| 1. |
- Sampson, Joshua N., et al.
(författare)
-
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
|
|
| 2. |
- Wang, Zhaoming, et al.
(författare)
-
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
|
|
| 3. |
- Jacobs, Kevin B, et al.
(författare)
-
Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
-
Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
-
Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
|
|
| 4. |
- Sigmundsson, Kristmundur, et al.
(författare)
-
Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice.
- 2018
-
Ingår i: Matrix Biology. - : Elsevier BV. - 0945-053X .- 1569-1802. ; 70, s. 5-19
-
Tidskriftsartikel (refereegranskat)abstract
- The efficacy of islet transplantation for diabetes treatment suffers from lack of cadaver-derived islets, islet necrosis and long transfer times prior to transplantation. Here, we developed a method for culturing mouse and human islets in vitro on α5-laminins, which are natural components of islet basement membranes. Adhering islets spread to form layers of 1-3 cells in thickness and remained normoxic and functional for at least 7 days in culture. In contrast, spherical islets kept in suspension developed hypoxia and central necrosis within 16 h. Transplantation of 110-150 mouse islets cultured on α5-laminin-coated polydimethylsiloxane membranes for 3-7 days normalized blood glucose already within 3 days in mice with streptozotocin-induced diabetes. RNA-sequencing of isolated and cultured mouse islets provided further evidence for the adhesion and spreading achieved with α5-laminin. Our results suggest that use of such in vitro expanded islets may significantly enhance the efficacy of islet transplantation treatment for diabetes.
|
|
| 5. |
- Barriga, Hanna M. G., et al.
(författare)
-
Coupling Lipid Nanoparticle Structure and Automated Single-Particle Composition Analysis to Design Phospholipase-Responsive Nanocarriers
- 2022
-
Ingår i: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 34:26
-
Tidskriftsartikel (refereegranskat)abstract
- Lipid nanoparticles (LNPs) are versatile structures with tunable physicochemical properties that are ideally suited as a platform for vaccine delivery and RNA therapeutics. A key barrier to LNP rational design is the inability to relate composition and structure to intracellular processing and function. Here Single Particle Automated Raman Trapping Analysis (SPARTA) is combined with small-angle X-ray and neutron scattering (SAXS/SANS) techniques to link LNP composition with internal structure and morphology and to monitor dynamic LNP-phospholipase D (PLD) interactions. This analysis demonstrates that PLD, a key intracellular trafficking mediator, can access the entire LNP lipid membrane to generate stable, anionic LNPs. PLD activity on vesicles with matched amounts of enzyme substrate is an order of magnitude lower, indicating that the LNP lipid membrane structure can be used to control enzyme interactions. This represents an opportunity to design enzyme-responsive LNP solutions for stimuli-responsive delivery and diseases where PLD is dysregulated.
|
|
| 6. |
- ovrebo, Oystein, et al.
(författare)
-
RegiSTORM : channel registration for multi-color stochastic optical reconstruction microscopy
- 2023
-
Ingår i: BMC Bioinformatics. - : BMC. - 1471-2105. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Stochastic optical reconstruction microscopy (STORM), a super-resolution microscopy technique based on single-molecule localizations, has become popular to characterize sub-diffraction limit targets. However, due to lengthy image acquisition, STORM recordings are prone to sample drift. Existing cross-correlation or fiducial marker-based algorithms allow correcting the drift within each channel, but misalignment between channels remains due to interchannel drift accumulating during sequential channel acquisition. This is a major drawback in multi-color STORM, a technique of utmost importance for the characterization of various biological interactions.Results: We developed RegiSTORM, a software for reducing channel misalignment by accurately registering STORM channels utilizing fiducial markers in the sample. RegiSTORM identifies fiducials from the STORM localization data based on their non-blinking nature and uses them as landmarks for channel registration. We first demonstrated accurate registration on recordings of fiducials only, as evidenced by significantly reduced target registration error with all the tested channel combinations. Next, we validated the performance in a more practically relevant setup on cells multi-stained for tubulin. Finally, we showed that RegiSTORM successfully registers two-color STORM recordings of cargo-loaded lipid nanoparticles without fiducials, demonstrating the broader applicability of this software.Conclusions: The developed RegiSTORM software was demonstrated to be able to accurately register multiple STORM channels and is freely available as open-source (MIT license) at https://github.com/oystein676/RegiSTORM.git and https://doi.org/10.5281/ zenodo.5509861 (archived), and runs as a standalone executable (Windows) or via Python (Mac OS, Linux).
|
|
| 7. |
- Sych, Taras, et al.
(författare)
-
High-throughput measurement of the content and properties of nano-sized bioparticles with single-particle profiler
- 2024
-
Ingår i: Nature Biotechnology. - : Nature Publishing Group. - 1087-0156 .- 1546-1696. ; 42:4
-
Tidskriftsartikel (refereegranskat)abstract
- Lipid nanoparticles, viruses, exosomes and liposomes are characterized by analysis of fluorescence fluctuations. We introduce a method, single-particle profiler, that provides single-particle information on the content and biophysical properties of thousands of particles in the size range 5-200 nm. We use our single-particle profiler to measure the messenger RNA encapsulation efficiency of lipid nanoparticles, the viral binding efficiencies of different nanobodies, and the biophysical heterogeneity of liposomes, lipoproteins, exosomes and viruses.
|
|
| 8. |
- Utterström, Johanna, et al.
(författare)
-
Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles
- 2022
-
Ingår i: Bioconjugate chemistry. - : AMER CHEMICAL SOC. - 1043-1802 .- 1520-4812. ; 33:4, s. 736-746
-
Tidskriftsartikel (refereegranskat)abstract
- Liposome-based drug delivery systems are widely used to improve drug pharmacokinetics but can suffer from slow and unspecific release of encapsulated drugs. Membrane-active peptides, based on sequences derived or inspired from antimicrobial peptides (AMPs), could offer means to trigger and control the release. Cholesterol is used in most liposomal drug delivery systems (DDS) to improve the stability of the formulation, but the activity of AMPs on cholesterol-rich membranes tends to be very low, complicating peptide-triggered release strategies. Here, we show a de novo designed AMP-mimetic peptide that efficiently triggers content release from cholesterol-containing lipid vesicles when covalently conjugated to headgroup-functionalized lipids. Binding to vesicles induces peptide folding and triggers a lipid phase separation, which in the presence of cholesterol results in high local peptide concentrations at the lipid bilayer surface and rapid content release. We anticipate that these results will facilitate the development of peptide-based strategies for controlling and triggering drug release from liposomal drug delivery systems.
|
|
| 9. |
- Aili, Daniel, et al.
(författare)
-
Bioresponsive peptide-inorganic hybrid nanomaterials
- 2010
-
Ingår i: Chemical Society Reviews. - : Royal Society of Chemistry. - 0306-0012 .- 1460-4744. ; 39:9, s. 3358-3370
-
Forskningsöversikt (refereegranskat)abstract
- Bioanalytical techniques that enable simple, fast and reliable high sensitivity monitoring of biomolecular interactions are of immense importance for diagnostics and drug development. This tutorial review provides an overview of recent progress in the development of peptide-based hybrid nanomaterials that transduce molecular interactions by exploiting the optical and magnetic properties of nanoparticles. Peptides have emerged as an interesting alternative to conventional biomolecular receptors, such as antibodies, and are facilitating the design of responsive hybrid nanomaterials that are both robust and sensitive for biodiagnostic applications.
|
|
| 10. |
- Aili, Daniel, et al.
(författare)
-
Hybrid Nanoparticle-Liposome Detection of Phospholipase Activity
- 2011
-
Ingår i: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 11:4, s. 1401-1405
-
Tidskriftsartikel (refereegranskat)abstract
- A flexible nanoparticle-based phospholipase (PL) assay is demonstrated in which the enzymatic substrate is decoupled from the nanoparticle surface. Liposomes are loaded with a polypeptide that is designed to heteroassociate with a second polypeptide immobilized on gold nanoparticies. Release of this polypeptide from the liposornes, triggered by PL, induces a folding-dependent nanoparticle bridging aggregation. The colorimetric response from this aggregation enables straightforward and continuous detection of PL in the picomolar range. The speed, specificity, and flexibility of this assay make it appropriate for a range of applications, from point of care diagnostics to high throughput pharmaceutical screening.
|
|
| 11. |
- Aili, Daniel, et al.
(författare)
-
Polypeptide Folding-Mediated Tuning of the Optical and Structural Properties of Gold Nanoparticle Assemblies
- 2011
-
Ingår i: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 11:12, s. 5564-5573
-
Tidskriftsartikel (refereegranskat)abstract
- Responsive hybrid nanomaterials with well-defined properties are of significant interest for the development of biosensors with additional applications in tissue engineering and drug delivery. Here, we present a detailed characterization using UV-vis spectroscopy and small angle X-ray scattering of a hybrid material comprised of polypeptide-decorated gold nanoparticles with highly controllable assembly properties. The assembly is triggered by a folding-dependent bridging of the particles mediated by the heteroassociation of immobilized helix-loop-helix polypeptides and a complementary nonlinear polypeptide present in solution. The polypeptides are de novo designed to associate and fold into a heterotrimeric complex comprised of two disulfide-linked four-helix bundles. The particles form structured assemblies with a highly defined interparticle gap (4.8 +/- 0.4 nm) that correlates to the size of the folded polypeptides. Transitions in particle aggregation dynamics, mass-fractal dimensions and ordering, as a function of particle size and the concentration of the bridging polypeptide, are observed; these have significant effects on the optical properties of the assemblies. The assembly and ordering of the particles are highly complex processes that are affected by a large number of variables including the number of polypeptides bridging the particles and the particle mobility within the aggregates. A fundamental understanding of these processes is of paramount interest for the development of novel hybrid nanomaterials with tunable structural and optical properties and for the optimization of nanoparticle-based colorimetric biodetection strategies.
|
|
| 12. |
- Bost, Jeremy P., et al.
(författare)
-
Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides
- 2022
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs.
|
|
| 13. |
- Datta-Chaudhuri, Timir, et al.
(författare)
-
The Fourth Bioelectronic Medicine Summit "Technology Targeting Molecular Mechanisms" : current progress, challenges, and charting the future
- 2021
-
Ingår i: Bioelectronic medicine. - : BioMed Central. - 2332-8886. ; 7:1
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- There is a broad and growing interest in Bioelectronic Medicine, a dynamic field that continues to generate new approaches in disease treatment. The fourth bioelectronic medicine summit "Technology targeting molecular mechanisms" took place on September 23 and 24, 2020. This virtual meeting was hosted by the Feinstein Institutes for Medical Research, Northwell Health. The summit called international attention to Bioelectronic Medicine as a platform for new developments in science, technology, and healthcare. The meeting was an arena for exchanging new ideas and seeding potential collaborations involving teams in academia and industry. The summit provided a forum for leaders in the field to discuss current progress, challenges, and future developments in Bioelectronic Medicine. The main topics discussed at the summit are outlined here.
|
|
| 14. |
- Gormley, Adam J., et al.
(författare)
-
Layer-by-Layer Self-Assembly of Polymer Films and Capsules through Coiled-Coil Peptides
- 2015
-
Ingår i: Chemistry of Materials. - : AMER CHEMICAL SOC. - 0897-4756 .- 1520-5002. ; 27:16, s. 5820-5824
-
Tidskriftsartikel (refereegranskat)abstract
- The layer-by-layer (LbL) technique is a simple and robust process for fabricating functional multilayer thin films. Here, we report the use of de novo designed polypeptides that self-assemble into coiled-coil structures (four-helix bundles) as a driving force for specific multilayer assembly. These pH- (sensitive between pH 4 and 7) and enzyme-responsive polypeptides were conjugated to polymers, and the LbL assembly of the polymer-peptide conjugates allowed the deposition of up to four polymer-peptide layers on planar surfaces and colloidal substrates. Stable hollow capsules were obtained, and by taking advantage of the peptides susceptibility to specific enzymatic cleavage, release of encapsulated cargo within the carriers can be triggered within 2 h in the presence of matrix metalloproteinase-7. The enormous diversity of materials that can form highly controllable and programmable coiled-coil interactions creates new opportunities and allows further exploration of the multilayer assembly and the formation of carrier capsules with unique functional properties.
|
|
| 15. |
- Guex, Anne Geraldine, et al.
(författare)
-
Highly porous scaffolds of PEDOT:PSS for bone tissue engineering
- 2017
-
Ingår i: Acta Biomaterialia. - : ELSEVIER SCI LTD. - 1742-7061 .- 1878-7568. ; 62, s. 91-101
-
Tidskriftsartikel (refereegranskat)abstract
- Conjugated polymers have been increasingly considered for the design of conductive materials in the field of regenerative medicine. However, optimal scaffold properties addressing the complexity of the desired tissue still need to be developed. The focus of this study lies in the development and evaluation of a conductive scaffold for bone tissue engineering. In this study PEDOT:PSS scaffolds were designed and evaluated in vitro using MC3T3-E1 osteogenic precursor cells, and the cells were assessed for distinct differentiation stages and the expression of an osteogenic phenotype. Ice-templated PEDOT:PSS scaffolds presented high pore interconnectivity with a median pore diameter of 53.6 +/- 5.9 mu m and a total pore surface area of 7.72 +/- 1.7 m(2).g(-1). The electrical conductivity, based on I-V curves, was measured to be 140 mu S.cm(-1) with a reduced, but stable conductivity of 6.1 mu S.cm(-1) after 28 days in cell culture media. MC3T3-E1 gene expression levels of ALPL, COL1A1 and RUNX2 were significantly enhanced after 4 weeks, in line with increased extracellular matrix mineralisation, and osteocalcin deposition. These results demonstrate that a porous material, based purely on PEDOT:PSS, is suitable as a scaffold for bone tissue engineering and thus represents a promising candidate for regenerative medicine. Statement of Significance Tissue engineering approaches have been increasingly considered for the repair of non-union fractions, craniofacial reconstruction or large bone defect replacements. The design of complex biomaterials and successful engineering of 3-dimensional tissue constructs is of paramount importance to meet this clinical need. Conductive scaffolds, based on conjugated polymers, present interesting candidates to address the piezoelectric properties of bone tissue and to induce enhanced osteogenesis upon implantation. However, conductive scaffolds have not been investigated in vitro in great measure. To this end, we have developed a highly porous, electrically conductive scaffold based on PEDOT:PSS, and provide evidence that this purely synthetic material is a promising candidate for bone tissue engineering. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd.
|
|
| 16. |
- Jumeaux, Coline, et al.
(författare)
-
MicroRNA Detection by DNA-Mediated Liposome Fusion
- 2018
-
Ingår i: ChemBioChem. - : Wiley. - 1439-7633 .- 1439-4227. ; 19:5, s. 434-438
-
Tidskriftsartikel (refereegranskat)abstract
- Membrane fusion is a process of fundamental importance in biological systems that involves highly selective recognition mechanisms for the trafficking of molecular and ionic cargos. Mimicking natural membrane fusion mechanisms for the purpose of biosensor development holds great potential for amplified detection because relatively few highly discriminating targets lead to fusion and an accompanied engagement of a large payload of signal-generating molecules. In this work, sequence-specific DNA-mediated liposome fusion is used for the highly selective detection of microRNA. The detection of miR-29a, a known flu biomarker, is demonstrated down to 18 nm within 30 min with high specificity by using a standard laboratory microplate reader. Furthermore, one order of magnitude improvement in the limit of detection is demonstrated by using a novel imaging technique combined with an intensity fluctuation analysis, which is coined two-color fluorescence correlation microscopy.
|
|
| 17. |
- Mathew, Renny, 1982-, et al.
(författare)
-
Nuclear Magnetic Resonance and Metadynamics Simulations Reveal the Atomistic Binding of ʟ-Serine and O-Phospho-ʟ-Serine at Disordered Calcium Phosphate Surfaces of Biocements
- 2022
-
Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 34:19, s. 8815-8830
-
Tidskriftsartikel (refereegranskat)abstract
- Interactions between biomolecules and structurally disordered calcium phosphate (CaP) surfaces are crucial for the regulation of bone mineralization by noncollagenous proteins, the organization of complexes of casein and amorphous calcium phosphate (ACP) in milk, as well as for structure–function relationships of hybrid organic/inorganic interfaces in biomaterials. By a combination of advanced solid-state NMR experiments and metadynamics simulations, we examine the detailed binding of O-phospho-l-serine (Pser) and l-serine (Ser) with ACP in bone-adhesive CaP cements, whose capacity of gluing fractured bone together stems from the close integration of the organic molecules with ACP over a subnanometer scale. The proximity of each carboxy, aliphatic, and amino group of Pser/Ser to the Ca2+ and phosphate species of ACP observed from the metadynamics-derived models agreed well with results from heteronuclear solid-state NMR experiments that are sensitive to the 13C–31P and 15N–31P distances. The inorganic/organic contacts in Pser-doped cements are also contrasted with experimental and modeled data on the Pser binding at nanocrystalline HA particles grown from a Pser-bearing aqueous solution. The molecular adsorption is driven mainly by electrostatic interactions between the negatively charged carboxy/phosphate groups and Ca2+ cations of ACP, along with H bonds to either protonated or nonprotonated inorganic phosphate groups. The Pser and Ser molecules anchor at their phosphate/amino and carboxy/amino moieties, respectively, leading to an extended molecular conformation across the surface, as opposed to an “upright standing” molecule that would result from the binding of one sole functional group.
|
|
| 18. |
- Minelli, Caterina, et al.
(författare)
-
Versailles project on advanced materials and standards (VAMAS) interlaboratory study on measuring the number concentration of colloidal gold nanoparticles
- 2022
-
Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 14, s. 4690-4704
-
Tidskriftsartikel (refereegranskat)abstract
- We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles.
|
|
| 19. |
- Reumann, Daniel, et al.
(författare)
-
In vitro modeling of the human dopaminergic system using spatially arranged ventral midbrain-striatum-cortex assembloids
- 2023
-
Ingår i: Nature Methods. - 1548-7105. ; 20:12, s. 2034-2047
-
Tidskriftsartikel (refereegranskat)abstract
- Ventral midbrain dopaminergic neurons project to the striatum as well as the cortex and are involved in movement control and reward-related cognition. In Parkinson's disease, nigrostriatal midbrain dopaminergic neurons degenerate and cause typical Parkinson's disease motor-related impairments, while the dysfunction of mesocorticolimbic midbrain dopaminergic neurons is implicated in addiction and neuropsychiatric disorders. Study of the development and selective neurodegeneration of the human dopaminergic system, however, has been limited due to the lack of an appropriate model and access to human material. Here, we have developed a human in vitro model that recapitulates key aspects of dopaminergic innervation of the striatum and cortex. These spatially arranged ventral midbrain-striatum-cortical organoids (MISCOs) can be used to study dopaminergic neuron maturation, innervation and function with implications for cell therapy and addiction research. We detail protocols for growing ventral midbrain, striatal and cortical organoids and describe how they fuse in a linear manner when placed in custom embedding molds. We report the formation of functional long-range dopaminergic connections to striatal and cortical tissues in MISCOs, and show that injected, ventral midbrain-patterned progenitors can mature and innervate the tissue. Using these assembloids, we examine dopaminergic circuit perturbations and show that chronic cocaine treatment causes long-lasting morphological, functional and transcriptional changes that persist upon drug withdrawal. Thus, our method opens new avenues to investigate human dopaminergic cell transplantation and circuitry reconstruction as well as the effect of drugs on the human dopaminergic system.
|
|
| 20. |
- Spicer, Christopher D., et al.
(författare)
-
Synthesis of Phospho-Amino Acid Analogues as Tissue Adhesive Cement Additives
- 2020
-
Ingår i: ACS CENTRAL SCIENCE. - : AMER CHEMICAL SOC. - 2374-7943 .- 2374-7951. ; 6:2, s. 226-231
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper we report the synthesis of a library of phospho-amino acid analogues, via a novel single-step allyl-phosphoester protection/Pd-mediated deprotection strategy. These phosphoserine and phosphotyrosine analogues were then applied as additives to create adhesive calcium phosphate cements, allowing us to probe the chemical origins of the increased surface binding strength. We demonstrate the importance of multiple calcium binding motifs in mediating adhesion, as well as highlighting the crucial role played by substrate hydrophobicity and orientation in controlling binding strength.
|
|
