Ontogeny of gene expression of group IB phospholipase A(2) isoforms in the red sea bream, Pagrus (Chrysophrys) major

The red sea bream (Pagrus major) was previously found to express mRNAs for two group IB phospholipase A(2) (PLA(2)) isoforms, DE-1 and DE-2, in the digestive organs, including the hepatopancreas, pyloric caeca, and intestine. To characterize the ontogeny of the digestive function of these PLA(2)s, the present study investigated the localization and expression of DE-1 and DE-2 PLA(2) genes in red sea bream larvae/juveniles and immature adults, by in situ hybridization. In the adults, DE-1 PLA(2) mRNA was expressed in pancreatic acinar cells. By contrast, DE-2 PLA(2) mRNA was detected not only in digestive tissues, such as pancreatic acinar cells, gastric glands of the stomach, epithelial cells of the pyloric caeca, and intestinal epithelial cells, but also in non-digestive ones, including cardiac and lateral muscle fibers and the cytoplasm of the oocytes. In the larvae, both DE-1 and DE-2 PLA(2) mRNAs first appeared in pancreatic tissues at 3 days post-hatching (dph) and in intestinal tissue at 1 dph, and expression levels for both gradually increased after this point. In the juvenile stage at 32 dph, DE-1 PLA(2) mRNA was highly expressed in pancreatic tissue, and DE-2 PLA(2) mRNA was detected in almost all digestive tissues, including pancreatic tissue, gastric glands, pyloric caeca, and intestine, including the myomere of the lateral muscles. In conclusion, both DE-1 and DE-2 PLA(2) mRNAs are already expressed in the digestive organs of red sea bream larvae before first feeding, and larvae will synthesize both DE-1 and DE-2 PLA(2) proteins

Cooperation and competition between the default mode network and frontal parietal network in the elderly

Recent research has shown that the Default Mode Network (DMN) typically exhibits increased activation during processing of social and personal information but shows deactivation during working memory (WM) tasks. Previously, we reported the Frontal Parietal Network (FPN) and DMN showed coactivation during task preparation whereas the DMN exhibited deactivation during task execution in working memory tasks. Aging research has shown that older adults exhibited decreased functional connectivity in the DMN relative to younger adults. Here, we investigated whether age-related cognitive decline is related to a reduced relationship between the FPN and DMN using a working memory task during the execution period. First, we replicated our previous finding that the FPN and DMN showed coactivation during the preparation period, whereas the DMN showed deactivation during the execution period. The older adults showed reduced DMN activity during task preparation and reduced deactivation during task execution; however, they exhibited a higher magnitude of activation in the FPN than the young individuals during task execution. Functional connectivity analyses showed that the elderly group, compared to the young group, showed weaker correlations within the FPN and the DMN, weaker positive correlations between the FPN and DMN during task preparation, and weaker negative correlations between the FPN and DMN during execution. The results suggest that cognitive decline in the older adults might be related to reduced connectivity within the DMN as well as between the FPN and DMN

Cooperative Domain Formation by Homologous Motifs in HOIL-1L and SHARPIN Plays A Crucial Role in LUBAC Stabilization

がんを誘発する酵素の新たなタンパク質間相互作用を解明 --抗がん剤の新たなターゲットを発見--. 京都大学プレスリリース. 2018-04-25.The linear ubiquitin chain assembly complex (LUBAC) participates in inflammatory and oncogenic signaling by conjugating linear ubiquitin chains to target proteins. LUBAC consists of the catalytic HOIP subunit and two accessory subunits, HOIL-1L and SHARPIN. Interactions between the ubiquitin-associated (UBA) domains of HOIP and the ubiquitin-like (UBL) domains of two accessory subunits are involved in LUBAC stabilization, but the precise molecular mechanisms underlying the formation of stable trimeric LUBAC remain elusive. We solved the co-crystal structure of the binding regions of the trimeric LUBAC complex and found that LUBAC-tethering motifs (LTMs) located N terminally to the UBL domains of HOIL-1L and SHARPIN heterodimerize and fold into a single globular domain. This interaction is resistant to dissociation and plays a critical role in stabilizing trimeric LUBAC. Inhibition of LTM-mediated HOIL-1L/SHARPIN dimerization profoundly attenuated the function of LUBAC, suggesting LTM as a superior target of LUBAC destabilization for anticancer therapeutics