The measurement of circulating nucleic acids has transformed the management of chronic viral infections such as HIV. The development of analogous markers for individuals with cancer could similarly enhance the management of their disease. DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. In this study, we applied a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in 162 plasma samples from 18 subjects undergoing multimodality therapy for colorectal cancer. We found that ctDNA measurements could be used to reliably monitor tumor dynamics in subjects with cancer who were undergoing surgery or chemotherapy. We suggest that this personalized genetic approach could be generally applied to individuals with other types of cancer.

Mouse embryonic stem (ES) cells are competent for production of all fetal and adult cell types. However, the utility of ES cells as a developmental model or as a source of defined cell populations for pharmaceutical screening or transplantation is compromised because their differentiation in vitro is poorly controlled. Specification of primary lineages is not understood and consequently differentiation protocols are empirical, yielding variable and heterogeneous outcomes. Here we report that neither multicellular aggregation nor coculture is necessary for ES cells to commit efficiently to a neural fate. In adherent monoculture, elimination of inductive signals for alternative fates is sufficient for ES cells to develop into neural precursors. This process is not a simple default pathway, however, but requires autocrine fibroblast growth factor (FGF). Using flow cytometry quantitation and recording of individual colonies, we establish that the bulk of ES cells undergo neural conversion. The neural precursors can be purified to homogeneity by fluorescence activated cell sorting (FACS) or drug selection. This system provides a platform for defining the molecular machinery of neural commitment and optimizing the efficiency of neuronal and glial cell production from pluripotent mammalian stem cells.

Uncovering the genetic basis of agronomic traits in crop landraces that have adapted to various agro-climatic conditions is important to world food security. Here we have identified ∼ 3.6 million SNPs by sequencing 517 rice landraces and constructed a high-density haplotype map of the rice genome using a novel data-imputation method. We performed genome-wide association studies (GWAS) for 14 agronomic traits in the population of Oryza sativa indica subspecies. The loci identified through GWAS explained ∼ 36% of the phenotypic variance, on average. The peak signals at six loci were tied closely to previously identified genes. This study provides a fundamental resource for rice genetics research and breeding, and demonstrates that an approach integrating second-generation genome sequencing and GWAS can be used as a powerful complementary strategy to classical biparental cross-mapping for dissecting complex traits in rice.

Abstract. We present a new data set of annual historical anthropogenic chemically reactive gases (CO, CH 4 , NH 3 , NO x , SO 2 , NMVOCs), carbonaceous aerosols (black carbon -BC, and organic carbon -OC), and CO 2 developed with the Community Emissions Data System (CEDS). We improve upon existing inventories with a more consistent and reproducible methodology applied to all emission species, updated emission factors, and recent estimates through 2014. The data system relies on existing energy consumption data sets and regional and country-specific inventories to produce trends over recent decades. All emission species are consistently estimated using the same activity data over all time periods. Emissions are provided on an annual basis at the level of country and sector and gridded with monthly seasonality. These estimates are comparable to, but generally slightly higher than, existing global inventories. Emissions over the most recent years are more uncertain, particularly in low-and middle-income regions where country-specific emission inventories are less available. Future work will involve refining and updating these emission estimates, estimating emissions' uncertainty, and publication of the system as open-source software.

Exosomes are 40–100 nm nano-sized vesicles that are released from many cell types into the extracellular space. Such vesicles are widely distributed in various body fluids. Recently, mRNAs and microRNAs (miRNAs) have been identified in exosomes, which can be taken up by neighboring or distant cells and subsequently modulate recipient cells. This suggests an active sorting mechanism of exosomal miRNAs, since the miRNA profiles of exosomes may differ from those of the parent cells. Exosomal miRNAs play an important role in disease progression, and can stimulate angiogenesis and facilitate metastasis in cancers. In this review, we will introduce the origin and the trafficking of exosomes between cells, display current research on the sorting mechanism of exosomal miRNAs, and briefly describe how exosomes and their miRNAs function in recipient cells. Finally, we will discuss the potential applications of these miRNA-containing vesicles in clinical settings.

The early detection of cancers through analysis of circulating DNA could have a substantial impact on morbidity and mortality. To achieve this goal, it is essential to determine the number of mutant molecules present in the circulation of cancer patients and to develop methods that are sufficiently sensitive to detect these mutations. Using a modified version of a recently developed assay for this purpose, we found that patients with advanced colorectal cancers consistently contained mutant adenomatous polyposis coli (APC) DNA molecules in their plasma. The median number of APC DNA fragments in such patients was 47,800 per ml of plasma, of which 8% were mutant. Mutant APC molecules were also detected in >60% of patients with early, presumably curable colorectal cancers, at levels ranging from 0.01% to 1.7% of the total APC molecules. These results have implications for the mechanisms through which tumor DNA is released into the circulation and for diagnostic tests based on this phenomenon.colorectal cancer ͉ plasma DNA ͉ tumor suppressor gene ͉ circulating DNA ͉ diagnosis

The MIX inventory is developed for the years 2008 and 2010 to support the Model Inter-Comparison Study for Asia (MICS-Asia) and the Task Force on Hemispheric Transport of Air Pollution (TF HTAP) by a mosaic of up-to-date regional emission inventories. Emissions are estimated for all major anthropogenic sources in 29 countries and regions in Asia. We conducted detailed comparisons of different regional emission inventories and incorporated the best available ones for each region into the mosaic inventory at a uniform spatial and temporal resolution. Emissions are aggregated to five anthropogenic sectors: power, industry, residential, transportation, and agriculture. We estimate the total Asian emissions of 10 species in 2010 as follows: 51.3 Tg SO2, 52.1 Tg NOx, 336.6 Tg CO, 67.0 Tg NMVOC (non-methane volatile organic compounds), 28.8 Tg NH3, 31.7 Tg PM10, 22.7 Tg PM2.5, 3.5 Tg BC, 8.3 Tg OC, and 17.3 Pg CO2. Emissions from China and India dominate the emissions of Asia for most of the species. We also estimated Asian emissions in 2006 using the same methodology of MIX. The relative change rates of Asian emissions for the period of 2006–2010 are estimated as follows: −8.1 % for SO2, +19.2 % for NOx, +3.9 % for CO, +15.5 % for NMVOC, +1.7 % for NH3, −3.4 % for PM10, −1.6 % for PM2.5, +5.5 % for BC, +1.8 % for OC, and +19.9 % for CO2. Model-ready speciated NMVOC emissions for SAPRC-99 and CB05 mechanisms were developed following a profile-assignment approach. Monthly gridded emissions at a spatial resolution of 0.25°  ×  0.25° are developed and can be accessed from http://www.meicmodel.org/dataset-mix

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen's d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen's d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.