Despite being a complex many-body system, the atomic nucleus exhibits simple structures for certain 'magic' numbers of protons and neutrons. The calcium chain in particular is both unique and ...puzzling: evidence of doubly magic features are known in 40,48Ca, and recently suggested in two radioactive isotopes, 52,54Ca. Although many properties of experimentally known calcium isotopes have been successfully described by nuclear theory, it is still a challenge to predict the evolution of their charge radii. Here we present the first measurements of the charge radii of 49,51,52Ca, obtained from laser spectroscopy experiments at ISOLDE, CERN. The experimental results are complemented by state-of-the-art theoretical calculations. The large and unexpected increase of the size of the neutron-rich calcium isotopes beyond N = 28 challenges the doubly magic nature of 52Ca and opens new intriguing questions on the evolution of nuclear sizes away from stability, which are of importance for our understanding of neutron-rich atomic nuclei.
The properties of exotic nuclei on the verge of existence play a fundamental part in our understanding of nuclear interactions. Exceedingly neutron-rich nuclei become sensitive to new aspects of ...nuclear forces. Calcium, with its doubly magic isotopes (40)Ca and (48)Ca, is an ideal test for nuclear shell evolution, from the valley of stability to the limits of existence. With a closed proton shell, the calcium isotopes mark the frontier for calculations with three-nucleon forces from chiral effective field theory. Whereas predictions for the masses of (51)Ca and (52)Ca have been validated by direct measurements, it is an open question as to how nuclear masses evolve for heavier calcium isotopes. Here we report the mass determination of the exotic calcium isotopes (53)Ca and (54)Ca, using the multi-reflection time-of-flight mass spectrometer of ISOLTRAP at CERN. The measured masses unambiguously establish a prominent shell closure at neutron number N = 32, in excellent agreement with our theoretical calculations. These results increase our understanding of neutron-rich matter and pin down the subtle components of nuclear forces that are at the forefront of theoretical developments constrained by quantum chromodynamics.
Lumican, a small leucine rich proteoglycan, inhibits MMP-14 activity and melanoma cell migration in vitro and in vivo. Snail triggers epithelial-mesenchymal transitions endowing epithelial cells with ...migratory and invasive properties during tumor progression. The aim of this work was to investigate lumican effects on MMP-14 activity and migration of Snail overexpressing B16F1 (Snail-B16F1) melanoma cells and HT-29 colon adenocarcinoma cells. Lumican inhibits the Snail induced MMP-14 activity in B16F1 but not in HT-29 cells. In Snail-B16F1 cells, lumican inhibits migration, growth, and melanoma primary tumor development. A lumican-based strategy targeting Snail-induced MMP-14 activity might be useful for melanoma treatment.
Cytokinin hormones are important regulators of development and environmental responses of plants that execute their action via the molecular machinery of signal perception and transduction. The ...limiting step of the whole process is the availability of the hormone in suitable concentrations in the right place and at the right time to interact with the specific receptor. Hence, the hormone concentrations in individual tissues, cells, and organelles must be properly maintained by biosynthetic and metabolic enzymes. Although there are merely two active cytokinins, isopentenyladenine and its hydroxylated derivative zeatin, a variety of conjugates they may form and the number of enzymes/isozymes with varying substrate specificity involved in their biosynthesis and conversion gives the plant a variety of tools for fine tuning of the hormone level. Recent genome-wide studies revealed the existence of the respective coding genes and gene families in plants and in some bacteria. This review summarizes present knowledge on the enzymes that synthesize cytokinins, form cytokinin conjugates, and carry out irreversible elimination of the hormones, including their phylogenetic analysis and possible variations in different organisms.
Epithelial-to-mesenchymal transition (EMT) in cancer cells, represents early stages of metastasis and is a promising target in colorectal cancer (CRC) therapy. There have been many attempts to ...identify markers and key pathways induced throughout EMT but the process is complex and depends on the cancer type and tumour microenvironment. Here we used the colon cancer cell line HT29, which stably overexpressed Snail, the key transcription factor in early EMT, as a model for colorectal adenocarcinoma cells with a pro-metastatic phenotype. We investigated miRNA expression regulation during that phenotypic switching. We found that overexpression of Snail in HT29 cells triggered significant changes in individual miRNA levels but did not change the global efficiency of miRNA processing. Snail abundance repressed the expression of miR-192 and miR-194 and increased miR-205, let-7i and SNORD13 levels. These identified changes correlated with the reported transcriptomic alterations in Snail-overexpressing HT29 cells. We also investigated how Snail affected the miRNA content of extracellular vesicles (EVs) released from HT29 cells. Our data suggest that the presence of Snail significantly alters the complex mRNA/miRNA interactions in the early steps of metastasis and also has an impact on the content of EVs released from HT29 cells.
Abstract Chemokines are a family of small proteins that have significant roles in inflammation, angiogenesis and cellular homing. Since inflammation and hemostasis/thrombosis have multiple ...overlapping roles and pathways, one could expect that some chemokines would also have biologically significant roles in hemostasis/thrombosis as well. This would especially be true for chemokines that are localized solely or predominantly within platelets and released in large amounts at sites of platelet activation such as platelet factor 4 (PF4, CXCL4) and its closely related chemokine, platelet basic protein (PBP, CXCL7). Our group and others have clearly demonstrated an in vivo role for PF4 in hemostasis/thrombosis, but not for PBP, which in contrast has clear proinflammatory properties. This review will focus on PF4 and its potential roles in hemostasis/thrombosis and the underlying pathways by which PF4 may be especially important in such pathologic thrombotic states as heparin-induced thrombocytopenia (HIT) and septic shock.
This paper investigates the reinforcement of rigid polyurethane foams with carbon nanotubes or graphite in order to improve their mechanical and thermal properties as well as fire resistance. A small ...addition of carbon nanotubes (up to 0.05wt.%) improves the mechanical strength by about 20%, which was attributed to the strengthening effect of nanotubes and the change in the foam structure, i.e. the smaller size of pores and their narrower distribution. For higher nanotube content, the pore size does not change but the overall porosity significantly increases which results in a decrease in the mechanical strength. The thermal stability of nanocomposite foams and their flammability increase as a result of the formation of a carbon layer forming at the polymer surface. The addition of graphite greatly improves the fire resistance of polyurethanes foams but significantly deteriorates the bending strength due to the poor adhesion to the polyurethane matrix.
Heparin-induced thrombocytopenia (HIT) is an immune-mediated thrombocytopenic disorder associated with a severe prothrombotic state. We investigated whether neutrophils and neutrophil extracellular ...traps (NETs) contribute to the development of thrombosis in HIT. Using an endothelialized microfluidic system and a murine passive immunization model, we show that HIT induction leads to increased neutrophil adherence to venous endothelium. In HIT mice, endothelial adherence is enhanced immediately downstream of nascent venous thrombi, after which neutrophils undergo retrograde migration via a CXCR2-dependent mechanism to accumulate into the thrombi. Using a microfluidic system, we found that PF4 binds to NETs, leading them to become compact and DNase resistant. PF4-NET complexes selectively bind HIT antibodies, which further protect them from nuclease digestion. In HIT mice, inhibition of NET formation through Padi4 gene disruption or DNase treatment limited venous thrombus size. PAD4 inactivation did affect arterial thrombi or severity of thrombocytopenia in HIT. Thus, neutrophil activation contributes to the development of venous thrombosis in HIT by enhancing neutrophil-endothelial adhesion and neutrophil clot infiltration, where incorporated PF4-NET-HIT antibody complexes lead to thrombosis propagation. Inhibition of neutrophil endothelial adhesion, prevention of neutrophil chemokine-dependent recruitment of neutrophils to thrombi, or suppression of NET release should be explored as strategies to prevent venous thrombosis in HIT.
► We conducted the methane fermentation of sugar beet pulp and spent hops. ► We checked the effect of enzymatic pretreatment of substrate on methane fermentation. ► The optimum processing condition ...for enzymatic pretreatment was determinated. ► Enzymatic pretreatment enhancement of biogas yield from anaerobic fermentation.
The effect of enzymatic pretreatment of sugar beet pulp and spent hops prior to methane fermentation was determined in this study. These industrial residues were subjected to enzymatic digestion before anaerobic fermentation because of high fiber content (of 85.1% dry matter (DM) and 57.7% DM in sugar beet pulp and spent hops, respectively). Their 24h hydrolysis with a mix of enzymatic preparations Celustar XL and Agropect pomace (3:1, v/v), with endoglucanase, xylanase and pectinase activities, was most effective. Reducing sugars concentrations in hydrolysates of sugar beet pulp and spent hops were by 88.9% and 59.4% higher compared to undigested materials. The highest yield of biogas was obtained from the enzymatic hydrolysate of sugar beet pulp (183.39mL/d from 1g COD at fermenter loading with organic matter of 5.43g COD/L×d). Fermentation of sugar beet pulp gave 19% less biogas. Methane fermentation of spent hops hydrolysate yielded 121.47mL/d biogas from 1g COD (at 6.02g COD/L×d, 13% more than from spent hops). These results provide evidence that suitable enzymatic pretreatment of lignocellulosic wastes improve biogas yield from anaerobic fermentation.
ABSTRACT
Endothelial thrombomodulin (TM) regulates coagulation and inflammation via several mechanisms, including production of activated protein C (APC). Recombinant APC and soluble fragments of TM ...(sTM) have been tested in settings associated with insufficiency of the endogenous TM/APC pathway, such as sepsis. We previously designed a fusion protein of TM single‐chain variable fragment antibody (scFv)/TM targeted to red blood cells (RBCs) to improve pharmacokinetics and antithrombotic effects without increasing bleeding. Here, scFv/ TM was studied in mouse models of systemic inflammation and ischemia‐reperfusion injury. Injected concomitantly with or before endotoxin, scFv/TM provided more potent protection against liver injury and release of pathological mediators than sTM, showing similar efficacy at up to 50‐fold lower doses. scFv/TM provided protection when injected after endotoxin, whereas sTM did not, and augmented APC production by thrombin ~50‐fold more than sTM. However, scFv/TM injected after endotoxin did not reduce thrombin/antithrombin complexes; nor did antibodies that block APC anticoagulant activity suppress the prophylactic anti‐inflammatory effect of scFv/TM. Therefore, similar to endogenous TM, RBC‐anchored scFv/TM activates several protective pathways. Finally, scFv/TM was more effective at reducing cerebral infarct volume and alleviated neurological deficits than sTM after cerebral ischemia/reperfusion injury. These results indicate that RBC‐targeted scFv/TM exerts multifaceted cytoprotective effects and may find utility in systemic and focal inflammatory and ischemic disorders.—Carnemolla, R., Villa, C.H., Greineder, C. F., Zaitseva, S., Patel, K.R., Kowalska, M.A., Atochin, D. N., Cines, D.B., Siegel, D.L., Esmon, C. T., Muzykantov, V. R. Targetingthrombomodulin to circulatingred blood cells augments its protective effects in models of endotoxemia and ischemia‐reperfusion injury FASEB J. 31, 761–770 (2017). http://www.fasebj.org
PDF
