Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which were associated with hepatitis B or C virus infections, including two sets of multicentric tumors. Although no common somatic mutations were identified in the multicentric tumor pairs, their whole-genome substitution patterns were similar, suggesting that these tumors developed from independent mutations, although their shared etiological backgrounds may have strongly influenced their somatic mutation patterns. Statistical and functional analyses yielded a list of recurrently mutated genes. Multiple chromatin regulators, including ARID1A, ARID1B, ARID2, MLL and MLL3, were mutated in ～50% of the tumors. Hepatitis B virus genome integration in the TERT locus was frequently observed in a high clonal proportion. Our whole-genome sequencing analysis of HCCs identified the influence of etiological background on somatic mutation patterns and subsequent carcinogenesis, as well as recurrent mutations in chromatin regulators in HCCs.     

Positive and negative peptide signals control stomatal density

The stoma is a micro valve found on aerial plant organs that promotes gas exchange between the atmosphere and the plant body. Each stoma is formed by a strict cell lineage during the early stages of leaf development. Molecular genetics research using the model plant Arabidopsis has revealed the genes involved in stomatal differentiation. Cysteine-rich secretory peptides of the EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family play crucial roles as extracellular signaling factors. Stomatal development is orchestrated by the positive factor STOMAGEN/EPFL9 and the negative factors EPF1, EPF2, and CHALLAH/EPFL6 in combination with multiple receptors. EPF1 and EPF2 are produced in the stomatal lineage cells of the epidermis, whereas STOMAGEN and CHALLAH are derived from the inner tissues. These findings highlight the complex cell-to-cell and intertissue communications that regulate stomatal development. To optimize gas exchange, particularly the balance between the uptake of carbon dioxide (CO(2)) and loss of water, plants control stomatal activity in response to environmental conditions. The CO(2) level and light intensity influence stomatal density. Plants sense environmental cues in mature leaves and adjust the stomatal density of newly forming leaves, indicating the involvement of long-distance systemic signaling. This review summarizes recent research progress in the peptide signaling of stomatal development and discusses the evolutionary model of the signaling machinery.     

Pummerer-type Functionalization of Aryl and Alkenyl Selenoxides

Heteroatom-stabilized carbenium ions have been widely recognized as potential electrophilic reagents. However, in contrast with the extensive works on thionium ion series, the highly labile character of selenoxide functionalities has caused serious limitation in the synthetic use in spite of their wide potentiality as synthetic equivalents of electrophilic selonium ions. In this paper, novel generation of selonium ions and the synthetic uses of the species for Pummerer-type α-functionalization and for cycloaddition by using the novel dienophilic behavior of π-conjugated selonium cations.     

Scanning electron microscopic observation of spermiophage cell within the lumen of the epididymal duct of the vasectomized Japanese monkey (Macacus fuscatus).

The spermiophagic process by intraluminal macrophages in the epididymal ducts of the vasectomized Japanese monkey was well visualized with scanning electron microscope. The fragments of disintegrated spermatozoa were seen in the phase enveloped in bulk by flap-like cytoplasmic extensions or in the phase ingested within the cytoplasm.     

Genesis of continental seismogenic zone and a new fault zone model

Experiments were conducted repeatedly on Mannari granite under different temperature and confining pressure conditions. Systematic micro- and submicro-structural and mechanical analyses of granite samples deformed under 1.5 GPa (confining pressure), at 25℃—650℃temperatures and at 2× 10^-6 s^-1 strain rate show the brittle-ductile deformation microstructures and microstructural associations similar to those observed in naturally deformed crustal rocks and minerals. Brittle fracturing and crystalline plasticity co-exist and react with each other in the brittle-ductile transition domain of the continental lithosphere. The interaction between the different mechanisms in the transitional domain results in the variation of anomalous strength values, which may best explain the genesis of the continental seismogenic zone. A new fault zone model is proposed on the basis of detailed micromechanical and microstructural analyses.     

Antibody to tumor necrosis factor (TNF) reduces endotoxin fever

Summary Antibody to tumor necrosis factor (TNF), injected intravenously, reduced endotoxin fever in the rabbit. The fever-reducing effect was apparent in the latter half of the febrile response.This work was supported by a Grants-in-Aid from the Ministry of Education, Science and Culture of Japan (Grant No. 62480112).