| 1. |
- Andersson, Rebecca, et al.
(författare)
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Differential role of cytosolic Hsp70s in longevity assurance and protein quality control
- 2021
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- 70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70's in yeast, Ssa1-4, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and accelerates replicative aging. In our efforts to identify which Hsp70 activities are most important for longevity assurance, we systematically investigated the capacity of Ssa4 to carry out the different activities performed by Ssa1/2 by overproducing Ssa4 in cells lacking these Hsp70 chaperones. We found that Ssa4, when overproduced in cells lacking Ssa1/2, rescued growth, mitigated aggregate formation, restored spatial deposition of aggregates into protein inclusions, and promoted protein degradation. In contrast, Ssa4 overproduction in the Hsp70 deficient cells failed to restore the recruitment of the disaggregase Hsp104 to misfolded/aggregated proteins, to fully restore clearance of protein aggregates, and to bring back the formation of the nucleolus-associated aggregation compartment. Exchanging the nucleotide-binding domain of Ssa4 with that of Ssa1 suppressed this 'defect' of Ssa4. Interestingly, Ssa4 overproduction extended the short lifespan of ssa1 Delta ssa2 Delta mutant cells to a lifespan comparable to, or even longer than, wild type cells, demonstrating that Hsp104-dependent aggregate clearance is not a prerequisite for longevity assurance in yeast. Author summary All organisms have proteins that network together to stabilize and protect the cell throughout its lifetime. One of these types of proteins are the Hsp70s (heat shock protein 70). Hsp70 proteins take part in folding other proteins to their functional form, untangling proteins from aggregates, organize aggregates inside the cell and ensure that damaged proteins are destroyed. In this study, we investigated three closely related Hsp70 proteins in yeast; Ssa1, 2 and 4, in an effort to describe the functional difference of Ssa4 compared to Ssa1 and 2 and to answer the question: What types of cellular stress protection are necessary to reach a normal lifespan? We show that Ssa4 can perform many of the same tasks as Ssa1 and 2, but Ssa4 doesn't interact in the same manner as Ssa1 and 2 with other types of proteins. This leads to a delay in removing protein aggregates created after heat stress. Ssa4 also cannot ensure that misfolded proteins aggregate correctly inside the nucleus of the cell. However, this turns out not to be necessary for yeast cells to achieve a full lifespan, which shows us that as long as cells can prevent aggregates from forming in the first place, they can reach a full lifespan.
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| 2. |
- Garemark, Jonas
(författare)
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Integrated Cellulosic Wood Aerogel Structures
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Highly porous aerogels based on renewable materials that possess structural functionality are appealing for sustainable energy regulation and harvesting. Achieving structural anisotropy provides advantageous directional diffusion and mechanical strength, however, introduces great engineering challenges, such as complex, costly, and time-consuming processing. Direct use of wood, where nanocellulose is favorably orientated, offers the opportunity of forming low-cost, scalable, and eco-friendly aerogels.This thesis explores a new type of nanostructured wood material design by filling the empty wood space with cellulosic aerogel structures based on its intrinsic biopolymers. The structure control is achieved through selective reassembly of the cell wall nanocomponents by cell wall partial dissolution and regeneration. The resultant structures, named integrated wood aerogels, show a unique combination of high specific surface area and strength due to partial retention of the wood hierarchical structure and formation of mesoporous nanofibrillated networks occupying the lumen. Different chemical systems are investigated, including DMAc/LiCl, ionic liquid (IL), and aqueous NaOH, and the processing-structure-property relationships are investigated. DMAc/LiCl is successfully used as proof of concept for integrated wood aerogel formation, but moisture sensitivity and toxicity of the system hinder further development. The IL [MTBD][MMP] is developed to solve the issues and to improve the structure control in cell wall dissolution and regeneration. An aqueous NaOH system advances the integrated cellulosic wood aerogel preparation further, considering low cost and greener chemistry. Wood composition, lignin in particular, is critical to the processing and final properties of the integrated wood aerogel. The influence of lignin content is investigated based on IL and NaOH systems. The influence of processing (such as chemical system, time and temperature) on the structure and properties (e.g. porosity, specific surface area, mechanical performance, thermal conductivity and charge density) of the aerogels are studied. Ascribing to the structure-property profile, the application of the integrated aerogel for efficient thermal insulation is demonstrated. Inspired by the water uptake in plants, high-performing pH-responsive wood power generators are formed based on water evaporation-induced electricity. The integrated aerogel structure greatly increases the solid/liquid interphase while allowing excellent mass diffusion.The methodologies presented in this thesis for selective nanoscale reassembly of the wood cell wall pave the way for advanced wood nanostructure control. The integrated wood aerogel structure reported here provides a universal material platform for advanced material design, such as a self-sustaining wood power generator. The facile and scalable processing contribute toward sustainable high-performing bioaerogels which can compete with fossil-based materials.
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| 3. |
- Jonsson, Gustav, et al.
(författare)
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Integrating yoga with psychological group-treatment for mixed depression and anxiety in primary healthcare: An explorative pilot study
- 2020
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Ingår i: Complementary Therapies in Clinical Practice. - : Elsevier. - 1744-3881 .- 1873-6947. ; 41
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Yoga has shown promise as a treatment for depression and anxiety. The present pilot study investigated the feasibility of an eight-week grouptreatment integrating emotion-focused psychoeducation, compassion-focused therapy, and Virya yoga for depression and anxiety in primary healthcare.Materials and methods: Patients seeking treatment for depression and anxiety in a primary healthcare centre completed either an integrative group-treatment (N = 14) or treatment as usual (TAU, N = 17). Outcome measures were analysed pre- and posttreatment. Correlations in the intervention group were investigated between treatment outcomes and amount of yoga practice between sessions.Results: Large within-group effect sizes on all outcome measures were found at posttreatment. Symptom reduction did not differ between groups (p = 0.155). Improvement in alexithymia correlated significantly (p < 0.05) with amount of yoga practice between sessions.Conclusion: Integrating yoga with a psychological group-treatment is a somewhat feasible approach to treatment for depression and anxiety in primary healthcare.
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| 4. |
- Krali, Olga, et al.
(författare)
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Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia
- 2023
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Ingår i: npj Precision Oncology. - : Springer Nature. - 2397-768X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Genomic analyses have redefined the molecular subgrouping of pediatric acute lymphoblastic leukemia (ALL). Molecular subgroups guide risk-stratification and targeted therapies, but outcomes of recently identified subtypes are often unclear, owing to limited cases with comprehensive profiling and cross-protocol studies. We developed a machine learning tool (ALLIUM) for the molecular subclassification of ALL in retrospective cohorts as well as for up-front diagnostics. ALLIUM uses DNA methylation and gene expression data from 1131 Nordic ALL patients to predict 17 ALL subtypes with high accuracy. ALLIUM was used to revise and verify the molecular subtype of 281 B-cell precursor ALL (BCP-ALL) cases with previously undefined molecular phenotype, resulting in a single revised subtype for 81.5% of these cases. Our study shows the power of combining DNA methylation and gene expression data for resolving ALL subtypes and provides a comprehensive population-based retrospective cohort study of molecular subtype frequencies in the Nordic countries.
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| 5. |
- Mavrona, Elena, et al.
(författare)
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Efficiency assessment of wood and cellulose-based optical elements for terahertz waves
- 2023
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Ingår i: Optical Materials Express. - : Optica Publishing Group. - 2159-3930 .- 2159-3930. ; 13:1, s. 92-103
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Tidskriftsartikel (refereegranskat)abstract
- Polarized THz time domain spectroscopy was used to study the anisotropic properties of wood-based materials for potential optical elements in the THz range, such as half-wave and quarter-wave plates. Wood samples of different species and sample thickness were studied experimentally showing high birefringence but rather high absorption. We elaborate on two approaches to optimize the optical properties for use as wave plates and assess them based on a figure of merit describing their efficiency as a function of birefringence and absorption. The first approach is to dry the wood samples, which significantly improves the efficiency of wave plates. The second approach is the use of artificially produced cellulose samples using 3D printing and freeze drying techniques, which also show birefringence caused by their similar macroscopic cellulose fibre structure. These materials have the potential as cost effective THz elements that are easy to tailor and produce for use at specific frequencies.
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| 6. |
- Sultan, Sahar, 1987-
(författare)
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Nanocellulose based 3D printed hydrogel scaffolds for cartilage and bone regeneration : Tuning of composition, pore structure and functions
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biobased-materials with customized scaffolds have played a prominent role in the success of tissue engineering (TE). Cellulose nanomaterials (CNM) isolated from the abundant biopolymer, cellulose, is explored in this thesis for TE engineering due to its versatile properties such as biocompatibility, high specific strength, surface functionality and water retention capacity. Hydrogel formation capability of CNM at low concentrations (1–2 wt%) and shear thinning behavior has facilitated its use in 3-dimensional (3D) printing as a fabrication technique for 2-dimensional (2D) and 3D scaffolds. This technique offers 3D scaffolds with tailored, controlled and complex geometries having precise micro and macro scaled structures. The current work focuses on CNM-based 3D printed hydrogel scaffolds with tuned composition and pore structure for cartilage and bone regeneration. Design of CNM hydrogel formulations with suitable rheological properties, hydrogel inks capable of ex-situ crosslinking, print resolution during printing due to swelling and mechanical and dimensional stability of the printed scaffolds in moist environment are key challenges that were addressed.Inspired by the hierarchical and gradient nature of natural tissues 3D printed hydrogel scaffolds with gradient pore structure and composition are reported for the first time with focus on cellulose nanocrystals (CNC) and TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-oxidized cellulose nanofibers (TOCNF) based hydrogel ink printing for advanced and functional scaffolds.CNC-based hydrogel ink was used to 3D print uniform and gradient porous cubic scaffolds for cartilage regeneration. This work highlighted the importance of nozzle movement to obtain high resolution scaffolds with higher z-axis. The anisotropic rigid CNC aligned themselves along the printing direction due to the shear induced orientation that was quantified between 61–76%. To obtain adequate mechanical properties (0.20–0.45 MPa) suitable for cartilage regeneration, the hydrogel ink solid content was increased almost two-fold (5.4 wt% to 9.9 wt%) while exhibiting and mimicking the viscoelasticity of natural cartilage tissues. To improve the bioactivity of the CNC-based 3D printed scaffolds, a surface treatment through dopamine coating was performed. This coating enhanced the hydrophilicity and capability of 3D printed scaffolds to bind bioactive molecules such as fibroblast growth factor (FGF-18) for soft TE scaffolds.Surface functionality of TOCNF was utilized to fabricate functional hybrid scaffolds (CelloZIF-8) through one-pot in- situ synthesis of Metal-Organic frameworks (MOFs) with varied ZIF-8 loadings (30.8–70.7%). The inherent porosity of the ZIF-8 was used for loading and stimuli-responsive (pH-dependent) releasing of drug molecule such as curcumin. The developed CelloMOF system was extended to other MOFs (MIL-100) and drugs (methylene blue). The shear thinning property of TOCNF was reserved after MOFs hybridization and was used to 3D print porous scaffolds with excellent shape fidelity. In Cello-Apatite, TOCNF was also used as template for in-situ synthesis of hydroxyapatite (HAP) where the HAP loading was 67 wt% to mimic the bone composition. In an attempt to address both cartilage and bone regeneration, a biphasic osteochondral 3D printed hydrogel scaffold has been introduced with tuned composition, pore structure and mechanical properties.The work presents a sustainable, cost effective and scalable approach for TE using biobased and toxic free water-based formulations using low temperature processes that are extendable to other biomaterials as well as to other applications, such as water treatment.
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| 7. |
- Taheri, Hesam, et al.
(författare)
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Selection of suitable cellulose nanofibers derived from eco-friendly sources for the production of lightweight cementitious composites with tuned rheological, mechanical, and microstructure properties
- 2024
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Ingår i: Cement & Concrete Composites. - : Elsevier BV. - 0958-9465 .- 1873-393X. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- Different cellulose nanofibers (CNF) and ordinary Portland cement (OPC) were combined to prepare CNF-OPC composite pastes at different water to cement ratios (W/C) to optimize density, thermal conductivity, and mechanical strength. The rheological data of CNF-OPC composites showed that the viscosity and yield stress of the mixtures were abruptly increased in comparison to those of OPC pastes at equal W/C. Rheological and morphological data showed that the uniformity of the CNF and degree of fiber entanglement plays a significant role in tuning the composite properties. CNF suspensions with short fibers were observed to improve the mechanical properties of the composite while suspensions with entangled fiber networks were found to decrease density and thermal conductivity. Loss of flexural strength of CNF-OPC compared to OPC was found to be to a lesser extent than loss of compressive strength. The dry density and thermal conductivity of the CNF-OPC composites were substantially reduced to the range of 750 (kg/m(3)) and 0.1 (W/m(-1)K(-1)) at W/C = 2. CNF caused a reduction in peak temperature and postponed the hydration peak by more than 2 h compared to OPC.
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| 8. |
- Tesi, Bianca, et al.
(författare)
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Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.MethodsgWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.FindingsThe prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).InterpretationOverall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
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| 9. |
- Tesi, Bianca, et al.
(författare)
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Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
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Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.Methods: gWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.Findings: The prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).Interpretation: Overall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.Funding: The study was supported by the Swedish Childhood Cancer Fund and the Ministry of Health and Social Affairs.
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| 10. |
- Tran, Van Chinh, 1990-
(författare)
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Wood Templated Organic Electronics
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In today’s digital era, electronics are integral to most activities in our daily lives, offering swift and global communication, powerful data processing tools, and advanced sensor devices. However, there are drawbacks to the exponentially growing demand for electronics, such as the depletion of fossil resources, and the complexities surrounding recycling electronic waste (E-waste). As we gradually step into the era of sustainability, it is necessary to explore alternative resources and develop greener electronic technologies. For this purpose, organic electronics (OE) has emerged as an interesting alternative, owning to its potential for low-energy fabrication and use of organic materials composed of Earth-abundant elements.The term "organic electronics" has been used widely to refer to electrical devices crafted from organic materials, typically semiconducting polymers (sCPs). This arises from the fact that most developed OE devices such as solar cells, transistors, supercapacitors, and batteries are centered around such materials. Along with the development of different semiconducting polymer varieties, materials from various natural resources have also been explored for devices’ electrodes, binders, and electrolytes. Among them, materials from the forest have emerged as abundant, renewable, and valuable options. For many years, wood has been tailored and utilized as a device template, while its components including cellulose fibrils and lignin have been widely used as structural or active components in OE. Lignin has now become an important electrode and electrolyte active material in energy storage devices.This thesis presents new approaches and findings in the utilization of wood and lignin as active components in different OE applications. The thesis centers around two primary themes, in which the first involves the development and utilization of conductive wood (CW), containing lignin, and lignin nanoparticles (LNPs) for supercapacitors and battery applications. The second theme focuses on developing and employing conductive wood as an active electrode in the creation of a wood electrochemical transistor. Within the first theme, I have uncovered the potential of storing electricity in wood utilizing its redox-active component, native lignin. The discovery is reinforced by the successful employment of LNPs as active materials in an organic battery. Within the second theme, I have demonstrated the world's first wooden transistor, characterized its electronic performance, and discussed the pretreatment procedure of the wood substrate that is necessary for achieving a working device. This thesis is anticipated to contribute to new and valuable knowledge for encouraging the development of low-cost and sustainable OE in the future.
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