Dynamic effects and large – amplitude motion in Jacobi and Poincaré shape transitions in atomic nuclei

The Jacobi and Poincaré shape transitions are very promising way to investigate the shape of the nucleus. The presented here quasi-phenomenological approach allows to estimate the experimental conditions which are necessary to observe these phenomena. The static energy minimum gives the spin ranges and the fissility of atomic nuclei soft for the shape transitions and available experimentally. Dynamical effects taken into account through the solving collective Hamiltonian for zero-point vibration estimation, changes the spin rages for the shape transitions. The static deformation of the nucleus constrained by the minimum of energy for given spin has been enhanced to dynamical nuclear shapes permitted by the zero point energy. The large amplitude vibrations around the static deformation gives the ensemble of nuclear shapes possible to be observed

Phosphorylation of thymidylate synthase affects slow-binding inhibition by 5-fluoro-dUMP and N4-hydroxy-dCMP

Endogenous thymidylate synthases, isolated from tissues or cultured cells of the same specific origin, have been reported to show differing slow-binding inhibition patterns. These were reflected by biphasic or linear dependence of the inactivation rate on time and accompanied by differing inhibition parameters. Considering its importance for chemotherapeutic drug resistance, the possible effect of thymidylate synthase inhibition by post-translational modification was tested, e.g. phosphorylation, by comparing sensitivities to inhibition by two slow-binding inhibitors, 5-fluoro-dUMP and N4-hydroxy-dCMP, of two fractions of purified recombinant mouse enzyme preparations, phosphorylated and non-phosphorylated, separated by metal oxide/hydroxide affinity chromatography on Al(OH)3 beads. The modification, found to concern histidine residues and influence kinetic properties by lowering Vmax, altered both the pattern of dependence of the inactivation rate on time from linear to biphasic, as well as slow-binding inhibition parameters, with each inhibitor studied. Being present on only one subunit of at least a great majority of phosphorylated enzyme molecules, it probably introduced dimer asymmetry, causing the altered time dependence of the inactivation rate pattern (biphasic with the phosphorylated enzyme) and resulting in asymmetric binding of each inhibitor studied. The latter is reflected by the ternary complexes, stable under denaturing conditions, formed by only the non-phosphorylated subunit of the phosphorylated enzyme with each of the two inhibitors and N5,10-methylenetetrahydrofolate. Inhibition of the phosphorylated enzyme by N4-hydroxy-dCMP was found to be strongly dependent on [Mg2+], cations demonstrated previously to also influence the activity of endogenous mouse TS isolated from tumour cells

Xanthoma-like skin changes in an elderly woman with normal lipid profile

No abstract available

Generation of two induced pluripotent stem cell lines from psoriatic patient with cardiovascular comorbidity

Psoriasis (Ps) is a chronic, inflammatory skin disease characterized by thickened, red and scaly plaques. Systemic inflammation associated with psoriasis results in an increased risk of death due to the development of psoriasis-associated comorbidities such as cardiovascular disease (CVD) and metabolic syndrome. Although the cardiometabolic features in psoriasis are clinically well described, the underlying molecular mechanisms linking these comorbidities remain poorly understood. Generation of induced pluripotent stem cells (hiPSCs) from peripheral blood mononuclear cells (PBMCs) and skin fibroblasts (SFs) of psoriatic patients provides a novel approach to investigate the pathway by which cutaneous inflammation promotes CV complications in this disorder

Pollinators, pests and yield-Multiple trade-offs from insecticide use in a mass-flowering crop

Multiple trade-offs likely occur between pesticide use, pollinators and yield (via crop flowers) in pollinator-dependent, mass-flowering crops (MFCs), causing potential conflict between conservation and agronomic goals. To date, no studies have looked at both outcomes within the same system, meaning win-win solutions for pollinators and yield can only be inferred. Here, we outline a new framework to explore these trade-offs, using red clover (Trifolium pratense) grown for seed production as an example. Specifically, we address how the insecticide thiacloprid affects densities of seed-eating weevils (Protapion spp.), pollination rates, yield, floral resources and colony dynamics of the key pollinator, Bombus terrestris. Thiacloprid did not affect the amount of nectar provided by, or pollinator visitation to, red clover flowers but did reduce weevil density, correlating to increased yield and gross profit. In addition, colonies of B. terrestris significantly increased their weight and reproductive output in landscapes with (compared with without) red clover, regardless of insecticide use. Synthesis and applications. We propose a holistic conceptual framework to explore trade-offs between pollinators, pesticides and yield that we believe to be essential for achieving conservation and agronomic goals. This framework applies to all insecticide-treated mass-flowering crops (MFCs) and can be adapted to include other ecological processes. Trialling the framework in our study system, we found that our focal insecticide, thiacloprid, improved red clover seed yield with no detected effects on its key pollinator, B. terrestris, and that the presence of red clover in the landscape can benefit pollinator populations

synthesis biological evaluation and molecular docking studies of new amides of 4 chlorothiocolchicine as anticancer agents

Abstract Colchicine belongs to a large group of microtubule polymerization inhibitors. Although the anti-cancer activity of colchicine and its derivatives has been established, none of them has found commercial application in cancer treatment due to side effects. Therefore, we designed and synthesized a series of six triple-modified 4-chlorothiocolchicine analogues with amide moieties and one urea derivative. These novel derivatives were tested against several different cancer cell lines (A549, MCF-7, LoVo, LoVo/DX) and primary acute lymphoblastic leukemia (ALL) cells and they showed activity in the nanomolar range. The obtained IC50 values for novel derivatives were lower than those obtained for unmodified colchicine and common anticancer drugs such as doxorubicin and cisplatin. Further studies of colchicine and selected analogues were undertaken to indicate that they induced apoptotic cell death in ALL-5 cells. We also performed in silico studies to predict binding modes of the 4-chlorothiocolchicine derivatives to different β tubulin isotypes. The results indicate that select triple-modified 4-chlorothiocolchicine derivatives represent highly promising novel cancer chemotherapeutics

Synthesis, biological evaluation and molecular docking studies of new amides of 4-bromothiocolchicine as anticancer agents

Abstract Colchicine is the major alkaloid isolated from the plant Colchicum autumnale, which shows strong therapeutic effects towards different types of cancer. However, due to the toxicity of colchicine towards normal cells its application is limited. To address this issue we synthesized a series of seven triple-modified 4-bromothiocolchicine analogues with amide moieties. These novel derivatives were active in the nanomolar range against several different cancer cell lines and primary acute lymphoblastic leukemia cells, specifically compounds: 5 – 9 against primary ALL-5 (IC50 = 5.3 – 14 nM), 5, 7– 9 against A549 (IC50 = 10 nM), 5, 7 – 9 against MCF-7 (IC50 = 11 nM), 5 – 9 against LoVo (IC50 = 7 – 12 nM), and 5, 7 – 9 against LoVo/DX (IC50 = 48 – 87 nM). These IC50 values were lower than those obtained for unmodified colchicine and common anticancer drugs such as doxorubicin and cisplatin. Further studies revealed that colchicine and selected analogues induced characteristics of apoptotic cell death but manifested their effects in different phases of the cell cycle in MCF-7 versus ALL-5 cells. Specifically, while colchicine and the studied derivatives arrested MCF-7 cells in mitosis, very little mitotically arrested ALL-5 cells were observed, suggesting effects were manifest instead in interphase. We also developed an in silico model of the mode of binding of these compounds to their primary target, β-tubulin. We conducted a correlation analysis (linear regression) between the calculated binding energies of colchicine derivatives and their anti-proliferative activity, and determined that the obtained correlation coefficients strongly depend on the type of cells used

Liszaj śluzowaty z towarzyszącym zespołem Sjögrena

Lichen myxedematosus belongs to the group of disorders with the deposition of mucins in the skin. The disease may coexist with monoclonal gammapathy, e.g. myeloma multiplex or Waldenström macroglobulinemia. A case of a 77-year-old man with lichen myxedematosus and monoclonal gammapathy is presented. Treatment with cyclophosphamide followed by intravenous immunoglobulins was initiated, however, no significant improvement of the skin condition was observed. Currently, the patient is receiving talidomide. This case report indicates, that lichen myxedematosus still remains a challenge for physicians and causes both diagnostics and therapeutic dilemma.Liszaj śluzowaty należy do grupy schorzeń związanych z odkładaniem się złogów mucyn w skórze. Choroba ta może dodatkowo współistnieć z gammapatią monoklonalną, na przykład szpiczakiem mnogim lub makroglobulinemią Waldenströma. W artykule został omówiony przypadek 77-letniego mężczyzny z liszajem śluzowatym i monoklonalną gammapatią. W leczeniu zmian skórnych zastosowano u niego w pierwszej kolejności cyklofosfamid, a następnie ludzkie immunoglobuliny G. Próby te nie przyniosły jednak zadowalającej poprawy, stąd pacjent został obecnie poddany terapii talidomidem. Opisywany przypadek wskazuje, że liszaj śluzowaty wciąż pozostaje wyzwaniem dla lekarzy i stwarza problemy zarówno diagnostyczne (brak jasnych kryteriów klasyfikacyjnych), jak i terapeutyczne