Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Investigation on the fracture mechanism of homogenized micro-crack crushing technology for portland cement concrete pavement rehabilitation

The homogenized micro-crack crushing technology for concrete pavement maintenance has received increased attention in China. To study the fracture mechanism of the homogenized micro-crack crushing technology, a low-velocity impact test system is developed and experiments using concrete slabs of different thicknesses are conducted with different drop heights and hammer weights. Furthermore, the fracture of concrete slabs under impact loading is simulated using the continuous-discontinuous element method. Finally, the fracture mechanism is investigated in a case study. It is concluded that a cylindrical compression-shear fracture surface appears under the impact head while the fractured blocks are still interlocked with each other. The main cracks in the concrete slabs are initiated and propagate parallel to the longer side of the impact head, whereas branch cracks develop perpendicular to the main cracks. These cracks radiate from the center of the impact head. The cracks inside the concrete develop upward from the bottom of the slabs. Because fractured blocks divided by micro-cracks can interlock with themselves and the crack distributions tend to be uniform, it is beneficial for portland cement concrete pavement rehabilitation to be overlaid by a hot-mix asphalt mixture

Ethylene controls cambium stem cell activity via promoting local auxin biosynthesis

The vascular cambium is the main secondary meristem in plants that produces secondary phloem (outside) and xylem (inside) on opposing sides of the cambium. The phytohormone ethylene has been implicated in vascular cambium activity, but the regulatory network underlying ethylene-mediated cambial activity remains to be elucidated. Here, we found that PETAL MOVEMENT-RELATED PROTEIN1 (RhPMP1), an ethylene-inducible HOMEODOMAIN-LEUCINE ZIPPER I transcription factor in woody plant rose (Rosa hybrida), regulates local auxin biosynthesis and auxin transport to maintain cambial activity. Knockdown of RhPMP1 resulted in smaller midveins and reduced auxin content, while RhPMP1 overexpression resulted in larger midveins and increased auxin levels compared with the wild-type plants. Furthermore, we revealed that Indole-3-pyruvate monooxygenase YUCCA 10 (RhYUC10) and Auxin transporter-like protein 2 (RhAUX2), encoding an auxin biosynthetic enzyme and an auxin influx carrier, respectively, are direct downstream targets of RhPMP1. In summary, our results suggest that ethylene promotes an auxin maximum in the cambium adjacent to the xylem to maintain cambial activity

Downregulation of UBE4B promotes CNS axon regrowth and functional recovery after stroke

Summary: The limited intrinsic regrowth capacity of corticospinal axons impedes functional recovery after cortical stroke. Although the mammalian target of rapamycin (mTOR) and p53 pathways have been identified as the key intrinsic pathways regulating CNS axon regrowth, little is known about the key upstream regulatory mechanism by which these two major pathways control CNS axon regrowth. By screening genes that regulate ubiquitin-mediated degradation of the p53 proteins in mice, we found that ubiquitination factor E4B (UBE4B) represses axonal regrowth in retinal ganglion cells and corticospinal neurons. We found that axonal regrowth induced by UBE4B depletion depended on the cooperative activation of p53 and mTOR. Importantly, overexpression of UbV.E4B, a competitive inhibitor of UBE4B, in corticospinal neurons promoted corticospinal axon sprouting and facilitated the recovery of corticospinal axon-dependent function in a cortical stroke model. Thus, our findings provide a translatable strategy for restoring corticospinal tract-dependent functions after cortical stroke