Redefinition of Nipponbathynella based on the four new species from East Asia (Crustacea: Bathynellacea: Parabathynellidae)

Four new species of the parabathynellid genus Nipponbathynella Schminke, 1973 are described from South Korea (Nipponbathynella leesookyungae sp. nov., Nipponbathynella donggangensis sp. nov. and Nipponbathynella wanjuensis sp. nov.) and Japan (Nipponbathynella shigaensis sp. nov.), raising the number of known species to seven. Nipponbathynella leesookyungae is characterized by the convex ventral surface of the labrum and the rich ornamentation (with three spinules and two teeth) of the exopod of male thoracopod VIII; N. donggangensis by the distal spine on the distal maxillular segment with many dentils; N. wanjuensis by the endopod of the male thoracopod VIII with one seta (instead of two) and the serrated endopodal spur of the uropod; and N. shigaensis by the basipod of thoracopods II–VII carrying strong hairs on their outer margin. The three new and one known (Nipponbathynella pectina) South Korean species share a bur-like inner lobe of the male thoracopod VIII, suggesting their close relationship. Based on the one-segmented exopod on thoracopod I and two-segmented exopod on the thoracopods II–VII, the bell-shaped male thoracopod VIII and the uropod with sympod carrying a large distal spine in addition to several proximal spines of smaller size, with endopod drawn into a spur and with exopod carrying a seta, a close phylogenetic relationship between Nipponbathynella and Arisubathynella Park and Eun, 2012 is proposed.

http://zoobank.org/urn:lsid:zoobank.org:pub:9650379F-C249-473C-AAA4-B3D638B96322     

BRD7 regulates the insulin-signaling pathway by increasing phosphorylation of GSK3β

Reduced hepatic expression levels of bromodomain-containing protein 7 (BRD7) have been suggested to play a role in the development of glucose intolerance in obesity. However, the molecular mechanism by which BRD7 regulates glucose metabolism has remained unclear. Here, we show that BRD7 increases phosphorylation of glycogen synthase kinase 3β (GSK3β) in response to activation of the insulin receptor-signaling pathway shortly after insulin stimulation and the nutrient-sensing pathway after feeding. BRD7 mediates phosphorylation of GSK3β at the Serine 9 residue and this effect on GSK3β occurs even in the absence of AKT activity. Using both in vitro and in vivo models, we further demonstrate that BRD7 mediates phosphorylation of ribosomal protein S6 kinase (S6K) and leads to increased phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and, therefore, relieves its inhibition of the eukaryotic translation initiation factor 4E (eIF4E). However, the increase in phosphorylation of 4E-BP1 with BRD7 overexpression is blunted in the absence of AKT activity. In addition, using liver-specific BRD7 knockout (LBKO) mice, we show that BRD7 is required for mTORC1 activity on its downstream molecules. These findings show a novel basis for understanding the molecular dynamics of glucose metabolism and suggest the unique function of BRD7 in the regulation of glucose homeostasis.     

Extensional scientific realism vs. intensional scientific realism

Extensional scientific realism is the view that each believable scientific theory is supported by the unique first-order evidence for it and that if we want to believe that it is true, we should rely on its unique first-order evidence. In contrast, intensional scientific realism is the view that all believable scientific theories have a common feature and that we should rely on it to determine whether a theory is believable or not. Fitzpatrick argues that extensional realism is immune, while intensional realism is not, to the pessimistic induction. I reply that if extensional realism overcomes the pessimistic induction at all, that is because it implicitly relies on the theoretical resource of intensional realism. I also argue that extensional realism, by nature, cannot embed a criterion for distinguishing between believable and unbelievable theories.     

Multispecies-compatible antitumor effects of a cross-species small-interfering RNA against mammalian target of rapamycin

Successful development of sequence-specific siRNA (small interfering RNA)-based drugs requires an siRNA design that functions consistently in different organisms. Utilizing the CAPSID program previously developed by our group, we here designed siRNAs against mammalian target of rapamycin (mTOR) that are entirely complementary among various species and investigated their multispecies-compatible gene-silencing properties. The mTOR siRNAs markedly reduced mTOR expression at both the mRNA and protein levels in human, mouse, and monkey cell lines. The reduction in mTOR expression resulted in inactivation of both mTOR complex I and II signaling pathways, as confirmed by reduced phosphorylation of p70S6K (70-kDa ribosomal protein S6 kinase), 4EBP1 (eIF4E-binding protein 1), and AKT, and nuclear accumulation of FOXO1 (forkhead box O1), with consequent cell-cycle arrest, proliferation inhibition, and autophagy activation. Moreover, interfering with mTOR activity in vivo using mTOR small-hairpin RNA-expressing recombinant adeno-associated virus led to significant antitumor effects in xenograft and allograft models. Thus, the present study demonstrates that cross-species siRNA successfully silences its target and readily produces multispecies-compatible phenotypic alterations-antitumor effects in the case of mTOR siRNA. Application of cross-species siRNA should greatly facilitate the development of siRNA-based therapeutic agents.     

Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer

Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer.     

A Study of a Stand- Alone Type Variable Speed Wind Tur bine System with Synchronous Generator

Most recently produced wind generators use variable-speed systems for high-efficiency operation and low mechanical stress.In this study of a variable-speed standalone system that uses a synchronous machine,a power converter for the system was developed and tested.The maximum power points were approximated in a line according to the wind speed changes,and the linear approximation MPPT algorithm was used to determine the duty ratio that corresponds to the intersection point of the observed power and linearized line using the power generated from the generator at a point.With the fabricated converter,it was verified that the voltage,current and theta were normal with the varied load current.     

CD43, a molecule defective in Wiskott-Aldrich syndrome, binds ICAM-1.

THE protein CD43 (also known as sialophorin, leukosialin, large sialoglycoprotein or gp115) is expressed on the surface of T lymphocytes, monocytes, neutrophils, platelets and some B lymphocytes. Expression of CD43 is deficient and/or defective in the X-chromosome-linked immunodeficiency disorder Wiscott-Aldrich syndrome, suggesting that CD43 might have a role in T-cell activation. We have shown that expression of human CD43 in an HLA-DR-specific murine T-cell hybridoma enhances the antigen-specific response to stimulation by the human lymphoblastoid cell line Daudi, and that Daudi cells bind specifically to purified immobilized CD43. These data indicate that the specific interaction of CD43 with a ligand on the surface of Daudi cells might contribute to T-cell activation. Here we report evidence that intercellular adhesion molecule-1 (ICAM-1, or CD54), is a ligand for CD43.