Bis{(E)-4-chloro-2-[(2-chloro-3-pyrid­yl)imino­methyl-κN]phenolato-κO}copper(II)

In the title complex, [Cu(C12H7Cl2N2O)2], the CuII center is tetra­coordinated by two phenolic O and two azomethine N atoms from two bidentate 4-chloro-2-[(2-chloro-3-pyrid­yl)imino­meth­yl]phenolate (L) ligands. In the crystal structure, the CuII atom has a distorted square-planar coordination environment. The dihedral angles between the benzene and pyridyl rings are 54.39 (3) and 80.14 (4)°, indicating that the pyridine ring has a considerably weaker steric hindrance. The packing of the mol­ecule is controlled by C—H⋯π(Ph) inter­actions and short O⋯Cl inter­actions [3.196 (4) Å], linking the mol­ecules into a chain-like structure along the c axis

MR-based motion correction for cardiac PET parametric imaging: a simulation study

Background: Both cardiac and respiratory motions bias the kinetic parameters measured by dynamic PET. The aim of this study was to perform a realistic positron emission tomography-magnetic resonance (PET-MR) simulation study using 4D XCAT to evaluate the impact of MR-based motion correction on the estimation of PET myocardial kinetic parameters using PET-MR. Dynamic activity distributions were obtained based on a one-tissue compartment model with realistic kinetic parameters and an arterial input function. Realistic proton density/T1/T2 values were also defined for the MRI simulation. Two types of motion patterns, cardiac motion only (CM) and both cardiac and respiratory motions (CRM), were generated. PET sinograms were obtained by the projection of the activity distributions. PET image for each time frame was obtained using static (ST), gated (GA), non-motion-corrected (NMC), and motion-corrected (MC) methods. Voxel-wise unweighted least squares fitting of the dynamic PET data was then performed to obtain K1 values for each study. For each study, the mean and standard deviation of K1 values were computed for four regions of interest in the myocardium across 25 noise realizations. Results: Both cardiac and respiratory motions introduce blurring in the PET parametric images if the motion is not corrected. Conventional cardiac gating is limited by high noise level on parametric images. Dual cardiac and respiratory gating further increases the noise level. In contrast to GA, the MR-based MC method reduces motion blurring in parametric images without increasing noise level. It also improves the myocardial defect delineation as compared to NMC method. Finally, the MR-based MC method yields lower bias and variance in K1 values than NMC and GA, respectively. The reductions of K1 bias by MR-based MC are 7.7, 5.1, 15.7, and 29.9% in four selected 0.18-mL myocardial regions of interest, respectively, as compared to NMC for CRM. MR-based MC yields 85.9, 75.3, 71.8, and 95.2% less K1 standard deviation in the four regions, respectively, as compared to GA for CRM. Conclusions: This simulation study suggests that the MR-based motion-correction method using PET-MR greatly reduces motion blurring on parametric images and yields less K1 bias without increasing noise level

Formulation of choline chloride/ascorbic acid natural deep eutectic solvent: Characterization, solubilization capacity and antioxidant property

In the present study, natural deep eutectic solvent composed of choline chloride and ascorbic acid (CHCL/AA NADES) was formulated for enhancing the solubility and antioxidant properties of antioxidant extracts from fruit wastes of Mangifera pajang. The solubilities of Mangifera pajang's antioxidant extracts in water and CHCL/AA NADES at different water contents (0–50 wt%) were investigated. It was observed that the antioxidant extracts were most soluble in the CHCL/AA NADES with 10 wt% of water, and the concentration of antioxidant was found to be approximately 15% and 4% as compared to water and pure CHCL/AA NADES, respectively. The positive effect of water on NADES can be related to the reduced viscosity of NADES, where the viscosity decreased up to 74% upon addition of water. Aside from that, all the tested CHCL/AA NADES enhanced the antioxidant capacity of antioxidant extracts by 1.3–14.64% compared to the antioxidant extracts in water. This finding highlights the role of CHCL/AA NADES as an antioxidant capacity enhancer. Noteworthy, the antioxidant extracts solubilized in the CHCL/AA NADES system formed a nano-scale cluster structure, as depicted by the TEM image, suggesting that the CHCL/AA NADES could potentially use in nanoformulation that provides protection to the antioxidant extracts

Particular distribution and expression pattern of endoglin (CD105) in the liver of patients with hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Endoglin (CD105) has been considered a prognostic marker for hepatocellular carcinoma (HCC), and widely used as an appropriate targeting for antiangenesis therapy in some cancers. Our aim was to evaluate the distribution and expression of CD105 in the liver of patients with HCC, and to discuss whether CD105 may be used as an appropriate targeting for antiangenesis therapy in HCC.</p> <p>Methods</p> <p>Three parts of liver tissues from each of 64 patients with HCC were collected: tumor tissues (TT), adjacent non-tumor (AT) liver tissues within 2 cm, and tumor free tissues (TF) 5 cm far from the tumor edge. Liver samples from 8 patients without liver diseases served as healthy controls (HC). The distribution and expression of CD105 in tissues were evaluated by immunohistochemistry, Western blotting analysis, and real-time PCR. HIF-1alpha and VEGF₁₆₅protein levels in tissues were analyzed by Immunohistochemistry and Western blotting analysis or ELISA.</p> <p>Results</p> <p>CD105 was positively stained mostly in a subset of microvessels 'endothelial sprouts' in TT of all patients while CD105 showed diffuse positive staining, predominantly on hepatic sinus endothelial cells in the surrounding of draining veins in TF and AT. The mean score of MVD-CD105 (mean ± SD/0.74 mm²) was 19.00 ± 9.08 in HC, 153.12 ± 53.26 in TF, 191.12 ± 59.17 in AT, and 85.43 ± 44.71 in TT, respectively. Using a paired <it>t </it>test, the expression of CD105 in AT and TF was higher than in TT at protein (MVD, <it>p </it>= 0.012 and <it>p </it>= 0.007, respectively) and mRNA levels (<it>p </it>< 0.001 and <it>p </it>= 0.009, respectively). Moreover, distribution and expression of CD105 protein were consistent with those of HIF-1alpha and VEGF₁₆₅protein in liver of patients with HCC. The level of <it>CD105 </it>mRNA correlated with VEGF₁₆₅level in TF (r = 0.790, <it>p </it>= 0.002), AT (r = 0.723, <it>p </it>< 0.001), and TT (r = 0.473, <it>p </it>= 0.048), respectively.</p> <p>Conclusion</p> <p>It is demonstrated that CD105 was not only present in neovessels in tumor tissues, but also more abundant in hepatic sinus endothelium in non-tumor tissues with cirrhosis. Therefore, CD105 may not be an appropriate targeting for antiangenesis therapy in HCC, especially with cirrhosis.</p

Vandetanib (Zactima, ZD6474) Antagonizes ABCC1- and ABCG2-Mediated Multidrug Resistance by Inhibition of Their Transport Function

ABCC1 and ABCG2 are ubiquitous ATP-binding cassette transmembrane proteins that play an important role in multidrug resistance (MDR). In this study, we evaluated the possible interaction of vandetanib, an orally administered drug inhibiting multiple receptor tyrosine kinases, with ABCC1 and ABCG2 in vitro.MDR cancer cells overexpressing ABCC1 or ABCG2 and their sensitive parental cell lines were used. MTT assay showed that vandetanib had moderate and almost equal-potent anti-proliferative activity in both sensitive parental and MDR cancer cells. Concomitant treatment of MDR cells with vandetanib and specific inhibitors of ABCC1 or ABCG2 did not alter their sensitivity to the former drug. On the other hand, clinically attainable but non-toxic doses of vandetanib were found to significantly enhance the sensitivity of MDR cancer cells to ABCC1 or ABCG2 substrate antitumor drugs. Flow cytometric analysis showed that vandetanib treatment significantly increase the intracellular accumulation of doxorubicin and rhodamine 123, substrates of ABCC1 and ABCG2 respectively, in a dose-dependent manner (P<0.05). However, no significant effect was shown in sensitive parental cell lines. Reverse transcription-PCR and Western blot analysis showed that vandetanib did not change the expression of ABCC1 and ABCG2 at both mRNA and protein levels. Furthermore, total and phosphorylated forms of AKT and ERK1/2 remained unchanged after vandetanib treatment in both sensitive and MDR cancer cells.Vandetanib is unlikely to be a substrate of ABCC1 or ABCG2. It overcomes ABCC1- and ABCG2-mediated drug resistance by inhibiting the transporter activity, independent of the blockade of AKT and ERK1/2 signal transduction pathways

Selection Signatures in Worldwide Sheep Populations

The diversity of populations in domestic species offers great opportunities to study genome response to selection. The recently published Sheep HapMap dataset is a great example of characterization of the world wide genetic diversity in sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify selection signatures in worldwide sheep populations. Compared to previous analyses, we made use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of linkage disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows pinpointing several new selection signatures in the sheep genome and distinguishing those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the ones previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environments

Ευρετικές προσεγγίσεις του μοναδιάστατου προβλήματος πακετοποίησης

Article 59.1, of the International Code of Nomenclature for Algae, Fungi, and Plants (ICN; Melbourne Code), which addresses the nomenclature of pleomorphic fungi, became effective from 30 July 2011. Since that date, each fungal species can have one nomenclaturally correct name in a particular classification. All other previously used names for this species will be considered as synonyms. The older generic epithet takes priority over the younger name. Any widely used younger names proposed for use, must comply with Art. 57.2 and their usage should be approved by the Nomenclature Committee for Fungi (NCF). In this paper, we list all genera currently accepted by us in Dothideomycetes (belonging to 23 orders and 110 families), including pleomorphic and non-pleomorphic genera. In the case of pleomorphic genera, we follow the rulings of the current ICN and propose single generic names for future usage. The taxonomic placements of 1261 genera are listed as an outline. Protected names and suppressed names for 34 pleomorphic genera are listed separately. Notes and justifications are provided for possible proposed names after the list of genera. Notes are also provided on recent advances in our understanding of asexual and sexual morph linkages in Dothideomycetes. A phylogenetic tree based on four gene analyses supported 23 orders and 75 families, while 35 families still lack molecular data

Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep

Stefan Hiendleder is a member of the International Sheep Genomics ConsortiumIn sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal’s health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154) has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E) at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V) and the extracellular domains (E31Q, I74F, and I102T) of TMEM154. A matrix-assisted laser desorption/ionization–time-of flight mass spectrometry (MALDI-TOF MS) assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes). The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks.Michael P. Heaton, Theodore S. Kalbfleisch, Dustin T. Petrik, Barry Simpson, James W. Kijas, Michael L. Clawson, Carol G. Chitko-McKown, Gregory P. Harhay, Kreg A. Leymaster, the International Sheep Genomics Consortiu