Metal–Organic Framework Templated Porous Carbon‐Metal Oxide/Reduced Graphene Oxide as Superior Support of Bimetallic Nanoparticles for Efficient Hydrogen Generation from Formic Acid

Ultrafine PdAg nanoparticles (NPs) are successfully immobilized on zirconia/porous carbon/reduced graphene oxide (ZrO₂/C/rGO) nanocomposite derived from metal organic framework/graphene oxide. Monodispersed PdAg NPs (diameter ≤2.5 nm) can be facilely anchored on the ZrO₂/C/rGO and the aggregation of metal NPs can be avoided utmostly. By virtue of the synergistic effect between metal NPs and support, the resulting PdAg@ZrO₂/C/rGO exhibits excellent activity (turnover frequency, 4500 h^?1 at 333 K) for the dehydrogenation of formic acid. As an effective strategy, it provides an opportunity to immobilize ultrafine metal NPs on metal oxide/porous carbon/reduced graphene oxide, which has tremendous application prospects in various catalytic fields.     

Soil burrowing Muscina angustifrons (Diptera: Muscidae) larvae excrete spores capable of forming mycorrhizae underground

Muscina angustifrons (Diptera: Muscidae) is a mycophagous species that exploits a variety of fungi, including ectomycorrhizal fungi. Larvae of this species have been shown to feed on sporocarps (including spores), and full-grown larvae leave sporocarps and pupate 0–6?cm below the soil surface. In this study, we examined whether M. angustifrons larvae are capable of transporting ectomycorrhizal fungal spores and enhancing ectomycorrhiza growth on host-plant roots. Full-grown larvae were found to move horizontally 10–20?cm from their feeding sites and burrow underground. These wandering larvae retained ectomycorrhizal fungal spores in their intestines, which were excreted following relocation to underground pupation sites. Excreted spores retained germination and infection capacities to form ectomycorrhiza on host-plant roots. In the infection experiments, ectomycorrhizal fungal spores applied in the vicinity of underground host-plant roots were more effective in forming ectomycorrhiza than those applied to the ground surface, suggesting that belowground transportation of spores by M. angustifrons larvae could enhance ectomycorrhizal formation. These results suggested that M. angustifrons larvae act as a short-distance spore transporter of ectomycorrhizal fungi.     

FGF4 is a limiting factor controlling the proportions of primitive endoderm and epiblast in the ICM of the mouse blastocyst

The primitive endoderm (PE) and epiblast (EPI) are two lineages derived from the inner cell mass (ICM) of the E3.5 blastocyst. Although it has been shown that FGF signaling is necessary and sufficient for PE specification in the ICM, it is unknown what mechanisms control the PE/EPI proportion in the embryo. Because modulation of FGF signaling alone is sufficient to convert all ICM cells to either PE or EPI, a model has been proposed in which the amount of FGF in the embryo controls the PE/EPI proportion. To test this model, we reduced the amount of FGF4, the major FGF in the preimplantation embryo, using various genotypes of Fgf4 mutants. We observed a maternal contribution of Fgf4 in PE specification, but it was dispensable for development. In addition, upon treatment of Fgf4 mutant embryos with exogenous FGF4, we observed a progressive increase of PE proportions in an FGF4 dose dependent manner, regardless of embryo genotype. We conclude that the amount of FGF4 is limited and regulates PE/EPI proportions in the mouse embryo.     

Insect Cell-Derived Cofactors Become Fully Functional after Proteinase K and Heat Treatment for High-Fidelity Amplification of Glycosylphosphatidylinositol-Anchored Recombinant Scrapie and BSE Prion Proteins

The central event in prion infection is the conformational conversion of host-encoded cellular prion protein (PrP^C) into the pathogenic isoform (PrP^Sc). Diverse mammalian species possess the cofactors required for in vitro replication of PrP^Sc by protein-misfolding cyclic amplification (PMCA), but lower organisms, such as bacteria, yeasts, and insects, reportedly lack the essential cofactors. Various cellular components, such as RNA, lipids, and other identified cofactor molecules, are commonly distributed in both eukaryotes and prokaryotes, but the reasons for the absence of cofactor activity in lower organisms remain to be elucidated. Previously, we reported that brain-derived factors were necessary for the in vitro replication of glycosylphosphatidylinositol-anchored baculovirus-derived recombinant PrP (Bac-PrP). Here, we demonstrate that following protease digestion and heat treatment, insect cell lysates had the functional cofactor activity required for Bac-PrP replication by PMCA. Mammalian PrP^Sc seeds and Bac-PrP^Sc generated by PMCA using Bac-PrP and insect cell-derived cofactors showed similar pathogenicity and produced very similar lesions in the brains of inoculated mice. These results suggested that the essential cofactors required for the high-fidelity replication of mammalian PrP^Sc were present in the insect cells but that the cofactor activity was masked or inhibited in the native state. We suggest that not only RNA, but also DNA, are the key components of PMCA, although other cellular factors were necessary for the expression of the cofactor activity of nucleic acids. PMCA using only insect cell-derived substances (iPMCA) was highly useful for the ultrasensitive detection of PrP^Sc of some prion strains.     

Extracellular High Mobility Group Box 1 Plays a Role in the Effect of Bone Marrow Mononuclear Cell Transplantation for Heart Failure

Transplantation of unfractionated bone marrow mononuclear cells (BMCs) repairs and/or regenerates the damaged myocardium allegedly due to secretion from surviving BMCs (paracrine effect). However, donor cell survival after transplantation is known to be markedly poor. This discrepancy led us to hypothesize that dead donor BMCs might also contribute to the therapeutic benefits from BMC transplantation. High mobility group box 1 (HMGB1) is a nuclear protein that stabilizes nucleosomes, and also acts as a multi-functional cytokine when released from damaged cells. We thus studied the role of extracellular HMGB1 in the effect of BMC transplantation for heart failure. Four weeks after coronary artery ligation in female rats, syngeneic male BMCs (or PBS only as control) were intramyocardially injected with/without anti-HMGB1 antibody or control IgG. One hour after injection, ELISA showed that circulating extracellular HMGB1 levels were elevated after BMC transplantation compared to the PBS injection. Quantitative donor cell survival assessed by PCR for male-specific sry gene at days 3 and 28 was similarly poor. Echocardiography and catheterization showed enhanced cardiac function after BMC transplantation compared to PBS injection at day 28, while this effect was abolished by antibody-neutralization of HMGB1. BMC transplantation reduced post-infarction fibrosis, improved neovascularization, and increased proliferation, while all these effects in repairing the failing myocardium were eliminated by HMGB1-inhibition. Furthermore, BMC transplantation drove the macrophage polarization towards alternatively-activated, anti-inflammatory M2 macrophages in the heart at day 3, while this was abolished by HMGB1-inhibition. Quantitative RT-PCR showed that BMC transplantation upregulated expression of an anti-inflammatory cytokine IL-10 in the heart at day 3 compared to PBS injection. In contrast, neutralizing HMGB1 by antibody-treatment suppressed this anti-inflammatory expression. These data suggest that extracellular HMGB1 contributes to the effect of BMC transplantation to recover the damaged myocardium by favorably modulating innate immunity in heart failure.     

Experimental Evidence for the Involvement of PDLIM5 in Mood Disorders in Hetero Knockout Mice

Background

Reports indicate that PDLIM5 is involved in mood disorders. The PDLIM5 (PDZ and LIM domain 5) gene has been genetically associated with mood disorders; it’s expression is upregulated in the postmortem brains of patients with bipolar disorder and downregulated in the peripheral lymphocytes of patients with major depression. Acute and chronic methamphetamine (METH) administration may model mania and the evolution of mania into psychotic mania or schizophrenia-like behavioral changes, respectively.

Methods

To address whether the downregulation of PDLIM5 protects against manic symptoms and cause susceptibility to depressive symptoms, we evaluated the effects of reduced Pdlim5 levels on acute and chronic METH-induced locomotor hyperactivity, prepulse inhibition, and forced swimming by using Pdlim5 hetero knockout (KO) mice.

Results

The homozygous KO of Pdlim5 is embryonic lethal. The effects of METH administration on locomotor hyperactivity and the impairment of prepulse inhibition were lower in Pdlim5 hetero KO mice than in wild-type mice. The transient inhibition of PDLIM5 (achieved by blocking the translocation of protein kinase C epsilon before the METH challenge) had a similar effect on behavior. Pdlim5 hetero KO mice showed increased immobility time in the forced swimming test, which was diminished after the chronic administration of imipramine. Chronic METH treatment increased, whereas chronic haloperidol treatment decreased, Pdlim5 mRNA levels in the prefrontal cortex. Imipramine increased Pdlim5 mRNA levels in the hippocampus.

Conclusion

These findings are partially compatible with reported observations in humans, indicating that PDLIM5 is involved in psychiatric disorders, including mood disorders.     

Phylogeny and Evolution of the SERA Multigene Family in the Genus <Emphasis Type="Italic">Plasmodium</Emphasis>

The serine repeat antigen gene family of Plasmodium falciparum (Pf-SERA) consists of nine gene members. By sequence similarity search, 45 genes were identified to be homologous to the Pf-SERA genes in the ongoing seven Plasmodium genome sequencing project databases for the species: P. reichenowi, P. vivax, P. knowlesi, P. yoelii, P. berghei, P. chabaudi, and P. gallinaceum. In combination with additional PCR-based sequencing, we found that almost all SERA genes in each species were aligned in a tandem cluster and sandwiched between two conserved hypothetical protein genes, except for P. reichenowi, which could not be confirmed. The minimum and maximum numbers of clustered genes were 2 and 12 for P. gallinaceum and P. vivax, respectively. The best tree of the maximum likelihood analysis demonstrated that all Plasmodium SERA homologues, except for SERA1 of P. gallinaceum (Pg-SERA1), can be classified into four groups, represented by Pf-SERA5, Pf-SERA6, Pf-SERA7, and Pf-SERA8. Genes in the Pf-SERA8 group, although highly divergent and distantly related to the sequences of other groups, were not pseudogenes. P. berghei SERA5, the counterpart of Pf-SERA8, was expressed in the mosquito stage. P. gallinaceum lacks the orthologues to Pf-SERA5, Pf-SERA6, and Pf-SERA7, suggesting that P. gallinaceum diverged from a common ancestor of all eight Plasmodium species examined before gene duplication(s) occurred to generate these paralogous groups. Here, we reveal an evolutionary trail of SERA gene cluster in the genus Plasmodium and discuss a phylogeny of Plasmodium species from the viewpoint of the evolution of a multigene family.     

Tumor suppressor candidate 5 (TUSC5) is expressed in brown adipocytes

Rat brain endothelial cell derived gene-1 (BEC-1) had considerable homology with tumor suppressor candidate 5 (TUSC5). TUSC5 was expressed abundantly, and its mRNA was inhibited by cold exposure in rat brown adipose tissue (BAT). In the present study, we investigated its regulatory mechanism using primary cultured rat brown preadipocytes (RBPA) and Zucker lean rats (ZL). We found that: (1) TUSC5 mRNA began to increase in a manner similar to C/EBP-alpha, PPAR-gamma, and adiponectin during differentiation in RBPA; (2) neither beta3-adrenoceptor agonist BRL 37344 nor dexamethasone affected TUSC5 mRNA in RBPA; (3) propranolol did not block the decrease of TUSC5 mRNA by cold exposure in ZL; (4) BRL 37344 did not influence TUSC5 mRNA in ZL; and (5) dexamethasone inhibited TUSC5 mRNA in a dose-dependent manner similar to UCP-1 in ZL. These data suggested that TUSC5 is involved in the differentiation, and its expression is regulated independently of the beta-adrenergic pathway in BAT.     

Allelic dimorphism-associated restriction of recombination in Plasmodium falciparum msp1

Allelic dimorphism is a characteristic feature of the Plasmodium falciparum msp1 gene encoding the merozoite surface protein 1, a strong malaria vaccine candidate. Meiotic recombination is a major mechanism for the generation of msp1 allelic diversity. Potential recombination sites have previously been mapped to specific regions within msp1 (a 5' 1-kb region and a 3' 0.4-kb region) with no evidence for recombination events in a central 3.5-kb region. However, evidence for the lack of recombination events is circumstantial and inconclusive because the number of msp1 sequences analysed is limited, and the frequency of recombination events has not been addressed previously in a high transmission area, where the frequency of meiotic recombination is expected to be high. In the present study, we have mapped potential allelic recombination sites in 34 full-length msp1 sequences, including 24 new sequences, from various geographic origins. We also investigated recombination events in blocks 6 to 16 by population genetic analysis of P. falciparum populations in Tanzania, where malaria transmission is intense. The results clearly provide no evidence of recombination events occurring between the two major msp1 allelic types, K1-type and Mad20-type, in the central region, but do show recombination events occurring throughout the entire gene within sequences of the Mad20-type. Thus, the present study indicates that allelic dimorphism of msp1 greatly affects inter-allelic recombination events, highlighting a unique feature of allelic diversity of P. falciparum msp1.