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"Roman, Maren"
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Model cellulosic surfaces
\"Molecular interactions of cellulose surfaces govern the three-dimensional assembly of plant cell walls and play important roles in the pulp and paper, textile, and food industries. Interactions of cellulose surfaces with other polysaccharides, proteins, polynucleotides, and mammalian cells are of interest for biomedical cellulose applications and, more recently, interactions of cellulolytic enzymes with cellulosic substrates is of interest in the production of bioethanol from lignocellulosic feedstocks. The study of interactions and sorption phenomena involving cellulose and cellulosic materials requires well-defined model surfaces. Several methods to prepare such model surfaces have been developed over the past fifteen years and an increasing number of cellulose interaction studies involving such model surfaces can be found in the literature.
Book
Effects of Chitosan Molecular Weight and Degree of Deacetylation on Chitosan−Cellulose Nanocrystal Complexes and Their Formation
This study was conducted to determine the effects of chitosan molecular weight and degree of deacetylation (DD) on chitosan–cellulose nanocrystal (CNC) polyelectrolyte–macroion complexes (PMCs) and their formation. Chitosan samples with three different molecular weights (81, 3 · 103, 6 · 103 kDa) and four different DDs (77, 80, 85, 89%) were used. The effects on PMC formation were determined by turbidimetric titration. An effect of the molecular weight of chitosan was not observed in turbidimetric titrations. Turbidity levels were higher for CNCs with lower sulfate group density and larger hydrodynamic diameter than for CNCs with higher sulfate group density and smaller hydrodynamic diameter. Conversely, turbidity levels were higher for chitosans with higher DD (higher charge density) than for chitosans with lower DD (lower charge density). PMC particles from chitosans with different molecular weights were characterized by scanning electron microscopy, laser Doppler electrophoresis, and dynamic light scattering. PMCs from high-molecular-weight chitosan were more spherical and those from medium-molecular-weight chitosan had a slightly larger hydrodynamic diameter than PMCs from the respective other two chitosans. The molecular weight of the chitosan was concluded to have no effect on the formation of chitosan–CNC PMC particles and only a minor effect on the shape and size of the particles. The higher turbidity levels for CNCs with lower sulfate group density and larger hydrodynamic diameter and for chitosans with higher DD were attributed to a larger number of CNCs being required for charge compensation.
Journal Article
Bioactive Cellulose Nanocrystal-Poly(ε-Caprolactone) Nanocomposites for Bone Tissue Engineering Applications
3D-printed bone scaffolds hold great promise for the individualized treatment of critical-size bone defects. Among the resorbable polymers available for use as 3D-printable scaffold materials, poly(ε-caprolactone) (PCL) has many benefits. However, its relatively low stiffness and lack of bioactivity limit its use in load-bearing bone scaffolds. This study tests the hypothesis that surface-oxidized cellulose nanocrystals (SO-CNCs), decorated with carboxyl groups, can act as multi-functional scaffold additives that (1) improve the mechanical properties of PCL and (2) induce biomineral formation upon PCL resorption. To this end, an in vitro biomineralization study was performed to assess the ability of SO-CNCs to induce the formation of calcium phosphate minerals. In addition, PCL nanocomposites containing different amounts of SO-CNCs (1, 2, 3, 5, and 10 wt%) were prepared using melt compounding extrusion and characterized in terms of Young's modulus, ultimate tensile strength, crystallinity, thermal transitions, and water contact angle. Neither sulfuric acid-hydrolyzed CNCs (SH-CNCs) nor SO-CNCs were toxic to MC3T3 preosteoblasts during a 24 h exposure at concentrations ranging from 0.25 to 3.0 mg/mL. SO-CNCs were more effective at inducing mineral formation than SH-CNCs in simulated body fluid (1x). An SO-CNC content of 10 wt% in the PCL matrix caused a more than 2-fold increase in Young's modulus (stiffness) and a more than 60% increase in ultimate tensile strength. The matrix glass transition and melting temperatures were not affected by the SO-CNCs but the crystallization temperature increased by about 5.5°C upon addition of 10 wt% SO-CNCs, the matrix crystallinity decreased from about 43 to about 40%, and the water contact angle decreased from 87 to 82.6°. The abilities of SO-CNCs to induce calcium phosphate mineral formation and increase the Young's modulus of PCL render them attractive for applications as multi-functional nanoscale additives in PCL-based bone scaffolds.
Journal Article
Hydrophobically modified pullulan adsorption onto rod-like cellulose nanocrystals
Interactions between polysaccharides have attracted great interests as a key to improving wood-fiber /thermoplastic composites. This study probes interactions between hydrophobically modified pullulans (HMPs) and rod-like cellulose nanoparticles (CNCs) in dilute solutions as a potential model system for the modification of wood fibers. A combination of UV–Vis spectroscopy, zeta-potential measurements, and light scattering techniques reveals the adsorption of pullulan derivatives onto cellulose nanocrystals even though hydrogen bonds are weakened. In UV–Vis spectroscopy and light scattering, aggregates were readily observed when UV cross-linking reactions occurred without cellulose nanocrystals and the system was relatively unaffected by the addition of cellulose nanocrystals after UV cross-linking. Otherwise, aggregates were not observed for long UV exposure time when both HMPs and CNCs existed in the ternary system. Large aggregates immediately precipitated when they were observed. Zeta-potential measurements also showed hydrophobically modified pullulan adsorption onto cellulose nanocrystal. Adsorbed hydrophobically modified pullulans screen the surface hydroxyl and sulfate groups of the cellulose nanocrystals. It could be demonstrated HMP/CNC/water ternary systems are effective model system of polysaccharide colloidal solutions having weak interactions.Graphic abstract
Journal Article
A graph-based approach for representing, integrating and analysing neuroscience data: the case of the murine basal ganglia
PurposeNeuroscience data are spread across a variety of sources, typically provisioned through ad-hoc and non-standard approaches and formats and often have no connection to the related data sources. These make it difficult for researchers to understand, integrate and reuse brain-related data. The aim of this study is to show that a graph-based approach offers an effective mean for representing, analysing and accessing brain-related data, which is highly interconnected, evolving over time and often needed in combination.Design/methodology/approachThe authors present an approach for organising brain-related data in a graph model. The approach is exemplified in the case of a unique data set of quantitative neuroanatomical data about the murine basal ganglia––a group of nuclei in the brain essential for processing information related to movement. Specifically, the murine basal ganglia data set is modelled as a graph, integrated with relevant data from third-party repositories, published through a Web-based user interface and API, analysed from exploratory and confirmatory perspectives using popular graph algorithms to extract new insights.FindingsThe evaluation of the graph model and the results of the graph data analysis and usability study of the user interface suggest that graph-based data management in the neuroscience domain is a promising approach, since it enables integration of various disparate data sources and improves understanding and usability of data.Originality/valueThe study provides a practical and generic approach for representing, integrating, analysing and provisioning brain-related data and a set of software tools to support the proposed approach.
Journal Article
Effect of Hyaluronan in Collagen Biomaterials on Human Macrophages and Fibroblasts In Vitro
In adults, scars are formed after deep skin wound injuries like burns. However, the fetal microenvironment allows for scarless skin regeneration. One component that is abundantly present in the fetal extracellular matrix is hyaluronan (HA). To study whether biomaterials with HA improve wound healing, type I collagen scaffolds with and without HA were prepared and characterized. Their immune effect was tested using macrophages and their phenotypes were analyzed through cell surface markers and cytokine expression after 48 h. Since fibroblasts are the main cellular component in the dermis, adult, fetal and eschar-derived cells were cultured on scaffolds for 14 days and evaluated using histology, gene and protein expression analyses. Biochemical assays demonstrated that HA was successfully incorporated and evenly distributed throughout the scaffolds. Macrophages (M0) cultured on Col I+HA scaffolds exhibited a profile resembling the M2c-like phenotype (CD206high, CD163high and IL10high). HA did not significantly affect gene expression in adult and fetal fibroblasts, but significantly reduced scarring-related genes, such as transforming growth factor beta 1 (TGFB1) and type X collagen alpha 1 chain (COL10A1), in myofibroblast-like eschar cells. These findings highlight the potential of incorporating HA into collagen-based skin substitutes to improve the wound healing response.
Journal Article
Discrimination of SARS-CoV-2 Infections From Other Viral Respiratory Infections by Scent Detection Dogs
Background: Testing of possibly infected individuals remains cornerstone of containing the spread of SARS-CoV-2. Detection dogs could contribute to mass screening. Previous research demonstrated canines' ability to detect SARS-CoV-2-infections but has not investigated if dogs can differentiate between COVID-19 and other virus infections. Methods: Twelve dogs were trained to detect SARS-CoV-2 positive samples. Three test scenarios were performed to evaluate their ability to discriminate SARS-CoV-2-infections from viral infections of a different aetiology. Naso- and oropharyngeal swab samples from individuals and samples from cell culture both infected with one of 15 viruses that may cause COVID-19-like symptoms were presented as distractors in a randomised, double-blind study. Dogs were either trained with SARS-CoV-2 positive saliva samples (test scenario I and II) or with supernatant from cell cultures (test scenario III). Results: When using swab samples from individuals infected with viruses other than SARS-CoV-2 as distractors (test scenario I), dogs detected swab samples from SARS-CoV-2-infected individuals with a mean diagnostic sensitivity of 73.8% (95% CI: 66.0–81.7%) and a specificity of 95.1% (95% CI: 92.6–97.7%). In test scenario II and III cell culture supernatant from cells infected with SARS-CoV-2, cells infected with other coronaviruses and non-infected cells were presented. Dogs achieved mean diagnostic sensitivities of 61.2% (95% CI: 50.7–71.6%, test scenario II) and 75.8% (95% CI: 53.0–98.5%, test scenario III), respectively. The diagnostic specificities were 90.9% (95% CI: 87.3–94.6%, test scenario II) and 90.2% (95% CI: 81.1–99.4%, test scenario III), respectively. Conclusion: In all three test scenarios the mean specificities were above 90% which indicates that dogs can distinguish SARS-CoV-2-infections from other viral infections. However, compared to earlier studies our scent dogs achieved lower diagnostic sensitivities. To deploy COVID-19 detection dogs as a reliable screening method it is therefore mandatory to include a variety of samples from different viral respiratory tract infections in dog training to ensure a successful discrimination process.
Journal Article
Unveiling the diversification and dispersal of the Lewinskya firma complex (Orthotrichaceae, Bryophyta) across Africa and India
Intercontinental disjunctions are one of the most attractive and interesting biogeographical patterns. Bryophytes often exhibit such distributions, which is partly explained by their great ability to disperse over long distances. However, such intercontinental ranges are sometimes a distorted reality caused by the existence of unnoticed species. This study investigates whether the disjunction between East Africa and southern India of the moss Lewinskya firma reflects the genuine distribution of a single species or implies pseudo-cryptic species (whose morphological differentiation is subtle and have therefore been masked). An integrative taxonomic approach combining morphological and molecular methods (genotyping by sequencing, GBS) was used, based on a representation of samples specifically collected from all the major mountainous regions where this moss occurs. Two species, L. firma s. str. and L. afroindica sp. nov. are involved, whose ranges completely overlap in East Africa, although genetic distance and morphological differences in leaf apex shape, vaginula hairs shape and papillosity, spore ornamentation and peristome constitution and ornamentation allow distinguishing both. In addition, the range of L. afroindica extends into both southern Africa and southern India. The phylogenetic reconstruction obtained shows a certain degree of differentiation of the Indian populations, although they are yet morphologically indistinguishable from African populations. The results thus highlight both the existence of overlooked species and the complexity of bryophyte biogeography.
Journal Article
Targeting HER2/HER3 co‐mutations in metastatic breast cancer: Case reports of exceptional responders to trastuzumab and pertuzumab therapy
Background Overexpression of HER2 plays an important role in cancer progression and is the target of multiple therapies in HER2‐positive breast cancer. Recent studies have also highlighted the presence of activating mutations in HER2, and HER3 that are predicted to enhance HER2 downstream pathway activation in a HER2‐dependent manner. Methods In this report, we present two exceptional responses in hormone receptor‐positive, HER2‐nonamplified, HER2/HER3 co‐mutated metastatic breast cancer patients who were treated with the anti‐HER2‐directed monoclonal antibodies, trastuzumab and pertuzumab. Results Both patients acheived exceptional responses to treatment, suggesting that combined trastuzumab, pertuzumab, and endocrine therapy could be a highly effective therapy for these patients and our observations could help prioritize trastuzumab deruxtecan as an early therapeutic choice for patients whose cancers have activating mutations in HER2.
Journal Article
Effects of tumor treating fields (TTFields) on human mesenchymal stromal cells
Purpose
Mesenchymal stromal cells (MSCs) within the glioblastoma microenvironment have been shown to promote tumor progression. Tumor Treating Fields (TTFields) are alternating electric fields with low intensity and intermediate frequency that exhibit anti-tumorigenic effects. While the effects of TTFields on glioblastoma cells have been studied previously, nothing is known about the influence of TTFields on MSCs.
Methods
Single-cell RNA sequencing and immunofluorescence staining were employed to identify glioblastoma-associated MSCs in patient samples. Proliferation and clonogenic survival of human bone marrow-derived MSCs were assessed after TTFields in vitro. MSC’ characteristic surface marker expression was determined using flow cytometry, while multi-lineage differentiation potential was examined with immunohistochemistry. Apoptosis was quantified based on caspase-3 and annexin-V/7-AAD levels in flow cytometry, and senescence was assessed with ß-galactosidase staining. MSCs’ migratory potential was evaluated with Boyden chamber assays.
Results
Single-cell RNA sequencing and immunofluorescence showed the presence of glioblastoma-associated MSCs in patient samples. TTFields significantly reduced proliferation and clonogenic survival of human bone marrow-derived MSCs by up to 60% and 90%, respectively. While the characteristic surface marker expression and differentiation capacity were intact after TTFields, treatment resulted in increased apoptosis and senescence. Furthermore, TTFields significantly reduced MSCs’ migratory capacity.
Conclusion
We could demonstrate the presence of tumor-associated MSCs in glioblastoma patients, providing a rationale to study the impact of TTFields on MSCs. TTFields considerably increase apoptosis and senescence in MSCs, resulting in impaired survival and migration. The results provide a basis for further analyses on the role of MSCs in glioblastoma patients receiving TTFields.
Journal Article