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1.	Orru, Anna Maria, 1976, et al. (författare) AHA! festival 2015 2015 Annan publikation (övrigt vetenskapligt/konstnärligt)abstract The AHA festival investigates the borders between art and science in a three-day event at the Chalmers University of Technology hosted by the Department of Architecture. An international festival intended to provide enlightening experiences, staging surprises, new thoughts and displaced perspectives that lead to alternative modes of thinking about the space between art and science. We invite scientists (physicists, historians, mathematicians, medical students), artists (dancers, musicians, painters, poets, chefs) and not least architects, who reside in these borderlands and wish to share their vision and work. The key intention is to celebrate both art and science as key knowledge building devices.
2.	Jing, Yujia, 1985 (författare) Hyperthermia-responsive liposomal systems 2015 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Abstract Sophisticated liposomal systems are emerging at an increasing rate to meet the demands for multifunctional drug carriers in chemotherapies in combined with hyperthermia. For example, liposomal drug carriers for temperature-controlled drug release under hyperthermic conditions have recently been tested in clinical trials. More advanced designs of liposomes are expected to release encapsulated contents and activate hidden surface-functions in response to heat stimulus. Towards this aim, the present thesis is focused on formulating asymmetric lipid systems that can preserve functional moieties, and reactivate the targeted function as well as release the encapsulated compounds upon local heating. The design of the asymmetric liposomal systems utilizes the heat-activated transmembrane lipid diffusion during gel to liquid-crystalline phase transitions of the lipid membranes.Rational design of advanced liposomal drug-delivery systems will require understanding of the physicochemical properties of lipid membranes under, e.g., hyperthermic conditions. Here, supported lipid membranes on planar solid surfaces were used for model studies of lipid composition yielding a gel to liquid crystalline phase-transition temperature in the range 40 – 45 °C. It was found that the liposome-to-membrane formation process is not only size-dependent but also governed by temperature. Two methods of preparing supported asymmetric lipid membranes were investigated. As a proof-of-concept, the upper leaflets were either replaced or chemically transformed by enzymatic hydrolysis. The processes were monitored using surface sensitive techniques such as quartz crystal microbalance with dissipation (QCM-D) and dual polarization interferometry (DPI). The asymmetric structures were stable at a room temperature, while lipid flip-flop was induced upon increasing of the temperature. Transmembrane lipid exchange in the asymmetric structure under hyperthermic conditions was demonstrated by detecting, through streptavidin binding, biotinylated lipids appearing at the top leaflet which were first located in the lower leaflet. The protocols developed for the supported lipid systems were adapted for the preparation of asymmetric liposomes. Biotinylated asymmetric liposomes were used as a model system to demonstrate the principle of heat-activated targeting of asymmetric liposomes to streptavidin-coated surfaces. More biologically relevant interaction was utilized to replace the biotin-streptavidin function, where asymmetric cationic liposomes were binding to anionic supported membrane immobilized surfaces upon heating. The described strategies for assembly of asymmetric supported membranes provide a guide to the development of multifunctional drug carriers. The protocols used in experiments with supported membranes were readily adapted to the preparation of asymmetric liposomes. The ongoing study tests the asymmetric liposomes in vitro, which is designed to demonstrate hyperthermia treatment can enhance accumulation of liposomes in FaDu cells, and at the same time activate release of the encapsulated components. The results of in vitro tests can be used to analyze the feasibility of utilizing the asymmetric liposomes as a platform in vivo to explore further improvement in their functions upon microwave hyperthermia.
3.	Söderlund, Zackarias (författare) Engineering the extracellular matrix to model diseases and orchestrate regeneration 2023 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The extracellular matrix is not only a scaffold to which cells attach, but it is also a matrix that communicates cell signals. Because of the interplay between cells and the extracellular matrix, changes in the extracellular matrix can steer cell fate. This opens up the opportunity to design and engineer the extracellular matrix to communicate changes to the cells. Thus, this thesis has focused on understanding which parameters and signals influence cells, but also on how to utilise this knowledge to engineer a completely defined extracellular matrix. The extracellular matrix can be modulated in several ways, such as cell attachment, degradation properties, porosity, stiffness as well as being easily functionalised with molecules of interest using click chemistry.Two of the papers in this thesis focus on the development of new tools for glycosaminoglycan research to get a better understanding of how this can be modulated to steer cell signalling. Glycosaminoglycans bind growth factors, which can then either act as a co-receptor to increase the potency of the growth factor or to protect the growth factors from being broken down or inactivated. The tools that we have developed open the possibility to better study the production of glycosaminoglycans from different types of cells and better understand what changes occur in glycosaminoglycan synthesis during disease.The second two papers in this thesis focus on understanding the extracellular matrix. Article number one focuses on the effect of different extracellular matrices and stretch on cells and their secretome. Article number two, which has been the focus of this thesis, utilises the new findings in the other articles about glycosaminoglycans and the extracellular matrix to create a synthetic and defined extracellular matrix. This extracellular matrix is modified with glycosaminoglycans to have a slow release of growth factors to instruct cells to differentiate both in vitro and in vivo.
4.	Fonzo, Vito Di, et al. (författare) Multi-sensor system for non-invasive online analysis and control in bioreactors 2013 Ingår i: BioMicroWorld 2013, Madrid, Spain, October 2-4. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Sökbart abstract via länken: http://www.formatex.info/biomicroworld2013/acceptedabstracts.php
5.	Sukhovey, Yurij G., et al. (författare) Difference between the biologic and chronologic age as an individualized indicator for the skin care intensity selection : skin topography and immune system state studies, parameter correlations with age difference 2019 Ingår i: Biomedical Dermatology. - : Springer Nature. - 2398-8460. ; 3 Tidskriftsartikel (refereegranskat)abstract Background: Present research addresses the issue of skin aging and corresponding skin treatment individualization. Particular research question was on the developing of simplified criterion supporting patient-specific decision on the necessity and intensity of skin treatment. Basing on the published results and a wide pool of experimental data, we have formulated a hypothesis that a difference between biologic and chronologic age can be used as an express criterion of skin aging.Methods: In present paper, we report the results of studies with 80 volunteers between 15 and 65 years of age, linking parameters reflecting immune state, skin state, and topography to the difference between biologic and chronologic age. Facial skin topography, skin moisture, sebum level, and skin elasticity were studied using commercial devices. Blood immunology studies were performed using venous blood samples. Correlations between all measured parameters and age difference were calculated. Also, cross correlations between skin cell profile and blood immune profile parameters, and skin roughness parameters were calculated.Results: Age dependencies of the blood immunological parameters on the biologic and chronologic age difference are less pronounced as compared to the changes in skin cell profile parameters. However, the changes in the tendencies when biologic age becomes equal to chronologic one are visible for all studied parameters.All measured skin roughness parameters show correlations with age difference, but average skin roughness and depth of the deepest profile valley have the largest correlation coefficient values. Many of the measured skin cell profile and blood immunology parameters show strong correlations with average skin roughness and deepest profile valley, with some of the coefficients exceeding 0.5–0.6.Conclusions: Basing on own experiments and published research results, it is possible to suggest using the difference between calculated biologic age and chronologic age as an individualized criterion supporting decisions on skin treatment strategy. Further research involving larger numbers of participants and aiming on optimizing the expressions for calculating biologic age could lead to reliable and easily available express criterion supporting the decision making for an individualized skin treatment.
6.	Lind-Halldén, Christina, et al. (författare) Genetic variation in the syntaxin-binding protein STXBP5 in type 1 von Willebrand disease patients 2018 Ingår i: Thrombosis and haemostasis. - 2567-689X. ; 118:8, s. 1382-1389 Tidskriftsartikel (refereegranskat)abstract von Willebrand factor (VWF) levels in healthy individuals and in patients with type 1 von Willebrand disease (VWD) are influenced by genetic variation in several genes, for example, VWF, ABO and STXBP5. Here, we comprehensively screen for STXBP5 variants and investigate their association with type 1 VWD in Swedish patients and controls. The coding region of the STXBP5 gene was re-sequenced in 107 type 1 VWD patients and the detected variants were genotyped in the type 1 VWD population and a Swedish control population (464 individuals). The functional effects of missense alleles were predicted in silico and the pattern of genetic variation in STXBP5 was analysed. Re-sequencing of 107 type 1 VWD patients identified three missense and three synonymous variants in the coding sequence of STXBP5. The low-frequency missense variants rs144099092 (0.005) and rs148830578 (0.029) were predicted to be damaging, but were not accumulated in patients. No other rare candidate mutations were detected. STXBP5 showed a high level of linkage disequilibrium and a low overall nucleotide diversity of π = 3.2 × 10-4 indicating intolerance to variants affecting protein function. Three previously type 1 VWD-associated single nucleotide polymorphisms were located on one haplotype that showed an increased frequency in patients versus controls. No differences in messenger ribonucleic acid abundance among haplotypes could be found using Genotype-Tissue Expression project data. In conclusion, a haplotype containing the STXBP5 Asn436Ser (rs1039084) mutation is associated with type 1 VWD and no rare STXBP5 mutations contribute to type 1 VWD in the Swedish population.
7.	Andersson, Sören, 1957-, et al. (författare) CHIMERIC MOMP ANTIGEN 2015 Patent (populärvet., debatt m.m.)
8.	Andersson, Sören, 1957-, et al. (författare) Chimeric MOMP antigen 2014 Patent (populärvet., debatt m.m.)abstract The present invention regards polypeptides capable of eliciting an immunological response that is protective against Chlamydia trachomatis. The polypeptide comprises a first amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 1 and a second amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 2. Furthermore, production of these polypeptides and pharmaceutical compositions comprising them are also provided.
9.	Campbell, Kate, 1987, et al. (författare) Self-Establishing Communities: A Yeast Model to Study the Physiological Impact of Metabolic Cooperation in Eukaryotic Cells 2019 Ingår i: Methods in Molecular Biology. - New York, NY : Springer New York. - 1940-6029 .- 1064-3745. ; , s. 263-282 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract All biosynthetically active cells are able to export and import metabolites, the small molecule intermediaries of metabolism. In dense cell populations, this hallmark of cells results in the intercellular exchange of a wide spectrum of metabolites. Such metabolite exchange enables metabolic specialization of individual cells, leading to far reaching biological implications, as a consequence of the intrinsic connection between metabolism and cell physiology. In this chapter, we discuss methods on how to study metabolite exchange interactions by using self-establishing metabolically cooperating communities (SeMeCos) in the budding yeast Saccharomyces cerevisiae. SeMeCos exploit the stochastic segregation of episomes to progressively increase the number of essential metabolic interdependencies in a community that grows out from an initially prototrophic cell. By coupling genotype to metabotype, SeMeCos allow for the tracking of cells while they specialize metabolically and hence the opportunity to study their progressive change in physiology.
10.	Jesorka, Aldo, 1967, et al. (författare) Microfluidic technology for investigation of protein function in single adherent cells 2019 Ingår i: Methods in Enzymology. - : Elsevier. - 1557-7988 .- 0076-6879. Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract Instrumental techniques and associated methods for single cell analysis, designed to investigate and measure a broad range of cellular parameters in search of unique features, address key limitations of conventional cell-based assays with their ensemble average response. While many different single cell techniques exist for suspension cultures, which can process and characterize large numbers of individual cells in rapid succession, the access to surface-immobilized cells in typical 2D and 3D culture environments remains challenging. Open space microfluidics has created new possibilities in this area, allowing for exclusive access to single cells in adherent cultures, even at high confluency. In this chapter, we briefly review new microtechnologies for the investigation of protein function in single adherent cells, and present an overview over related recent applications of the multifunctional pipette (Biopen), a microfluidic multi-solution dispensing system that uses hydrodynamic confinement in open volume environments in order to establish a superfusion zone over selected single cells in adherent cultures.
11.	Khorshidi, Mohammad Ali, 1981- (författare) Live Single Cell Imaging and Analysis Using Microfluidic Devices 2013 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Today many cell biological techniques study large cell populations where an average estimate of individual cells’ behavior is observed. On the other hand, single cell analysis is required for studying functional heterogeneities between cells within populations. This thesis presents work that combines the use of microfluidic devices, optical microscopy and automated image analysis to design various cell biological assays with single cell resolution including cell proliferation, clonal expansion, cell migration, cell-cell interaction and cell viability tracking. In fact, automated high throughput single cell techniques enable new studies in cell biology which are not possible with conventional techniques.In order to automatically track dynamic behavior of single cells, we developed a microwell based device as well as a droplet microfluidic platform. These high throughput microfluidic assays allow automated time-lapse imaging of encapsulated single cells in micro droplets or confined cells inside microwells. Algorithms for automatic quantification of cells in individual microwells and micro droplets are developed and used for the analysis of cell viability and clonal expansion. The automatic counting protocols include several image analysis steps, e.g. segmentation, feature extraction and classification. The automatic quantification results were evaluated by comparing with manual counting and revealed a high success rate. In combination these automatic cell counting protocols and our microfluidic platforms can provide statistical information to better understand behavior of cells at the individual level under various conditions or treatments in vitro exemplified by the analysis of function and regulation of immune cells. Thus, together these tools can be used for developing new cellular imaging assays with resolution at the single cell level.To automatically characterize transient migration behavior of natural killer (NK) cells compartmentalized in microwells, we developed a method for single cell tracking. Time-lapse imaging showed that the NK cells often exhibited periods of high motility, interrupted with periods of slow migration or complete arrest. These transient migration arrest periods (TMAPs) often overlapped with periods of conjugations between NK cells and target cells. Such conjugation periods sometimes led to cell-mediated killing of target cells. Analysis of cytotoxic response of NK cells revealed that a small sub-class of NK cells called serial killers was able to kill several target cells. In order to determine a starting time point for cell-cell interaction, a novel technique based on ultrasound was developed to aggregate NK and target cells into the center of the microwells. Therefore, these assays can be used to automatically and rapidly assess functional and migration behavior of cells to detect differences between health and disease or the influence of drugs.The work presented in this thesis gives good examples of how microfluidic devices combined with automated imaging and image analysis can be helpful to address cell biological questions where single cell resolution is necessary.
12.	Lindskog, Cecilia (författare) The Human Protein Atlas : an important resource for basic and clinical research 2016 Ingår i: Expert Review of Proteomics. - : Informa UK Limited. - 1478-9450 .- 1744-8387. ; 13:7, s. 627-629 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
13.	Nilsson, Avlant, 1985, et al. (författare) Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis 2020 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:19, s. 10294-10304 Tidskriftsartikel (refereegranskat)abstract Many cancer cells consume glutamine at high rates; counterintuitively, they simultaneously excrete glutamate, the first intermediate in glutamine metabolism. Glutamine consumption has been linked to replenishment of tricarboxylic acid cycle (TCA) intermediates and synthesis of adenosine triphosphate (ATP), but the reason for glutamate excretion is unclear. Here, we dynamically profile the uptake and excretion fluxes of a liver cancer cell line (HepG2) and use genome-scale metabolic modeling for in-depth analysis. We find that up to 30% of the glutamine is metabolized in the cytosol, primarily for nucleotide synthesis, producing cytosolic glutamate. We hypothesize that excreting glutamate helps the cell to increase the nucleotide synthesis rate to sustain growth. Indeed, we show experimentally that partial inhibition of glutamate excretion reduces cell growth. Our integrative approach thus links glutamine addiction to glutamate excretion in cancer and points toward potential drug targets.
14.	Padra, János T, et al. (författare) Optimization of Alcian blue pH1.0 histo-staining protocols to match mass spectrometric quantification of sulfomucins and circumvent false positive results due to sialomucins. 2022 Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 32:1, s. 6-10 Tidskriftsartikel (refereegranskat)abstract Sulfomucins are in some body-locations and species a normal occurrence, whereas in other situations a sign of pathology. Sulfomucin content on histological sections and isolated material is frequently analyzed with Alcian blue staining at pH1.0. However, since the stain detects the charge, a high density of other charged molecules, such as sialic acids has potential to impede specificity. Here, we compared the outcome from four staining protocols with the level of sulfation determined by liquid chromatography-tandem mass spectrometry analysis (MS) on samples from various tissues with variable sulfation and sialylation levels. We found that a protocol we designed, including rinsing with MetOH and 0.5M NaCl buffer at pH1.0 eliminates false positive staining of tissues outperforming commonly recommended solutions. In tissues with low to moderately sulfated mucins (e.g. human stomach and salmonid epithelia) this method enables accurate relative quantification (e.g. sulfate scoring comparisons between healthy and diseased tissues) whereas the range of the method is not suitable for comparisons between tissues with high sulfomucin content (e.g. pig stomach and colon).
15.	Sun, He (författare) Antibiotic resistance in biogas processes 2021 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Anaerobic digestion (AD) is a well-established technology that can play a key role in development of a sustainable society. In AD, organic wastes such as animal manure, food waste and crop residues are used as substrate and converted to biogas and digestate, which represent green energy and a biofertiliser. Due to intensive use of veterinary antibiotics, antibiotic residues, antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) enter the AD process via the substrates and end up in the digestate. Thus, digestate may represent a source of spread of antibiotic resistance. Antibiotic resistance is one of the greatest global public health challenges of our time and is predicted to cause around 300 million premature deaths by 2050, so countering its spread is critically important. However, research on the antibiotic resistance level in AD is still quite limited. This thesis contributed essential new knowledge by a) identifying ARB communities in digestates originating from food waste, crops and dairy manure; b) assessing antibiotic resistance in plant-based substrates; c) investigating phenotypic and genotypic resistance pattern and resistance transferability of isolated ARB; and d) comparing molecular and culture-dependent methods in evaluation of antibiotic resistance. Bacillus and closely-related genera such as Paenibacillus and Lysinibacillus were found to dominate the ARB community isolated from digestate, irrespective of substrate type. Most ARGs identified for these ARB were located on chromosomes, although several ARB strains had extra-chromosomal genomes. Only one was identified as a plasmid (pAMαl), which proved to be nontransferable in plasmid conjugation testing. Thus, the dominant ARB community from the digestates studied likely poses a limited risk of antibiotic resistance spread, although even plant-based substrates were found to contain variant antibiotic resistance components. Combined use of molecular and culturedependent methods was required to reveal the true antibiotic resistance situation in the AD process.
16.	Munthe, Christian, 1962 (författare) Will IVF ever be the norm? 2014 Ingår i: Future of IVF - A Brave New World? ESHRE symposium, September 26-27, Stockholm. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
17.	Palmquist, Anders, 1977, et al. (författare) Complex geometry and integrated macro-porosity: Clinical applications of electron beam melting to fabricate bespoke bone-anchored implants 2023 Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 156, s. 125-145 Forskningsöversikt (refereegranskat)abstract The last decade has witnessed rapid advancements in manufacturing technologies for biomedical implants. Additive manufacturing (or 3D printing) has broken down major barriers in the way of producing complex 3D geometries. Electron beam melting (EBM) is one such 3D printing process applicable to metals and alloys. EBM offers build rates up to two orders of magnitude greater than comparable laser-based technologies and a high vacuum environment to prevent accumulation of trace elements. These features make EBM particularly advantageous for materials susceptible to spontaneous oxidation and nitrogen pick-up when exposed to air (e.g., titanium and titanium-based alloys). For skeletal reconstruction(s), anatomical mimickry and integrated macro-porous architecture to facilitate bone ingrowth are undoubtedly the key features of EBM manufactured implants. Using finite element modelling of physiological loading conditions, the design of a prosthesis may be further personalised. This review looks at the many unique clinical applications of EBM in skeletal repair and the ground-breaking innovations in prosthetic rehabilitation. From a simple acetabular cup to the fifth toe, from the hand-wrist complex to the shoulder, and from vertebral replacement to cranio-maxillofacial reconstruction, EBM has experienced it all. While sternocostal reconstructions might be rare, the repair of long bones using EBM manufactured implants is becoming exceedingly frequent. Despite the various merits, several challenges remain yet untackled. Nevertheless, with the capability to produce osseointegrating implants of any conceivable shape/size, and permissive of bone ingrowth and functional loading, EBM can pave the way for numerous fascinating and novel applications in skeletal repair, regeneration, and rehabilitation. Statement of significance: Electron beam melting (EBM) offers unparalleled possibilities in producing contaminant-free, complex and intricate geometries from alloys of biomedical interest, including Ti6Al4V and CoCr. We review the diverse range of clinical applications of EBM in skeletal repair, both as mass produced off-the-shelf implants and personalised, patient-specific prostheses. From replacing large volumes of disease-affected bone to complex, multi-material reconstructions, almost every part of the human skeleton has been replaced with an EBM manufactured analog to achieve macroscopic anatomical-mimickry. However, various questions regarding long-term performance of patient-specific implants remain unaddressed. Directions for further development include designing personalised implants and prostheses based on simulated loading conditions and accounting for trabecular bone microstructure with respect to physiological factors such as patient's age and disease status.
18.	Ahluwalia, Bani, et al. (författare) Differences in Metabolite Composition of Aloe barbadensis Mill. Extracts Lead to Differential Effects on Human Blood T Cell Activity In Vitro 2022 Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1420-3049. ; 27:19 Tidskriftsartikel (refereegranskat)abstract Aloe barbadensis Mill. (Aloe) is used for diverse therapeutic properties including immunomodulation. However, owing to the compositionally complex nature of Aloe, bioactive component(s) responsible for its beneficial properties, though thought to be attributed to polysaccharides (acemannan), remain unknown. We therefore aimed to determine the metabolite composition of various commercial Aloe extracts and assess their effects on human blood T cell activity in vitro. Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated polyclonally in presence or absence of various Aloe extracts. T cell phenotype and proliferation were investigated by flow cytometry. Aloe extracts were analyzed using targeted 1H-NMR spectroscopy for standard phytochemical quality characterization and untargeted gas chromatography mass spectrometry (GC-MS) for metabolite profiling. Aloe extracts differing in their standard phytochemical composition had varying effects on T cell activation, proliferation, apoptosis, and cell-death in vitro, although this was not related to the acemannan content. Furthermore, each Aloe extract had its own distinct metabolite profile, where extracts rich in diverse sugar and sugar-derivatives were associated with reduced T cell activity. Our results demonstrate that all commercial Aloe extracts are unique with distinct metabolite profiles, which lead to differential effects on T cell activity in vitro, independent of the acemannan content.
19.	Akbari, Ali, et al. (författare) Free and hydrogel encapsulated exosome-based therapies in regenerative medicine. 2020 Ingår i: Life sciences. - : Elsevier BV. - 1879-0631 .- 0024-3205. ; 249 Tidskriftsartikel (refereegranskat)abstract Over the last few decades, mesenchymal stem cells-derived exosomes (MSCs-Ex) have attracted a lot of attention as a therapeutic tool in regenerative medicine. Exosomes are extracellular vehicles (EVs) that play important roles in cell-cell communication through various processes such as stress response, senescence, angiogenesis, and cell differentiation. Success in the field of regenerative medicine sparked exploration of the potential use of exosomes as key therapeutic effectors of MSCs to promote tissue regeneration. Various approaches including direct injection, intravenous injection, intraperitoneal injection, oral administration, and hydrogel-based encapsulation have been exploited to deliver exosomes to target tissues in different disease models. Despite significant advances in exosome therapy, it is unclear which approach is more effective for administering exosomes. Herein, we critically review the emerging progress in the applications of exosomes in the form of free or association with hydrogels as therapeutic agents for applications in regenerative medicine.
20.	Borzacchiello, A, et al. (författare) Rheological characterization of vocal folds after injection augmentation in a preliminary animal study 2004 Ingår i: Journal of bioactive and compatible polymers (Print). - London : Sage Publications. - 0883-9115 .- 1530-8030. ; 19:4, s. 331-341 Tidskriftsartikel (refereegranskat)abstract The investigation of vocal folds viscoelastic properties in an animal model (rabbit) after injection of various augmentation substances, 6 months after injection, is reported. The injected materials were: hyaluronan-based materials (Hylan B gel and Deflux(R)), cross-linked collagen (Zyplast(R)) and polytetrafluoroethylene (Teflon(R)). Rheological properties of the augmentation substances were also evaluated. The results from these animal experiments indicate that the viscoelastic properties of the vocal folds injected with Deflux(R), Zyplast(R) and Hylan B gel are similar to the healthy vocal folds (non-injected samples) used as control, thus demonstrating that these materials are good candidates for further studies aimed at restoring/preserving the vibratory capacity of the vocal folds with injection treatment in glottal insufficiency.
21.	Cepeda, D., et al. (författare) CDK-mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer 2013 Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 5:7, s. 999-1018 Tidskriftsartikel (refereegranskat)abstract SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F-box mutant unable to support MYC ubiquitylation results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer. FBXO28 is identified as part of a SCF complex acting as a regulator of tumor cell proliferation and an important modifier of MYC function. FBXO28 may be a new prognostic factor in breast cancer and a new potential drug target in MYC- driven tumors.
22.	Charkoftaki, Georgia, et al. (författare) Yale School of Public Health Symposium on tissue imaging mass spectrometry : illuminating phenotypic heterogeneity and drug disposition at the molecular level 2018 Ingår i: Human Genomics. - : Springer Science and Business Media LLC. - 1473-9542 .- 1479-7364. ; 12 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
23.	Chen, Xin, 1980, et al. (författare) Dataset for suppressors of amyloid-beta toxicity and their functions in recombinant protein production in yeast 2022 Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 42 Tidskriftsartikel (refereegranskat)abstract The production of recombinant proteins at high levels often induces stress-related phenotypes by protein misfolding or aggregation. These are similar to those of the yeast Alzheimer's disease (AD) model in which amyloid-beta peptides (A beta 42) were accumulated [1,2] . We have previously identified suppressors of A beta 42 cytotoxicity via the genome-wide synthetic genetic array (SGA) [3] and here we use them as metabolic engineering targets to evaluate their potentiality on recombinant protein production in yeast Saccharomyces cerevisiae. In order to investigate the mechanisms linking the genetic modifications to the improved recombinant protein production, we perform systems biology approaches (transcriptomics and proteomics) on the resulting strain and intermediate strains. The RNAseq data are preprocessed by the nf-core/RNAseq pipeline and analyzed using the Platform for Integrative Analysis of Omics (PIANO) package [4] . The quantitative proteome is analyzed on an Orbitrap Fusion Lumos mass spectrometer interfaced with an Easy-nLC1200 liquid chromatography (LC) system. LC-MS data files are processed by Proteome Discoverer version 2.4 with Mascot 2.5.1 as a database search engine. The original data presented in this work can be found in the research paper titled "Suppressors of Amyloid-beta Toxicity Improve Recombinant Protein Produc-tion in yeast by Reducing Oxidative Stress and Tuning Cellu-lar Metabolism", by Chen et al. [5] . (C) 2022 The Author(s). Published by Elsevier Inc.
24.	Claesson, Rolf, et al. (författare) Characterization of Aggregatibacter actinomycetemcomitans Serotype b Strains with Five Different, Including Two Novel, Leukotoxin Promoter Structures 2020 Ingår i: Vaccines. - Basel, Switzerland : MDPI. - 2076-393X. ; 8:3 Tidskriftsartikel (refereegranskat)abstract The JP2 genotype of A. actinomycetemcomitans, serotype b has attracted much interest during the past three decades due to its close association with periodontitis in young individuals and the enhanced expression of a leukotoxin (LtxA). A typical feature of this genotype is a 530-base pair (bp) deletion in the ltxCABD promoter region controlling leukotoxin expression. In the present work, we have characterized serotype b strains with four additional promoter types. Two novel types have been recognized, that is, one with a 230-bp deletion and one with a 172-bp duplication. Moreover, a strain with a 640-bp deletion and three strains with a full-length promoter, including the type strain Y4, were included in the present study. The seven strains were characterized by multi locus sequence typing (MLST) and arbitrarily primed polymerase chain reaction (PCR) and assessed for LtxA production. MLST showed that the strains with the non-JP2-like deletions represented distinct monophyletic groups, whereas the JP2 strain, HK1651, represented a separate branch. LtxA production was high in all three strains with a promoter deletion, whereas the other four strains showed significantly lower levels. It can be concluded that the genetic characterization and determination of LtxA production of A. actinomycetemcomitans isolates from individuals with periodontitis can contribute to the identification of novel virulent genotypes of this bacterium.
25.	Darmanis, Spyros, et al. (författare) Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors 2013 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. e81712- Tidskriftsartikel (refereegranskat)abstract BackgroundPatients with well-differentiated small intestine neuroendocrine tumors (WD-SI-NET) are most often diagnosed at a metastatic stage of disease, which reduces possibilities for a curative treatment. Thus new approaches for earlier detection and improved monitoring of the disease are required.Materials and methodsSuspension bead arrays targeting 124 unique proteins with antibodies from the Human Protein Atlas were used to profile biotinylated serum samples. Discoveries from a cohort of 77 individuals were followed up in a cohort of 132 individuals both including healthy controls as well as patients with untreated primary WD-SI-NETs, lymph node metastases and liver metastases.Results A set of 20 antibodies suggested promising proteins for further verification based on technically verified statistical significance. Proceeding, we assessed the classification performance in an independent cohort of patient serum, achieving, classification accuracy of up to 85% with different subsets of antibodies in respective pairwise group comparisons. The protein profiles of nine targets, namely IGFBP2, IGF1, SHKBP1, ETS1, IL1α, STX2, MAML3, EGR3 and XIAP were verified as significant contributors to tumor classification.ConclusionsWe propose new potential protein biomarker candidates for classifying WD-SI-NET at different stage of disease. Further evaluation of these proteins in larger sample sets and with alternative approaches is needed in order to further improve our understanding of their functional relation to WD-SI-NET and their eventual use in diagnostics.
26.	de Oliveira, Felipe Marques Souza, et al. (författare) Detection of post-translational modifications using solid-phase proximity ligation assay. 2018 Ingår i: New biotechnology. - : Elsevier BV. - 1876-4347 .- 1871-6784. ; 45:October, s. 51-59 Tidskriftsartikel (refereegranskat)abstract Post-translational modifications (PTMs) regulate protein activities to help orchestrate and fine-tune cellular processes. Dysregulation of PTMs is often related with disorders and malignancies, and may serve as a precise biomarker of disease. Developing sensitive tools to measure and monitor low-abundant PTMs in tissue lysates or serum will be instrumental for opening up new PTM-based diagnostic avenues. Here, we investigate the use of solid-phase proximity ligation assay (SP-PLA) for detection of different PTMs. The assay depends on the recognition of the target protein molecule and its modification by three affinity binders. Using antibodies and lectins, we applied the method for detection of glycosylated CD44 and E-Cadherin, and phosphorylated p53 and EGFR. The assay was found to have superior dynamic range and limit of detection compared to standard ELISAs. In summary, we have established the use of SP-PLA as an appropriate method for sensitive detection of PTMs in lysates and sera, which may provide a basis for future PTM-based diagnostic and prognostic biomarkers.
27.	El-Sayed, R., et al. (författare) Degradation of pristine and oxidized single wall carbon nanotubes by CYP3A4 2019 Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 515:3, s. 487-492 Tidskriftsartikel (refereegranskat)abstract Carbon nanotubes (CNTs) are a class of carbon based nanomaterials which have attracted substantial attention in recent years as they exhibit outstanding physical, mechanical and optical properties. In the last decade many studies have emerged of the underlying mechanisms behind CNT toxicity including malignant transformation, the formation of granulomas, inflammatory responses, oxidative stress, DNA damage and mutation. In the present investigation, we studied the biodegradation of single-walled carbon nanotubes (SWCNTs) by Cytochrome P450 enzymes (CYP3A4) through using Raman spectroscopy. CYP3A4 is known isozyme accountable for metabolizing various endogenous and exogenous xenobiotics. CYP3A4 is expressed dominantly in the liver and other organs including the lungs. Our results suggest that CYP3A4 has a higher affinity for p-SWNTs compared to c-SWNTs. HEK293 cellular viability was not compromised when incubated with SWNT. However, CYP3A4 transfected HEK293 cell line showed no digestion of c-SWNTs after incubation for 96 h. Cellular uptake of c-SWNTs was observed by electron microscopy and localization of c-SWNTs was confirmed in endosomal vesicles and in the cytoplasm. This is the first study CYP3A4 degrading both p-SWNTs and c-SWNTs in an in vitro setup. Interestingly, our results show that CYP3A4 is more proficient in degrading p-SWNTs than c-SWNTs. We also employed computational modeling and docking assessments to develop a further understanding of the molecular interaction mechanism. © 2019 Elsevier Inc.
28.	Esberg, Anders, et al. (författare) Oral Microbiota Profile in Patients with Anti-Neutrophil Cytoplasmic Antibody–Associated Vasculitis 2022 Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 10:8 Tidskriftsartikel (refereegranskat)abstract Microbiota has been associated with autoimmune diseases, with nasal Staphylococcus aureus being implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV). Little is known about the role of oral microbiota in AAV. In this study, levels of IgG antibodies to 53 oral bacterial species/subspecies were screened using immunoblotting in plasma/serum in pre-symptomatic AAV-individuals (n = 85), matched controls, and established AAV-patients (n = 78). Saliva microbiota from acute-AAV and controls was sequenced from 16s rDNA amplicons. Information on dental status was extracted from a national register. IgG levels against oral bacteria were lower in established AAV versus pre-AAV and controls. Specifically, pre-AAV samples had, compared to controls, a higher abundance of periodontitis-associated species paralleling more signs of periodontitis in established AAV-patients than controls. Saliva microbiota in acute-AAV showed higher within-sample diversity but fewer detectable amplicon-sequence variants and taxa in their core microbiota than controls. Acute-AAV was not associated with increased abundance of periodontal bacteria but species in, e.g., Arthrospira, Staphylococcus, Lactobacillus, and Scardovia. In conclusion, the IgG profiles against oral bacteria differed between pre-AAV, established AAV, and controls, and microbiota profiles between acute AAV and controls. The IgG shift from a pre-symptomatic stage to established disease cooccurred with treatment of immunosuppression and/or antibiotics.
29.	Garcia-Bennett, Alfonso, et al. (författare) In vitro generation of motor neuron precursors from mouse embryonic stem cells using mesoporous nanoparticles 2014 Ingår i: Nanomedicine. - : Future Medicine Ltd. - 1743-5889 .- 1748-6963. ; 9:16, s. 2457-2466 Tidskriftsartikel (refereegranskat)abstract Aim: Stem cell-derived motor neurons (MNs) are utilized to develop replacement strategies for spinal cord disorders. Differentiation of embryonic stem cells into MN precursors involves factors and their repeated administration. We investigated if delivery of factors loaded into mesoporous nanoparticles could be effective for stem cell differentiation in vitro.Materials & methods: We used a mouse embryonic stem cell line expressing green fluorescent protein under the promoter for the MN-specific gene Hb9 to visualize the level of MN differentiation. The differentiation of stem cells was evaluated by expression of MN-specific transcription factors monitored by quantitative real-time PCR reactions and immunocytochemistry.Results: Mesoporous nanoparticles have strong affiliation to the embryoid bodies, penetrate inside the embryoid bodies and come in contact with differentiating cells.Conclusion: Repeated administration of soluble factors into a culture medium can be avoided due to a sustained release effect using mesoporous silica.
30.	Guo, Hao, et al. (författare) A humanized monoclonal antibody targeting secreted anterior gradient 2 effectively inhibits the xenograft tumor growth. 2016 Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 475:1, s. 57-63 Tidskriftsartikel (refereegranskat)abstract Anterior Gradient 2 (AGR2) is a potential anti-tumor target and we previously reported a murine antibody 18A4 with specific binding to AGR2. However, humanization is a must to overcome immunogenicity before considering for clinical use and optimized vectors for mammalian expression are also necessary for following industrialized manufacture. Here, we describe an anti-tumor humanized antibody blocking secreted AGR2 activity. We employed the CDR grafting technique and deimmunization analysis to construct humanized antibody variants of 18A4, and 18A4Hu I was selected as the best humanization candidate, characterized by physical and chemical property comparison. Mouse xenograft study showed that 18A4Hu I could effectively inhibit the xenograft tumor growth, antibody blocking epitope analysis using AGR2 mutants indicated that the inhibition activity of 18A4Hu I is exerted probably through blocking the AGR2 functions which rely on the amino acid sites of E60-H76 and A86-E153. What's more, in this report, we also describe a pHAb-FAST vector system which is specifically designed for humanized antibody mammalian expression vector fast construction. With pHAb-FAST system, expression vector of 18A4Hu I could be quickly constructed only through twice overlapping PCR reactions. To our knowledge, AGR2-targeted 18A4Hu I is a promising humanized anti-tumor drug candidate, and pHAb-FAST system is a useful optimized mammalian expression vector construction tool. Our findings are supposed to accelerate the development of antibody-based cancer therapy.
31.	Hulsart-Billstrom, Gry, et al. (författare) Iodine-enhanced contrast applicable for microcomputed tomography 2014 Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - 1932-6254 .- 1932-7005. ; 8, s. 245-246 Tidskriftsartikel (refereegranskat)
32.	Lehner, C., et al. (författare) The blood-tendon barrier: Identification and characterisation of a novel tissue barrier in tendon blood vessels 2016 Ingår i: European Cells and Materials. - 1473-2262. ; 31, s. 296-311 Tidskriftsartikel (refereegranskat)abstract Tissue barriers function as “gate keepers” between different compartments (usually blood and tissue) and are formed by specialised membrane-associated proteins, localising to the apicolateral plasma membrane domain of epithelial and endothelial cells. By sealing the paracellular space, the free diffusion of solutes and molecules across epithelia and endothelia is impeded. Thereby, tissue barriers contribute to the establishment and maintenance of a distinct internal and external environment, which is crucial during organ development and allows maintenance of an organ-specific homeostatic milieu. So far, various epithelial and endothelial tissue barriers have been described, including the blood-brain barrier, the blood-retina barrier, the blood-testis barrier, the blood-placenta barrier, and the cerebrospinal fluid (CSF)-brain barrier, which are vital for physiological function and any disturbance of these barriers can result in severe organ damage or even death. Here, we describe the identification of a novel barrier, located in the vascular bed of tendons, which we term the blood-tendon barrier (BTB). By using immunohistochemistry, transmission electron microscopy, and tracer studies we demonstrate the presence of a functional endothelial barrier within tendons restricting the passage of large blood-borne molecules into the surrounding tendon tissue. We further provide in vitro evidence that the BTB potentially contributes to the creation of a distinct internal tissue environment impacting upon the proliferation and differentiation of tendon-resident cells, effects which might be fundamental for the onset of tendon pathologies. © 2016, AO Research Institute. All rights reserved.
33.	Mahale, Sagar, et al. (författare) HnRNPK maintains single strand RNA through controlling double-strand RNA in mammalian cells. 2022 Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1 Tidskriftsartikel (refereegranskat)abstract Although antisense transcription is a widespread event in the mammalian genome, double-stranded RNA (dsRNA) formation between sense and antisense transcripts is very rare and mechanisms that control dsRNA remain unknown. By characterizing the FGF-2 regulated transcriptome in normal and cancer cells, we identified sense and antisense transcripts IER3 and IER3-AS1 that play a critical role in FGF-2 controlled oncogenic pathways. We show that IER3 and IER3-AS1 regulate each other's transcription through HnRNPK-mediated post-transcriptional regulation. HnRNPK controls the mRNA stability and colocalization of IER3 and IER3-AS1. HnRNPK interaction with IER3 and IER3-AS1 determines their oncogenic functions by maintaining them in a single-stranded form. hnRNPK depletion neutralizes their oncogenic functions through promoting dsRNA formation and cytoplasmic accumulation. Intriguingly, hnRNPK loss-of-function and gain-of-function experiments reveal its role in maintaining global single- and double-stranded RNA. Thus, our data unveil the critical role of HnRNPK in maintaining single-stranded RNAs and their physiological functions by blocking RNA-RNA interactions.
34.	Mega, Alessandro, et al. (författare) Astrocytes enhance glioblastoma growth. 2020 Ingår i: Glia. - : Wiley. - 0894-1491 .- 1098-1136. ; 68:2, s. 316-327 Tidskriftsartikel (refereegranskat)abstract Glioblastoma (GBM) is a deadly disease with a need for deeper understanding and new therapeutic approaches. The microenvironment of glioblastoma has previously been shown to guide glioblastoma progression. In this study, astrocytes were investigated with regard to their effect on glioblastoma proliferation through correlative analyses of clinical samples and experimental in vitro and in vivo studies. Co-culture techniques were used to investigate the GBM growth enhancing potential of astrocytes. Cell sorting and RNA sequencing were used to generate a GBM-associated astrocyte signature and to investigate astrocyte-induced GBM genes. A NOD scid GBM mouse model was used for in vivo studies. A gene signature reflecting GBM-activated astrocytes was associated with poor prognosis in the TCGA GBM dataset. Two genes, periostin and serglycin, induced in GBM cells upon exposure to astrocytes were expressed at higher levels in cases with high "astrocyte signature score". Astrocytes were shown to enhance glioblastoma cell growth in cell lines and in a patient-derived culture, in a manner dependent on cell-cell contact and involving increased cell proliferation. Furthermore, co-injection of astrocytes with glioblastoma cells reduced survival in an orthotopic GBM model in NOD scid mice. In conclusion, this study suggests that astrocytes contribute to glioblastoma growth and implies this crosstalk as a candidate target for novel therapies.
35.	Möller, Thomas, 1986, et al. (författare) In Vivo Chondrogenesis in 3D Bioprinted Human Cell-laden Hydrogel Constructs 2017 Ingår i: Plastic and Reconstructive Surgery - Global Open. - 2169-7574 .- 0032-1052 .- 1529-4242. ; 5:2, s. Article no e1227 - Tidskriftsartikel (refereegranskat)abstract Background: The three-dimensional (3D) bioprinting technology allows creation of 3D constructs in a layer-by-layer fashion utilizing biologically relevant materials such as biopolymers and cells. The aim of this study is to investigate the use of 3D bioprinting in a clinically relevant setting to evaluate the potential of this technique for in vivo chondrogenesis. Methods: Thirty-six nude mice (Balb-C, female) received a 5-x 5-x 1-mm piece of bioprinted cell-laden nanofibrillated cellulose/alginate construct in a subcutaneous pocket. Four groups of printed constructs were used: (1) human (male) nasal chondrocytes (hNCs), (2) human (female) bone marrow-derived mesenchymal stem cells (hBMSCs), (3) coculture of hNCs and hBMSCs in a 20/80 ratio, and (4) Cell-free scaffolds (blank). After 14, 30, and 60 days, the scaffolds were harvested for histological, immunohistochemical, and mechanical analysis. Results: The constructs had good mechanical properties and keep their structural integrity after 60 days of implantation. For both the hNC constructs and the cocultured constructs, a gradual increase of glycosaminoglycan production and hNC proliferation was observed. However, the cocultured group showed a more pronounced cell proliferation and enhanced deposition of human collagen II demonstrated by immunohistochemical analysis. Conclusions: In vivo chondrogenesis in a 3D bioprinted human cell-laden hydrogel construct has been demonstrated. The trophic role of the hBMSCs in stimulating hNC proliferation and matrix deposition in the coculture group suggests the potential of 3D bioprinting of human cartilage for future application in reconstructive surgery.
36.	Nawaz, Muhammad (författare) Extracellular vesicle-mediated transport of non-coding RNAs between stem cells and cancer cells: implications in tumor progression and therapeutic resistance. 2017 Ingår i: Stem cell investigation. - : AME Publishing Company. - 2306-9759 .- 2313-0792. ; 4 Forskningsöversikt (refereegranskat)abstract Recent years have witnessed intensive progress in studying extracellular vesicles (EVs), both for understanding their basic biology and contribution to variety of diseases, biomarker discovery, and their potential as gene delivery vectors and source of innovative therapies. As such, stem cell-derived EVs have contributed significant knowledge which led to the development of cell-free therapies in regenerative medicine. Although, the role of stem cell-derived EVs in maintaining stemness, differentiation and repairing tissue injuries is relatively well-understood; however, knowledge about the contribution of stem cell-derived EVs in cancer progression is just emerging. The aim of this review is, therefore, to discuss the recent developments in stem cell-derived EVs and tumor progression, placing a particular focus on non-coding RNA (ncRNA) mediated cancer progression and resistance against therapies. This includes the failure of normal hematopoiesis and the progression of myeloid neoplasms, enhanced capacity of cancer cells to proliferate and metastasize, and the conversion of normal cells into cancer cells, activation of angiogenic pathways and dormancy in cancer cells. These processes are shared by mesenchymal stem cells (MSCs), cancer stem like-cells and cancer cells in an intricate intratumoral network in order to create self-strengthening tumor niche. In this context, EV-ncRNAs serve as mediators to relay bystander effects of secreting cancer stem cells (CSCs) into recipient cells for priming a tumor permissive environment and relaying therapeutic resistance. Collectively, this knowledge will improve our understandings and approaches in finding new therapeutic targets in the context of CSCs, which could be benefited through engineering EVs for innovative therapies.
37.	Neiman, Maja, et al. (författare) Selectivity analysis of single binder assays used in plasma protein profiling 2013 Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 13:23-24, s. 3406-3410 Tidskriftsartikel (refereegranskat)abstract The increasing availability of antibodies toward human proteins enables broad explorations of the proteomic landscape in cells, tissues, and body fluids. This includes assays with antibody suspension bead arrays that generate protein profiles of plasma samples by flow cytometer analysis. However, antibody selectivity is context dependent so it is necessary to corroborate on-target detection over off-target binding. To address this, we describe a concept to directly verify interactions from antibody-coupled beads by analysis of their eluates by Western blots and MS. We demonstrate selective antibody binding in complex samples with antibodies toward a set of chosen proteins with different abundance in plasma and serum, and illustrate the need to adjust sample and bead concentrations accordingly. The presented approach will serve as an important tool for resolving differential protein profiles from antibody arrays within plasma biomarker discoveries.
38.	Orre, Lukas Minus, et al. (författare) SubCellBarCode : Proteome-wide Mapping of Protein Localization and Relocalization 2019 Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 73:1, s. 166-182.e7 Tidskriftsartikel (refereegranskat)abstract Subcellular localization is a main determinant of protein function; however, a global view of cellular proteome organization remains relatively unexplored. We have developed a robust mass spectrometry-based analysis pipeline to generate a proteome-wide view of subcellular localization for proteins mapping to 12,418 individual genes across five cell lines. Based on more than 83,000 unique classifications and correlation profiling, we investigate the effect of alternative splicing and protein domains on localization, complex member co-localization, cell-type-specific localization, as well as protein relocalization after growth factor inhibition. Our analysis provides information about the cellular architecture and complexity of the spatial organization of the proteome; we show that the majority of proteins have a single main subcellular location, that alternative splicing rarely affects subcellular location, and that cell types are best distinguished by expression of proteins exposed to the surrounding environment. The resource is freely accessible via www.subcellbarcode.org.
39.	Panda, Pritam Kumar, PhD Student, 1991-, et al. (författare) Molecular nanoinformatics approach assessing the biocompatibility of biogenic silver nanoparticles with channelized intrinsic steatosis and apoptosis 2022 Ingår i: Green Chemistry. - : Royal Society of Chemistry (RSC). - 1463-9262 .- 1463-9270. ; 24:3, s. 1190-1210 Tidskriftsartikel (refereegranskat)abstract The developmental rapidity of nanotechnology poses higher risks of exposure to humans and the environment through manufactured nanomaterials. The multitude of biological interfaces, such as DNA, proteins, membranes, and cell organelles, which come in contact with nanoparticles, is influenced by colloidal and dynamic forces. Consequently, the ensued nano-bio interface depends on dynamic forces, encompasses many cellular absorption mechanisms along with various biocatalytic activities, and biocompatibility that needs to be investigated in detail. Addressing the issue, the study offers a novel green synthesis strategy for antibacterial AgNPs with higher biocompatibility and elucidates the mechanistic in vivo biocompatibility of silver nanoparticles (AgNPs) at the cellular and molecular levels. The analysis ascertained the biosynthesis of G-AgNPs with the size of 25 ± 10 nm and zeta potential of-29.2 ± 3.0 mV exhibiting LC50 of 47.2 μg mL-1 in embryonic zebrafish. It revealed the mechanism as a consequence of abnormal physiological metabolism in oxidative stress and neutral lipid metabolism due to dose-dependent interaction with proteins such as he1a, sod1, PEX protein family, and tp53 involving amino acids such as arginine, glutamine and leucine leading to improper apoptosis. The research gave a detailed insight into the role of diverse AgNPs-protein interactions with a unique combinatorial approach from first-principles density functional theory and in silico analyses, thus paving a new pathway to comprehending their intrinsic properties and usage.
40.	Paré, Guillaume, et al. (författare) Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding 2013 Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 127:13, s. 1404- Tidskriftsartikel (refereegranskat)abstract BackgroundFixed-dose unmonitored treatment with dabigatran etexilate is effective and has a favorable safety profile in prevention of stroke in atrial fibrillation patients compared to warfarin. We hypothesized that genetic variants could contribute to inter-individual variability in blood concentrations of the active metabolite of dabigatran etexilate, and influence the safety and efficacy of dabigatran.Methods and ResultsWe successfully conducted a genome-wide association study in 2,944 RE-LY participants. The CES1 SNP rs2244613 was associated with trough concentrations, and the ABCB1 SNP rs4148738 and CES1 SNP rs8192935 were associated with peak concentrations at genome-wide significance (P<9 x 10-8) with a gene-dose effect. Each minor allele of the CES1 SNP rs2244613 was associated with lower trough concentrations (15% decrease per allele, 95%CI 10-19%; P=1.2 x 10-8) and a lower risk of any bleeding (OR=0.67, 95%CI 0.55-0.82; P=7 x 10-5) in dabigatran-treated participants, with a consistent but non-significant lower risk of major bleeding (OR=0.66, 95%CI 0.43-1.01). The interaction between treatment (warfarin versus all dabigatran) and carrier status was statistically significant (P=0.002) with carriers having less bleeding with dabigatran than warfarin (HR=0.59, 95%CI 0.46-0.76; P=5.2 x 10-5) in contrast to no difference in noncarriers (HR=0.96, 95%CI 0.81-1.14; P=0.65). There was no association with ischemic events, and neither rs4148738 nor rs8192935 was associated with bleeding or ischemic events.ConclusionsGenome-wide association analysis identified that carriage of CES1 rs2244613 minor allele occurred in 32.8% of patients in RELY and was associated with lower exposure to active dabigatran metabolite. The presence of the polymorphism was associated with a lower risk of bleeding.
41.	Sahu, Siddharth S., et al. (författare) Exploiting Electrostatic Interaction for Highly Sensitive Detection of Tumor-Derived Extracellular Vesicles by an Electrokinetic Sensor 2021 Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:36, s. 42513-42521 Tidskriftsartikel (refereegranskat)abstract We present an approach to improve the detection sensitivity of a streaming current-based biosensor for membrane protein profiling of small extracellular vesicles (sEVs). The experimental approach, supported by theoretical investigation, exploits electrostatic charge contrast between the sensor surface and target analytes to enhance the detection sensitivity. We first demonstrate the feasibility of the approach using different chemical functionalization schemes to modulate the zeta potential of the sensor surface in a range -16.0 to -32.8 mV. Thereafter, we examine the sensitivity of the sensor surface across this range of zeta potential to determine the optimal functionalization scheme. The limit of detection (LOD) varied by 2 orders of magnitude across this range, reaching a value of 4.9 x 10(6) particles/mL for the best performing surface for CD9. We then used the optimized surface to profile CD9, EGFR, and PD-L1 surface proteins of sEVs derived from non-small cell lung cancer (NSCLC) cell-line H1975, before and after treatment with EGFR tyrosine kinase inhibitors, as well as sEVs derived from pleural effusion fluid of NSCLC adenocarcinoma patients. Our results show the feasibility to monitor CD9, EGFR, and PD-L1 expression on the sEV surface, illustrating a good prospect of the method for clinical application.
42.	Stranneheim, Henrik, et al. (författare) Rapid pulsed whole genome sequencing for comprehensive acute diagnostics of inborn errors of metabolism 2014 Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15, s. 1090- Tidskriftsartikel (refereegranskat)abstract Background: Massively parallel DNA sequencing (MPS) has the potential to revolutionize diagnostics, in particular for monogenic disorders. Inborn errors of metabolism (IEM) constitute a large group of monogenic disorders with highly variable clinical presentation, often with acute, nonspecific initial symptoms. In many cases irreversible damage can be reduced by initiation of specific treatment, provided that a correct molecular diagnosis can be rapidly obtained. MPS thus has the potential to significantly improve both diagnostics and outcome for affected patients in this highly specialized area of medicine. Results: We have developed a conceptually novel approach for acute MPS, by analysing pulsed whole genome sequence data in real time, using automated analysis combined with data reduction and parallelization. We applied this novel methodology to an in-house developed customized work flow enabling clinical-grade analysis of all IEM with a known genetic basis, represented by a database containing 474 disease genes which is continuously updated. As proof-of-concept, two patients were retrospectively analysed in whom diagnostics had previously been performed by conventional methods. The correct disease-causing mutations were identified and presented to the clinical team after 15 and 18 hours from start of sequencing, respectively. With this information available, correct treatment would have been possible significantly sooner, likely improving outcome. Conclusions: We have adapted MPS to fit into the dynamic, multidisciplinary work-flow of acute metabolic medicine. As the extent of irreversible damage in patients with IEM often correlates with timing and accuracy of management in early, critical disease stages, our novel methodology is predicted to improve patient outcome. All procedures have been designed such that they can be implemented in any technical setting and to any genetic disease area. The strategy conforms to international guidelines for clinical MPS, as only validated disease genes are investigated and as clinical specialists take responsibility for translation of results. As follow-up in patients without any known IEM, filters can be lifted and the full genome investigated, after genetic counselling and informed consent.
43.	Syed, Zulfeqhar Ali (författare) Mucin-like proteins in Drosophila development 2014 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Mucins are large and highly glycosylated proteins and major component of the mucus that coats the lining of epithelial organs. Mucins are characterized by the presence of extended regions rich in the amino acids Proline, Threonine and Serine (PTS domain), where the Serines and Threonines are O-glycosylated to form sugar-rich mucin domains. Mucins are classified into secreted gel-forming mucins and transmembrane mucins with possible signaling functions. The amino acid sequence of the PTS domains tends to be poorly conserved between species and different mucins. The goal of this thesis was to identify and study potential mucin-like proteins in Drosophila melanogaster. We devised a simple bioinformatic approach and developed a program that can identify PTS domains based on amino acid content. We thereby identified 36 mucins and mucin-related proteins. All proteins appear to be secreted, except for two that harbor a predicted transmembrane domain. Expression analysis at different stages of the Drosophila life cycle revealed that many mucins are expressed in the larval gut, consistent with a function in mucosal barrier formation. Interestingly, some of the mucins showed dynamic expression in different tubular organs during embryogenesis. Among these was Mur96B/Tenectin (Tnc) that was further studied to dissect its role in epithelial organ development. We found that Tnc is critical for diameter expansion of the developing hindgut. Tnc forms a transient matrix that fills the hindgut lumen and drives expansion in a dose-dependent manner, presumably by generating a luminal pressure. This study revealed a new mechanism in organ development, whereby the extent of lumen volume expansion can be regulated by the accumulation of single glycoprotein. In parallel to the bioinformatic approach, we identified a Drosophila protein that shares conserved domains with human SUSD2 and the non-mucin parts of human MUC4, called Mesh. We aimed to analyze Mesh function as a means to address the roles of these domains. Mesh was found to be is expressed in the digestive tract epithelium from mid-embryogenesis and throughout larval and adult life, localizing to the apical junction belt. Mesh is required for correct organization of the Scribble-complex, a main polarity complex conserved between fly and mammals, to prevent excess expansion of apical cell surface and for microvilli organization. The results demonstrate that mucin-like proteins, containing the PTS domains or other mucin-related domains, are essential for epithelial organ development in Drosophila.
44.	Visuttijai, Kittichate, 1979-, et al. (författare) Lowered Expression of Tumor Suppressor Candidate MYO1C Stimulates Cell Proliferation, Suppresses Cell Adhesion and Activates AKT 2016 Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:10 Tidskriftsartikel (refereegranskat)abstract Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent losses distal to TP53. Myo1c can tightly and specifically bind to PIP2, the substrate of Phosphoinositide 3-kinase (PI3K), and to Rictor, suggesting a role for MYO1C in the PI3K pathway. This study was designed to examine MYO1C expression status in a panel of well-stratified endometrial carcinomas as well as to assess the biological significance of MYO1C as a tumor suppressor in vitro. We found a significant correlation between the tumor stage and lowered expression of MYO1C in endometrial carcinoma samples. In cell transfection experiments, we found a negative correlation between MYO1C expression and cell proliferation, and MYO1C silencing resulted in diminished cell migration and adhesion. Cells expressing excess of MYO1C had low basal level of phosphorylated protein kinase B (PKB, a.k.a. AKT) and cells with knocked down MYO1C expression showed a quicker phosphorylated AKT (pAKT) response in reaction to serum stimulation. Taken together the present study gives further evidence for tumor suppressor activity of MYO1C and suggests MYO1C mediates its tumor suppressor function through inhibition of PI3K pathway and its involvement in loss of contact inhibition.
45.	Zieba, Agata, et al. (författare) The Human Endometrium-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling 2015 Ingår i: Omics. - : MARY ANN LIEBERT, INC. - 1536-2310 .- 1557-8100. ; 19:11, s. 659-668 Tidskriftsartikel (refereegranskat)abstract The human uterus includes the complex endometrial mucosa, the endometrium that undergoes dynamic, hormone-dependent alterations throughout the life of fertile females. Here we have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling to analyze gene expression patterns in the normal endometrium. Human endometrial tissues from five women were used for deep sequencing (RNA-Seq). The mRNA and protein expression data from the endometrium were compared to 31 (RNA) and 44 (protein) other normal tissue types, to identify genes with elevated expression in the endometrium and to localize the expression of corresponding proteins at a cellular resolution. Based on the expression levels of transcripts, we could classify all putative human protein coding genes into categories defined by expression patterns and found altogether 101 genes that showed an elevated pattern of expression in the endometrium, with only four genes showing more than five-fold higher expression levels in the endometrium compared to other tissues. In conclusion, our analysis based on transcriptomics and antibody-based protein profiling reports here comprehensive lists of genes with elevated expression levels in the endometrium, providing important starting points for a better molecular understanding of human reproductive biology and disease.
46.	Enroth, Stefan, et al. (författare) Effects of Long-Term Storage Time and Original Sampling Month on Biobank Plasma Protein Concentrations 2016 Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 12, s. 309-314 Tidskriftsartikel (refereegranskat)abstract The quality of clinical biobank samples is crucial to their value for life sciences research. A number of factors related to the collection and storage of samples may affect the biomolecular composition. We have studied the effect of long-time freezer storage, chronological age at sampling, season and month of the year and on the abundance levels of 108 proteins in 380 plasma samples collected from 106 Swedish women. Storage time affected 18 proteins and explained 4.8–34.9% of the observed variance. Chronological age at sample collection after adjustment for storage-time affected 70 proteins and explained 1.1–33.5% of the variance. Seasonal variation had an effect on 15 proteins and month (number of sun hours) affected 36 proteins and explained up to 4.5% of the variance after adjustment for storage-time and age. The results show that freezer storage time and collection date (month and season) exerted similar effect sizes as age on the protein abundance levels. This implies that information on the sample handling history, in particular storage time, should be regarded as equally prominent covariates as age or gender and need to be included in epidemiological studies involving protein levels.
47.	Matar, Amal (författare) Considering a Baby? Responsible Screening for the Future : Ethical and social implications for implementation and use of preconception expanded carrier screening in Sweden 2019 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Preconception expanded carrier screening is a novel technology that involves the offer of a screening test for many recessive diseases (via an expanded screening panel) to prospective parents, with no priori risk. Test positive couples have a number of reproductive choices; prenatal diagnosis and aborting affected fetus, IVF and preimplantation genetic diagnosis, sperm or ovum donation or simply accept the risk. The test had been piloted in studies and can potentially be implemented in Europe. Therefore, it seemed pertinent to evaluate stakeholders’ perspectives on ethical and social implications of implementing and using preconception ECS in Sweden.Two main stakeholders were examined; healthcare professionals and health policymaking experts, via a mix of qualitative methods for data collection and data analysis. In Study I, we employed in-depth interviews to collect data and content analysis to analyze it. In Studies III and IV, expert interviews were used to gather data while thematic analysis was utilized to interpret it. Furthermore, in Study II, an ethical concept namely; reproductive autonomy, was critically discussed within a setting that expects a couple to make a conjoint reproductive decision about preconception ECS, while each partner still upholds his or her individual autonomy.The main findings of the empirical studies (Studies I, III and IV) echo to a great extent the prevailing ethical and social debates associated with the novel technology. Respondents expressed concerns with reproductive autonomy, medicalization, prioritization of health resources, discrimination and long term societal changes. Furthermore, respondents emphasized the importance to observe Swedish values, such as human dignity, equality and solidarity, when assessing a preconception ECS program. In addition, they described practicalities of implementation and political considerations that are pertinent to the Swedish context. Finally, some respondents recognized the advantages of reduced suffering and decrease in fetal anomalies and abortion as a consequence of preconception ECS.Study II, proposed a notion of couple autonomy, where certain demands if met, a couple’s reproductive decision can be accepted by healthcare staff as autonomous.The findings, in this thesis, steer towards non implementation of preconception ECS in its current status within the publicly-funded healthcare system in Sweden. This is because healthcare providers and experts were of the opinion that it would not solve a medical need, threaten Swedish values and use up resources extensively.
48.	Matar, Amal (författare) Couples Considering a Baby? Screen for the Future : Ethical and Implementation Aspects of Preconception Genetic Carrier Screening 2016 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)
49.	Bondesson, Johan, 1991, et al. (författare) Definition of Tubular Anatomic Structures from Arbitrary Stereo Lithographic Surface 2017 Ingår i: Initiative Seminar Engineering Health, 8-9 November 2017, Chalmers. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract An accurate description of anatomies and dynamics of vessels is crucial to understand their characteristics and improve surgical techniques, thus it is the basis, in addition to surgeon experience, on which stent design and operation procedures rely. The process of producing this description is user intensive, and recent improvement in image processing of medical3D imaging allows for a more automated workflow. However, there is a need to bridge the gap from a processed geometry to a robust mathematical computational grid. By sequentially segmenting a tubular anatomic structure, here defined by a stereo lithographic (STL) surface, an initial centerline is formed by connecting centroids of orthogonal cross-sectional contours along the length of the structure. Relying on the initial centerline, a set of non-overlapping 2D cross sectional contours are defined along the centerline, a centerline which is updated after the 2D contours are produced. After a second iteration of producing 2D contours and updating the centerline, a full description of the structure is created. Our method for describing vessel geometry shows good coherence to existing method. The main advantages of our method include the possibility of having arbitrary triangulated STL surface input, automated centerline definition, safety against intersecting cross-sectional contours and automatic clean-up of local kinks and wrinkles.
50.	Andersson, Marlene, et al. (författare) Biomimetic spinning of artificial spider silk from a chimeric minispidroin 2017 Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 254 Tidskriftsartikel (refereegranskat)abstract Herein we present a chimeric recombinant spider silk protein (spidroin) whose aqueous solubility equals that of native spider silk dope and a spinning device that is based solely on aqueous buffers, shear forces and lowered pH. The process recapitulates the complex molecular mechanisms that dictate native spider silk spinning and is highly efficient; spidroin from one liter of bacterial shake-flask culture is enough to spin a kilometer of the hitherto toughest as-spun artificial spider silk fiber.

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