State-space modeling clarifies productivity regime shifts of Japanese flying squid

Regime shifts of climatic and environmental conditions potentially affect the productivity of fishery resources, posing challenges in stock management. The stocks of the Japanese flying squid (Todarodes pacificus) are suspected to suffer from regime shifts, but detecting the occurrence of regime shifts in this species is generally difficult and unreliable because the short-lived nature of this species inherently confounds the effect of regime shifts with observation and process errors. Here we developed a new state-space assessment model to evaluate the influence of regime shifts on the spawner-recruit relationship of the Japanese flying squid. The model simultaneously estimates the population dynamics of multiple stocks that could share some life history parameters, thereby stabilizing parameter inference. We demonstrate that two regime shifts in productivity around 1991 and 2015 caused two- to threefold changes of maximum sustainable yields. The model with regime shifts clarifies the relationship between fishing pressure and spawner abundance that is difficult to detect in a model with no regime shift. The state-space approach is a promising tool for accurately assessing stock status by separating the recruitment process from observation errors and is expected to contribute to the effective management of marine biological resources sensitive to regime shifts.     

The Cell Adhesion Molecule Necl-4/CADM4 Serves as a Novel Regulator for Contact Inhibition of Cell Movement and Proliferation

Contact inhibition of cell movement and proliferation is critical for proper organogenesis and tissue remodeling. We show here a novel regulatory mechanism for this contact inhibition using cultured vascular endothelial cells. When the cells were confluently cultured, Necl-4 was up-regulated and localized at cell–cell contact sites where it cis-interacted with the vascular endothelial growth factor (VEGF) receptor. This interaction inhibited the tyrosine-phosphorylation of the VEGF receptor through protein-tyrosine phosphatase, non-receptor type 13 (PTPN13), eventually reducing cell movement and proliferation. When the cells were sparsely cultured, Necl-4 was down-regulated but accumulated at leading edges where it inhibited the activation of Rho-associated protein kinase through PTPN13, eventually facilitating the VEGF-induced activation of Rac1 and enhancing cell movement. Necl-4 further facilitated the activation of extracellular signal-regulated kinase 1/2, eventually enhancing cell proliferation. Thus, Necl-4 serves as a novel regulator for contact inhibition of cell movement and proliferation cooperatively with the VEGF receptor and PTPN13.     

Genetic structure of the clonal herb Tanakaea radicans (Saxifragaceae) at multiple spatial scales,revealed by nuclear and mitochondrial microsatellite markers

The genus Tanakaea is a plant genus that consists of one or two evergreen herbaceous species in Japan and China. As rithophytic plant species occur on shaded rocks, the populations are usually isolated and sporadically found in disjunct areas. To evaluate the genetic structure of the species at multiple spatial scales, 10 nuclear and mitochondrial microsatellite markers were developed. The novel markers showed high genetic variations (two to 15 alleles and H_e from 0.400 to 0.894). Clonal samples were identified with the probability of identity of 9.0E‐8. When evaluated with 11 populations in Japan, significant genetic differentiation between regional population groups was detected (F_ST = 0.313 between Shikoku and Honshu islands), suggesting they have long been isolated from each other. Overall, these markers will be useful for population genetic research to investigate clonal structure and genetic diversity and levels of genetic differentiation between the geographically isolated populations.     

Separation of glycosphingolipids with titanium dioxide

We introduce the principle of a new technique to isolate glycosphingolipids (GSLs) from phospholipids. Neutral and acidic GSLs in organic solvent bind to titanium dioxide under neutral pH and can be eluted with 5 mg/ml of 2,5-dihydroxybenzoic acid in methanol. This special property is applicable for eliminating phospholipids, including sphingomyelin, which cannot be eliminated by a typical mild alkaline treatment. By using this technique, we demonstrated the rapid separation of minor components of GSLs, namely sulfatide and gangliosides from rabbit serum and liver, respectively. The minor GSL components were effectively purified despite both sources containing tremendous amount of phospholipids and simple lipids such as cholesterol, cholesteryl esters and triglycerides.     

Direct In Vivo Reprogramming with Sendai Virus Vectors Improves Cardiac Function after Myocardial Infarction

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Peptide nanotube aligning side chains onto one side

A novel pseudo cyclic penta‐β‐peptide composed of a β‐naphthylalanine, two β‐alanines, and a sequence of ethylenediamine‐succinic acid (CP5ES) is synthesized and investigated on peptide nanotube (PNT) formation. When the PNT is formed with the maximum number of intermolecular hydrogen bonds between the cyclic peptides, the sequence enables the alignment of the side chains, naphthyl groups, on one side of the PNT. Microscopic and spectroscopic observations of CP5ES crystals reveal that CP5ES forms rod‐ or needle‐shaped molecular assemblies showing exciton coupling of the Cotton effect and predominant monomer emission, which are different from a reference cyclic tri‐β‐peptide composed of a β‐naphthylalanine and two β‐alanines. Insertion of a sequence of ethylenediamine‐succinic acid into β‐amino acids in the cyclic skeleton is therefore suggested to be effective to make the side chains aligning on one side of the PNT. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.     

Development and characterization of EST‐SSR markers in an East Asian temperate plant genus Diabelia (Caprifoliaceae)

A set of expressed sequence tag (EST) simple sequence repeat (SSR) markers were developed and characterized using next‐generation sequencing technology for the genus Diabelia (Caprifoliaceae). De novo assembly of RNA‐seq reads resulted in 58 669 contigs with the N50 length of 1211 bp. A total of 2746 contigs were identified to harbor SSR motifs, of which 48 primer pairs were designed and 11 were shown to be polymorphic across three morphospecies of Diabelia. When evaluated with 30 individuals, the number of alleles per locus ranged from 2 to 11 and the expected heterozygosity varied from 0.399 to 0.873, respectively. Distance‐based clustering indicated that the EST‐SSR markers can provide sufficient power to distinguish the three species (or populations). These markers will be useful for evaluating the range‐wide genetic diversity of each species and examining genetic divergence and gene flow between the three species.     

Electrostatically constrained alpha-helical peptide inhibits replication of HIV-1 resistant to enfuvirtide

Alpha-helical peptides, such as T-20 (enfuvirtide) and C34, derived from the gp41 carboxyl-terminal heptad repeat (C-HR) of HIV-1, inhibit membrane fusion of HIV-1 and the target cells. Although T-20 effectively suppresses the replication of multi-drug resistant HIV variants both in vitro and in vivo, prolonged therapy with T-20 induces emergence of T-20 resistant variants. In order to suppress the emergence of such resistant variants, we introduced charged and hydrophilic amino acids, glutamic acid (E) and lysine (K), at the solvent accessible site of C34. In particular, the modified peptide, SC34EK, demonstrates remarkably potent inhibition of membrane fusion by the resistant HIV-1 variants as well as wild-type viruses. The activity was specific to HIV-1 and little influenced by serum components. We found a strong correlation between the anti-HIV-1 activities of these peptides and the thermostabilities of the 6-helix bundles that are formed with these peptides. We also obtained the crystal structure of SC34EK in complex with a 36 amino acid sequence (N36) comprising the amino-terminal heptad repeat of HIV-1. The EK substitutions in the sequence of SC34EK were directed toward the solvent and generated an electrostatic potential, which may result in enhanced alpha-helicity of the peptide inhibitor. The 6-helix bundle complex of SC34EK with N36 appears to be structurally similar to that of C34 and N36. Our approach to enhancing alpha-helicity of the peptide inhibitor may enable future design of highly effective and specific HIV-1 inhibitors.     

Constitutively expressed catalytic proteasomal subunits are up-regulated during neuronal differentiation and required for axon initiation, elongation and maintenance

Inhibition of the proteasome by lactacystin, a specific blocker of the catalytic beta-subunits, results in transient neurite outgrowth by neuronal cell lines. Vice versa, as demonstrated in this study, treatment of pheochromocytoma (PC12) cells with nerve growth factor (NGF) or other differentiating agents reduces proteasomal activity. This is accompanied by an increase in mRNA and protein levels of the catalytically active subunits beta1, beta2 and beta5, but not of their inducible counterparts, indicating changes in subunit composition of the proteasome during neuronal differentiation. In contrast to neuronal cell lines, however, pre-treatment of primary neurons with proteasome inhibitors completely prevents axon formation, and lower concentrations of lactacystin (0.5-5 microm) significantly reduce axonal elongation and branching in vitro. Furthermore, established axonal networks degenerate rapidly and long-term survival of peripheral neurons is impaired in the presence of proteasome inhibitors. Axonal pathology is reminiscent of the morphological changes observed in neurodegenerative disorders and supports a crucial role of the constitutive catalytic subunits in axon initiation, maintenance and regeneration.