed many micro-cluster regions, namely hotspots, showed much higher Per fluorescent intensity than the other common regions. In the area of atherosclerotic plaque, the Per hotspots were colocalized with the micro-regions with the most severe inflammatory response. The hotspots with very high enrichment in PAHs were likely to stimulate the local inflammation and cause excessive damage of the aorta, which resulted in a significant increase of the relative area of atherosclerosis lesion and aggravated atherosclerosis, as observed in PAH exposed mice.

Bioaccumulation of perylene in Escherichia coli and Staphylococcus aureus was visualized and quantified in real time with high sensitivity at high temporal resolution. For the first time, single-molecule fluorescence microscopy (SMFM) with a microfluidic flow chamber and temperature control has enabled us to record the dynamic process of perylene bioaccumulation in single bacterial cells and examine the cell-to-cell heterogeneity. Although with identical genomes, individual E. coli cells exhibited a high degree of heterogeneity in perylene accumulation dynamics, as shown by the high coefficient of variation (C.V = 1.40). This remarkable heterogeneity was exhibited only in live E. coli cells. However, the bioaccumulation of perylene in live and dead S. aureus cells showed similar patterns with a low degree of heterogeneity (C.V = 0.36). We found that the efflux systems associated with Tol C played an essential role in perylene bioaccumulation in E. coli, which caused a significantly lower accumulation and a high cell-to-cell heterogeneity. In comparison with E. coli, the Gram-positive bacteria S. aureus lacked an efficient efflux system against perylene. Therefore, perylene bioaccumulation in S. aureus was simply a passive diffusion process across the cell membrane.

Upward continuation can be used to separate a regional gravity anomaly resulting from deep sources from the observed gravity. We present a practical method, based on model studies, to derive an optimum upward continuation height for regional-residual gravity separation. Using this method we can calculate an optimal height for upward continuation. Although mathematically there is no optimum height, this method provides an objective procedure to calculate a best height for upward continuation. We initially use a 2D model to calculate an optimum separation height, as given by the maximum crosscorrelation between the upward continuation of the observed gravity and a known regional anomaly. For an unknown regional field, we calculate a series of crosscorrelations between the upward continuations at two successive heights. The average height of the maximum deflection of these crosscorrelation values yields the optimum height for regional-residual separation. The method was applied to the Bouguer gravity anomaly over a mineral deposit in the Jilin province in northeast China. When we subtract the estimated regional anomaly obtained in this manner from the Bouguer anomaly, we can obtain a residual anomaly that clearly shows the location of two known iron bodies.

Regional gravity and aeromagnetic data covering the area of 32°–38° N, 118°–127° E at the scale of 1:1,000,000 are coordinated and integrated in a synthetic study of the South China Yellow Sea and adjacent areas. Depth to magnetic crystalline basement and its structure are determined by magnetic anomaly inversion. Depth to and thickness of the Paleozoic rock are also revealed by gravity anomaly inversion with constrains of the basement and known seismic information from several profiles. Structure units, main faults, basin boundaries, and sub-suppressions are outlined on the basis of gravity data interpretation.

Pawlowski (1995) presents an excellent method for preferential continuation for potential‐field anomaly enhancement, and it is an appreciated attempt to solve a very common problem in gravity separation. Upward continuation of a gravity anomaly is a very common method for regional‐residual separation in China. One of the main problems in the conventional upward continuation is that it overattenuates regional‐field or useful long‐wavelength information due to deep sources. Sometimes attenuated‐upward continuation of an observed anomaly to a height has to be regarded as the original regional field at the observation plane in order to use gravity inversion to map deep interfaces such as the Moho. Application of the preferential continuation to gravity anomaly in some areas in China has shown very good effectiveness in solving the above problem (Xu and Zeng, 2000).