Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1

Journey to the Center of the Gyre: The Fate of the Tohoku Tsunami Debris Field

The 9.0 magnitude Tohoku earthquake that struck off the coast of Japan on March 11, 2011, was the fourth largest earthquake in recorded history and the largest ever to hit a densely populated region (Bertero, 2011; Lekkas et al., 2011). The ensuing tsunami inundated an area of about 561 km2 (Geospatial Information Authority, 2011), washing away an estimated 24.9 million tonnes of debris, including wood, sediments, plastics, industrial chemicals, and structural components (Oh, 2011). Two weeks following the tsunami, the meltdown of the Fukushima Daiichi nuclear reactors released radioactive elements into the atmosphere and coastal waters. Atmospheric deposition was found to be an important source of radioactivity in surface waters and may have contaminated the debris field, although the extent of this contamination remains unknown (Buesseler et al., 2012; Honda et al., 2012).Here, we follow the debris field along its predicted path from its source in Japanese coastal waters through the Kuroshio-Oyashio Extension, the North Pacific Current, and the California Current. From there, it will loop back toward the Hawaiian Islands, ultimately accumulating in the North Pacific Gyre (International Pacific Research Center, 2011b; Figure 1). Relying on precedents from previous natural disasters and ongoing observations, we attempt to predict the impact of this debris field on marine and coastal ecosystems in each of these regions. We predict that the Tohoku debris field will create a rare perturbation for ecosystems interconnected across the North Pacific, exacerbating the accumulating human impacts on the world ocean

Parallel assembly of actin and tropomyosin, but not myosin II, during de novo actin filament formation in live mice

Many actin filaments in animal cells are co-polymers of actin and tropomyosin. In many cases, non-muscle myosin II associates with these co-polymers to establish a contractile network. However, the temporal relationship of these three proteins in the de novo assembly of actin filaments is not known. Intravital subcellular microscopy of secretory granule exocytosis allows the visualisation and quantification of the formation of an actin scaffold in real time, with the added advantage that it occurs in a living mammal under physiological conditions. We used this model system to investigate the de novo assembly of actin, tropomyosin Tpm3.1 (a short isoform of TPM3) and myosin IIA (the form of non-muscle myosin II with its heavy chain encoded by Myh9) on secretory granules in mouse salivary glands. Blocking actin polymerization with cytochalasin D revealed that Tpm3.1 assembly is dependent on actin assembly. We used time-lapse imaging to determine the timing of the appearance of the actin filament reporter LifeAct–RFP and of Tpm3.1–mNeonGreen on secretory granules in LifeAct–RFP transgenic, Tpm3.1–mNeonGreen and myosin IIA–GFP (GFP-tagged MYH9) knock-in mice. Our findings are consistent with the addition of tropomyosin to actin filaments shortly after the initiation of actin filament nucleation, followed by myosin IIA recruitment.Andrius Masedunskas, Mark A. Appaduray, Christine A. Lucas, María Lastra Cagigas, Marco Heydecker, Mira Holliday, Joyce C.M. Meiring, Jeff Hook, Anthony Kee, Melissa White, Paul Thomas, Yingfan Zhang, Robert S. Adelstein, Tobias Meckel, Till Böcking, Roberto Weigert, Nicole S. Bryce, Peter W. Gunning, and Edna C. Hardema