- Systematical study of the mechanistic factors regulating genome dynamics in vivo by CRISPRsie. [Journal Article]
- JMJ Mol Cell Biol 2019 Jul 22
- Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase. [Journal Article]
- NatNature 2019 Jul 22
- The bacterial pathogen Legionella pneumophila creates an intracellular niche permissive for its replication by extensively modulating host cell functions using hundreds of effector proteins delivered…
The bacterial pathogen Legionella pneumophila creates an intracellular niche permissive for its replication by extensively modulating host cell functions using hundreds of effector proteins delivered via its Dot/Icm secretion system1. Among these, members of the SidE family (SidEs) regulate multiple cellular processes by a unique phosphoribosyl ubiquitination mechanism that bypasses the canonical ubiquitination machinery2-4. The activity of SidEs is regulated by SidJ, another Dot/Icm effector5, but the mechanism of such regulation is not completely understood6,7. Here we demonstrate that SidJ inhibits the activity of SidEs by inducing covalent attachment of glutamate moieties to E860 of SdeA, which is one of the catalytic residues for the mono-ADP-ribosyltransferase activity involved in ubiquitin activation2. The inhibition by SidJ is spatially restricted in host cells because its activity requires the eukaryote-specific protein calmodulin (CaM). We solved a structure of SidJ-CaM in complex with adenosine monophosphate (AMP) and found that the ATP utilized is cleaved at the α phosphate position by SidJ which in the absence of glutamate or modifiable SdeA undergoes self-AMPylation. Our results reveal an unprecedented mechanism of regulation in bacterial pathogenicity in which a glutamylation reaction that inhibits the activity of virulence factors is activated by host factor-dependent acyl-adenylation.
- Dual-specificity phosphatase (DUSP) genetic variants predict pulmonary hypertension in patients with bronchopulmonary dysplasia. [Journal Article]
- PRPediatr Res 2019 Jul 22
- CONCLUSIONS: We identified three DUSP SNPs as potential BPD-PH biomarkers. Combining clinical and DUSP genetic data yields the most robust predictor for PH in BPD.
- Overcoming Tamoxifen Resistance by Regulation of Del-1 in Breast Cancer. [Journal Article]
- OOncology 2019 Jul 22; :1-9
- CONCLUSIONS: TAM-R breast cancer is characterized by Del-1 overexpression and tumor progression can be inhibited by Del-1 depletion, which restores TAM sensitivity. Thus, therapeutic strategies that target Del-1 may be effective for the treatment of hormone-resistant breast cancer.
- Pharmacological characterization of the seven human NOX isoforms and their inhibitors. [Journal Article]
- RBRedox Biol 2019 Jul 11; 26:101272
- CONCLUSIONS: Our findings indicate that experimental results obtained with widely used NOX inhibitors must be carefully interpreted and highlight the challenge of developing reliable pharmacological inhibitors of these key molecular targets.
- Dynamics of postural control during bilateral stance - Effect of support area, visual input and age. [Journal Article]
- HMHum Mov Sci 2019 Jul 19; 67:102462
- The present study investigated the effect of support area, visual input and aging of the dynamics of postural control during bilateral stance. Fifteen young (22.1 ± 1.7 years) and fifteen older (68.3…
The present study investigated the effect of support area, visual input and aging of the dynamics of postural control during bilateral stance. Fifteen young (22.1 ± 1.7 years) and fifteen older (68.3 ± 2.7 years) individuals completed four different 90 s bilateral stance trials: 1) shoulder wide feet distance with eyes open, 2) shoulder wide feet distance with eyes closed, 3) narrow feet distance with eyes open, and 4) narrow feet distance with eyes closed on a force plate form. The anterior (AP) and mediolateral (ML) center of pressure (COP) trajectories were calculated from the middle 60 s of the ground reaction forces and moments. Sample entropy (SaEn), correlation dimension (CoD), the largest Lyapunov exponent (LyE) and entropic half-life (ENT½) were calculated for the COP in both directions. In young individuals, a narrower support area resulted in a restricted movement solution space with lower SaEn, lower LyE and longer ENT½ in the executed motor control strategy, whereas it increased the CoD in the older individuals. During the eyes closed trials, SaEn, CoD and LyE increased and decreased ENT½ for both groups in the AP direction and increased SaEn and LyE in the ML direction for the older individuals alone. This indicates that aging is associated with direction- and task-dependent changes in the dynamics of the executed COP movements during postural stance tasks.
- Layer-specific hyperelastic and viscoelastic characterization of human descending thoracic aortas. [Journal Article]
- JMJ Mech Behav Biomed Mater 2019 Jul 15; 99:27-46
- A layer-specific hyperelastic and viscoelastic characterization of human descending thoracic aortas was experimentally performed. Healthy aortas from twelve beating heart donors with an average age o…
A layer-specific hyperelastic and viscoelastic characterization of human descending thoracic aortas was experimentally performed. Healthy aortas from twelve beating heart donors with an average age of 49.4 years, were received from Transplant Québec. Axial and circumferential strips were prepared from the specimens. They were dissected into intima, media and adventitia layers. Measurements of the opening angles were used to identify the circumferential residual stresses. Uniaxial tensile tests on axial and circumferential strips, together with the Gasser-Ogden-Holzapfel material model, were used to characterize the hyperelastic behaviour of the three aortic layers for each donor. Uniaxial harmonic excitations at different frequency, superimposed to initial stretch values, were used to characterize the viscoelastic behaviour. The storage modulus and the loss tangent were obtained for each layer in both directions; comparison to intact aortic wall was also performed. The generalized Maxwell model, within the framework of nonlinear viscoelasticity with internal variables, was used to obtain the constitutive material parameters. Results showed a positive correlation (p < 0.05 for circumferential media and adventitia) between stiffness and donor age for the three layers of the aorta in both axial and circumferential directions. A significant increase (around 50%) of the storage modulus (i.e. dynamic stiffness) was observed between the quasi-static value and loading at 1 Hz frequency, while further increase in frequency marginally affected its value. The loss tangent was only slightly influenced by the stretch value, which justified the use of the viscoelastic model adopted. Finally, similar loss tangent values were found for the three aortic layers.
- Novel PNIPAm-based electrospun nanoﬁbres used directly as a drug carrier for "on-off" switchable drug release. [Journal Article]
- CSColloids Surf B Biointerfaces 2019 Jul 08; 182:110347
- Stimuli-responsive smart polymers have been studied extensively. In this work, thermoresponsive poly (N-isopropylacrylamide-N-methylolacrylamide-acrylamide) (PNIPAm-NMA-Am) was successfully synthesis…
Stimuli-responsive smart polymers have been studied extensively. In this work, thermoresponsive poly (N-isopropylacrylamide-N-methylolacrylamide-acrylamide) (PNIPAm-NMA-Am) was successfully synthesised via radical polymerisation, as confirmed by proton nuclear magnetic resonance and fourier transform infrared spectroscopy. PNIPAm-NMA-Am was electrospun into nanoﬁbres, allowing its use as a drug carrier after simple thermal treatment. Thermogravimetric analysis, scanning electron microscopy, and atomic force microscopy results also revealed that the as-prepared PNIPAm-NMA-Am nanofibres have a uniform small diameter, good thermal stability and excellent integrity in aqueous environments. Additionally, the properties of this PNIPAm-NMA-Am nanofibres were tunable with temperature changes below and above the lower critical solution temperature of 48 °C. The drug release properties of PNIPAm-NMA-Am10 nanofibres as a drug carrier were studied via ultraviolet-visible spectroscopy and the results showed that 80% of the drug was released from the nanofibres after six heating and cooling (60-10 °C) cycles within 60 min. Only a small amount of the drug was released during the cooling process, which directly demonstrates "on-off" functionality of PNIPAm-NMA-Am nanofibres for controlled drug release. Finally, cell culture studies indicated that the PNIPAm-NMA-Am nanoﬁbres have not cytotoxicity. Thus, the novel PNIPAm-NMA-Am nanofibres show great potential in the biomedical ﬁeld as drug carriers.
- Degradable dendritic nanogels as carriers for antimicrobial peptides. [Journal Article]
- JCJ Colloid Interface Sci 2019 Jul 13; 554:592-602
- In the present study, we investigate degradable anionic dendritic nanogels (DNG) as carriers for antimicrobial peptides (AMPs). In such systems, the dendritic part contains carboxylic acid-based anio…
In the present study, we investigate degradable anionic dendritic nanogels (DNG) as carriers for antimicrobial peptides (AMPs). In such systems, the dendritic part contains carboxylic acid-based anionic binding sites for cationic AMPs, whereas linear poly(ethylene glycol) (PEG) chains form a shell for promotion of biological stealth. In order to clarify factors influencing membrane interactions of such systems, we here address effects of nanogel charge, cross-linking, and degradation on peptide loading/release, as well as consequences of these factors for lipid membrane interactions and antimicrobial effects. The DNGs were found to bind the AMPs LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) and DPK-060 (GKHKNKGKKNGKHNGWKWWW). For the smaller DPK-060 peptide, loading was found to increase with increasing nanogel charge density. For the larger LL-37, on the other hand, peptide loading was largely insensitive to nanogel charge density. In line with this, results on the secondary structure, as well as on the absence of stabilization from proteolytic degradation by the nanogels, show that the larger LL-37 is unable to enter into the interior of the nanogels. While 40-60% nanogel degradation occurred over 10 days, promoted at high ionic strength and lower cross-linking density/higher anionic charge content, peptide release at physiological ionic strength was substantially faster, and membrane destabilization not relying on nanogel degradation. Ellipsometry and liposome leakage experiments showed both free peptide and peptide/DNG complexes to cause membrane destabilization, indicated also by antimicrobial activities being comparable for nanogel-bound and free peptide. Finally, the DNGs were demonstrated to display low toxicity towards erythrocytes even at peptide concentrations of 100 µM.
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- Synthesis, functionalization and properties of uniform europium-doped sodium lanthanum tungstate and molybdate (NaLa(XO4)2, X = Mo,W) probes for luminescent and X-ray computed tomography bioimaging. [Journal Article]
- JCJ Colloid Interface Sci 2019 Jul 13; 554:520-530
- A one-pot simple procedure for the synthesis of uniform, ellipsoidal Eu3+-doped sodium lanthanum tungstate and molybdate (NaLa(XO4)2, X = W, Mo) nanophosphors, functionalized with carboxylate groups…
A one-pot simple procedure for the synthesis of uniform, ellipsoidal Eu3+-doped sodium lanthanum tungstate and molybdate (NaLa(XO4)2, X = W, Mo) nanophosphors, functionalized with carboxylate groups, is described. The method is based on a homogeneous precipitation process at 120 °C from appropriate Na+, Ln3+ and tungstate or molybdate precursors dissolved in ethylene glycol/water mixtures containing polyacrylic acid. A comparative study of the luminescent properties of both luminescent materials as a function of the Eu3+ doping level has been performed to find the optimum nanophosphor, whose efficiency as X-ray computed tomography contrast agent is also evaluated and compared with that of a commercial probe. Finally, the cell viability and colloidal stability in physiological pH medium of the optimum samples have also been studied to assess their suitability for biomedical applications.