| 1. |
- Chowdhury, Azazul, et al.
(author)
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Signaling in Insulin-Secreting MIN6 Pseudoislets and Monolayer Cells
- 2013
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:12, s. 5954-5962
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Journal article (peer-reviewed)abstract
- Cell cell interactions are of fundamental importance for cellular function. In islets of Langerhans, which control blood glucose levels by secreting insulin in response to the blood . glucose concentration, the secretory response of intact islets is c higher than that of insulin-producing beta-cells not arranged in the islet architecture. The objective was to define mechanisms by which cellular performance is enhanced when cells are arranged in a) three-dimensional space. The task was addressed by making a c comprehensive analysis based on protein expression patterns " generated from insulin-secreting MIN6 cells grown as islet-like c clusters, so-called pseudoislets, and in monolayers. After culture, glucose-stimulated insulin secretion (GSIS) was measured from monolayers and pseudoislets. GSIS rose 6-fold in pseudoislets but only 3-fold in monolayers when the glucose concentration was increased from 2 to 20 mmol/L. Proteins from pseudoislets and monolayers were extracted and analyzed by liquid-chromatography mass spectrometry, and differentially expressed proteins were mapped onto KEGG pathways. Protein profiling identified 1576 proteins, which were common to pseudoislets and monolayers. When mapped onto KEGG pathways, 11 highly enriched pathways were identified. On the basis of differences in expression of proteins belonging to the pathways in pseudoislets and monolayers, predictions of differential pathway activation were performed. Mechanisms enhancing insulin secretory capacity of the beta-cell, when situated in the islet, include pathways regulating glucose metabolism, cell interaction, and translational regulation.
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| 2. |
- Gustafsson, Olof, et al.
(author)
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High-Performance Virus Removal Filter Paper for Drinking Water Purification
- 2018
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In: Global Challenges. - : Wiley. - 2056-6646. ; 2:7
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Journal article (peer-reviewed)abstract
- Access to drinking water is one of the greatest global challenges today. In this study, the virus removal properties of mille‐feuille nanocellulose‐based filter papers of varying thicknesses from simulated waste water (SWW) matrix are evaluated for drinking water purification applications. Filtrations of standard SWW dispersions at various total suspended solid (TSS) content are performed, including spiking tests with 30 nm surrogate latex particles and 28 nm ΦX174 bacteriophages. Filter papers of thicknesses 9 and 29 µm are used, and the filtrations are performed at two different operational pressures, i.e., 1 and 3 bar. The presented data using SWW matrix show, for the first time, that a filter paper made from 100% nanocellulose has the capacity to efficiently remove even the smallest viruses, i.e., up to 99.9980–99.9995% efficiency, at industrially relevant flow rates, i.e., 60–500 L m−2 h−1, and low fouling, i.e., V max > 103–104 L m−2. The filter paper presented in this work shows great promise for the development of robust, affordable, and sustainable water purification systems.
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| 3. |
- Gustafsson, Olof, et al.
(author)
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Scalable and Sustainable Total Pathogen Removal Filter Paper for Point-of-Use Drinking Water Purification in Bangladesh
- 2019
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In: ACS Sustainable Chemistry and Engineering. - : AMER CHEMICAL SOC. - 2168-0485. ; 7:17, s. 14373-14383
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Journal article (peer-reviewed)abstract
- This article describes for the first time the full cycle of development from raw material cultivation to real-life application of a truly sustainable and scalable filter paper material intended for point-of-use drinking water purification in Bangladesh. The filter paper, featuring tailored pathogen removal properties, is produced from nanocellulose extracted from Pithophora green macroalgae, growing locally in Bangladesh, a new unexploited resource that can address a global problem. We demonstrate that the Pithophora cellulose filter paper can be used as a total pathogen barrier to remove all types of infectious viruses and bacteria from water. The performance of the filter is validated using surrogate latex nanobeads, in vitro model viruses, and real-life water samples collected from the Turag River and Dhanmondi Lake in Dhaka, Bangladesh. Access to clean drinking water is a persistent problem in Bangladesh, affecting tens of millions of people every day. The mortality rate due to water-borne diarreal infections, including viral infections, among susceptible population groups, especially among children under age of 5, is still very high. The proposed solution can dramatically improve the quality of lives for millions of people in the entire Southeast Asian region including and beyond the borders of Bangladesh.
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| 4. |
- Gustafsson, Olof, et al.
(author)
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Significance of Brownian Motion for Nanoparticle and Virus Capture in Nanocellulose-Based Filter Paper
- 2018
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In: Membranes. - : MDPI AG. - 2077-0375. ; 8:4
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Journal article (peer-reviewed)abstract
- Pressure-dependent breakthrough of nanobioparticles in filtration was observed and it was related to depend on both convective forces due to flow and diffusion as a result of Brownian motion. The aim of this work was to investigate the significance of Brownian motion on nanoparticle and virus capture in a nanocellulose-based virus removal filter paper through theoretical modeling and filtration experiments. Local flow velocities in the pores of the filter paper were modeled through two different approaches (i.e., with the Hagen–Poiseuille equation) and by evaluating the superficial linear flow velocity through the filter. Simulations by solving the Langevin equation for 5 nm gold particles and 28 nm ΦX174 bacteriophages showed that hydrodynamic constraint is favored for larger particles. Filtration of gold nanoparticles showed no difference in retention for the investigated fluxes, as predicted by the modeling of local flow velocities. Filtration of ΦX174 bacteriophages exhibited a higher retention at higher filtration pressure, which was predicted to some extent by the Hagen–Poiseuille equation but not by evaluation of the superficial linear velocity. In all, the hydrodynamic theory was shown able to explain some of the observations during filtration.
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| 5. |
- Gustafsson, Simon, 1988-, et al.
(author)
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Protein-Nanocellulose Interactions in Paper Filters for Advanced Separation Applications
- 2017
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In: Langmuir. - : AMER CHEMICAL SOC. - 0743-7463 .- 1520-5827. ; 33:19, s. 4729-4736
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Journal article (peer-reviewed)abstract
- Protein-based pharmaceutics are widely explored for healthcare applications, and 6 out of 10 best-selling drugs today are biologicals. The goal of this work was to evaluate the protein nanocellulose interactions in paper filter for advanced separation applications such as virus removal filtration and bioprocessing. The protein recovery was measured for bovine serum albumin (BSA), gamma-globulin, and lysozyme using biuret total protein reagent and polyacrylamide gel electrophoresis (PAGE), and the throughput was characterized in terms of flux values from fixed volume filtrations at various protein concentrations and under worst case experimental conditions. The affinity of cellulose to bind various proteins, such as BSA, lysozyme, gamma-globulin, and human IgG was quantified using a quartz crystal microbalance (QCMB) by developing a new method of fixing the cellulose fibers to the electrode surface without cellulose dissolution-precipitation. It was shown that the. mille-feuille filter exhibits high protein recovery, that is, similar to 99% for both BSA and lysozyme. However, gamma-globulin does not pass through the membrane due to its large size (i.e., >180 kDa). The PAGE data show no substantial change in the amount of dimers and trimers before and after filtration. QCMB analysis suggests a low affinity between the nanocellulose surface and proteins. The nanocellulose-based filter exhibits desirable inertness as a filtering material intended for protein purification.
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| 6. |
- Manell, Hannes, et al.
(author)
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Altered Plasma Levels of Glucagon, GLP-1 and Glicentin During OGTT in Adolescents With Obesity and Type 2 Diabetes
- 2016
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 101:3, s. 1181-1189
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Journal article (peer-reviewed)abstract
- CONTEXT: Proglucagon-derived hormones are important for glucose metabolism, but little is known about them in pediatric obesity and type 2 diabetes mellitus (T2DM).OBJECTIVE: Fasting and postprandial levels of proglucagon-derived peptides glucagon, GLP-1, and glicentin in adolescents with obesity across the glucose tolerance spectrum were investigated.DESIGN: This was a cross-sectional study with plasma hormone levels quantified at fasting and during an oral glucose tolerance test (OGTT).SETTING: This study took place in a pediatric obesity clinic at Uppsala University Hospital, Sweden.PATIENTS AND PARTICIPANTS: Adolescents with obesity, age 10-18 years, with normal glucose tolerance (NGT, n = 23), impaired glucose tolerance (IGT, n = 19), or T2DM (n = 4) and age-matched lean adolescents (n = 19) were included.MAIN OUTCOME MEASURES: Outcome measures were fasting and OGTT plasma levels of insulin, glucagon, active GLP-1, and glicentin.RESULTS: Adolescents with obesity and IGT had lower fasting GLP-1 and glicentin levels than those with NGT (0.25 vs 0.53 pM, P < .05; 18.2 vs 23.6 pM, P < .01) and adolescents with obesity and T2DM had higher fasting glucagon levels (18.1 vs 10.1 pM, P < .01) than those with NGT. During OGTT, glicentin/glucagon ratios were lower in adolescents with obesity and NGT than in lean adolescents (P < .01) and even lower in IGT (P < .05) and T2DM (P < .001).CONCLUSIONS: Obese adolescents with IGT have lowered fasting GLP-1 and glicentin levels. In T2DM, fasting glucagon levels are elevated, whereas GLP-1 and glicentin levels are maintained low. During OGTT, adolescents with obesity have more products of pancreatically than intestinally cleaved proglucagon (ie, more glucagon and less GLP-1) in the plasma. This shift becomes more pronounced when glucose tolerance deteriorates.
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| 7. |
- Manukyan, Levon, et al.
(author)
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Developmental exposure to a very low dose of bisphenol A induces persistent islet insulin hypersecretion in Fischer 344 rat offspring
- 2019
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In: Environmental Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0013-9351 .- 1096-0953. ; 172, s. 127-136
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Journal article (peer-reviewed)abstract
- Background: In children with obesity, accentuated insulin secretion has been coupled with development of type 2 diabetes mellitus (T2DM). Bisphenol A (BPA) is a chemical with endocrine- and metabolism-disrupting properties which can be measured in a majority of the population. Exposure to BPA has been associated with the development of metabolic diseases including T2DM.Objective: The aim of this study was to investigate if exposure early in life to an environmentally relevant low dose of BPA causes insulin hypersecretion in rat offspring.Methods: Pregnant Fischer 344 rats were exposed to 0.5 (BPA0.5) or 50 (BPA50) jig BPA/kg BW/day via drinking water from gestational day 3.5 until postnatal day 22. Pancreata from dams and 5- and 52-week-old offspring were procured and islets were isolated by collagenase digestion. Glucose-stimulated insulin secretion and insulin content in the islets were determined by ELISA.Results: Basal (5.5 mM glucose) islet insulin secretion was not affected by BPA exposure. However, stimulated (11 mM glucose) insulin secretion was enhanced by about 50% in islets isolated from BPA0.5-exposed 5- and 52 week-old female and male offspring and by 80% in islets from dams, compared with control. In contrast, the higher dose, BPA50, reduced stimulated insulin secretion by 40% in both 5- and 52-week-old female and male offspring and dams, compared with control.Conclusion: A BPA intake 8 times lower than the European Food Safety Authority's (EFSA's) current tolerable daily intake (TDI) of 4 mu g/kg BW/day of BPA delivered via drinking water during gestation and early development causes islet insulin hypersecretion in rat offspring up to one year after exposure. The effects of BPA exposure on the endocrine pancreas may promote the development of metabolic disease including T2DM.
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| 8. |
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| 9. |
- Manukyan, Levon, et al.
(author)
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Growth Media Filtration Using Nanocellulose-based Virus Removal Filter for Upstream Biopharmaceutical Processing
- 2019
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In: Journal of Membrane Science. - : Elsevier BV. - 0376-7388 .- 1873-3123. ; 572, s. 464-474
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Journal article (peer-reviewed)abstract
- The feasibility of using nanocellulose-based mille-feuille filter paper for upstream applications in serum-free growth media filtration, i.e. Dulbecco’s modified Eagle’s medium (DMEM) and Luria-Bertani medium (LBM), was tested. The filter performance with respect to F.174 bacteriophage (28nm) removal as a model small-size virus was characterized for filters of varying thicknesses, i.e. 11 and 33 mu m, at varying operating pressures, i.e. 1 and 3bar. The filters demonstrated generally good model small-size virus removal properties with LRV = 5, especially for 33 mu m filters. The 33 mu m filters were more robust and exhibited better virus removal and throughput properties than 11 mu m filters, although their flux was generally lower. The performance of the 33 and 11 mu m nanocellulose-based filter papers was further verified for upscaled bioporcessing by 10-fold increase in the loading volume. The results of the present work show that the 33 mu m nanocellulose-based filter paper could be an interesting alternative for large volume cell culture medium filtration during upstream bioprocessing.
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| 10. |
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