Dihydrotanshinone,a Natural Diterpenoid,Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor

Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.     

Application of the novel Droplet digital PCR technology for identification of meat species

The authenticity and traceability of meat products are issues of primary importance to ensure food safety. Unfortunately, food adulteration (e.g. the addition of inexpensive cuts to minced meat products) and mislabelling (e.g. the inclusion of meat from species other than those declared) happens frequently worldwide. The aim of this study was to apply a droplet digital PCR assay for the detection and quantification (copies μL⁻¹) of the beef, pork, horse, sheep, chicken and turkey in meat products. The analysis conducted on commercial meat showed the presence of traces of DNA from other animal species than those declared. We show that the method is highly sensitive, specific and accurate (accuracy = 100%). This method could be adopted by competent food safety authorities to verify compliance with the labelling of meat products and to ensure quality and safety throughout the meat supply chain, from primary production to consumption.     

HRTEM observation of the monoclinic-to-tetragonal m-t) phase transition in nanocrystalline ZrO2

The orientation relations m(100) || t(001), m[001] || t[110]; m(011) || t(100), m[100] || t[001]; m(100) || t(110), m[001] || t[001]; m(013) || t(116), m[001] || t[001] (indices for the primitive tetragonal cell) have been found between the tetragonal (t) and monoclinic (m) domains during the electron irradiation-induced m-t phase transition observed in-situ with HREM within isolated zirconia nanoparticles. Geometric models of the m-t interfaces are proposed.     

Acetohydroxy acid synthase and threonine deaminase activities, and the biosynthesis of isoleucine-leucine-valine in Streptococcus bovis

Acetohydroxy acid synthase (AHAS) and threonine deaminase (TD) activities were found in Streptococcus bovis and shown to be involved in the biosynthesis of the branched chain amino acids isoleucine, leucine and valine. Apparent lack of repression of AHAS synthesis by the end-products and reduced sensitivity of S. bovis growth to analogues of the branched chain amino acids suggested that secretion of isoleucine, leucine and valine in the growth medium may be a consequence of the regulatory features of AHAS. A glycyl-leucine-resistant mutant with reduced TD activity secreted a reduced amount of isoleucine and an increased amount of valine, which might be a result of the reduced rate of synthesis of the isoleucine precursor alpha-ketobutyrate and of a consequent preferential carbon flow through the valine branch of the pathway.     

Automated Parallelization of Discrete State-Space Generation

We consider the problem of generating a large state-space in a distributed fashion. Unlike previously proposed solutions that partition the set of reachable states according to a hashing function provided by the user, we explore heuristic methods that completely automate the process. The first step is an initial random walk through the state space to initialize a search tree, duplicated in each processor. Then, the reachability graph is built in a distributed way, using the search tree to assign each newly found state to classes assigned to the available processors. Furthermore, we explore two remapping criteria that attempt to balance memory usage or future workload, respectively. We show how the cost of computing the global snapshot required for remapping will scale up for system sizes in the foreseeable future. An extensive set of results is presented to support our conclusions that remapping is extremely beneficial.     

Overview of recent operating experience regarding plant aging

Recent, as well as past, studies of reactor trip frequencies and other types of operating experience have shown that relatively high frequencies are likely in new plants with little accumulated operating time. In order to better understand all the factors which contribute to high frequencies in new plants, the authors have made a comparison of reactor trip frequencies between plants which went into operation in the 1960's and the early 1970's and those which have gone into operation more recently. Trip frequency versus accumulated operating time for two plant groups are compared to see the extent to which design differences (e.g., capacity, thermal margin) affect trip frequency.This paper also presents a review of some recent events in which plant age has played a major role. The events which are reviewed have been identified through the normal systematic event analysis program conducted by the NRC. Information regarding these events was obtained through followup by reviews conducted by NRC Resident Inspectors as well as event reports submitted by licensees.     

Hybrid photocatalytic membranes embedding decatungstate for heterogeneous photooxygenation

The incorporation of decatungstate in polymeric membranes provides new heterogeneous photocatalysts for the oxidation of organic substrates under oxygen atmosphere at 25 °C. Photocatalytic membranes have been prepared yielding polymeric films with a high thermal, chemical and mechanical stability (PVDF, PDMS, Hyflon). Surface spectroscopy techniques including transmittance and reflectance UV-Vis and FT-IR have been used to assess the photocatalyst integrity within the polymeric support. Catalyst screening has been performed under both homogeneous and heterogeneous photooxygenation conditions. The photocatalyst activity has been evaluated in terms of the substrate conversion, turnover numbers, and recycling experiments. A membrane induced selectivity behavior has been evidenced by comparison with homogeneous oxidations.