Micro RNA Expression after Ingestion of Fucoidan; A Clinical Study

Fucoidans are a class of fucose‐rich sulfated polysaccharides derived from brownmacroalgae that exert a range of biological activities in vitro and in vivo. To generate an unbiasedassessment of pathways and processes affected by fucoidan, a placebo‐controlled double‐blind pilotstudy was performed in healthy volunteers. Blood samples were taken immediately before and 24h after ingestion of a single dose of 1 g of Undaria pinnatifida fucoidan (UPF) or placebo. Levels ofisolated miRNAs were analyzed using Taqman Open Array Human MicroRNA panels. Out of 754miRNAs screened, UPF affected a total of 53 miRNAs. Pathway analysis using the TALOS dataanalysis tool predicted 29 different pathways and processes that were largely grouped into cellsurface receptor signaling, cancer‐related pathways, the majority of which were previouslyassociated with fucoidans. However, this analysis also identified nine pathways and processes thathave not been associated with fucoidans before. Overall, this study illustrates that even a single doseof fucoidans has the potential to affect the expression of genes related to fundamental cellularprocesses. Moreover, it confirms previous data that fucoidans influence immunity, cancer cells,inflammation, and neurological function

Anti-inflammatory activity of fucoidan extracts in vitro

Fucoidans are sulfated, complex, fucose-rich polymers found in brown seaweeds. Fucoidans have been shown to have multiple bioactivities, including anti-inflammatory effects, and are known to inhibit inflammatory processes via a number of pathways such as selectin blockade and enzyme inhibition, and have demonstrated inhibition of inflammatory pathologies in vivo. In this current investigation, fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for modulation of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) by human peripheral blood mononuclear cells (PBMCs) and in a human macrophage line (THP-1). Fucoidan extracts exhibited no signs of cytotoxicity in THP-1 cells after incubation of 48 h. Additionally, all fucoidan extracts reduced cytokine production in LPS stimulated PBMCs and human THP-1 cells in a dose-dependent fashion. Notably, the 5-30 kDa subfraction from Macrocystis pyrifera was a highly effective inhibitor at lower concentrations. Fucoidan extracts from all species had significant anti-inflammatory effects, but the lowest molecular weight subfractions had maximal effects at low concentrations. These observations on various fucoidan extracts offer insight into strategies that improve their efficacy against inflammation-related pathology. Further studies should be conducted to elucidate the mechanism of action of these extracts

GFS, a preparation of Tasmanian Undaria pinnatifida is associated with healing and inhibition of reactivation of Herpes

BACKGROUND: We sought to assess whether GFS, a proprietary preparation of Tasmanian Undaria pinnatifida, has effects on healing or re-emergence of Herpetic infections, and additionally, to assess effects of GFS in vitro. Undaria is the most commonly eaten seaweed in Japan, and contains sulphated polyanions and other components with potential anti-viral activity. Herpes simplex virus type 1 (HSV-1) infections have lower reactivation rates and Herpes type 2 (HSV-2) infections have lower incidence in Japan than in the west. METHODS: Patients with active (15 subjects) or latent (6 subjects) Herpetic infections (HSV-1, 2, EBV, Zoster) were monitored for response to ingestion of GFS. GFS extract was tested in vitro for human T cell mitogenicity and anti-Herpes activity. RESULTS: Ingestion of GFS was associated with increased healing rates in patients with active infections. In addition, patients with latent infection remained asymptomatic whilst ingesting GFS. GFS extract inhibited Herpes viruses in vitro and was mitogenic to human T cells in vitro. CONCLUSIONS: Ingestion of GFS has inhibitory effects on reactivation and is associated with increased rate of healing after Herpetic outbreaks. GFS extract potently inhibited Herpes virus in vitro, and had mitogenic effects on human T cells

A Long Baseline Neutrino Oscillation Experiment Using J-PARC Neutrino Beam and Hyper-Kamiokande

Document submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresHyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hep-ex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW $\times$ 10$^7$ sec integrated proton beam power (corresponding to $1.56\times10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5$-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the $CP$ phase $\delta_{CP}$ can be determined to better than 19 degrees for all possible values of $\delta_{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\,\sigma$ ($5\,\sigma$) for $76$ ($58$) of the $\delta_{CP}$ parameter space

Selective Loss of Cysteine Residues and Disulphide Bonds in a Potato Proteinase Inhibitor II Family

Disulphide bonds between cysteine residues in proteins play a key role in protein folding, stability, and function. Loss of a disulphide bond is often associated with functional differentiation of the protein. The evolution of disulphide bonds is still actively debated; analysis of naturally occurring variants can promote understanding of the protein evolutionary process. One of the disulphide bond-containing protein families is the potato proteinase inhibitor II (PI-II, or Pin2, for short) superfamily, which is found in most solanaceous plants and participates in plant development, stress response, and defence. Each PI-II domain contains eight cysteine residues (8C), and two similar PI-II domains form a functional protein that has eight disulphide bonds and two non-identical reaction centres. It is still unclear which patterns and processes affect cysteine residue loss in PI-II. Through cDNA sequencing and data mining, we found six natural variants missing cysteine residues involved in one or two disulphide bonds at the first reaction centre. We named these variants Pi7C and Pi6C for the proteins missing one or two pairs of cysteine residues, respectively. This PI-II-7C/6C family was found exclusively in potato. The missing cysteine residues were in bonding pairs but distant from one another at the nucleotide/protein sequence level. The non-synonymous/synonymous substitution (Ka/Ks) ratio analysis suggested a positive evolutionary gene selection for Pi6C and various Pi7C. The selective deletion of the first reaction centre cysteine residues that are structure-level-paired but sequence-level-distant in PI-II illustrates the flexibility of PI-II domains and suggests the functionality of their transient gene versions during evolution

Inactivation of Staphylococcal Phenol Soluble Modulins by Serum Lipoprotein Particles

Staphylococcus aureus virulence has been associated with the production of phenol soluble modulins (PSM). PSM are known to activate, attract and lyse neutrophils. However, the functional characterizations were generally performed in the absence of human serum. Here, we demonstrate that human serum can inhibit all the previously-described activities of PSM. We observed that serum can fully block both the cell lysis and FPR2 activation of neutrophils. We show a direct interaction between PSM and serum lipoproteins in human serum and whole blood. Subsequent analysis using purified high, low, and very low density lipoproteins (HDL, LDL, and VLDL) revealed that they indeed neutralize PSM. The lipoprotein HDL showed highest binding and antagonizing capacity for PSM. Furthermore, we show potential intracellular production of PSM by S. aureus upon phagocytosis by neutrophils, which opens a new area for exploration of the intracellular lytic capacity of PSM. Collectively, our data show that in a serum environment the function of PSM as important extracellular toxins should be reconsidered

Skeletal Morphology of Opius dissitus and Biosteres carbonarius (Hymenoptera: Braconidae), with a Discussion of Terminology

The Braconidae, a family of parasitic wasps, constitute a major taxonomic challenge with an estimated diversity of 40,000 to 120,000 species worldwide, only 18,000 of which have been described to date. The skeletal morphology of braconids is still not adequately understood and the terminology is partly idiosyncratic, despite the fact that anatomical features form the basis for most taxonomic work on the group. To help address this problem, we describe the external skeletal morphology of Opius dissitus Muesebeck 1963 and Biosteres carbonarius Nees 1834, two diverse representatives of one of the least known and most diverse braconid subfamilies, the Opiinae. We review the terminology used to describe skeletal features in the Ichneumonoidea in general and the Opiinae in particular, and identify a list of recommend terms, which are linked to the online Hymenoptera Anatomy Ontology. The morphology of the studied species is illustrated with SEM-micrographs, photos and line drawings. Based on the examined species, we discuss intraspecific and interspecific morphological variation in the Opiinae and point out character complexes that merit further study

Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed