Selectively enhanced expression of prophenoloxidase activating enzyme 1 (PPAE1) at a bacteria clearance site in the white shrimp, Litopenaeus vannamei

<p>Abstract</p> <p>Background</p> <p>The prophenoloxidase-activating (PO activating) system plays an important role in the crustacean innate immunity, particularly in wound healing and pathogen defense. A key member of this system is prophenoloxidase-activating enzyme (PPAE), which is the direct activator of prophenoloxidase (proPO). Despite their importance in crustacean PO activating system, the studies on them remain limited.</p> <p>Results</p> <p>Here we report on a PPAE of white shrimp, <it>Litopenaeus vannamei </it>(lvPPAE1), which showed 94% similarity to PPAE1 of <it>Penaeus monodon</it>. We found that lvPPAE1 in fluid hemocytes was down regulated after challenge by <it>Vibrio harveyi </it>but was enhanced when shrimps were exposed to a bacteria-rich environment for long-term. In <it>vivo </it>gene silence of lvPPAE1 by RNAi can significantly reduce the phenoloxidase activity (PO) and increase the susceptibility of shrimps to <it>V. harveyi</it>. Although lvPPAE1 was down-regulated in fluid hemocytes by <it>Vibrio </it>challenge, its expression increased significantly in gill after bacteria injection, which is the primary bacteria-clearance tissue.</p> <p>Conclusion</p> <p>Suppressed expression in fluid hemocytes and enhanced expression in gill indicates selectively enhanced expression at the bacterial clearance site. This is a novel feature for PPAE expression. The results will contribute to our understanding of the PO activating system in crustaceans.</p

Characterization of Porcine Endogenous Retrovirus Clones from the NIH Miniature Pig BAC Library

Pigs have been considered as donors for xenotransplantation in the replacement of human organs and tissues. However, porcine endogenous retroviruses (PERVs) might transmit new infectious disease to humans during xenotransplantation. To investigate PERV integration sites, 45 PERV-positive BAC clones, including 12 PERV-A, 16 PERV-B, and 17 PERV-C clones, were identified from the NIH miniature pig BAC library. The analysis of 12 selected full-length sequences of PERVs, including the long terminal repeat (LTR) region, identified the expected of open reading frame length, an indicative of active PERV, in all five PERV-C clones and one of the four PERV-B clones. Premature stop codons were observed in only three PERV-A clones. Also, eleven PERV integration sites were mapped using a 5000-rad IMpRH panel. The map locations of PERV-C clones have not been reported before, thus they are novel PERV clones identified in this study. The results could provide basic information for the elimination of site-specific PERVs in selection of pigs for xenotransplantation

A Giant Colonic Hamartoma and Multiple Colonic Hamartomatous Polyps in a Middle-Aged Man

Colonic hamartomas are rare polypoid lesions. We report an unusual case of multiple colonic hamartomatous polyps, including a giant hamartoma, unrelated to hereditary or familial polyposis syndromes, in a 48-year-old man. The diameter of the largest polyp was 9.5 cm, and endoscopy revealed that the lesion caused colonic obstruction. The clinical, endoscopic and histological aspects of this case are discussed

Design strategy of highly efficient nonlinear optical orange‐colored crystals with two electron‐withdrawing groups

A new class of highly efficient nonlinear optical organic salt crystals is reported. In nonlinear optics based on organic materials, it is well known that using two electron-withdrawing groups (EWGs) onto cationic electron acceptors instead of conventional one EWG remarkably enhances microscopic optical nonlinearity for chromophores. However, the corresponding organic crystals possessing enhanced large macroscopic optical nonlinearity have not been reported yet. Herein, a design strategy is proposed for obtaining highly efficient nonlinear optical crystals based on two EWGs in cationic electron acceptors. Introducing a phenolic electron donor, promoting a head-to-tail interionic assembly, along with a two-EWG N-pyrimidinyl pyridinium electron acceptor in cationic chromophores results in a preferred non-centrosymmetric, perfectly parallel alignment of chromophores in crystal. Newly designed OPR (4-(4-hydroxystyryl)-1-(pyrimidin-2-yl)pyridinium) crystals exhibit approximately two times larger effective first hyperpolarizability than that of analogous N-alkyl OHP (4-(4-hydroxystyryl)-1-methylpyridinium) crystals based on only one EWG. OPR crystals exhibit comparable second-order optical nonlinearity to benchmark red-colored DAST (4-(4-(dimethylamino)styryl)-1-methylpyridinium 4-methylbenzenesulfonate) crystals, but a significant blue-shifted absorption resulting in orange-color crystals. Therefore, phenolic organic salt crystals using two EWGs are highly promising materials for various nonlinear optical applications

A Probiotic Mixture Regulates T Cell Balance and Reduces Atopic Dermatitis Symptoms in Mice

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a complex etiology involving the immune response. Recent studies have demonstrated the role of certain probiotics in the treatment and prevention of AD. However, the mechanism by which these probiotics regulate the immune system remains unclear. In this study, we examined the immunomodulatory capacity of Duolac ATP, a mixed formulation of probiotics, both in vitro and in vivo. Results showed that the expression of programmed death-ligand 1(PD-L1) was significantly upregulated on bone marrow-derived dendritic cells (BMDCs) treated with Duolac ATP. Furthermore, the anti-inflammatory cytokines IL-10 and TGF-beta were both upregulated when BMDCs were treated with Duolac ATP. The percentage of proliferated regulatory T cells (Tregs) was enhanced when CD4+ T cells were co-cultured with Duolac ATP-treated BMDCs on plates coated with anti-CD3/CD28 antibodies. Intriguingly, IL-10 secretion from CD4+ T cells was also observed. The AD symptoms, histologic scores, and serum IgE levels in AD mice were significantly decreased after oral treatment with Duolac ATP. Moreover, the Th1-mediated response in AD-induced mice treated with oral Duolac ATP showed upregulation of IL-2 and IFN-gamma as well as of downstream signaling molecules T-bet, STAT-1, and STAT-4. Conversely, Duolac ATP suppressed Th2 and Th17 responses in AD-like mice, as evidenced by the downregulation of GATA-3, C-maf, IL-4, IL-5, and IL-17. Additionally, Duolac ATP increased the number of Tregs found at Peyer’s patches (PP) in treated AD mice. These results suggest that Duolac ATP modulates DCs to initiate both Th1 and Treg responses in AD mice. Thus, Duolac ATP represents a potential preventative agent against AD and could serve as an effective immunomodulator in AD patients

Locally-applied 5-fluorouracil-loaded slow-release patch prevents pancreatic cancer growth in an orthotopic mouse model

To obtain improved efficacy against pancreatic cancer, we investigated the efficacy and safety of a locally-applied 5-fluorouracil (5-FU)-loaded polymeric patch on pancreatic tumors in an orthotopic nude-mouse model. The 5-FU-releasing polymeric patch was produced by 3D printing. After application of the patch, it released the drug slowly for 4 weeks, and suppressed BxPC-3 pancreas cancer growth. Luciferase imaging of BxPC3-Luc cells implanted in the pancreas was performed longitudinally. The drug patch delivered a 30.2 times higher level of 5-FU than an intra-peritoneal (i.p.) bolus injection on day-1. High 5-FU levels were accumulated within one week by the patch. Four groups were compared for efficacy of 5-FU. Drug-free patch as a negative control (Group I); 30% 5-FU-loaded patch (4.8 mg) (Group II); 5-FU i.p. once (4.8 mg) (Group III); 5-FU i.p. once a week (1.2 mg), three times (Group IV). The tumor growth rate was significantly faster in Group I than Group II, III, IV (p=0.047 at day-8, p=0.022 at day-12, p=0.002 at day-18 and p=0.034 at day-21). All mice in Group III died of drug toxicity within two weeks after injection. Group II showed more effective suppression of tumor growth than Group IV (p=0.018 at day-12 and p=0.017 at day-21). Histological analysis showed extensive apoptosis in the TUNEL assay and by Ki -67 staining. Western blotting confirmed strong expression of cleaved caspase-3 in Group II. No significant changes were found hematologically and histologically in the liver, kidney and spleen in Groups I, II, IV but were found in Group III.113Ysciescopu

Critical Behavior of Frustrated Josephson Junction Arrays with Bond Disorder

The scaling behavior of the current-voltage ($IV$) characteristics of a two-dimensional proximity-coupled Josephson junction array (JJA) with quenched bond disorder was investigated for frustrations $f=1/5$, 1/3, 2/5, and 1/2. For all these frustrations including 1/5 and 2/5 where a strongly first-order phase transition is expected in the absence of disorder, the $IV$ characteristics exhibited a good scaling behavior. The critical exponent $\nu$ indicates that bond disorder may drive the phase transitions of frustrated JJA's to be continuous but not into the Ising universality class, contrary to what was observed in Monte Carlo simulations. The dynamic critical exponent $z$ for JJA's was found to be only 0.60 - 0.77.Comment: RevTeX4, 4 pages, 4 figures, the manuscript is replaced with the published versio

Spinal epidural hematoma related to an epidural catheter in a cardiac surgery patient -A case report-

The addition of thoracic epidural anesthesia to general anesthesia during cardiac surgery may have a beneficial effect on clinical outcome. However, epidural catheter insertion in a patient anticoagulated with heparin may increase the risk of epidural hematoma. We report a case of epidural hematoma in a 55-year-old male patient who had a thoracic epidural placed under general anesthesia preceding uneventful mitral valve replacement and tricuspid valve annular plasty. During the immediate postoperative period and first postoperative day, prothrombin time (PT) and activate partial thromboplastin time (aPTT) were mildly prolonged. On the first postoperative day, he complained of motor weakness of the lower limbs and back pain. An immediate MRI of the spine was performed and it revealed an epidural hematoma at the T5-6 level. Rapid surgical decompression resulted in a recovery of his neurological abnormalities to near normal levels. Management and preventing strategies of epidural hematoma are discussed

Organic broadband THz generators optimized for efficient near‐infrared optical pumping

New organic THz generators are designed herein by molecular engineering of the refractive index, phonon mode, and spatial asymmetry. These benzothiazolium crystals simultaneously satisfy the crucial requirements for efficient THz wave generation, including having nonlinear optical chromophores with parallel alignment that provide large optical nonlinearity; good phase matching for enhancing the THz generation efficiency in the near-infrared region; strong intermolecular interactions that provide restraining THz self-absorption; high solubility that promotes good crystal growth ability; and a plate-like crystal morphology with excellent optical quality. Consequently, the as-grown benzothiazolium crystals exhibit excellent characteristics for THz wave generation, particularly at near-infrared pump wavelengths around 1100 nm, which is very promising given the availability of femtosecond laser sources at this wavelength, where current conventional THz generators deliver relatively low optical-to-THz conversion efficiencies. Compared to a 1.0-mm-thick ZnTe crystal as an inorganic benchmark, the 0.28-mm-thick benzothiazolium crystal yields a 19 times higher peak-to-peak THz electric field with a broader spectral bandwidth (>6.5 THz) when pumped at 1140 nm. The present work provides a valuable approach toward realizing organic crystals that can be pumped by near-infrared sources for efficient THz wave generation

Frustrated two-dimensional Josephson junction array near incommensurability

To study the properties of frustrated two-dimensional Josephson junction arrays near incommensurability, we examine the current-voltage characteristics of a square proximity-coupled Josephson junction array at a sequence of frustrations f=3/8, 8/21, 0.382 $(\approx (3-\sqrt{5})/2)$, 2/5, and 5/12. Detailed scaling analyses of the current-voltage characteristics reveal approximately universal scaling behaviors for f=3/8, 8/21, 0.382, and 2/5. The approximately universal scaling behaviors and high superconducting transition temperatures indicate that both the nature of the superconducting transition and the vortex configuration near the transition at the high-order rational frustrations f=3/8, 8/21, and 0.382 are similar to those at the nearby simple frustration f=2/5. This finding suggests that the behaviors of Josephson junction arrays in the wide range of frustrations might be understood from those of a few simple rational frustrations.Comment: RevTex4, 4 pages, 4 eps figures, to appear in Phys. Rev.