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  • 1.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Ntzouni, Maria
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Wright, Dominic
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Khan, Kabirul Islam
    Chattogram Vet and Anim Sci Univ, Bangladesh.
    Lopez-Bejar, Manel
    Univ Autonoma Barcelona, Spain.
    Martinez-Serrano, Cristina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Chicken seminal fluid lacks CD9-and CD44-bearing extracellular vesicles2020Inngår i: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The avian seminal fluid (SF) is a protein-rich fluid, derived from the testis, the rudimentary epididymis and, finally, from the cloacal gland. The SF interacts with spermatozoa and the inner cell lining of the female genital tract, to modulate sperm functions and female immune responsiveness. Its complex proteome might either be free or linked to extracellular vesicles (EVs) as it is the case in mammals, where EVs depict the tetraspanin CD9; and where those EVs derived from the epididymis (epididymosomes) also present the receptor CD44. In the present study, sperm-free SF from Red Jungle Fowl, White Leghorn and an advanced intercross (AIL, 12th generation) were studied using flow cytometry of the membrane marker tetraspanin CD9, Western blotting of the membrane receptor CD44 and electron microscopy in non-enriched (whole SF) or enriched fractions obtained by precipitation using a commercial kit (Total Exosome Precipitation Solution). Neither CD9- nor CD44 could be detected, and the ultrastructure confirmed the relative absence of EVs, raising the possibility that avian SF interacts differently with the female genitalia as compared to the seminal plasma of mammals.

  • 2.
    Bergkvist, Liza
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Van Andel Res Inst, MI USA.
    Du, Zhen
    Univ Cambridge, England; Univ Cambridge, England.
    Elovsson, Greta
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Appelqvist, Hanna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Itzhaki, Laura S.
    Univ Cambridge, England.
    Kumita, Janet R.
    Univ Cambridge, England.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Brorsson, Ann-Christin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Mapping pathogenic processes contributing to neurodegeneration in Drosophila models of Alzheimers disease2020Inngår i: FEBS Open Bio, E-ISSN 2211-5463Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alzheimers disease (AD) is the most common form of dementia, affecting millions of people and currently lacking available disease-modifying treatments. Appropriate disease models are necessary to investigate disease mechanisms and potential treatments. Drosophila melanogaster models of AD include the A beta fly model and the A beta PP-BACE1 fly model. In the A beta fly model, the A beta peptide is fused to a secretion sequence and directly overexpressed. In the A beta PP-BACE1 model, human A beta PP and human BACE1 are expressed in the fly, resulting in in vivo production of A beta peptides and other A beta PP cleavage products. Although these two models have been used for almost two decades, the underlying mechanisms resulting in neurodegeneration are not yet clearly understood. In this study, we have characterized toxic mechanisms in these two AD fly models. We detected neuronal cell death and increased protein carbonylation (indicative of oxidative stress) in both AD fly models. In the A beta fly model, this correlates with high A beta(1-42) levels and down-regulation of the levels of mRNA encoding lysosomal-associated membrane protein 1, lamp1 (a lysosomal marker), while in the A beta PP-BACE1 fly model, neuronal cell death correlates with low A beta(1-42) levels, up-regulation of lamp1 mRNA levels and increased levels of C-terminal fragments. In addition, a significant amount of A beta PP/A beta antibody (4G8)-positive species, located close to the endosomal marker rab5, was detected in the A beta PP-BACE1 model. Taken together, this study highlights the similarities and differences in the toxic mechanisms which result in neuronal death in two different AD fly models. Such information is important to consider when utilizing these models to study AD pathogenesis or screening for potential treatments.

  • 3.
    Bhattarai, Sabina
    et al.
    Department of Dermatology and Venereology, Kathmandu Medical College and Teaching Hospital, Kathmandu, Nepal.
    Pandey, Arti S
    Department of Biochemistry, Kathmandu Medical College and Teaching Hospital, Kathmandu, Nepal.
    Bastakoti, Sherya
    Department of Dermatology and Venereology, Kathmandu Medical College and Teaching Hospital, Kathmandu, Nepal.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Bhusal, Mohan
    Department of Dermatology and Venereology, Kathmandu Medical College and Teaching Hospital, Kathmandu, Nepal.
    A case of keratitis, ichthyosis, and deafness syndrome with rickets2020Inngår i: JAAD case reports, ISSN 2352-5126, Vol. 6, nr 1, s. 9-12Artikkel i tidsskrift (Fagfellevurdert)
  • 4.
    Bratengeier, Cornelia
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Liszka, Aneta
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Hoffman, Johan
    KTH Royal Inst Technol, Sweden.
    Bakker, Astrid D.
    Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Fahlgren, Anna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    High shear stress amplitude in combination with prolonged stimulus duration determine induction of osteoclast formation by hematopoietic progenitor cellsInngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To date, it is unclear how fluid dynamics stimulate mechanosensory cells to induce an osteoprotective or osteodestructive response. We investigated how murine hematopoietic progenitor cells respond to 2 minutes of dynamic fluid flow stimulation with a precisely controlled sequence of fluid shear stresses. The response was quantified by measuring extracellular adenosine triphosphate (ATP), immunocytochemistry of Piezo1, and sarcoplasmic/endoplasmic Ca2+ reticulum ATPase 2 (SERCA2), and by the ability of soluble factors produced by mechanically stimulated cells to modulate osteoclast differentiation. We rejected our initial hypothesis that peak wall shear stress rate determines the response of hematopoietic progenitor cells to dynamic fluid shear stress, as it had only a minor correlation with the abovementioned parameters. Low stimulus amplitudes corresponded to activation of Piezo1, SERCA2, low concentrations of extracellular ATP, and inhibition of osteoclastogenesis and resorption area, while high amplitudes generally corresponded to osteodestructive responses. At a given amplitude (3 Pa) and waveform (square), the duration of individual stimuli (duty cycle) showed a strong correlation with the release of ATP and osteoclast number and resorption area. Collectively, our data suggest that hematopoietic progenitor cells respond in a viscoelastic manner to loading, since a combination of high shear stress amplitude and prolonged duty cycle is needed to trigger an osteodestructive response. Plain Language Summary In case of painful joints or missing teeth, the current intervention is to replace them with an implant to keep a high-quality lifestyle. When exercising or chewing, the cells in the bone around the implant experience mechanical loading. This loading generally supports bone formation to strengthen the bone and prevent breaking, but can also stimulate bone loss when the mechanical loading becomes too high around orthopedic and dental implants. We still do not fully understand how cells in the bone can distinguish between mechanical loading that strengthens or weakens the bone. We cultured cells derived from the bone marrow in the laboratory to test whether the bone loss response depends on (i) how fast a mechanical load is applied (rate), (ii) how intense the mechanical load is (amplitude), or (iii) how long each individual loading stimulus is applied (duration). We mimicked mechanical loading as it occurs in the body, by applying very precisely controlled flow of fluid over the cells. We found that a mechanosensitive receptor Piezo1 was activated by a low amplitude stimulus, which usually strengthens the bone. The potential inhibitor of Piezo1, namely SERCA2, was only activated by a low amplitude stimulus. This happened regardless of the rate of application. At a constant high amplitude, a longer duration of the stimulus enhanced the bone-weakening response. Based on these results we deduce that a high loading amplitude tends to be bone weakening, and the longer this high amplitude persists, the worse it is for the bone.

  • 5.
    Engström, Karolina
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Vanky, Farkas
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Rehnberg, Malin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Trinks, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Jonasson, Jon
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Green, Anna
    Orebro Univ, Sweden.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Novel SMAD3 p.Arg386Thr genetic variant co-segregating with thoracic aortic aneurysm and dissection2020Inngår i: Molecular Genetics & Genomic Medicine, ISSN 2324-9269, artikkel-id e1089Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Pathogenic variants in the SMAD3 gene affecting the TGF-beta/SMAD3 signaling pathway with aortic vessel involvement cause Loeys-Dietz syndrome 3, also known as aneurysms-osteoarthritis syndrome. Methods Description of clinical history of a family in Sweden using clinical data, DNA sequencing, bioinformatics, and pedigree analysis. Results We report a novel SMAD3 variant, initially classified as a genetic variant of uncertain clinical significance (VUS), and later found to be co-segregating with aortic dissection in the family. The index patient presented with a dissecting aneurysm of the aorta including the ascending, descending, and abdominal parts. Genotype analysis revealed a heterozygous missense SMAD3 variant: NM_005902.3(SMAD3): c.11576G amp;gt; C (p.Arg386Thr). The same variant was also identified in a 30 years old formalin-fixed paraffin-embedded block of tissue from a second cousin, who died at 26 years of age from a dissecting aneurysm of the aorta. Conclusion A "variant of uncertain significance" according to the ACMG guidelines has always a scope for reappraisal. Genetic counselling to relatives, and the offering of surveillance service is important to families with aortic aneurysm disease. The report also highlight the potential use of FFPE analysis from deceased relatives to help in the interpretation of variants.

  • 6.
    Gutefeldt, Kerstin
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Hedman, Christina
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Thyberg, Ingrid
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Bachrack Lindström, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Arnqvist, Hans
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Spångeus, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Low health-related quality of life is strongly linked to upper extremity impairments in type 1 diabetes with a long duration2020Inngår i: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To compare health-related quality of life (HRQOL) in type 1 diabetes and non-diabetic controls and possible links to upper extremity impairments (UEIs). Prevalence of sick-leave and causes were investigated.

    Materials and methods: This Swedish population-based case-control study included type 1 diabetes patients <67 years old and with a diabetes duration ≥20 years. Participants completed a postal questionnaire including Short Form 36, and questions regarding UEIs, and sick-leave.

    Results: In total, 773 patients, aged 50 ± 10 years (diabetes duration 35 ± 10 years), and 708 non-diabetic controls, aged 54 ± 9 years, completed the study. Patients reported significantly lower HRQOL compared with controls. The difference was greatest for general health, vitality, and bodily pain. Patients with shoulder or hand but not finger impairments scored significantly lower than asymptomatic patients. The prevalence of sick leave was higher in patients vs. controls (23% vs. 9%, p < 0.001), and nearly half cited impairments from back, muscles, or joints as the main reason.

    Conclusions: Health-related quality of life is lower in type 1 diabetes than controls and in patients with shoulder and hand impairments than in asymptomatic. Musculoskeletal impairments (back/muscle/joints) have impact on work ability. Identification of UEIs is important for initiating preventative-, therapeutic-, and rehabilitative interventions.

    • Implications for rehabilitation
    • Upper extremity impairments (UEIs) that are common in type 1 diabetes, and associated with reduced health-related quality of life, should preferably be screened for on a regular basis along with other known diabetes complications.

    • Early identification of UEIs is important to improve health by initiating preventive as well as therapeutic multi-professional rehabilitative interventions.

    • Sick leave is higher in type 1 diabetes than in controls. Musculoskeletal impairments, including the back, muscles, and joints, are a common cause for sick leave warranting further studies.

  • 7.
    Pupkaite, Justina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Collagen Hydrogels for Regenerative Medicine2020Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The need for regenerative therapies to repair damaged or deteriorated organs and tissues, such as heart, skin, and cornea, is rising due to donor shortage and aging of the world’s population. Many proposed regenerative therapeutic approaches include a combination of cells, bioactive compounds, and hydrogels. Although collagen hydrogels have shown a lot of promise in regenerative medicine research, there are still challenges in their design and application strategies. Therefore, this thesis describes the development of novel collagen hydrogel designs for improved use in tissue bonding, cell delivery, and myocardial infarction therapy applications.

    Firstly, a visible-light crosslinked collagen hydrogel for tissue photobonding was developed. Methacrylated collagen hydrogel was crosslinked using the photoinitiator rose Bengal and visible light. The properties of the resulting hydrogel were tunable by changing the hydrogel composition. Biomimetic and ex vivo skin models were used to demonstrate the ability of the hydrogel to bond tissues whose edges are separated. Additionally, using the hydrogel led to less scarring compared to traditional sutures in a mouse skin incision model.

    Secondly, collagen was modified with thiol groups to design a hydrogel crosslinked using the thiol-Michael addition click reaction for cell encapsulation and delivery. The hydrogels demonstrated excellent shear-thinning and self-healing properties, allowing for injection after the crosslinking was complete. Additionally, the hydrogels showed minimal swelling and maintained their shape in an aqueous buffer for a prolonged period. Cell encapsulation and delivery using the hydrogels was demonstrated in vitro with mesenchymal stromal cells and endothelial cells.

    Thirdly, recombinant human collagen III hydrogels were prepared by crosslinking the collagen with EDC and NHS. The hydrogels contained either 1% or 2% collagen. Therapeutic strategies for these hydrogels were investigated, including the timing and dosage of the treatment, in a mouse MI model. Comparing 1% hydrogel injection at a single early time point (3 h) and three time points (3 h, 7 and 14 days) post-MI revealed improved cardiac function, reduced scar size and inflammation, and increased vascularization in the single injection group. Additionally, increasing the collagen III dose to 2% in the hydrogel at a single early time point (3 h) injection did not confer any additional functional improvement compared to 1% and resulted in scar size and vascular density comparable to control (PBS injection). In summary, this work contributes to the development of collagen hydrogel therapies for regenerative medicine by presenting a visible-light crosslinked collagen hydrogel for tissue bonding, a novel click-crosslinked collagen hydrogel with excellent shear-thinning properties for cell delivery, and the use of a recombinant human collagen III hydrogel in post-MI therapy, highlighting the importance of optimizing the timing and dosage of biomaterial therapies.

    Delarbeid
    1. Collagen-Based Photoactive Agent for Tissue Bonding
    Åpne denne publikasjonen i ny fane eller vindu >>Collagen-Based Photoactive Agent for Tissue Bonding
    Vise andre…
    2017 (engelsk)Inngår i: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 9, nr 11, s. 9265-9270Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Using a combination of methacrylated, collagen and the photosensitizer rose Bengal, a new light-activated biomimetic material for tissue sutureless bonding was developed. This formulation was cross-linked using green light. In vivo tests in mice demonstrate the suitability of the material for sutureless wound closure.

    sted, utgiver, år, opplag, sider
    AMER CHEMICAL SOC, 2017
    Emneord
    tissue photobonding; rose Bengal; collagen; wound healing; cross-linking
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-136583 (URN)10.1021/acsami.7b01984 (DOI)000397478100010 ()28282110 (PubMedID)
    Merknad

    Funding Agencies|Natural Sciences and Engineering Research Council (NSERC) [RGPIN- 2015-0632, 342107]; AFA Forsakring, Sweden; UOHI start-up grant [1255]; Burroughs Wellcome Fund

    Tilgjengelig fra: 2017-04-21 Laget: 2017-04-21 Sist oppdatert: 2020-03-23
    2. Injectable Shape-Holding Collagen Hydrogel for Cell Encapsulation and Delivery Cross-linked Using Thiol-Michael Addition Click Reaction
    Åpne denne publikasjonen i ny fane eller vindu >>Injectable Shape-Holding Collagen Hydrogel for Cell Encapsulation and Delivery Cross-linked Using Thiol-Michael Addition Click Reaction
    2019 (engelsk)Inngår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 20, nr 9, s. 3475-3484Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Injectable hydrogels based on extracellular matrix-derived polymers show much promise in the field of tissue engineering and regenerative medicine. However, the hydrogels reported to date have at least one characteristic that limits their potential for clinical use, such as excessive swelling, complicated and potentially toxic cross-linking process, or lack of shear thinning and self-healing properties. We hypothesized that a collagen hydrogel cross-linked using thiol-Michael addition click reaction would be able to overcome these limitations. To this end, collagen was modified to introduce thiol groups, and hydrogels were prepared by cross-linking with 8-arm polyethylene glycol-maleimide. Rheological measurements on the hydrogels revealed excellent shear-thinning and self-healing properties. Additionally, only minimal swelling (6%) was observed over a period of 1 month in an aqueous buffer solution. Finally, tests using mesenchymal stromal cells and endothelial cells showed that the hydrogels are cell-compatible and suitable for cell encapsulation and delivery. Thus, the reported thiolated-collagen hydrogel cross-linked using thiol-Michael addition click reaction overcomes most of the challenges in the injectable hydrogel design and is an excellent candidate for cell delivery in regenerative medicine and tissue engineering applications. The hydrogel reported here is the first example of a self-healing hydrogel containing covalent cross-links.

    sted, utgiver, år, opplag, sider
    American Chemical Society, 2019
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-164539 (URN)10.1021/acs.biomac.9b00769 (DOI)
    Tilgjengelig fra: 2020-03-23 Laget: 2020-03-23 Sist oppdatert: 2020-03-23bibliografisk kontrollert
  • 8.
    Pupkaite, Justina
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Polymer Chemistry, Department of Chemistry, Uppsala University, Uppsala, Sweden.
    Rosenquist, Jenny
    Polymer Chemistry, Department of Chemistry, Uppsala University, Uppsala, Sweden.
    Hilborn, Jöns
    Polymer Chemistry, Department of Chemistry, Uppsala University, Uppsala, Sweden.
    Samanta, Ayan
    Polymer Chemistry, Department of Chemistry, Uppsala University, Uppsala, Sweden.
    Injectable Shape-Holding Collagen Hydrogel for Cell Encapsulation and Delivery Cross-linked Using Thiol-Michael Addition Click Reaction2019Inngår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 20, nr 9, s. 3475-3484Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Injectable hydrogels based on extracellular matrix-derived polymers show much promise in the field of tissue engineering and regenerative medicine. However, the hydrogels reported to date have at least one characteristic that limits their potential for clinical use, such as excessive swelling, complicated and potentially toxic cross-linking process, or lack of shear thinning and self-healing properties. We hypothesized that a collagen hydrogel cross-linked using thiol-Michael addition click reaction would be able to overcome these limitations. To this end, collagen was modified to introduce thiol groups, and hydrogels were prepared by cross-linking with 8-arm polyethylene glycol-maleimide. Rheological measurements on the hydrogels revealed excellent shear-thinning and self-healing properties. Additionally, only minimal swelling (6%) was observed over a period of 1 month in an aqueous buffer solution. Finally, tests using mesenchymal stromal cells and endothelial cells showed that the hydrogels are cell-compatible and suitable for cell encapsulation and delivery. Thus, the reported thiolated-collagen hydrogel cross-linked using thiol-Michael addition click reaction overcomes most of the challenges in the injectable hydrogel design and is an excellent candidate for cell delivery in regenerative medicine and tissue engineering applications. The hydrogel reported here is the first example of a self-healing hydrogel containing covalent cross-links.

  • 9.
    Sandestig, Anna
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Engström, Karolina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Pepler, Alexander
    CeGaT GmbH, Germany; Praxis Humangenet, Germany.
    Danielsson, Ingela
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Odelberg-Johnson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Biskup, Saskia
    CeGaT GmbH, Germany; Praxis Humangenet, Germany.
    Holz, Anja
    CeGaT GmbH, Germany; Praxis Humangenet, Germany.
    Stefanova, Margarita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    NUP188 Biallelic Loss of Function May Underlie a New Syndrome: Nucleoporin 188 Insufficiency Syndrome?2020Inngår i: Molecular Syndromology, ISSN 1661-8769, E-ISSN 1661-8777, Vol. 10, nr 6, s. 313-319Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is no clearly established association between the gene NUP188 and human pathology. Only a few reports of patients with different clinical presentation and different heterozygous or compound heterozygous missense or splice region variants have been identified in several sequencing projects; however, a causative association between the clinical features and the identified variants has not been established. For the first time, we report 2 unrelated patients with 2 different homozygous nonsense gene variants of NUP188, p.Tyr96* and p.Gln113*, respectively. Although having different supposedly truncating mutations, the patients presented with strikingly comparable phenotypes including pre- and postnatal microcephaly, trigonocephaly, congenital bilateral cataract, microphthalmia, cleft lip and palate or high-arched palate, camptodactyly, rocker-bottom feet, heart anomalies, specific brain changes (such as loss of periventricular white matter), thin corpus callosum, and delayed myelinization. Both patients showed very similar facial features such as laterally extended arched eyebrows, wide convex nose with a wide prominent nasal bridge, and prominent angulated antihelix. They were both born small for gestational age and died shortly after birth at the age of 67 and 140 days, respectively, as a result of central respiratory failure. Our findings strongly suggest a correlation between the homozygous nonsense gene variants of NUP188 and a severe phenotype of a new developmental syndrome with poor prognosis resulting from nucleoporin 188 homolog protein insufficiency.

  • 10.
    Wu, Wendy Yi-Ying
    et al.
    Umea Univ, Sweden.
    Johansson, Gunnar
    Umea Univ, Sweden.
    Wibom, Carl
    Umea Univ, Sweden.
    Brannstrom, Thomas
    Umea Univ, Sweden.
    Malmström, Annika
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, LAH Linköping.
    Henriksson, Roger
    Umea Univ, Sweden.
    Golovleva, Irina
    Umea Univ, Sweden.
    Bondy, Melissa L.
    Stanford Univ, CA 94305 USA; Baylor Coll Med, TX 77030 USA.
    Andersson, Ulrika
    Umea Univ, Sweden.
    Dahlin, Anna M.
    Umea Univ, Sweden.
    Melin, Beatrice
    Umea Univ, Sweden.
    The Genetic Architecture of Gliomagenesis-Genetic Risk Variants Linked to Specific Molecular Subtypes2019Inngår i: CANCERS, Vol. 11, nr 12, artikkel-id 2001Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Genome-wide association studies have identified 25 germline genetic loci that increase the risk of glioma. The somatic tumor molecular alterations, including IDH-mutation status and 1p/19q co-deletion, have been included into the WHO 2016 classification system for glioma. To investigate how the germline genetic risk variants correlate with the somatic molecular subtypes put forward by WHO, we performed a meta-analysis that combined findings from 330 Swedish cases and 876 controls with two other recent studies. In total, 5,103 cases and 10,915 controls were included. Three categories of associations were found. First, variants in TERT and TP53 were associated with increased risk of all glioma subtypes. Second, variants in CDKN2B-AS1, EGFR, and RTEL1 were associated with IDH-wildtype glioma. Third, variants in CCDC26 (the 8q24 locus), C2orf80 (close to IDH), LRIG1, PHLDB1, ETFA, MAML2 and ZBTB16 were associated with IDH-mutant glioma. We therefore propose three etiopathological pathways in gliomagenesis based on germline variants for future guidance of diagnosis and potential functional targets for therapies. Future prospective clinical trials of patients with suspicion of glioma diagnoses, using the genetic variants as biomarkers, are necessary to disentangle how strongly they can predict glioma diagnosis.

  • 11.
    Wäster, Petra
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Eriksson, Ida
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Vainikka, Linda
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Öllinger, Karin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Extracellular vesicles released by melanocytes after UVA irradiation promote intercellular signaling via miR212020Inngår i: Pigment Cell & Melanoma Research, ISSN 1755-1471, E-ISSN 1755-148XArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Skin pigmentation is controlled by complex crosstalk between melanocytes and keratinocytes and is primarily induced by exposure to ultraviolet (UV) irradiation. Several aspects of UVA-induced signaling remain to be explored. In skin cells, UVA induces plasma membrane damage, which is repaired by lysosomal exocytosis followed by instant shedding of extracellular vesicles (EVs) from the plasma membrane. The released EVs are taken up by neighboring cells. To elucidate the intercellular crosstalk induced by UVA irradiation, EVs were purified from UVA-exposed melanocytes and added to keratinocytes. Transcriptome analysis of the keratinocytes revealed the activation of TGF-beta and IL-6/STAT3 signaling pathways and subsequent upregulation of microRNA (miR)21. EVs induced phosphorylation of ERK and JNK, reduced protein levels of PDCD4 and PTEN, and augment antiapoptotic signaling. Consequently, keratinocyte proliferation and migration were stimulated and UV-induced apoptosis was significantly reduced. Interestingly, melanoma cells and melanoma spheroids also generate increased amounts of EVs with capacity to stimulate proliferation and migration upon UVA. In conclusion, we present a novel intercellular crosstalk mediated by UVA-induced lysosome-derived EVs leading to the activation of proliferation and antiapoptotic signaling via miR21.

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