All cancers harbor molecular alterations in their genomes. The transcriptional consequences of these somatic mutations have not yet been comprehensively explored in lung cancer. Here we present the first large scale RNA sequencing study of lung adenocarcinoma, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events, and expression outliers. Our results reveal the genetic basis of 200 lung adenocarcinomas in Koreans including deep characterization of 87 surgical specimens by transcriptome sequencing. We identified driver somatic mutations in cancer genes including EGFR, KRAS, NRAS, BRAF, PIK3CA, MET, and CTNNB1. Candidates for novel driver mutations were also identified in genes newly implicated in lung adenocarcinoma such as LMTK2, ARID1A, NOTCH2, and SMARCA4. We found 45 fusion genes, eight of which were chimeric tyrosine kinases involving ALK, RET, ROS1, FGFR2, AXL, and PDGFRA. Among 17 recurrent alternative splicing events, we identified exon 14 skipping in the protooncogene MET as highly likely to be a cancer driver. The number of somatic mutations and expression outliers varied markedly between individual cancers and was strongly correlated with smoking history of patients. We identified genomic blocks within which gene expression levels were consistently increased or decreased that could be explained by copy number alterations in samples. We also found an association between lymph node metastasis and somatic mutations in TP53. These findings broaden our understanding of lung adenocarcinoma and may also lead to new diagnostic and therapeutic approaches.

Colloidal quantum dot (CQD) photovoltaics offer a promising approach to harvest the near-IR region of the solar spectrum, where half of the sun's power reaching the earth resides. High external quantum efficiencies have been obtained in the visible region in lead chalcogenide CQD photovoltaics. However, the corresponding efficiencies for band gap radiation in the near-infrared lag behind because the thickness of CQD photovoltaic layers from which charge carriers can be extracted is limited by short carrier diffusion lengths. Here, we investigate, using a combination of electrical and optical characterization techniques, ligand passivation strategies aimed at tuning the density and energetic distribution of charge trap states at PbS nanocrystal surfaces. Electrical and optical measurements reveal a more than 7-fold enhancement of the mobility-lifetime product of PbS CQD films treated with 3-mercaptopropionic acid (MPA) in comparison to traditional organic passivation strategies that have been examined in the literature. We show by direct head-to-head comparison that the greater mobility-lifetime products of MPA-treated devices enable markedly greater short-circuit current and higher power conversion efficiency under AM1.5 illumination. Our findings highlight the importance of selecting ligand treatment strategies capable of passivating a diversity of surface states to enable shallower and lower density trap distributions for better transport and more efficient CQD solar cells.

Although massively parallel sequencing approaches have been widely used to study genomic variation, simple alignment of short reads to a reference genome cannot be used to investigate the full range of structural variation and phased diploid architecture, which are important for precision medicine. By contrast, the single-molecule real-time (SMRT) sequencing platform produces long reads that can resolve repetitive structures effectively. We integrated this technology with several other sequencing approaches to construct a high-quality

The mammalian meiosis-specific KASH protein KASH5 connects the telomere-associated SUN1 protein to the cytoplasmic force–generating mechanism involved in meiotic chromosome movement.

A new meiosis-specific cohesin complex implicated in the cohesin code for homologous pairingRAD21L is identified as a new meiosis-specific cohesin with a unique spatiotemporal distribution. RAD21L and REC8 have symmetrical, mutually exclusive localization on the not-yet-synapsed homologues, implying that cohesins could establish a code for homologue recognition.

IntroductionAngiogenesis is a critical process in physiologic and pathologic conditions, including embryo development, wound healing, tumor progression, and inflammatory diseases. 1 Inflammation and angiogenesis are closely associated, and pathologic angiogenesis has been implicated in the development of chronic inflammatory diseases. Interplay between inflammation and angiogenesis is mediated largely by cytokines, chemokines, and growth factors. Some of these molecules, including vascular endothelial growth factor (VEGF), induce endothelial permeability, allowing the infiltration of leukocytes to inflammatory sites, resulting in tissue damage. 2 Interleukin-33 (IL-33) is a newly identified cytokine of the IL-1 family, which also includes the inflammatory cytokines IL-1␣, It has been shown to signal via ST2 receptor. 4 IL-33 expression is broadly detected in various tissues, including stomach, lung, spinal cord, brain, and skin, as well as in cells, including smooth muscle cells and epithelial cells lining bronchus and small airways. 4 Notably, IL-33 expression is induced by IL-1␤ and tumor necrosis factor-␣ (TNF-␣) in lung and dermal fibroblast and, to a lesser extent, by macrophage activation. 4 IL-33 treatment has been shown to induce T-helper (Th) type 2 responses in mice as indicated by an increase in Th2 cytokine production and serum immunoglobulin. Systemic treatment of mice with IL-33 results in pathologic changes in the lung and the digestive tract. In the lung, vascular changes accompanied with eosinophilic and mononuclear infiltrates were observed in small muscular arteries. 4 Recently, functions of IL-33 in cardiovascular diseases have been reported. For example, IL-33 can reduce the development of atherosclerosis in apolipoprotein E Ϫ/Ϫ mice on a high-fat diet. 5 Furthermore, IL-33/ST2 complexes also have been shown to activate cardioprotective signaling pathways. 6 IL-33 is produced as a 30-kDa precursor protein that is cleaved in vitro by caspase-1, releasing the mature 18-kDa form. 4 Upon binding to the ST2 receptor, IL-33 promotes the activation of nuclear factor (NF)-B and mitogen-activated protein kinase (MAPK), leading to increased transcription of Th2 cytokines. 4 The ST2 receptor, a member of IL-1 receptor family, has long been known as an orphan receptor. Despite its structural and functional similarity to IL-1 receptor family, the ST2 receptor does not bind to IL-1␣ or IL-1␤ or other members of the IL-1 family. Two isoforms, a soluble (sST2) and a membrane bound form (ST2L), are produced through differential mRNA processing. 7,8 ST2L is expressed mainly in mast cells and Th2 cells. 7,8 Both ST2 forms also are expressed in freshly isolated human umbilical vein endothelial cells (HUVECs), and they are up-regulated by proinflammatory stimuli such as TNF, IL-1␣, and IL-1␤. 9 Nitric oxide (NO) production in endothelial cells (ECs) is transiently regulated by multiple inflammatory angiogenic factors such as VEGF and angiopoietin-1. 10,11 NO, in turn, modulates the angiogenic function of these ...

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During meiosis, homologous chromosome (homolog) pairing is promoted by several layers of regulation that include dynamic chromosome movement and meiotic recombination. However, the way in which homologs recognize each other remains a fundamental issue in chromosome biology. Here, we show that homolog recognition or association initiates upon entry into meiotic prophase before axis assembly and double-strand break (DSB) formation. This homolog association develops into tight pairing only during or after axis formation. Intriguingly, the ability to recognize homologs is retained in Sun1 knockout spermatocytes, in which telomere-directed chromosome movement is abolished, and this is the case even in Spo11 knockout spermatocytes, in which DSB-dependent DNA homology search is absent. Disruption of meiosis-specific cohesin RAD21L precludes the initial association of homologs as well as the subsequent pairing in spermatocytes. These findings suggest the intriguing possibility that homolog recognition is achieved primarily by searching for homology in the chromosome architecture as defined by meiosis-specific cohesin rather than in the DNA sequence itself.