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1.
Cell Commun Signal ; 21(1): 51, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882818

RESUMO

BACKGROUND: Metastasis is the main cause of death in patients with colorectal cancer (CRC). Apart from platelets, platelet-derived microparticles (PMPs) are also considered important factors that can modify the activity of cancer cells. PMPs are incorporated by cancer cells and can also serve as intracellular signalling vesicles. PMPs are believed to affect cancer cells by upregulating their invasiveness. To date, there is no evidence that such a mechanism occurs in colorectal cancer. It has been shown that platelets can stimulate metalloproteases (MMPs) expression and activity via the p38MAPK pathway in CRC cells, leading to their elevated migratory potential. This study aimed to investigate the impact of PMPs on the invasive potential of CRC cells of various phenotypes via the MMP-2, MMP-9 and p38MAPK axis. METHODS: We used various CRC cell lines, including the epithelial-like HT29 and the mesenchymal-like SW480 and SW620. Confocal imaging was applied to study PMP incorporation into CRC cells. The presence of surface receptors on CRC cells after PMP uptake was evaluated by flow cytometry. Transwell and scratch wound-healing assays were used to evaluate cell migration. The level of C-X-C chemokine receptor type 4 (CXCR4), MMP-2, and MMP-9 and the phosphorylation of ERK1/2 and p38MAPK were measured by western blot. MMP activity was determined using gelatine-degradation assays, while MMP release was evaluated by ELISA. RESULTS: We found that CRC cells could incorporate PMPs in a time-dependent manner. Moreover, PMPs could transfer platelet-specific integrins and stimulate the expression of integrins already present on tested cell lines. While mesenchymal-like cells expressed less CXCR4 than epithelial-like CRC cells, PMP uptake did not increase its intensity. No significant changes in CXCR4 level either on the surface or inside CRC cells were noticed. Levels of cellular and released MMP-2 and MMP-9 were elevated in all tested CRC cell lines after PMP uptake. PMPs increased the phosphorylation of p38MAPK but not that of ERK1/2. Inhibition of p38MAPK phosphorylation reduced the PMP-induced elevated level and release of MMP-2 and MMP-9 as well as MMP-dependent cell migration in all cell lines. CONCLUSIONS: We conclude that PMPs can fuse into both epithelial-like and mesenchymal-like CRC cells and increase their invasive potential by inducing the expression and release of MMP-2 and MMP-9 via the p38MAPK pathway, whereas CXCR4-related cell motility or the ERK1/2 pathway appears to not be affected by PMPs. Video Abstract.


Assuntos
Micropartículas Derivadas de Células , Neoplasias Colorretais , Humanos , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Transdução de Sinais , Invasividade Neoplásica
2.
BMC Vet Res ; 19(1): 227, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919690

RESUMO

BACKGROUND: Infectious keratitis is a common ophthalmic condition in canine patients. Sequelae can include keratomalacia and corneal perforation, a vision threatening outcome. Photoactivated chromophore for keratitis - corneal cross-linking (PACK-CXL) is a non-surgical, adjunctive treatment method for infectious keratitis. The goal of this retrospective, multicenter study was to determine risk factors for treatment failure following PACK-CXL in canine patients suffering from suspected infectious keratitis. Medical records from four veterinary ophthalmology services were reviewed, and information related to patient demographics, ophthalmic findings, the PACK-CXL protocol used, and epithelialization time was collected and analyzed. Due to the potential for intervariable relationships, an additive Bayesian network (ABN) analysis was performed to evaluate these complex relationships. RESULTS: Records for 671 eyes (668 dogs) were included in the analysis. Based on the ABN, in the population included here, patients who underwent an accelerated PACK-CXL protocol were less likely to experience treatment failure versus patients treated with a slow protocol. Mutual dependencies between exposure variables were identified by ABN, which would have been overlooked using classical regression. Corneal re-epithelialization time was shortened following PACK-CXL combined with topical medical therapy compared to PACK-CXL alone. CONCLUSIONS: No risk factors associated with treatment failure were identified in the population included in the present study. Canine patients may benefit from the use of accelerated PACK-CXL protocols, especially when combined with topical antibiotics and anti-collagenolytic therapy. The reasons for this apparent positive impact on treatment outcome remain unclear.


Assuntos
Doenças do Cão , Infecções Oculares Bacterianas , Ceratite , Fotoquimioterapia , Animais , Cães , Teorema de Bayes , Crosslinking Corneano/veterinária , Reagentes de Ligações Cruzadas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/veterinária , Ceratite/tratamento farmacológico , Ceratite/veterinária , Fotoquimioterapia/veterinária , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Raios Ultravioleta
3.
Blood ; 135(10): 743-754, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31722003

RESUMO

Sepsis is characterized by multiorgan system dysfunction that occurs because of infection. It is associated with high morbidity and mortality and is in need of improved therapeutic interventions. Neutrophils play a crucial role in sepsis, releasing neutrophil extracellular traps (NETs) composed of DNA complexed with histones and toxic antimicrobial proteins that ensnare pathogens, but also damage host tissues. At presentation, patients often have a significant NET burden contributing to the multiorgan damage. Therefore, interventions that inhibit NET release would likely be ineffective at preventing NET-based injury. Treatments that enhance NET degradation may liberate captured bacteria and toxic NET degradation products (NDPs) and likely be of limited therapeutic benefit as well. We propose that interventions that stabilize NETs and sequester NDPs may be protective in sepsis. We showed that platelet factor 4 (PF4), a platelet-associated chemokine, binds and compacts NETs, increasing their resistance to DNase I. We now show that PF4 increases NET-mediated bacterial capture, reduces the release of NDPs, and improves outcome in murine models of sepsis. A monoclonal antibody KKO which binds to PF4-NET complexes, further enhances DNase resistance. However, the Fc portion of this antibody activates the immune response and increases thrombotic risk, negating any protective effects in sepsis. Therefore, we developed an Fc-modified KKO that does not induce these negative outcomes. Treatment with this antibody augmented the effects of PF4, decreasing NDP release and bacterial dissemination and increasing survival in murine sepsis models, supporting a novel NET-targeting approach to improve outcomes in sepsis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunoglobulina G/uso terapêutico , Sepse/tratamento farmacológico , Animais , Anticorpos Monoclonais/química , Células Cultivadas , Modelos Animais de Doenças , Feminino , Heparina/imunologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Fragmentos Fc das Imunoglobulinas/química , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Imunoglobulina G/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fator Plaquetário 4/genética , Fator Plaquetário 4/imunologia , Sepse/complicações , Sepse/imunologia , Trombocitopenia/induzido quimicamente , Trombocitopenia/complicações , Trombocitopenia/patologia , Trombocitopenia/terapia
4.
Blood ; 135(23): 2085-2093, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32187355

RESUMO

Thromboembolism complicates disorders caused by immunoglobulin G (IgG)-containing immune complexes (ICs), but the underlying mechanisms are incompletely understood. Prior evidence indicates that induction of tissue factor (TF) on monocytes, a pivotal step in the initiation, localization, and propagation of coagulation by ICs, is mediated through Fcγ receptor IIa (FcγRIIa); however, the involvement of other receptors has not been investigated in detail. The neonatal Fc receptor (FcRn) that mediates IgG and albumin recycling also participates in cellular responses to IgG-containing ICs. Here we asked whether FcRn is also involved in the induction of TF-dependent factor Xa (FXa) activity by IgG-containing ICs by THP-1 monocytic cells and human monocytes. Induction of FXa activity by ICs containing IgG antibodies to platelet factor 4 (PF4) involved in heparin-induced thrombocytopenia (HIT), ß-2-glycoprotein-1 implicated in antiphospholipid syndrome, or red blood cells coated with anti-(α)-Rh(D) antibodies that mediate hemolysis in vivo was inhibited by a humanized monoclonal antibody (mAb) that blocks IgG binding to human FcRn. IgG-containing ICs that bind to FcγR and FcRn induced FXa activity, whereas IgG-containing ICs with an Fc engineered to be unable to engage FcRn did not. Infusion of an α-FcRn mAb prevented fibrin deposition after microvascular injury in a murine model of HIT in which human FcγRIIa was expressed as a transgene. These data implicate FcRn in TF-dependent FXa activity induced by soluble and cell-associated IgG-containing ICs. Antibodies to FcRn, now in clinical trials in warm autoimmune hemolytic anemia to lower IgG antibodies and IgG containing ICs may also reduce the risk of venous thromboembolism.


Assuntos
Anticorpos Monoclonais Humanizados/imunologia , Heparina/toxicidade , Antígenos de Histocompatibilidade Classe I/metabolismo , Imunoglobulina G/metabolismo , Receptores Fc/metabolismo , Trombocitopenia/imunologia , Tromboplastina/metabolismo , Animais , Anticoagulantes/toxicidade , Complexo Antígeno-Anticorpo , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Masculino , Camundongos , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/patologia , Fator Plaquetário 4/genética , Fator Plaquetário 4/metabolismo , Receptores Fc/genética , Receptores Fc/imunologia , Trombocitopenia/induzido quimicamente , Trombocitopenia/metabolismo , Trombocitopenia/patologia
5.
Phys Rev Lett ; 122(19): 192502, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31144969

RESUMO

The change in mean-square nuclear charge radii δ⟨r^{2}⟩ along the even-A tin isotopic chain ^{108-134}Sn has been investigated by means of collinear laser spectroscopy at ISOLDE/CERN using the atomic transitions 5p^{2} ^{1}S_{0}→5p6 s^{1}P_{1} and 5p^{2} ^{3}P_{0}→5p6s ^{3}P_{1}. With the determination of the charge radius of ^{134}Sn and corrected values for some of the neutron-rich isotopes, the evolution of the charge radii across the N=82 shell closure is established. A clear kink at the doubly magic ^{132}Sn is revealed, similar to what has been observed at N=82 in other isotopic chains with larger proton numbers, and at the N=126 shell closure in doubly magic ^{208}Pb. While most standard nuclear density functional calculations struggle with a consistent explanation of these discontinuities, we demonstrate that a recently developed Fayans energy density functional provides a coherent description of the kinks at both doubly magic nuclei, ^{132}Sn and ^{208}Pb, without sacrificing the overall performance. A multiple correlation analysis leads to the conclusion that both kinks are related to pairing and surface effects.

6.
Nature ; 498(7454): 346-9, 2013 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-23783629

RESUMO

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.

7.
Phys Rev Lett ; 121(10): 102501, 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30240248

RESUMO

Differences in mean-square nuclear charge radii of ^{100-130}Cd are extracted from high-resolution collinear laser spectroscopy of the 5s ^{2}S_{1/2}→5p ^{2}P_{3/2} transition of the ion and from the 5s5p ^{3}P_{2}→5s6s ^{3}S_{1} transition in atomic Cd. The radii show a smooth parabolic behavior on top of a linear trend and a regular odd-even staggering across the almost complete sdgh shell. They serve as a first test for a recently established new Fayans functional and show a remarkably good agreement in the trend as well as in the total nuclear charge radius.

8.
FASEB J ; 31(2): 761-770, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27836986

RESUMO

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. Targeting thrombomodulin to circulating red blood cells augments its protective effects in models of endotoxemia and ischemia-reperfusion injury.


Assuntos
Endotoxemia/prevenção & controle , Eritrócitos/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Trombomodulina/administração & dosagem , Trombomodulina/uso terapêutico , Animais , Inflamação/tratamento farmacológico , Masculino , Proteínas de Fusão de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Trombomodulina/química
9.
Exp Cell Res ; 359(1): 163-170, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28778796

RESUMO

Filamin A (FLNA) is actin filament cross-linking protein involved in cancer progression. Its importance in regulating cell motility is directly related to the epithelial to mesenchymal transition (EMT) of tumor cells. However, little is known about the mechanism of action of FLNA at this early stage of cancer invasion. Using immunochemical methods, we evaluated the levels and localization of FLNA, pFLNA[Ser2152], ß1 integrin, pß1 integrin[Thr788/9], FAK, pFAK[Y379], and talin in stably transfected HT29 adenocarcinoma cells overexpressing Snail and looked for the effect of Snail in adhesion and migration assays on fibronectin-coated surfaces before and after FLNA silencing. Our findings indicate that FLNA upregulation correlates with Snail-induced EMT in colorectal carcinoma. FLNA localizes in the cytoplasm and at the sites of focal adhesion (FA) of invasive cells. Silencing of FLNA inhibits Snail-induced cell adhesion, reduces the size of FA sites, induces the relocalization of talin from the cytoplasm to the membrane area and augments cell migratory properties. Our findings suggest that FLNA may not act as a classic integrin inhibitor in invasive carcinoma cells, but is involved in other pro-invasive pathways. FLNA upregulation, which correlates with cell metastatic properties, maybe an additional target for combination therapy in colorectal carcinoma tumor progression.


Assuntos
Adenocarcinoma/patologia , Movimento Celular , Neoplasias do Colo/patologia , Transição Epitelial-Mesenquimal , Filaminas/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Regulação para Cima , Adenocarcinoma/metabolismo , Adesão Celular , Células Clonais , Neoplasias do Colo/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Adesões Focais , Inativação Gênica , Células HT29 , Humanos , Integrina beta1/metabolismo , Invasividade Neoplásica , Fosforilação
10.
Am J Respir Cell Mol Biol ; 56(2): 261-270, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27755915

RESUMO

Platelets and neutrophils contribute to the development of acute lung injury (ALI). However, the mechanism by which platelets make this contribution is incompletely understood. We investigated whether the two most abundant platelet chemokines, CXCL7, which induces neutrophil chemotaxis and activation, and CXCL4, which does neither, mediate ALI through complementary pathogenic pathways. To examine the role of platelet-derived chemokines in the pathogenesis of ALI using Cxcl7-/- and Cxcl4-/- knockout mice and mice that express human CXCL7 or CXCL4, we measured levels of chemokines in these mice. ALI was then induced by acid aspiration, and the severity of injury was evaluated by histology and by the presence of neutrophils and protein in the bronchoalveolar lavage fluid. Pulmonary vascular permeability was studied in vivo by measuring extravasation of fluorescently labeled dextran. Murine CXCL7, both recombinant and native protein released from platelets, can be N-terminally processed by cathepsin G to yield a biologically active CXCL7 fragment. Although Cxcl7-/- mice are protected from lung injury through the preservation of endothelial/epithelial barrier function combined with impaired neutrophils transmigration, Cxcl4-/- mice are protected through improved barrier function without affecting neutrophils transmigration to the airways. Sensitivity to ALI is restored by transgenic expression of CXCL7 or CXCL4. Platelet-derived CXCL7 and CXCL4 contribute to the pathogenesis of ALI through complementary effects on neutrophil chemotaxis and through activation and vascular permeability.


Assuntos
Lesão Pulmonar Aguda/sangue , Plaquetas/metabolismo , Quimiocinas CXC/sangue , Fator Plaquetário 4/sangue , Animais , Permeabilidade Capilar , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Camundongos Transgênicos
11.
Biochim Biophys Acta ; 1860(11 Pt A): 2445-2453, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27450890

RESUMO

BACKGROUND: The epithelial-mesenchymal transition (EMT) is considered a core process that facilitates the escape of cancer cells from the primary tumor site. The transcription factor Snail was identified as a key regulator of EMT; however, the cascade of regulatory events leading to metastasis remains unknown and new predictive markers of the process are awaited. METHODS: Gene expressions were analysed using real-time PCR, protein level by Western immunoblotting and confocal imaging. The motility of the cells was examined using time-lapse microscopy. Affymetrix GeneChip Human Genome U133 Plus 2.0 analysis was performed to identify transcriptomic changes upon Snail. Snail silencing was performed using siRNA nucleofection. NMU detection was performed by ELISA. RESULTS: HT29 cells overexpressing Snail showed changed morphology, functions and transcriptomic profile indicating EMT induction. Changes in expression of 324 genes previously correlated with cell motility were observed. Neuromedin U was the second highest upregulated gene in HT29-Snail cells. This increase was validated by real-time PCR. Additionally elevated NMU protein was detected by ELISA in cell media. CONCLUSIONS: These results show that Snail in HT29 cells regulates early phenotype conversion towards an intermediate epithelial state. We provided the first evidence that neuromedin U is associated with Snail regulatory function of metastatic induction in colon cancer cells. GENERAL SIGNIFICANCE: We described the global, early transcriptomic changes induced through Snail in HT29 colon cancer cells and suggested NMU involvement in this process.


Assuntos
Transição Epitelial-Mesenquimal , Neuropeptídeos/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Regulação para Cima , Células HT29 , Humanos , Neuropeptídeos/genética , Fatores de Transcrição da Família Snail/genética , Transcriptoma
12.
Blood ; 125(10): 1623-32, 2015 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-25477496

RESUMO

Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, bleeding diathesis, and other variable symptoms. The bleeding diathesis has been attributed to δ storage pool deficiency, reflecting the malformation of platelet dense granules. Here, we analyzed agonist-stimulated secretion from other storage granules in platelets from mouse HPS models that lack adaptor protein (AP)-3 or biogenesis of lysosome-related organelles complex (BLOC)-3 or BLOC-1. We show that α granule secretion elicited by low agonist doses is impaired in all 3 HPS models. High agonist doses or supplemental adenosine 5'-diphosphate (ADP) restored normal α granule secretion, suggesting that the impairment is secondary to absent dense granule content release. Intravital microscopy following laser-induced vascular injury showed that defective hemostatic thrombus formation in HPS mice largely reflected reduced total platelet accumulation and affirmed a reduced area of α granule secretion. Agonist-induced lysosome secretion ex vivo was also impaired in all 3 HPS models but was incompletely rescued by high agonist doses or excess ADP. Our results imply that (1) AP-3, BLOC-1, and BLOC-3 facilitate protein sorting to lysosomes to support ultimate secretion; (2) impaired secretion of α granules in HPS, and to some degree of lysosomes, is secondary to impaired dense granule secretion; and (3) diminished α granule and lysosome secretion might contribute to pathology in HPS.


Assuntos
Plaquetas/fisiologia , Síndrome de Hermanski-Pudlak/sangue , Complexo 3 de Proteínas Adaptadoras/deficiência , Complexo 3 de Proteínas Adaptadoras/genética , Complexo 3 de Proteínas Adaptadoras/fisiologia , Difosfato de Adenosina/farmacologia , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Degranulação Celular/fisiologia , Modelos Animais de Doenças , Fatores de Troca do Nucleotídeo Guanina , Síndrome de Hermanski-Pudlak/etiologia , Síndrome de Hermanski-Pudlak/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Lectinas/deficiência , Lectinas/genética , Lectinas/fisiologia , Lisossomos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Selectina-P/sangue , Proteínas SNARE/sangue , Vesículas Secretórias/fisiologia , Trombina/farmacologia , Trombose/sangue , Trombose/etiologia , Proteínas de Transporte Vesicular/deficiência , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/fisiologia
14.
Phys Rev Lett ; 116(3): 032501, 2016 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-26849588

RESUMO

Isomer shifts have been determined in ^{111-129}Cd by high-resolution laser spectroscopy at CERN-ISOLDE. The corresponding mean square charge-radii changes, from the 1/2^{+} and the 3/2^{+} ground states to the 11/2^{-} isomers, have been found to follow a distinct parabolic dependence as a function of the atomic mass number. Since the isomers have been previously associated with simplicity due to the linear mass dependence of their quadrupole moments, the regularity of the isomer shifts suggests a higher order of symmetry affecting the ground states in addition. A comprehensive description assuming nuclear deformation is found to accurately reproduce the radii differences in conjunction with the known quadrupole moments. This intuitive interpretation is supported by covariant density functional theory.

15.
Phys Rev Lett ; 116(18): 182502, 2016 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-27203317

RESUMO

Collinear laser spectroscopy is performed on the _{30}^{79}Zn_{49} isotope at ISOLDE-CERN. The existence of a long-lived isomer with a few hundred milliseconds half-life is confirmed, and the nuclear spins and moments of the ground and isomeric states in ^{79}Zn as well as the isomer shift are measured. From the observed hyperfine structures, spins I=9/2 and I=1/2 are firmly assigned to the ground and isomeric states. The magnetic moment µ (^{79}Zn)=-1.1866(10)µ_{N}, confirms the spin-parity 9/2^{+} with a νg_{9/2}^{-1} shell-model configuration, in excellent agreement with the prediction from large scale shell-model theories. The magnetic moment µ (^{79m}Zn)=-1.0180(12)µ_{N} supports a positive parity for the isomer, with a wave function dominated by a 2h-1p neutron excitation across the N=50 shell gap. The large isomer shift reveals an increase of the intruder isomer mean square charge radius with respect to that of the ground state, δ⟨r_{c}^{2}⟩^{79,79m}=+0.204(6) fm^{2}, providing first evidence of shape coexistence.

16.
Phys Rev Lett ; 115(23): 232501, 2015 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-26684113

RESUMO

Masses adjacent to the classical waiting-point nuclide ^{130}Cd have been measured by using the Penning-trap spectrometer ISOLTRAP at ISOLDE/CERN. We find a significant deviation of over 400 keV from earlier values evaluated by using nuclear beta-decay data. The new measurements show the reduction of the N=82 shell gap below the doubly magic ^{132}Sn. The nucleosynthesis associated with the ejected wind from type-II supernovae as well as from compact object binary mergers is studied, by using state-of-the-art hydrodynamic simulations. We find a consistent and direct impact of the newly measured masses on the calculated abundances in the A=128-132 region and a reduction of the uncertainties from the precision mass input data.

17.
Phys Rev Lett ; 114(20): 202501, 2015 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-26047224

RESUMO

The recently confirmed neutron-shell closure at N=32 has been investigated for the first time below the magic proton number Z=20 with mass measurements of the exotic isotopes (52,53)K, the latter being the shortest-lived nuclide investigated at the online mass spectrometer ISOLTRAP. The resulting two-neutron separation energies reveal a 3 MeV shell gap at N=32, slightly lower than for 52Ca, highlighting the doubly magic nature of this nuclide. Skyrme-Hartree-Fock-Bogoliubov and ab initio Gorkov-Green function calculations are challenged by the new measurements but reproduce qualitatively the observed shell effect.

18.
Arterioscler Thromb Vasc Biol ; 34(1): 120-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24177324

RESUMO

OBJECTIVE: Histones are detrimental in late sepsis. Both activated protein C (aPC) and heparin can reverse their effect. Here, we investigated whether histones can modulate aPC generation in a manner similar to another positively charged molecule, platelet factor 4, and how heparinoids (unfractionated heparin or oxygen-desulfated unfractionated heparin with marked decrease anticoagulant activity) may modulate this effect. APPROACH AND RESULTS: We measured in vitro and in vivo effects of histones, platelet factor 4, and heparinoids on aPC formation, activated partial thromboplastin time, and murine survival. In vitro, histones and platelet factor 4 both affect thrombin/thrombomodulin aPC generation following a bell-shaped curve, with a peak of >5-fold enhancement. Heparinoids shift these curves rightward. Murine aPC generation studies after infusions of histones, platelet factor 4, and heparinoids supported the in vitro data. Importantly, although unfractionated heparin and 2-O, 3-O desulfated heparin both reversed the lethality of high-dose histone infusions, only mice treated with 2-O, 3-O desulfated heparin demonstrated corrected activated partial thromboplastin times and had significant levels of aPC. CONCLUSIONS: Our data provide a new contextual model of how histones affect aPC generation, and how heparinoid therapy may be beneficial in sepsis. These studies provide new insights into the complex interactions controlling aPC formation and suggest a novel therapeutic interventional strategy.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Heparinoides/farmacologia , Histonas/sangue , Fator Plaquetário 4/sangue , Proteína C/metabolismo , Sepse/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Ativação Enzimática , Heparina/análogos & derivados , Heparina/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tempo de Tromboplastina Parcial , Fator Plaquetário 4/deficiência , Fator Plaquetário 4/genética , Sepse/sangue , Sepse/enzimologia , Trombina/metabolismo , Trombomodulina/metabolismo
19.
Int J Cosmet Sci ; 37(4): 408-16, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25704610

RESUMO

OBJECTIVE: The aim of the study was to determine the optimal conditions, that is the content of hemp oil and time of homogenization to obtain stable dispersion systems. METHODS: For this purpose, six emulsions were prepared, their stability was examined empirically and the most correctly formulated emulsion composition was determined using a computer simulation. Variable parameters (oil content and homogenization time) were indicated by the optimization software based on Kleeman's method. Physical properties of the synthesized emulsions were studied by numerous techniques involving particle size analysis, optical microscopy, Turbiscan test and viscosity of emulsions. RESULTS: The emulsion containing 50 g of oil and being homogenized for 6 min had the highest stability. Empirically determined parameters proved to be consistent with the results obtained using the computer software. The computer simulation showed that the most stable emulsion should contain from 30 to 50 g of oil and should be homogenized for 2.5-6 min. CONCLUSIONS: The computer software based on Kleeman's method proved to be useful for quick optimization of the composition and production parameters of stable emulsion systems. Moreover, obtaining an emulsion system with proper stability justifies further research extended with sensory analysis, which will allow the application of such systems (containing hemp oil, beneficial for skin) in the cosmetic industry.


Assuntos
Cannabis , Cosméticos , Estabilidade de Medicamentos , Emulsões , Óleos de Plantas/análise
20.
Int J Cosmet Sci ; 37(1): 82-91, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25319767

RESUMO

OBJECTIVE: Formation of emulsion systems based on interesterified fats was the objective of the study. Enzymatic interesterification was carried out between enzymatic mutton tallow and walnut oil in the proportions 2 : 3 (w/w) to produce fats not available in nature. At the beginning of the interesterification process, the balance between the interesterification and fat hydrolysis was intentionally disturbed by adding more water to the catalyst (Lipozyme IR MR) of the reaction to produce more of the polar fraction monoacylglycerols [MAGs] and diacylglycerols [DAGs]. To obtain a greater quantity of MAGs and DAGs in the reaction environment via hydrolysis, water was added (11, 13, 14, 16 w-%) to the enzymatic preparation. The obtained fats were used to form emulsions. METHODS: The emulsions were evaluated with respect to sensory and skin moisturizing properties by 83 respondents. Determination of emulsion stability using temperature and centrifugal tests was carried out. Morphology and the type of emulsions were determined. RESULTS: The respondents described the skin to which the emulsions in testing were applied as smooth, pleasant to touch and adequately moisturized. CONCLUSIONS: The work has demonstrated that interesterification of a mutton tallow and walnut oil blend resulted in new fats with very interesting characteristics of triacylglycerols that are not present in the environment. The results of the present work indicate the possibility of application of fats with the largest quantity of MAGs and DAGs as a fat base of emulsions in the cosmetic industries. The hypothesis assumed in this work of producing additional quantities of MAGs and DAGs (in the process of enzymatic interesterification) responsible for the stability of the system was confirmed. It should be pointed out that the emulsions based on interesterified fats exhibited a greater level of moisturization of the skin than the emulsions containing non-interesterified fat. Also, in the respondents' opinion, the emulsion containing fat, which was modified during enzymatic interesterification when 13% of water was added to the enzymatic preparation, exhibited the best sensory profile.


Assuntos
Cosméticos , Emulsões , Gorduras/química , Juglans/química , Óleos de Plantas/química , Animais , Esterificação , Ovinos
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