Limited fossil resources require innovative monomers and polymers derived from renewable feedstocks such as plant biomass. Thermosetting epoxy resins largely rely on petrochemical bisphenol-type ...monomers, which give high performance materials but are controversial due to their effects on human health. Herein, we present two biobased epoxy resins by direct dehydrogenative dimerization of eugenol, the main component of clove oil. Taking the
Principles of Green Chemistry
into account, we developed electrochemical dehydrodimerization at reticulated vitreous carbon (RVC) electrodes using methanol as environmentally benign solvent. Thus, fluorinated solvents such as 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) or commonly used oxidizers such as potassium ferricyanide (K
3
Fe(CN)
6
) are avoided and a high reaction mass efficiency (RME) of 47% is obtained. Alkylation and epoxidation gave two epoxy resins MDDE-2E and ADDE-4E with 2 and 4 epoxy functionalities, respectively. Curing with MHHPA gave durable epoxy materials with
T
g
's of 153 °C for MDDE-2E (for DGEBA: 151 °C) and an extraordinary 216 °C for ADDE-4E, reflecting the increased network density of the cured epoxy material. Thermal degradation under nitrogen and air was observed at temperatures above 300 °C with
T
10%
of 304 and 347 °C, respectively. In contrast to DGEBA, high char rates and slower degradation above 400 °C indicate flame-retarding properties of the eugenol-derived epoxy resins.
A biobased epoxy resin was prepared from tall oil fatty acids (TOFAs), a byproduct of the pulping industry. As free carboxylic acids compromise resin stability, TOFA was subjected to non-Kolbe ...decarboxylation to give alkenes upon loss of CO2. Thereby, the degree of unsaturation is significantly increased. This electrosynthetic protocol using an undivided cell setup and inexpensive graphite electrodes in a galvanostatic operation mode was scaled to a 1.5 L reactor, making use of electric current as a green and waste-free reagent. Simple, cost-efficient epoxidation using oxone subsequently gives an epoxy resin of low viscosity. Curing with anhydrides yields thermoset materials. Dynamic mechanical analyses and tensile and flexural tests were conducted to determine the effect of different curing agents on the thermomechanical properties. For methyl tetrahydrophthalic anhydride (MTHPA) and methyl-5-norbornene-2,3-dicarboxylic anhydride (MNA), good mechanical properties were observed, whereas dodecenyl succinic anhydride (DDSA) resulted in a brittle material with low T g.
Despite advances in transplant medicine, prevalence of complications after hematopoietic stem cell transplantation (HSCT) remains high. The impact of pre-HSCT oral health factors on the incidence and ...severity of complications post-HSCT is poorly understood. The aim of this prospective, observational study was to analyze oral health in patients planned for HSCT. Patients ≥18 years requiring HSCT were included from five sites between 2011-2018. General health, oral findings and patient-reported symptoms were registered in 272 patients. Oral symptoms around disease onset were reported by 43 patients (15.9%) and 153 patients (58.8%) reported oral complications during previous chemotherapy. One third of patients experienced oral symptoms at the oral examination before conditioning regimen and HSCT. In total, 124 (46.1%) patients had dental caries, 63 (29.0%) had ≥one tooth with deep periodontal pockets, 147 (75.0%) had ≥one tooth with bleeding on probing. Apical periodontitis was observed in almost 1/4 and partially impacted teeth in 17 (6.3%) patients. Oral mucosal lesions were observed in 84 patients (30.9%). A total of 45 (17.4%) of 259 patients had at least one acute issue to be managed prior to HSCT. In conclusion, oral symptoms and manifestations of oral disease were prevalent in patients planned for HSCT. The extent of oral and acute dental diseases calls for general oral screening of patients pre-HSCT.
Abstract
The main protease (M
pro
) of SARS-CoV-2 is critical for viral function and a key drug target. M
pro
is only active when reduced; turnover ceases upon oxidation but is restored by ...re-reduction. This suggests the system has evolved to survive periods in an oxidative environment, but the mechanism of this protection has not been confirmed. Here, we report a crystal structure of oxidized M
pro
showing a disulfide bond between the active site cysteine, C145, and a distal cysteine, C117. Previous work proposed this disulfide provides the mechanism of protection from irreversible oxidation. M
pro
forms an obligate homodimer, and the C117-C145 structure shows disruption of interactions bridging the dimer interface, implying a correlation between oxidation and dimerization. We confirm dimer stability is weakened in solution upon oxidation. Finally, we observe the protein’s crystallization behavior is linked to its redox state. Oxidized M
pro
spontaneously forms a distinct, more loosely packed lattice. Seeding with crystals of this lattice yields a structure with an oxidation pattern incorporating one cysteine-lysine-cysteine (SONOS) and two lysine-cysteine (NOS) bridges. These structures further our understanding of the oxidative regulation of M
pro
and the crystallization conditions necessary to study this structurally.
Malaria is caused by the protozoan parasite
, which undergoes a complex life cycle in a human host and a mosquito vector. The parasite's cyclic GMP (cGMP)-dependent protein kinase (PKG) is essential ...at multiple steps of the life cycle. Phosphoproteomic studies in
erythrocytic stages and
ookinetes have identified proteolysis as a major biological pathway dependent on PKG activity. To further understand PKG's mechanism of action, we screened a yeast two-hybrid library for
proteins that interact with
PKG (PfPKG) and tested peptide libraries to identify its phosphorylation site preferences. Our data suggest that PfPKG has a distinct phosphorylation site and that PfPKG directly phosphorylates parasite RPT1, one of six AAA
ATPases present in the 19S regulatory particle of the proteasome. PfPKG and RPT1 interact
, and the interacting fragment of RPT1 carries a PfPKG consensus phosphorylation site; a peptide carrying this consensus site competes with the RPT1 fragment for binding to PfPKG and is efficiently phosphorylated by PfPKG. These data suggest that PfPKG's phosphorylation of RPT1 could contribute to its regulation of parasite proteolysis. We demonstrate that proteolysis plays an important role in a biological process known to require
PKG: invasion by sporozoites of hepatocytes. A small-molecule inhibitor of proteasomal activity blocks sporozoite invasion in an additive manner when combined with a
PKG-specific inhibitor. Mining the previously described parasite PKG-dependent phosphoproteomes using the consensus phosphorylation motif identified additional proteins that are likely to be direct substrates of the enzyme.
Background:Persons at high risk for developing rheumatoid arthritis (RA) may benefit from a low-risk pharmacological intervention aimed at primary prevention. Statins are safe and widely-used drugs; ...previous studies demonstrated disease-modifying effects of statins in RA patients1 as well as an association between statin use and a decreased risk of RA development2.Objectives:We designed a multi-center, randomized, double-blind, placebo-controlled trial to investigate if atorvastatin use for 3 years could prevent arthritis.Methods:Persons at high risk for RA, defined by the presence of arthralgia and anti-citrullinated protein antibody (ACPA) concentration >3xULN or both ACPA and rheumatoid factor (RF), were randomized to atorvastatin 40 mg daily or placebo for 3 years. Eligible participants were ≥18 years, had no indication for lipid-lowering therapy and had no clinical synovitis. The primary endpoint was development of clinical arthritis. Our goal was to include 220 patients, based on an anticipated 30% risk reduction by atorvastatin. Analysis was by intention-to-treat.Results:189 patients were screened, 175 were eligible, but only 67 persons were included of whom 62 were randomized (figure 1). The main reason for non-inclusion was unwillingness to use study medication (n=58, 54%). Inclusion was stopped after 38 months due to the low inclusion rate. Analyses were performed 1 year after inclusion stop. Mean follow up was 18 (0-36) months. Mean age was 48 years and 74% of participants were female. 14 persons (23%) developed clinical arthritis: 8/31 (26%) in the atorvastatin group and 6/31 (19%) in the placebo group (HR 0.8, 95% CI 0.3-2.2) after a median period of 7.5 (IQR 5.3-21.8) months (atorvastatin) and 4 (0-14.8) months (placebo). In the atorvastatin group, 17 persons completed the study according to protocol, 6 dropped out and 8 continued follow-up after prematurely stopping study medication. In the placebo group, 16 persons completed the study according to protocol, 11 dropped out and 4 continued follow-up after prematurely stopping study medication. Median duration of study medication use was 9 (6-26) months (atorvastatin group) and 8 (3-17) months (placebo group).Conclusion:The results of this trial are inconclusive due to severe difficulties with patient inclusion and low treatment adherence. The difficulty to enter and retain participants in this prevention trial is highly relevant given the current interest in treating RA in an ever earlier phase. At-risk individuals’ perceptions should be taken into account when designing preventive trials and will be important in optimizing acceptance and adherence to preventive treatment. Currently we are finalizing research into the motivation and barriers for participation in different primary prevention trials of RA and the willingness to initiate different types of preventive treatment in individuals in the at-risk phase of RA.References:1McCary et al. Lancet. 2004; 19;363(9426):2015-212Chodick G et al. PLoS Med. 2010;7(9):e1000336Disclosure of Interests:Laurette van Boheemen: None declared, S.A. Turk: None declared, M.H. van Beers - Tas: None declared, W.H. Bos Grant/research support from: abbvie, sanofi, roche, celgene, ucb, novartis, Speakers bureau: abbvie, Sanofi, eli lilly, Diane Marsman: None declared, E.N. Griep: None declared, M. Starmans: None declared, C.D. Popa: None declared, A.M. van Sijl: None declared, Maarten Boers: None declared, Michael Nurmohamed Grant/research support from: Not related to this research, Consultant of: Not related to this research, Speakers bureau: Not related to this research, Dirkjan van Schaardenburg: None declared
Abstract
The Ganges–Brahmaputra–Meghna (GBM) river basins exhibit extremes in surface water availability at seasonal to annual time scales. However, because of a lack of basinwide hydrological data ...from in situ platforms, whether they are real time or historical, water management has been quite challenging for the 630 million inhabitants. Under such circumstances, a large-scale and spatially distributed hydrological model, forced with more widely available satellite meteorological data, can be useful for generating high resolution basinwide hydrological state variable data streamflow, runoff, and evapotranspiration (ET) and for decision making on water management. The Variable Infiltration Capacity (VIC) hydrological model was therefore set up for the entire GBM basin at spatial scales ranging from 12.5 to 25 km to generate daily fluxes of surface water availability (runoff and streamflow). Results indicate that, with the selection of representative gridcell size and application of correction factors to evapotranspiration calculation, it is possible to significantly improve streamflow simulation and overcome some of the insufficient sampling and data quality issues in the ungauged basins. Assessment of skill of satellite precipitation forcing datasets revealed that the Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis (TMPA) product of 3B42RT fared comparatively better than the Climate Prediction Center (CPC) morphing technique (CMORPH) product for simulation of streamflow. The general conclusion that emerges from this study is that spatially distributed hydrologic modeling for water management is feasible for the GBM basins under the scenario of inadequate in situ data availability. Satellite precipitation forcing datasets provide the necessary skill for water balance studies at interannual and interseasonal scales. However, further improvement in skill may be required if these datasets are to be used for flood management at daily to weekly time scales and within a data assimilation framework.
1 Department of Kinesiology, University of Waterloo,
Waterloo, Ontario, Canada N2L 3G1; and Departments of
2 Veterinary Biomedical Sciences,
3 Veterinary Pathobiology, and 4 Medical
Physiology ...and 5 Dalton Cardiovascular Research
Center, University of Missouri, Columbia, Missouri 65211
Vascular oxidative stress
contributes to endothelial dysfunction. Aerobic exercise training
improves vascular function. The purpose of this study was to test the
hypothesis that exercise training would improve the balance of
antioxidant to prooxidant enzymes and reduce markers of oxidative
stress in aortic endothelial cells (AEC). Female Yucatan miniature pigs
either remained sedentary (SED) or were exercise trained (EX) for
16-19 wk. EX pigs had increased AEC SOD-1 protein levels and Cu/Zn
SOD activity of the whole aorta compared with SED pigs. Protein levels
of other antioxidant enzymes (SOD-2, catalase) were not affected by
exercise training. Protein levels of p67 phox , a subunit of
the prooxidant enzyme NAD(P)H oxidase, were reduced in EX vs. SED AEC.
These EX adaptations were associated with lower AEC malondialdehyde
levels and decreased phosphorylation of ERK-1/2. Endothelial nitric
oxide synthase protein, protein nitrotyrosine content, and heme
oxygenase-1 protein were not different in EX vs. SED pigs. We conclude
that chronic aerobic exercise training influenced both antioxidant and
prooxidant enzymes and decreased indexes of oxidative stress in AEC.
These adaptations may contribute to improved endothelial function with
exercise training.
superoxide dismutase; nitric oxide; NAD(P)H oxidase; endothelial
function; antioxidant enzymes; ERK
Vascular function, vascular structure, and homeostasis are thought to be regulated in part by nitric oxide (NO) released by endothelial cell nitric oxide synthase (eNOS), and NO released by eNOS ...plays an important role in modulating metabolism of skeletal and cardiac muscle in health and disease. The pig is an optimal model for human diseases because of the large number of important similarities between the genomic, metabolic and cardiovascular systems of pigs and humans. To gain a better understanding of cardiovascular regulation by eNOS we produced pigs carrying an endogenous eNOS gene driven by a Tie-2 promoter and tagged with a V5 His tag. Nuclear transfer was conducted to create these animals and the effects of two different oocyte activation treatments and two different culture systems were examined. Donor cells were electrically fused to the recipient oocytes. Electrical fusion/activation (1 mM calcium in mannitol: Treatment 1) and electrical fusion (0.1 mM calcium in mannitol)/chemical activation (200 µM Thimerosal for 10 min followed by 8 mM DTT for 30 min: Treatment 2) were used. Embryos were surgically transferred to the oviducts of gilts that exhibited estrus on the day of fusion or the day of transfer. Two cloned transgenic piglets were born from Treatment 1 and low oxygen, and another two from Treatment 2 and normal oxygen. PCR, RT-PCR, Western blotting and immunohistochemistry confirmed that the pigs were transgenic, made message, made the fusion protein and that the fusion protein localized to the endothelial cells of placental vasculature from the conceptuses as did the endogenous eNOS. Thus both activation conditions and culture systems are compatible with development to term. These pigs will serve as the founders for a colony of miniature pigs that will help to elucidate the function of eNOS in regulating muscle metabolism and the cardiorespiratory system.
A field trial on green onion crops in the autumn of 2020 transpired at a private farm in the District Al- Saniyah, Al-Diwaniyah Governorate, Iraq. The presented study aimed at characterizing green ...onion (Allium cepa L.) plants with NPK fertilization and foliar application of hornwort extract for growth and yield traits. In this experiment, the first factor comprised three NPK levels (0, 50%, and 100%) of NPK (150:100:150 kg ha-1) recommended fertilizer added to the soil, while the second factor included the foliar application of hornwort extract with two different concentrations (0, 20 ml L-1). The experiment in a randomized complete block design (RCBD) with factorial arrangement had three replications. Consequently, the recommended dose of NPK (100%) and spraying hornwort extract at 20 ml L-1 revealed a significant increase in the studied traits, i.e., plant height, length of the longest tubular leaf, number of leaves, fresh weight of tubular leaves, number of bulbs per plant, weight of the bulb, the diameter of the bulb, leaf chlorophyll content, bulb carbohydrate content, leaf carotenoid content, and plant yield. The interactions of both factors also showed a favorable effect on the mentioned traits in green onion.
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