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- Östling, Jörgen, et al.
(author)
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IL-17-high asthma with features of a psoriasis immunophenotype
- 2019
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In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 144:5, s. 1198-1213
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Journal article (peer-reviewed)abstract
- Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin.Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
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- Rennert, C, et al.
(author)
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Adaptive Subsets Limit the Anti-Tumoral NK-Cell Activity in Hepatocellular Carcinoma
- 2021
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In: Cells. - : MDPI AG. - 2073-4409. ; 10:6
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Journal article (peer-reviewed)abstract
- Hepatocellular carcinoma (HCC) is a global health burden with increasing incidence, poor prognosis and limited therapeutic options. Natural killer (NK) cells exhibit potent anti-tumoral activity and therefore represent potential targets for immunotherapeutic approaches in HCC treatment. However, the anti-tumoral activity of NK cells in HCC associated with different etiologies, and the impact of the heterogeneous NK cell subset, e.g., adaptive and conventional subsets, are not understood in detail. By comparatively analyzing the NK-cell repertoire in 60 HCC patients, 33 liver cirrhosis patients and 36 healthy donors (HD), we show in this study that the NK-cell repertoire is linked to HCC etiology, with increased frequencies of adaptive NK cells in Hepatitis B virus (HBV)-associated HCC. Adaptive NK cells exhibited limited anti-tumoral activity toward liver cancer cells; however, this was not a result of a specific NK-cell impairment in HCC but rather represented an intrinsic feature, since the characteristics of circulating and intra-tumoral adaptive NK cells were conserved between HD, HCC and liver cirrhosis patients. Hence, the expansion of adaptive NK cells with reduced anti-tumoral activity, detectable in HBV-associated HCC, may have implications for tumor surveillance and therapy.
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- Fichtner, Frauke, et al.
(author)
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Effect of preparation method on compactability of paracetamol granules and agglomerates
- 2007
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 336:1, s. 148-158
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Journal article (peer-reviewed)abstract
- The objective of this study was to investigate the effect of fracture strength of paracetamol particles on their compactability. For this purpose two series of paracetamol particles were prepared by crystal agglomeration and by granulation using different solvents. A free flowing particle size fraction of all types of particles was characterized with respect to their shape, degree of agglomeration and single fracture strength. The powders were compressed to tablets and the compression mechanism of the particles and the evolution in tablet micro-structure were assessed by compression parameters derived from the Heckel and Kawakita equations and by a tablet permeabililty coefficient. Tablet tensile strength and porosity were determined. The degree of deformation and fragmentation during compression varied between agglomerates and granules and was dependent on their failure strength. The granules varied in compactability with particle failure strength while the agglomerates showed limited variation. It is proposed that, the dominant mechanism of compression for the granules was permanent deformation while for the agglomerates it was fragmentation. It was thus found that the compression mechanism of the particles was dependent on both the degree of agglomeration and the particle failure strength.
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- Fichtner, Frauke, et al.
(author)
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Particle size distribution and evolution in tablet structure during and after compaction
- 2005
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 292:02-jan, s. 211-225
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Journal article (peer-reviewed)abstract
- The objective of this study was to investigate the effect of the distribution in size of free-flowing particles for the evolution in tablet structure and tablet strength. For sucrose and sodium chloride, three powders of different size distributions were prepared by mixing predetermined quantities of particle size fractions. For paracetamol, three batches with varying particle size distributions were prepared by crystallisation. The powders were formed into tablets. Tablet porosity and tensile strength were determined directly after compaction and after short-term storage at two different relative humidities. Tablets were also formed after admixture of a lubricant (magnesium stearate) and the tablet tensile strength was determined. For the test materials used in this study, the spread in particle size had no influence on the evolution in tablet porosity and tensile strength during compression. However, the spread in particle size had a significant and complex influence on the short-term post-compaction increase in tablet tensile strength. The effect of the spread was related to the instability mechanism and the presence of lubricant. It is concluded that the distribution in size of free-flowing particles is not critical for the tablet porosity but may give significant effects on tablet tensile strength due to a post-compaction reaction.
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- Kreisz, Philipp, et al.
(author)
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S1 basic leucine zipper transcription factors shape plant architecture by controlling C/N partitioning to apical and lateral organs
- 2024
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 121:7
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Journal article (peer-reviewed)abstract
- Plants tightly control growth of their lateral organs, which led to the concept of apical dominance. However, outgrowth of the dormant lateral primordia is sensitive to the plant's nutritional status, resulting in an immense plasticity in plant architecture. While the impact of hormonal regulation on apical dominance is well characterized, the prime importance of sugar signaling to unleash lateral organ formation has just recently emerged. Here, we aimed to identify transcriptional regulators, which control the trade-off between growth of apical versus lateral organs. Making use of locally inducible gain-of-function as well as single and higher-order loss-of-function approaches of the sugar-responsive S1-basic-leucine-zipper (S1-bZIP) transcription factors, we disclosed their largely redundant function in establishing apical growth dominance. Consistently, comprehensive phenotypical and analytical studies of S1-bZIP mutants show a clear shift of sugar and organic nitrogen (N) allocation from apical to lateral organs, coinciding with strong lateral organ outgrowth. Tissue-specific transcriptomics reveal specific clade III SWEET sugar transporters, crucial for long-distance sugar transport to apical sinks and the glutaminase GLUTAMINE AMIDO-TRANSFERASE 1_2.1, involved in N homeostasis, as direct S1-bZIP targets, linking the architectural and metabolic mutant phenotypes to downstream gene regulation. Based on these results, we propose that S1-bZIPs control carbohydrate (C) partitioning from source leaves to apical organs and tune systemic N supply to restrict lateral organ formation by C/N depletion. Knowledge of the underlying mechanisms controlling plant C/N partitioning is of pivotal importance for breeding strategies to generate plants with desired architectural and nutritional characteristics.
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- Minakshi, M., et al.
(author)
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Phase evolution in calcium molybdate nanoparticles as a function of synthesis temperature and its electrochemical effect on energy storage
- 2019
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In: Nanoscale Advances. - : Royal Society of Chemistry. - 2516-0230. ; 1:2, s. 565-580
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Journal article (peer-reviewed)abstract
- The design of a suitable electrode is an essential and fundamental research challenge in the field of electrochemical energy storage because the electronic structures and morphologies determine the surface redox reactions. Calcium molybdate (CaMoO4) was synthesized by a combustion route at 300 °C and 500 °C. We describe new findings on the behaviour of CaMoO4 and evaluate the influence of crystallinity on energy storage performance. A wide range of characterization techniques was used to obtain detailed information about the physical and morphological characteristics of CaMoO4. The characterization results enable the phase evolution as a function of the electrode synthesis temperature to be understood. The crystallinity of the materials was found to increase with increasing temperature but with no second phases observed. Molecular dynamics simulation of electronic structures correlated well with the experimental findings. These results show that to enable faster energy storage and release for a given surface area, amorphous CaMoO4 is required, while larger energy storage can be obtained by using crystalline CaMoO4. CaMoO4 has been evaluated as a cathode material in classical lithium-ion batteries recently. However, determining the surface properties in a sodium-ion system experimentally, combined with computational modelling to understand the results has not been reported. The superior electrochemical properties of crystalline CaMoO4 are attributed to its morphology providing enhanced Na+ ion diffusivity and electron transport. However, the presence of carbon in amorphous CaMoO4 resulted in excellent rate capability, suitable for supercapacitor applications.
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