Identification of compounds responsible for the anthelmintic effects of chicory (Cichorium intybus) by molecular networking and bio-guided fractionation

10 páginas, 7 figuras.Increasing resistance towards anthelmintic drugs has necessitated the search for alternative treatments for the control of gastrointestinal nematode parasites. Animals fed on chicory (Cichorium intybus L.), a temperate (pasture) crop, have reduced parasite burdens, hence making C. intybus a potentially useful source for novel anthelmintic compounds or a diet-based preventive/therapeutic option. Here, we utilized in vitro bioassays with the parasitic nematode Ascaris suum and molecular networking techniques with five chicory cultivars to identify putative active compounds. Network analysis predicted sesquiterpene lactones (SL) as the most likely group of anthelmintic compounds. Further bioassay-guided fractionation supported these predictions, and isolation of pure compounds demonstrated that the SL 8-deoxylactucin (8-DOL) is the compound most strongly associated with anti-parasitic activity. Furthermore, we showed that 8-DOL acts in a synergistic combination with other SL to exert the anti-parasitic effects. Finally, we established that chicory-derived extracts also showed activity against two ruminant nematodes (Teladorsagia circumcincta and Cooperia oncophora) in in vitro assays. Collectively, our results confirm the anti-parasitic activity of chicory against a range of nematodes, and pave the way for targeted extraction of active compounds or selective breeding of specific cultivars to optimize its future use in human and veterinary medicine.We are very grateful for the guidance and support by Dr. Thomas Ostenfeld Larsen and Christopher Phippen, Technical University of Denmark, Natural product discovery, and the laboratory assistance of Mette Schjelde, University of Copenhagen. This work was funded by the Danish Council for Independent Research (Grant DFF–6111-00394). Fractionation and purification of compounds were further supported by the Green Development and Demonstration Program (GUDP) (Project No. 34009-17-1220). MPE was supported by CONICYT Chile (FONDE-CYT Postdoctorado #317087

Triaxial Deformation and Nuclear Shape Transition in \u3csup\u3e192\u3c/sup\u3eAu

Background: Nuclei in the A≈190 mass region show gradual shape changes from prolate through nonaxial deformed shapes and ultimately towards spherical shapes as the Pb region is approached. Exploring how this shape evolution occurs will help us understand the evolution of collectivity in this region. Purpose: The level scheme of the 192Au nucleus in A ≈ 190 region was studied in order to deduce its deformations. Methods: High-spin states of 192Au have been populated in the 186W(11B, 5n) reaction at a beam energy of 68 MeV and their γ decay was studied using the YRAST Ball detector array at the Wright Nuclear Structure Laboratory (WNSL), Yale University. Results: Based on double and triple γ-ray coincidence data the level scheme of 192Au has been extended up to Iπ = 32+ at an excitation energy of ∼6 MeV. Conclusion: The results are discussed in the framework of pairing and deformation self-consistent total Routhian surface (TRS) and cranked shell model (CSM) calculations. The comparison of the experimental observations with the calculations indicates that this nucleus takes a nonaxial shape similar to other Au nuclei in this region

High-spin States in \u3csup\u3e191, 193\u3c/sup\u3eAu and \u3csup\u3e192\u3c/sup\u3ePt: Evidence for Oblate Deformation and Triaxial Shapes

High-spin states of 191, 193Au and 192Pt have been populated in the 186W(11B, xn) and 186W(11B, p4n) reactions, respectively, at a beam energy of 68 MeV and their γ decay was studied using the YRAST Ball detector array at the Wright Nuclear Structure Laboratory at Yale University. The level scheme of 193Au has been extended up to Iπ = 55/2+. New transitions were observed also in 191Au and 192Pt. Particle-plus-Triaxial-Rotor (PTR) and Total Routhian Surface (TRS) calculations were performed to determine the equilibrium deformations of the Au isotopes. The predictions for oblate deformations in these nuclei are in agreement with the experimental data. Development of nonaxial shapes is discussed within the framework of the PTR model

CHOP Mediates Endoplasmic Reticulum Stress-Induced Apoptosis in Gimap5-Deficient T Cells

Gimap5 (GTPase of the immunity-associated protein 5) has been linked to the regulation of T cell survival, and polymorphisms in the human GIMAP5 gene associate with autoimmune disorders. The BioBreeding diabetes-prone (BBDP) rat has a mutation in the Gimap5 gene that leads to spontaneous apoptosis of peripheral T cells by an unknown mechanism. Because Gimap5 localizes to the endoplasmic reticulum (ER), we hypothesized that absence of functional Gimap5 protein initiates T cell death through disruptions in ER homeostasis. We observed increases in ER stress-associated chaperones in T cells but not thymocytes or B cells from Gimap5−/− BBDP rats. We then discovered that ER stress-induced apoptotic signaling through C/EBP-homologous protein (CHOP) occurs in Gimap5−/− T cells. Knockdown of CHOP by siRNA protected Gimap5−/− T cells from ER stress-induced apoptosis, thereby identifying a role for this cellular pathway in the T cell lymphopenia of the BBDP rat. These findings indicate a direct relationship between Gimap5 and the maintenance of ER homeostasis in the survival of T cells

Single-neutron orbits near Ni-78 : Spectroscopy of the N=49 isotope Zn-79

Peer reviewe

New and comprehensive β - and βp-decay spectroscopy results in the vicinity of Sn 100

26 pags., 30 figs., 11 tabs.A decay spectroscopy experiment on proton-rich nuclei in the vicinity of the doubly magic Sn100 was carried out at RIKEN Nishina Center. More than 20 nuclei with 43≤Z≤50 and N≤51, produced by fragmentation reactions were investigated via analyses of β-decay, βp-decay, and subsequent γ-ray data. Owing to higher statistics, the precision on the half-lives of many of the ground states and isomers was improved. β-decay endpoint energies of 11 states in 8 nuclei were measured for the first time, and the corresponding QEC and excitation energies were generally consistent with various mass models. Many β-delayed proton emission branching ratios were measured either for the first time or with higher precision compared to literature values, and some of them differed by more than 2σ. Many of the large discrepancies were associated with nuclei with long-lived isomeric states, highlighting large systematic uncertainties involved in these measurements. Twenty-five new γ rays were observed, and ten new states are proposed with unambiguous excitation energies, spins, and parities. Most of the energies of the excited states were consistent within 300 keV or 20%, whichever was greater, compared to shell model predictions in the proton/neutron (p1/2,g9/2) model space assuming a Sr76 core. A signature of a new (1/2-) isomer in Cd97 with T1/2=0.73(7) s was found, in good agreement with shell model predictions.The authors would like to thank the personnel at the RIKEN Nishina Center for providing the exotic radioactive isotope beam with record intensities. This experiment was performed at RI Beam Factory operated by RIKEN Nishina Center and CNS, University of Tokyo. We acknowledge the EUROBALL Owners Committee for loaning the germanium detectors and the PreSpec Collaboration for the readout electronics of the cluster detectors of EURICA. Support for the WAS3ABi setup was provided by the Rare Isotope Science Project, funded by the Ministry of Education, Science and Technology (MEST) and National Research Foundation (NRF) of Korea, as well as KAKENHI (Grant No. 25247045) of Japan Society for the Promotion of Science (JSPS). The authors acknowledge the support of the DFG cluster of excellence “Origin and Structure of the Universe,” German BMBF under Contract No. 05P15PKFNA and the Spanish Ministerio de Economía y Competitividad via Project No. FPA2017- 84756-C4-2-P. Part of the research was funded by the Natural Sciences and Engineering Research Council (NSERC) of Canada and also supported by FJ-NSP (French-Japanese International Associated Laboratory for Nuclear Structure Problems)

Direct experimental evidence for a multiparticle-hole ground state configuration of deformed Mg-33

The first direct experimental evidence of a multiparticle-hole ground state configuration of the neutron-rich Mg-33 isotope has been obtained via intermediate energy (400 A MeV) Coulomb dissociation measurement. The major part similar to(70 +/- 13)% of the cross section is observed to populate the excited states of Mg-32 after the Coulomb breakup of Mg-33. The shapes of the differential Coulomb dissociation cross sections in coincidence with different core excited states favor that the valence neutron occupies both the s(1/2) and p(3/2) orbitals. These experimental findings suggest a significant reduction and merging of sd-pf shell gaps at N similar to 20 and 28. The ground state configuration of Mg-33 is predominantly a combination of Mg-32(3.0,3.5MeV; 2(-), 1(-)) circle times nu(s1/2), Mg-32(2.5MeV; 2(+)) circle times nu(p3/2), and Mg-32(0; 0(+)) circle times nu(p3/2). The experimentally obtained quantitative spectroscopic information for the valence neutron occupation of the s and p orbitals, coupled with different core states, is in agreement with Monte Carlo shell model (MCSM) calculation using 3 MeV as the shell gap at N = 20