Presence Of Beings Research Articles

Alpha and gamma mangostins inhibit wild-type B SARS-CoV-2 more effectively than the SARS-CoV-2 variants and the major target is unlikely the 3C-like protease

BackgroundAnti-SARS-CoV-2 and immunomodulatory drugs are important for treating clinically severe patients with respiratory distress symptoms. Alpha- and gamma-mangostins (AM and GM) were previously reported as potential 3C-like protease (3CLpro) and Angiotensin-converting enzyme receptor 2 (ACE2)-binding inhibitors in silico. ObjectiveWe aimed to evaluate two active compounds, AM and GM, from Garcinia mangostana for their antivirals against SARS-CoV-2 in live virus culture systems and their cytotoxicities using standard methods. Also, we aimed to prove whether 3CLpro and ACE2 neutralization were major targets and explored whether any additional targets existed. MethodsWe tested the translation and replication efficiencies of SARS-CoV-2 in the presence of AM and GM. Initial and subgenomic translations were evaluated by immunofluorescence of SARS-CoV-2 3CLpro and N expressions at 16 h after infection. The viral genome was quantified and compared with the untreated group. We also evaluated the efficacies and cytotoxicities of AM and GM against four strains of SARS-CoV-2 (wild-type B, B.1.167.2, B.1.36.16, and B.1.1.529) in Vero E6 cells. The potential targets were evaluated using cell-based anti-attachment, time-of-drug addition, in vitro 3CLpro activities, and ACE2-binding using a surrogated viral neutralization test (sVNT). Moreover, additional targets were explored using combinatorial network-based interactions and Chemical Similarity Ensemble Approach (SEA). ResultsAM and GM reduced SARS-CoV-2 3CLpro and N expressions, suggesting that initial and subgenomic translations were globally inhibited. AM and GM inhibited all strains of SARS-CoV-2 at EC50 of 0.70–3.05 μM, in which wild-type B was the most susceptible strain (EC50 0.70–0.79 μM). AM was slightly more efficient in the variants (EC50 0.88–2.41 μM), resulting in higher selectivity indices (SI 3.65–10.05), compared to the GM (EC50 0.94–3.05 μM, SI 1.66–5.40). GM appeared to be more toxic than AM in both Vero E6 and Calu-3 cells. Cell-based anti-attachment and time-of-addition suggested that the potential molecular target could be at the post-infection. 3CLpro activity and ACE2 binding were interfered with in a dose-dependent manner but were insufficient to be a major target. Combinatorial network-based interaction and chemical similarity ensemble approach (SEA) suggested that fatty acid synthase (FASN), which was critical for SARS-CoV-2 replication, could be a target of AM and GM. ConclusionAM and GM inhibited SARS-CoV-2 with the highest potency at the wild-type B and the lowest at the B.1.1.529. Multiple targets were expected to integratively inhibit viral replication in cell-based system.

Investigation of the bulk and point defect properties in uranium–plutonium mixed oxides (U,Pu)O2 using DFT+U: Effect of a low americium content

We report an investigation of the effect of a low Am impurity content on bulk and point defect properties of mixed actinide oxide (U,Pu)O2. Using the generalized gradient approximation, (GGA + U) we study U0.75−zPu0.25AmzO2 with z = 3 and 6%. Several of its bulk properties have never been reported in the literature or are poorly known. The Hubbard term U is used to take into account the strong correlation effects related to the actinide 5f electrons. We find an electronic charge transfer between uranium and americium cations in the bulk crystal. Am(+IV) cations tend to easily reduce to Am(+III), and this reduction of Am(+IV) is compensated by the oxidation of U(+IV) to U(+V) in stoichiometric compounds. In turn, oxygen hypostoichiometry is accommodated by the reduction of U(+V) cations [which result from the presence of Am (+III) cations] before any reduction of the Pu cations. Furthermore, we show that Am induces a significant increase in the mixing enthalpy as well as a decrease in the lattice parameter of the (U,Pu)O2 solid solution, which is in agreement with early experimental studies. Finally, we show that americium facilitates the formation of oxygen vacancies in (U,Am)O2 compared to UO2, whereas it induces an increase in the formation energy of oxygen vacancies in (U,Pu,Am)O2 compared to (U,Pu)O2.

Investigation of the effects of indoxyl sulfate, a uremic toxin, on the intracellular oxidation level and phagocytic activity using an HL-60-differentiated human macrophage cell model

Indoxyl sulfate (IS), a uremic toxin, is a sulfate-conjugated metabolite originated from tryptophan. Accumulating uremic toxins may worsen renal diseases and further complicate related disorders including impaired immune functions under oxidative stress conditions. However, it has remained unclear whether or not IS can directly cause the cellular immune dysfunction. We investigated the effects of IS on the intracellular oxidation level and phagocytic activity in a HL-60-differantiated human macrophage cell model. Incubation of the cells in the presence of IS resulted in increasing intracellular oxidation level and decreasing phagocytic activity. In addition to inhibitors for NADH oxidase (NOX), organic anion transporting polypeptide2B1 (OATP2B1), protein kinase C (PKC), and phosphoinositide 3-kinase (PI3K), a representative antioxidant Trolox, was also shown to significantly relieve the IS-induced oxidation and restore weakened phagocytosis. Collectively, IS may directly down-regulate the phagocytic immune function of macrophages through the oxidation mechanisms including OATP2B1, PKC, PI3K, and NOX pathways. Abbreviations: CKD: Chronic kidney disease; IS: Indoxyl sulfate; ROS: Reactive oxygen species; NOX: NADH oxidase; OATP2B1: Organic anion transporting polypeptide2B1; PKC: Protein kinase C; PI3K: Phosphoinositide 3-kinase; 2-APT: 2-acetylphenothiazine.

Improving the efficacy of PES-based mixed matrix membranes incorporated with citric acid–amylose-modified MWCNTs for HA removal from water

Either difficulty of dispersion of carbon nanotubes (CNTs) in the solvent or low compatibility between polymeric chains of membrane and CNTs results in major drawbacks to using CNTs in the structure of mixed matrix membranes. CNTs’ functionalization has already gained increasing attention to overcome such problems. Herein, polyethersulfone-based mixed matrix membranes incorporated with citric acid–amylose-decorated multiwall carbon nanotubes (Am–MWCNTs–CA) were fabricated. These new synthesized nanoparticles and nanocomposite membranes were characterized by spectroscopic measurement methods such as IR spectroscopy, UV–Vis spectroscopy, 1H NMR spectroscopy, 13C NMR spectroscopy, water contact angle, attenuated total reflection-infrared, atomic force microscopy (AFM), and scanning electron microscopy (SEM). The pure water flux of the modified membrane incorporated with 0.5 w/v% Am–MWCNTs–CA increased over 130% in comparison with the unmodified membrane. Flux recovery ratio results illustrated that the membrane modified with 0.5 w/v% Am–MWCNTs–CA showed superior antifouling capacity of over 95.2%. SEM and AFM images showed significant and observable changes in surface morphology along with the formation of large finger-like macrovoids in the presence of Am–MWCNTs–CA. The presence of more COOH and OH functional groups on the surface of the modified membranes enforced the Donnan exclusion theory to reject rather divalent ions due to the migration of Am–MWCNTs–CA nanocomposite to the surface of membranes. In addition, humic acid removal capability of the prepared membranes was also calculated to be as high as 97.4% for the membrane embedded with 0.5 w/v% Am–MWCNTs–CA (M3).

AM fungi enhance the function of ecological floating bed in the treatment of saline industrial wastewater.

Treatment of saline wastewater attracts more and more attention due to its negative effects on the environment in China. Although salt removal from high-saline wastewater is well done in many industry factories, few technologies are available to remove salt from low-saline wastewater (total dissolved solids, TDS < 10,000mg/L). In this study, ecological floating bed (EFB) enhanced by arbuscular mycorrhizal fungi (AMF) Glomus etunicatum was constructed to remove salt from simulated low-saline wastewater. Results showed that AM formation in Canna indica was not affected by salt stress, and a higher mycorrhizal colonization rate was even observed under salt stress relative to the control treatment. In saline wastewater containing TDS 5000mg/L, EFB with AM inoculation (AM-EFB) removed 15.9% of TDS, 19.9% of COD, 14.2% of TN, 22.5% of TP, and 11.6-23.0% of salt ions (Na, K, Mg, and Ca) more than EFB without AM inoculation (NM-EFB) in September, and 13.0% of TDS, 15.8% of COD, 17.5% of TN, 16.6% of TP, and 8.60-22.2% of salt ions (Na, K, Mg, and Ca) more than NM-EFB in October respectively. AMF increased plant uptake to Na and the translocation of Na from root to shoot, especially at the initial stage of the experiment. Additionally, EFB function declined when environmental temperature declined independent of AM inoculation, but the presence of AM increased EFB function in the treatment of saline wastewater relative to NM-EFB. This study provides a new strategy for the treatment of low-saline wastewater and the EFB application in a low-temperature environment.

Safety of the Recombinant Herpes-Zoster Subunit Vaccine in Allogeneic Stem Cell Transplant Patients

<h3>Introduction</h3> After allogeneic stem cell transplant (SCT), varicella zoster virus (VZV) necessitates long term chemoprophylaxis due to limitations of the live vaccine. The recombinant subunit vaccine containing VZV glycoprotein E with AS01_B adjuvant system (HZ/su, or Shingrix) has safety and efficacy data after autologous transplantation. However, data is absent in the setting of allogeneic SCT. Due to the highly immunogenic AS01b subunit component, concerns regarding stimulation of graft versus host disease (GVHD) reaction have prompted some institutions to avoid routine HZ/su vaccination early after SCT. <h3>Objectives</h3> The primary objective was to evaluate the total number of GVHD events following post-transplant vaccinations. <h3>Methods</h3> Single center retrospective chart review of SCT patients who received post-transplant vaccinations within their first year of transplant. Patients who received HZ/su + post-transplant vaccines between 2017 and 2018 were compared to a control arm who received only the post-transplant vaccines between 2015 and 2016. We collected data regarding timing of the vaccines, presence of IS therapy at time of vaccination, and changes in GVHD therapy after vaccination. We assessed GVHD events within 3 months after each vaccination. <h3>Results</h3> Forty-seven patients received HZ/su + post-transplant- vaccines compared to 49 control patients who received only the post-transplant vaccines. More patients in the control arm were on IS at time of vaccination. Being on IS was a risk factor for GVHD events, especially in the control group. Although there were more alternative donor transplant patients receiving HZ/su vaccine, there were no increase in events. <h3>Conclusion</h3> Overall, HZ/su vaccine does not seem to increase the incidence of GVHD events after vaccination. However, the presence of IS at the time of vaccination may be associated with an increased risk of GVHD events. Given the limitations of our study, prospective trials are needed to evaluate timing and risk factors to consider before HZ/su vaccination.

An investigation of the thermal and (bio)degradability of PBS copolyesters based on isosorbide

As an essential biodegradable polyester species, poly(butylene succinate) (PBS) is restricted for wider applications due to its low thermal/mechanical properties and unsatisfactory (bio)degradability. Current practice of introducing either stiff or flexible building blocks into PBS main chains remains challenging to achieve a synergistic enhancement of the thermal and (bio)degradability of this material. We herewith report a series of PBS copolyesters based on the carbohydrate-derived isosorbide (1,4:3,6-dianhydro-D-glucidol, IS) (PBIS) by utilizing its unique intrinsic characters of being rigid and hydrophilic. The target copolyesters were constructed with a broad scope of IS content (0–100 mol%) and with random microstructures. The Mn values and the intrinsic viscosities of these polyesters are in the scopes of 7300–38,700 g mol−1 and 0.33–0.82 dL g−1, respectively. The results shown in this work clearly demonstrated that the presence of IS enhances the Tg values almost linearly and simultaneously promotes (neutral, acidic) hydrolytic and enzymatic degradations (with porcine pancreas) of the copolyesters. PBIS copolyester containing 20 mol% IS displays comparable hydrolytic and enzymatic degradation rates with those of PBSA (20 mol% adipic acid), but a substantially 23 °C higher Tg value. Detailed characterization of the molecular structures, micro-sequential structures, molecular weights and polydipersities, thermal properties, hydrophilicities and (bio)degradability are provided. The (bio)degradation and degradation mechanism study of these copolyesters are reported for the first time.

Endocannabinoid-mediated modulation of Gq protein-coupled receptor mediates vascular hyporeactivity to nor-adrenaline during polymicrobial sepsis.

Endocannabinoids level are reported to increase in sepsis, however, the role of vascular cannabinoid receptor-1 (CB1R) in sepsis-induced vascular hyporeactivity is yet to be unravelled. Polymicrobial sepsis was induced by caecal ligation and puncture in mice. Isometric tension in isolated aortic rings during early (6 h) and late (20 h) phases of sepsis was recorded and expression of mRNA of monoacylglycerol lipase (MAGL) and cannabinoid receptor-1 (CB1R) was investigated. Sepsis significantly (p < 0.001) reduced the mean survival time in mice along with increase in bacterial load in blood and peritoneal lavage. Compared to Sham-operated (SO) mice, vascular reactivity to nor-adrenaline (NA) was significantly (p < 0.05) attenuated in both early and late phases of sepsis. NA-induced vasoconstriction was significantly (p < 0.05) potentiated by inhibition of diacylglycerol lipase (DAGL) and attenuated by inhibition of MAGL in SO mice. Pre-incubation with KT 109, a DAGL inhibitor, significantly (p < 0.05) improved the vascular hypo-reactivity to NA during both the phases of sepsis. mRNA expression of MAGL in aorta was significantly (p < 0.05) attenuated during both the phases of sepsis. But in the presence of AM 251, specific antagonist of CB1R, vascular reactivity to NA was significantly (p < 0.05) restored along with significant (p < 0.05) increase in mRNA expression of CB1R in aortic rings from both early and late phases of septic mice. 2-AG regulates vascular response to NA and increased aortic expression of CB1R is responsible for vascular hyporeactivity to NA in sepsis, and in vitro inhibition of this receptor by AM 251 restored the vascular reactivity.

Coexistence of adenomyosis uteri and endometrial cancer is associated with an improved prognosis compared with endometrial cancer only.

The present study aimed to identify differences in protein expression in cases of endometrioid endometrial cancer (EEC) with and without coexisting adenomyosis uteri (AM), and to evaluate the histopathological and prognostic distinctions. The total cohort included 22 patients in Group A (patients with concomitant AM and EEC) and 35 patients in Group B (patients affected only by EEC). Evaluation of the following factors was performed: Tumour grade, International Federation of Gynaecology and Obstetrics (FIGO) stage, survival, and expression of estrogen receptor β (ERβ), glycodelin and inhibin βB. Group A (AM and EEC) was associated with a lower tumour grade (G1, 90.9 vs. 45.7%; P=0.001) and a lower FIGO stage (FIGO stage I, 100 vs. 80%; P=0.002) compared with Group B (EEC only). In the survival analysis, Group A was associated with a significantly higher 5-year survival rate (95 vs. 82%; P=0.024) than Group B. In addition, the expression of ERβ in Group A was significantly higher (P<0.001), whereas the expression of glycodelin is significantly lower (P=0.028), compared with Group B. The results of the present study indicate that the presence of AM in cases of EEC may be a positive prognostic factor.

Neutral electrolyzed water (NEW), chlorine dioxide, organic acid based product, and ultraviolet-C for inactivation of microbes in fresh-cut vegetable washing waters

The effect of decontamination methods on fresh-cut vegetable washing waters was evaluated. NEW, ClO2, organic acid-based product FPW, and UV-C were tested with and without an interfering carrot juice of 1% (IS), on Yersinia enterocolitica and Yersinia pseudotuberculosis, Escherichia coli, and yeast Candida lambica. The use of ClO2 (50 ppm active chlorine) resulted in >4 log reduction of Y. enterocolitica, Y. pseudotuberculosis, E. coli and >3 log reduction of C. lambica. The antibacterial effect of NEW was less effective in the presence of IS when compared with ClO2. The inactivation of C. lambica by FPW reached a maximum of 2.8 log cfu/mL (concentration 0.125%), but the antimicrobial effect was delayed by the IS. The effect of FPW on E. coli was significantly reduced by 1% IS. The inactivation of E. coli and C. lambica with UV-C IS decreased the inactivation and lengthened its time. Filtration improved the effect of UV-C inactivation. Practical applications When chemical decontamination methods were used in fresh-cut vegetable processing, the presence of organic matter in process water increased the reaction times and the need for higher concentrations of the chemical decontamination and the time of physical decontamination. Yersinia required longer inactivation times than E. coli. When UV-C is used for decontamination of process waters, waters should be filtered to enhance the disinfection efficacy.

Trivalent Actinide Uptake by Iron (Hydr)oxides.

The retention of Am(III) by coprecipitation with or adsorption onto preformed magnetite was investigated by X-ray diffraction (XRD), solution chemistry, and X-ray absorption spectroscopy (XAS). In the coprecipitation experiment, XAS data indicated the presence of seven O atoms at 2.44(1) Å, and can be explained by an Am incorporation at Fe structural sites at the magnetite surface. Next-nearest Fe were detected at distances suggesting that Am and Fe polyhedra share corners in geometries ranging from bent to close to linear Am-O-Fe bonds. After aging for two years, the coordination number and the distance to the first O shell significantly decreased, and atomic shells were detected at higher distances. These data suggest a structural reorganization and an increase in structural order around sorbed Am. Upon contact with preformed Fe3O4, Am(III) forms surface complexes with cosorbed Fe at the surface of magnetite, a possible consequence of the high concentration of dissolved Fe. In a separate experiment, chloride green rust (GR) was synthesized in the presence of Am(III), and subsequently converted to Fe(OH)2(s) intermixed with magnetite. XAS data indicated that the actinide is successively located first at octahedral brucite-like sites in the GR precursor, then in Fe(OH)2(s), an environment markedly distinct from that of Am(III) in Fe3O4. The findings indicate that the magnetite formation pathway dictates the magnitude of Am(III) incorporation within this solid.

Group Hexavalent Actinide Separations: A New Approach to Used Nuclear Fuel Recycling.

Hexavalent Np, Pu, and Am individually, and as a group, have all been cocrystallized with UO2(NO3)2·6H2O, constituting the first demonstration of an An(VI) group cocrystallization. The hexavalent dioxo cations of Np, Pu, and Am cocrystallize with UO2(NO3)2·6H2O in near proportion with a simple reduction in temperature, while the lower valence states, An(III) and An(IV), are only slightly removed from solution. A separation of An(VI) species from An(III) ions by crystallization has been demonstrated, with an observed separation factor of 14. Separation of An(VI) species from key fission products, (95)Zr, (95)Nb, (137)Cs, and (144)Ce, has also been demonstrated by crystallization, with separation factors ranging from 6.5 to 71 in the absence of Am(VI), while in the presence of Am(VI), the separation factors were reduced to 0.99-7.7. One interesting observation is that Am(VI) shows increased stability in the cocrystallized form, with no reduction observed after 13 days, as opposed to in solution, in which >50% is reduced after only 10 days. The ability to cocrystallize and stabilize hexavalent actinides from solution, especially Am(VI), introduces a new separations approach that can be applied to closing the nuclear fuel cycle.

Mycorrhizal colonization represents functional equilibrium on root morphology and carbon distribution of trifoliate orange grown in a split-root system

Trifoliate orange seedlings were grown in perspex pots of a split-root system, where one half of the split roots was inoculated with or without arbuscular mycorrhizal fungi (AMF, Acaulospora scrobiculata or Funneliformis mosseae). Five months after inoculation, the growth performance, leaf, stem and root biomass and photosynthetic rate were generally significantly higher in AM than in non-AM seedlings. Greater root morphological traits were observed in the AM root side than in the non-AM side for the same plant and in AM than in non-AM plants. AM seedlings had significantly higher leaf sucrose and glucose contents and total (leaf+root) glucose and fructose contents as compared to non-AM ones. In the split roots, the AM side displayed substantially higher sucrose, glucose and fructose contents than the non-AM side for the same plant, and in AM than in non-AM plants. These results showed greater C movement into the non-AM side from an AM-colonized plant than from a non-AM-colonized plant. These results conclude that the presence of AM in one side of the split roots benefited C acquisition and root development to another half non-AM side, suggesting functional equilibrium and resource allocation of AM within a root system.

Surgical and oncological impact of main pancreatic duct spread in invasive ductal adenocarcinoma: A clinicopathological study of 184 resected cases.

This study examined main pancreatic ductal spread in invasive ductal adenocarcinoma (IDC) of the pancreas. Data from IDC patients who underwent radical surgery from 1990 to 2013 in our hospital were examined retrospectively. Incidence of intraductal spread of pancreatic cancer (IS), distance from the tumor edge, direction of IS and clinicopathological factors associated with the presence of IS were retrospectively examined with data from IDC patients who underwent radical surgery. Among 260 IDC patients who underwent surgery, 184 eligible cases, IS was identified in 42 patients (22.8%) and mean length of IS was 18.7 ± 21.6 mm. Mean distances on the ampullary and distal sides of IS were 11.1 mm and 11.6 mm. IS was significantly more frequent in localized tumors (UICC T1-2 vs. 3-4, p = 0.007), with tumor diameter ≤2 cm (p = 0.034) and in cases with scarce microscopic perineural invasion (p = 0.047). Among patients who underwent pancreaticoduodenectomy and distal pancreatectomy, IS presence (11.6 vs. 21.8%), mean distance to the contralateral side (11.4 vs. 11.6 mm), and IS ≥ 2 cm (3.3 vs. 4.7%) showed no significant differences. Overall survival did not differ significantly between IS-positive and -negative patients in the full analysis set or propensity score-matched patients (42 matched pairs). In setting resectional margins at 2 cm, a small proportion of cases (3.8%) showed positive surgical margins. Localized tumor (UICC: T1-2, or <2 cm in diameter) requires more care with surgical margins, warranting intraoperative frozen sections.

The behaviour under irradiation of molybdenum matrix for inert matrix fuel containing americium oxide (CerMet concept)

Americium is a strong contributor to the long term radiotoxicity of high activity nuclear waste. Transmutation by irradiation in nuclear reactors or Accelerator Driven System (ADS, subcritical reactors dedicated to transmutation) of long-lived nuclides like 241Am is therefore an option for the reduction of radiotoxicity of waste packages to be stored in a repository. In order to safely burn americium in a fast reactor or ADS, it must be incorporated in a matrix that could be metallic (CerMet target) or ceramic (CerCer target). One of the most promising matrix to incorporate Am is molybdenum. In order to address the issues (swelling, stability under irradiation, gas retention and release) of using Mo as matrix to transmute Am, two irradiation experiments have been conducted recently at the High Flux Reactor (HFR) in Petten (The Netherland) namely HELIOS and BODEX. The BODEX experiment is a separate effect test, where the molybdenum behaviour is studied without the presence of fission products using 10B to “produce” helium, the HELIOS experiment included a more representative fuel target with the presence of Am and fission product. This paper covers the results of Post Irradiation Examination (PIE) of the two irradiation experiments mentioned above where molybdenum behaviour has been deeply investigated as possible matrix to transmute americium (CerMet fuel target). The behaviour of molybdenum looks satisfying at operating temperature but at high temperature (above 1000 °C) more investigation should be performed.

Comparative XRPD and XAS study of the impact of the synthesis process on the electronic and structural environments of uranium–americium mixed oxides

Uranium–americium mixed oxides are potential compounds to reduce americium inventory in nuclear waste via a partitioning and transmutation strategy. A thorough assessment of the oxygen-to-metal ratio is paramount in such materials as it determines the important underlying electronic structure and phase relations, affecting both thermal conductivity of the material and its interaction with the cladding and coolant. In 2011, various XAS experiments on U1−xAmxO2±δ samples prepared by different synthesis methods have reported contradictory results on the charge distribution of U and Am. This work alleviates this discrepancy. The XAS results confirm that, independently of the synthesis process, the reductive sintering of U1−xAmxO2±δ leads to the formation of similar fluorite solid solution indicating the presence of Am+III and U+V in equimolar proportions.

Anti-Inflammatory Effect of By-Products fromHaliotis discus hannaiin RAW 264.7 Cells

Several reports promoted the potential of shellfish due to their ability to act as antioxidant, anti-inflammatory, and antimicrobial agents. Pacific abalone,Haliotis discus hannaiviscera is, reported to possess bioactivities such as antioxidative stress and anti-inflammatory. In this study, anti-inflammatory potential of mucus-secreting glands from shell-shucking waste ofH. discus hannaiwas evaluated using RAW 264.7 mouse macrophage cell model. Results indicated that presence ofH. discus hannaimucosubstance by-products (AM) significantly lowered the nitric oxide (NO) production along the expressional suppression of inflammatory mediators such as cytokines TNF-α, IL-1β, and IL-6 and enzymes iNOS and COX-2. Also, AM was shown to increase expression of anti-inflammatory response mediator HO-1. Presence of AM also scavenged the free radicalsin vitro. In conclusion, by-products ofH. discus hannaiare suggested to possess notable anti-inflammatory potential which promotes the possibility of utilization as functional food ingredient.

Oligomeric States of Full Length Influenza a Virus M2 Proteins on Biological Membranes

The integral matrix protein M2 of influenza A virus forms a pH-gated proton channel in the viral lipid envelope upon infecting host cells. The conductance of protons through the M2 channels in the low-pH endosomes (pH < 5.0)[1] acidifies the viral interior and facilitates the dissociation of the viral genome from the matrix protein M1. Although X-ray crystallography[2] and NMR[3] studies using truncated proteins concluded that M2 stably forms a tetrameric channel that opens at acidic pH, the oligomeric state of the full length protein on biomembranes is not clear yet. In the present study, we examined the oligomeric state of the full length M2 protein on the plasma membrane of living cells by using fluorescence resonance energy transfer (FRET) among the M2 proteins labeled with fluorophores by the coiled-coil method[4]. Contrary to previous models, M2 formed dimers at neutral pH and the dimers were converted to tetramers at pH 4.9. The tetramerization and channel activity were completely inhibited in the presence of the antiviral Amantadine hydrochloride (Am) at low pH. In contrast, the S31N mutant resistant to Am formed dimers independent of pH and the presence of Am, and the channel activity was not blocked by Am. These results indicate that the resistance of the S31N mutant could be attributed to its ability to conduct protons as dimers without forming tetramers.

PHS20 Cost Associated to the Management of Inappropriate Shocks in Patients With an Implantable Cardioverter Defibrillator – Cardina Study

Inappropriate shocks are the most common complications of ICD, causing a negative effect on patients' morbidity and mortality. Little is known with regards to the cost associated to the management of IS. The aim of the study was to determine IS related factors and to evaluate its associated hospital cost. All patients implanted with an ICD where retrospectively analyzed through clinical chart reviews in a Spanish hospital from 2003 to 2011. Demographic variables, baseline cardiomyopathy, comorbidities, indication and type of ICD implanted were registered. During the follow up period we identified the presence of IS, its reasons and associated costs. A total of 227 patients were implanted with an ICD, mean age 63.2 years (26-82). Eighty-six percent were men, 64.6% with ischemic cardiomyopathy, 78.4% with heart failure, 70.4% with EF<35% and 13.1% with AF. The proportion of single, dual and three chambers ICD was 54.6%, 20.3% and 25.1% respectively. After a median follow up of 4.46 years, 27 patients had had 42 IS episodes. Average time since implant to first IS was 1.3 years (range 0.02 to 3.84 years). Patients suffering from IS had higher mortality (33.3% vs 13.7%; p<0.05). Amost 67% of the episodes were due to supraventricular tachycardia, 12% to noise detection, 19% to Wave T overdetection and 2.3% due to other causes. Sixty-three percentages of the episodes generated an emergency visit and a 39% generated a non-scheduled visit to the cardiologist. Seven episodes (16.7%) required hospitalization, six of whom required a surgical intervention. Average length of stay was 5.1 days. Finally, overall mean hospital cost appeared to be €5,175 per episode. The cost of inappropriate shocks is driven by the reason of its cause. The great majorities of the episodes were due to supraventricular arrhythmias and finally resolved without the need for hospitalization.

Reactive sintering of U1−yAmyO2±x in overstoichiometric conditions

Abstract In the framework of Partitioning & Transmutation (P&T), U1−yAmyO2±x materials are promising fuels for Am recycling. In this context, these materials were fabricated in the ATALANTE facility by a process which consists of pelletizing and reactive sintering. Since it was effective in studies conducted on UO2+x, sintering in overstoichiometric conditions was investigated. In this work, three Am contents (10, 20 and 30%) and four temperatures (from 1000 to 1300 °C) were studied. It was shown that low-density and multiphasic compounds were obtained. Moreover, XRD and XAFS analyses pointed out that the total reduction of Am(+IV) to Am(+III) and solid solution formation occur during sintering at temperatures inferior to 1300 °C. Although previous studies on UO2+x showed that high oxygen potential enhanced the diffusion process, this work proved that this effect is clearly modified by the presence of Am. Finally, sintering in overstoichiometric conditions is not yet suitable for Am-bearing fuel fabrication.