The self-assembly of nanoscale elements into three-dimensional structures with precise shapes and sizes is important in fields such as nanophotonics, metamaterials and biotechnology. Short molecular ...linkers have previously been used to create assemblies of nanoparticles, but the approach is limited to small interparticle distances, typically less than 10 nm. Alternatively, DNA origami can precisely organize nanoscale objects over much larger length scales. Here we show that rigid DNA origami scaffolds can be used to assemble metal nanoparticles, quantum dots and organic dyes into hierarchical nanoclusters that have a planet-satellite-type structure. The nanoclusters have a tunable stoichiometry, defined distances of 5-200 nm between components, and controllable overall sizes of up to 500 nm. We also show that the nanoscale components can be positioned along the radial DNA spacers of the nanostructures, which allows short- and long-range interactions between nanoparticles and dyes to be studied in solution. The approach could, in the future, be used to construct efficient energy funnels, complex plasmonic architectures, and porous, nanoengineered scaffolds for catalysis.
We report that plasmonic nanoantennas made by DNA origami can be used as reliable and efficient probes for surface-enhanced Raman spectroscopy (SERS). The nanoantenna is built up by two gold ...nanoparticles that are linked together by a three-layered DNA origami block at a separation distance of 6 nm in order to achieve plasmonic coupling and the formation of a plasmonic “hot spot”. The plasmonic properties of the hybrid structure are optically characterized by dark-field imaging and polarization-dependent spectroscopy. SERS measurements on molecules that are embedded in the DNA origami that bridges the nanoantenna gap were performed in order to demonstrate the excellent performance of these structures for enhancing spectroscopic signals. A strong enhancement of the Raman signal was recorded from measurements on single hot spots compared to measurements in bulk. Finally, we show that the laser polarization with respect to the dimer orientation has a strong impact on the SERS performance.
Bacterial nanocellulose (BNC), synthesized by the bacterium Gluconacetobacter xylinus, is composed of highly hydrated fibrils (99 % water) with high mechanical strength. These exceptional material ...properties make BNC a novel biomaterial for many potential medical and tissue engineering applications. Recently, BNC with cellulose content of 15 % has been proposed as an implant material for auricular cartilage replacement, since it matches the mechanical requirements of human auricular cartilage. This study investigates the biocompatibility of BNC with increased cellulose content (17 %) to evaluate its response in vitro and in vivo. Cylindrical BNC structures (Ø48 × 20 mm) were produced, purified in a built-in house perfusion system, and compressed to increase the cellulose content in BNC hydrogels. The reduction of endotoxicity of the material was quantified by bacterial endotoxin analysis throughout the purification process. Afterward, the biocompatibility of the purified BNC hydrogels with cellulose content of 17 % was assessed in vitro and in vivo, according to standards set forth in ISO 10993. The endotoxin content in non-purified BNC (2,390 endotoxin units (EU)/ml) was reduced to 0.10 EU/ml after the purification process, level well below the endotoxin threshold set for medical devices. Furthermore, the biocompatibility tests demonstrated that densified BNC hydrogels are non-cytotoxic and cause a minimal foreign body response. In support with our previous findings, this study concludes that BNC with increased cellulose content of 17 % is a promising non-resorbable biomaterial for auricular cartilage tissue engineering, due to its similarity with auricular cartilage in terms of mechanical strength and host tissue response.
Acute optic neuritis treatment lacks standardized protocols. The value of oral prednisone taper (OPT) following intravenous methylprednisolone (IVMP) on visual outcome parameters in optic neuritis ...(ON) has never been explored. In the present retrospective study, we investigated whether OPT after IVMP affects the structural and functional visual outcomes of inaugural clinically isolated syndrome (CIS)- or multiple sclerosis (MS)-ON. Adult patients with acute, inaugural, unilateral CIS- or MS-ON, treated with IVMP in Germany and Israel were stratified into patients treated with IVMP alone-versus IVMP and OPT. Inclusion criteria were age ≥18, CIS or MS diagnosis according to McDonald criteria 2017, available visual acuity (VA) at nadir before treatment initiation and at follow-up ≥5 months, as well as a spectral domain optic coherence tomography (OCT) data scan at follow-up. Exclusion criteria included recurrent ON, concomitant ophthalmological comorbidities, optical coherence tomography (OCT) of insufficient quality and ON-related escalation therapy after IVMP. The structural outcome was defined as the average retinal nerve fiber layer (RNFL) difference between the ON-affected and the unaffected eye, while the functional outcome was defined as the final high-contrast best-corrected VA (HC-BCVA) at follow-up compared to nadir. The comparative analysis was performed using linear regression analysis, adjusted for sex, age, and days-to-treatment. Fifty-one patients met the inclusion criteria (25% male). The mean age was 33.9 (±10.23) years. Twenty-six patients (51%) received OPT following IVMP. There was no difference in nadir HC-BCVA between the groups (0.39 No OPT; 0.49 With OPT, P = 0.36). Adjusted linear regression analysis did not indicate an influence of OPT on RNFL thickness or on HC-BCVA (beta coefficient for RNFL difference in percentages: 0.51, 95%-CI: -4.58, 5.59, beta coefficient for logMAR: 0.11, 95%; CI -0.12, 0.35 at follow-up. In conclusion, the addition of OPT to IVMP did not affect RNFL thickness or the final VA in a retrospective cohort of 51 patients with inaugural acute CIS- or MS-ON. The results of this exploratory study are currently being re-examined in a large-scale, demographically diverse, prospective study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A bridging chloride anion between two electrophilic phosphorus centers was observed for the first time in the molecular structure of the novel P–P bonded cation LDipp 2P2Cl3+ (2 + ; LDipp = ...1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene). Cation 2 + is prepared by the reduction of the monophosphorus species LDippPCl2+ (1 + ) with sodium. DFT calculations, AIM and mechanochemical (compliance constants) analyses are used to examine the bonding situation of this unusual species. The monochloro-substituted cation LDipp 2P2Cl+ (3 + ) was likewise observed as a reduction product of 1 + .
CNS myelination by oligodendrocytes requires directed transport of myelin membrane components and a timely and spatially controlled membrane expansion. In this study, we show the functional ...involvement of the R-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (R-SNARE) proteins VAMP3/cellubrevin and VAMP7/TI-VAMP in myelin membrane trafficking. VAMP3 and VAMP7 colocalize with the major myelin proteolipid protein (PLP) in recycling endosomes and late endosomes/lysosomes, respectively. Interference with VAMP3 or VAMP7 function using small interfering RNA-mediated silencing and exogenous expression of dominant-negative proteins diminished transport of PLP to the oligodendroglial cell surface. In addition, the association of PLP with myelin-like membranes produced by oligodendrocytes cocultured with cortical neurons was reduced. We furthermore identified Syntaxin-4 and Syntaxin-3 as prime acceptor Q-SNAREs of VAMP3 and VAMP7, respectively. Analysis of VAMP3-deficient mice revealed no myelination defects. Interestingly, AP-3δ-deficient mocha mice, which suffer from impaired secretion of lysosome-related organelles and missorting of VAMP7, exhibit a mild dysmyelination characterized by reduced levels of select myelin proteins, including PLP. We conclude that PLP reaches the cell surface via at least two trafficking pathways with distinct regulations: (1) VAMP3 mediates fusion of recycling endosome-derived vesicles with the oligodendroglial plasma membrane in the course of the secretory pathway; (2) VAMP7 controls exocytosis of PLP from late endosomal/lysosomal organelles as part of a transcytosis pathway. Our in vivo data suggest that exocytosis of lysosome-related organelles controlled by VAMP7 contributes to myelin biogenesis by delivering cargo to the myelin membrane.
Like a fingerprint, ear shape is a unique personal feature that should be reconstructed with a high fidelity during reconstructive surgery. Ear cartilage tissue engineering (TE) advantageously offers ...the possibility to use novel 3D manufacturing techniques to reconstruct the ear, thus allowing for a detailed auricular shape. However it also requires detailed patient-specific images of the 3D cartilage structures of the patient's intact contralateral ear (if available). Therefore the aim of this study was to develop and evaluate an imaging strategy for acquiring patient-specific ear cartilage shape, with sufficient precision and accuracy for use in a clinical setting.
Magnetic resonance imaging (MRI) was performed on 14 volunteer and six cadaveric auricles and manually segmented. Reproducibility of cartilage volume (Cg.V), surface (Cg.S) and thickness (Cg.Th) was assessed, to determine whether raters could repeatedly define the same volume of interest. Additionally, six cadaveric auricles were harvested, scanned and segmented using the same procedure, then dissected and scanned using high resolution micro-CT. Correlation between MR and micro-CT measurements was assessed to determine accuracy.
Good inter- and intra-rater reproducibility was observed (precision errors <4% for Cg.S and <9% for Cg.V and Cg.Th). Intraclass correlations were good for Cg.V and Cg.S (>0.82), but low for Cg.Th (<0.23) due to similar average Cg.Th between patients. However Pearson's coefficients showed that the ability to detect local cartilage shape variations is unaffected. Good correlation between clinical MRI and micro-CT (r>0.95) demonstrated high accuracy.
This study demonstrated that precision and accuracy of the proposed method was high enough to detect patient-specific variation in ear cartilage geometry. The present study provides a clinical strategy to access the necessary information required for the production of 3D ear scaffolds for TE purposes, including detailed patient-specific shape. Furthermore, the protocol is applicable in daily clinical practice with existing infrastructure.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, we investigated the effects of human primary chondrocytes, derived from routine septorhino- and otoplasties on a novel nondegradable biomaterial. This biomaterial, porous bacterial ...nanocellulose, is produced by Gluconacetobacter xylinus. Porosity is generated by paraffin beads embedded during the fermentation process. Human primary chondrocytes were able to adhere to bacterial nanocellulose and produce cartilaginous matrix proteins such as aggrecan (after 14 days) and collagen type II (after 21 days) in the presence of differentiation medium. Cells were located within the pores and in a dense cell layer covering the surface of the biomaterial. Cells were able to re-differentiate, as cell shape and extra cellular matrix gene expression showed a chondrogenic phenotype in three-dimensional bacterial nanocellulose culture. Collagen type I and versican expression decreased during three-dimensional culture. Variations in pore sizes of 150–300 µm and 300–500 µm did not influence cartilaginous extra cellular matrix synthesis. Varying seeding densities from 9.95 × 102 to 1.99 × 103 cells/mm2 and 3.98 × 103 cells/mm2 did not result in differences in quality of extra cellular matrix neo-synthesis. Our results demonstrated that both nasal and auricular chondrocytes are equally suitable to synthesize new extra cellular matrix on bacterial nanocellulose. Therefore, we propose both cell sources in combination with bacterial nanocellulose as promising candidates for the special needs of auricular reconstruction.
We have recently described a novel modular targeting platform for T cell recruitment that not only efficiently replaces but also is superior to conventional T cell-engaging bispecific antibodies as ...it allows for the flexible targeting of several antigens and the delivery of co-stimulatory ligands to malignant lesions, thereby enhancing the antitumor potential of redirected T cells.
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