| 1. |
- El Jellas, Khadija, et al.
(författare)
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Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis : How to Correctly Identify MODY8 Cases
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:4, s. 1455-1466
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Tidskriftsartikel (refereegranskat)abstract
- Context: Maturity onset diabetes of the young, type 8 (MODY8) is associated with mutations in the CEL gene, which encodes the digestive enzyme carboxyl ester lipase. Several diabetes cases and families have in recent years been attributed to mutations in CEL without any functional or clinical evidence provided. Objective: To facilitate correct MODY8 diagnostics, we screened 2 cohorts of diabetes patients and delineated the phenotype. Methods: Young, lean Swedish and Finnish patients with a diagnosis of type 2 diabetes (352 cases, 406 controls) were screened for mutations in the CEL gene. We also screened 58 Czech MODY cases who had tested negative for common MODY genes. For CEL mutation-positive subjects, family history was recorded, and clinical investigations and pancreatic imaging performed. Results: Two cases (1 Swedish and 1 Czech) with germline mutation in CEL were identified. Clinical and radiological investigations of these 2 probands and their families revealed dominantly inherited insulin-dependent diabetes, pancreatic exocrine dysfunction, and atrophic pancreas with lipomatosis and cysts. Notably, hereditary pancreatitis was the predominant phenotype in 1 pedigree. Both families carried single-base pair deletions in the proximal part of the CEL variable number of tandem repeat (VNTR) region in exon 11. The mutations are predicted to lead to aberrant protein tails that make the CEL protein susceptible to aggregation. Conclusion: The diagnosis of MODY8 requires a pancreatic exocrine phenotype and a deletion in the CEL VNTR in addition to dominantly inherited diabetes. CEL screening may be warranted also in families with hereditary pancreatitis of unknown genetic etiology.
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| 2. |
- Johansson, Henrik J., et al.
(författare)
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Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Malassezia sympodialis is a dominant commensal fungi in the human skin mycobiome but is also associated with common skin disorders including atopic eczema (AE). M. sympodialis releases extracellular vesicles, designated MalaEx, which are carriers of small RNAs and allergens, and they can induce inflammatory cytokine responses. Here we explored how MalaEx are involved in hostmicrobe interactions by comparing protein content of MalaEx with that of the parental yeast cells, and by investigating interactions of MalaEx with cells in the skin. Cryo-electron tomography revealed a heterogeneous population of MalaEx. iTRAQ based quantitative proteomics identified in total 2439 proteins in all replicates of which 110 were enriched in MalaEx compared to the yeast cells. Among the MalaEx enriched proteins were two of the M. sympodialis allergens, Mala s 1 and s 7. Functional experiments indicated an active binding and internalization of MalaEx into human keratinocytes and monocytes, and MalaEx were found in close proximity of the nuclei using super-resolution fluorescence 3D-SIM imaging. Our results provides new insights into host-microbe interactions, supporting that MalaEx may have a role in the sensitization and maintenance of inflammation in AE by containing enriched amounts of allergens and with their ability to interact with skin cells.
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| 3. |
- Lee, Hunsang, et al.
(författare)
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Live-cell topology assessment of URG7, MRP6(102) and SP-C using glycosylatable green fluorescent protein in mammalian cells
- 2014
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 450:4, s. 1587-1592
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Tidskriftsartikel (refereegranskat)abstract
- Experimental tools to determine membrane topology of a protein are rather limited in higher eukaryotic organisms. Here, we report the use of glycosylatable GFP (gGFP) as a sensitive and versatile membrane topology reporter in mammalian cells. gGFP selectively loses its fluorescence upon N-linked glycosylation in the ER lumen. Thus, positive fluorescence signal assigns location of gGFP to the cytosol whereas no fluorescence signal and a glycosylated status of gGFP map the location of gGFP to the ER lumen. By using mammalian gGFP, the membrane topology of disease-associated membrane proteins, URG7, MRP6(102), SP-C(Val) and SP-C(Leu) was confirmed. URG7 is partially targeted to the ER, and inserted in C-in, form. MRP6(102) and SP-C(Leu/Val) are inserted into the membrane in C-out form. A minor population of untargeted SP-C is removed by proteasome dependent quality control system.
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| 4. |
- Simonson, Oscar E., et al.
(författare)
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In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome
- 2015
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Ingår i: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 4:10, s. 1199-1213
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stromal cells (MSCs) have been investigated as a treatment for various inflammatory diseases because of their immunomodulatory and reparative properties. However, many basic questions concerning their mechanisms of action after systemic infusion remain unanswered. We performed a detailed analysis of the immunomodulatory properties and proteomic profile of MSCs systemically administered to two patients with severe refractory acute respiratory distress syndrome (ARDS) on a compassionate use basis and attempted to correlate these with in vivo anti-inflammatory actions. Both patients received 2 x 10(6) cells per kilogram, and each subsequently improved with resolution of respiratory, hemodynamic, and multiorgan failure. In parallel, a decrease was seen in multiple pulmonary and systemic markers of inflammation, including epithelial apoptosis, alveolar-capillary fluid leakage, and proinflammatory cytokines, microRNAs, and chemokines. In vitro studies of the MSCs demonstrated a broad anti-inflammatory capacity, including suppression of T-cell responses and induction of regulatory phenotypes in T cells, monocytes, and neutrophils. Some of these in vitro potency assessments correlated with, and were relevant to, the observed in vivo actions. These experiences highlight both the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects. The findings also suggest, but do not prove, a beneficial effect of lung protective strategies using adoptively transferred MSCs in ARDS. Appropriate randomized clinical trials are required to further assess any potential clinical efficacy and investigate the effects on in vivo inflammation. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1199-1213
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| 5. |
- Abdelrazak Morsy, Mohammad Hamdy, et al.
(författare)
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SOX11 is a novel binding partner and endogenous inhibitor of SAMHD1 ara-CTPase activity in mantle cell lymphoma
- 2024
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 143:19, s. 1953-1964
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Tidskriftsartikel (refereegranskat)abstract
- Sterile alpha motif and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara -C) resistance in several hematological malignancies. Targeting SAMHD1's ara-CTPase activity has recently been demonstrated to enhance ara -C ef fi cacy in acute myeloid leukemia. Here, we identify the transcription factor SRY-related HMGbox containing protein 11 (SOX11) as a novel direct binding partner and fi rst known endogenous inhibitor of SAMHD1. SOX11 is aberrantly expressed not only in mantle cell lymphoma (MCL), but also in some Burkitt lymphomas. Coimmunoprecipitation of SOX11 followed by mass spectrometry in MCL cell lines identi fi ed SAMHD1 as the top SOX11 interaction partner, which was validated by proximity ligation assay. In vitro, SAMHD1 bound to the HMG box of SOX11 with low-micromolar af fi nity. In situ crosslinking studies further indicated that SOX11-SAMHD1 binding resulted in a reduced tetramerization of SAMHD1. Functionally, expression of SOX11 inhibited SAMHD1 ara-CTPase activity in a dose-dependent manner resulting in ara -C sensitization in cell lines and in a SOX11-inducible mouse model of MCL. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identi fi ed SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its fi rst known endogenous inhibitor with potentially important implications for clinical therapy strati fi cation.
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| 6. |
- Ahlgren, Benjamin, et al.
(författare)
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A simplified model for linear correlation between annual yield and DNI for parabolic trough collectors
- 2018
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Ingår i: Energy Conversion and Management. - : Elsevier. - 0196-8904 .- 1879-2227. ; 174, s. 295-308
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Tidskriftsartikel (refereegranskat)abstract
- This paper proposes a simple method for estimating annual thermal performance of parabolic trough collectors (PTCs) based on a linear relation with annual DNI for a certain latitude. A case study with simulations for a novel concentrating solar collector in 316 locations for three operating temperature scenarios worldwide was carried out and showed promising results for the latitudes and continents investigated. For a certain latitude and mean operating temperature, the annual yield of a PTC was found to be linearly proportional to yearly DNI. The proposed method will serve as a simplified alternative to the steady-state and quasi-dynamic methods already used. Estimating performance based on yearly DNI can be used by design engineers to do quick preliminary planning of solar plants. Customers can also use this method to evaluate existing solar collector installations. A TRNSYS/TRNSED tool that uses a steady-state model has been developed to carry out the simulations and it has been validated against a PTC array at Technical University of Denmark (DTU). The results show that the simplified method can give reliable estimates of long-term performance of parabolic trough collectors.
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| 7. |
- Ahonen, Pasi, et al.
(författare)
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Writing resistance together
- 2020
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Ingår i: Gender, Work and Organization. - : John Wiley & Sons. - 0968-6673 .- 1468-0432. ; 27:4, s. 447-470
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Tidskriftsartikel (refereegranskat)abstract
- This piece of writing is a joint initiative by the participants in the Gender, Work and Organization writing workshop organized in Helsinki, Finland, in June 2019. This is a particular form of writing differently. We engage in collective writing and embody what it means to write resistance to established academic practices and conventions together. This is a form of emancipatory initiative where we care for each other as writers and as human beings. There are many author voices and we aim to keep the text open and dialogical. As such, this piece of writing is about suppressed thoughts and feelings that our collective picket line allows us to express. In order to maintain the open-ended nature of the text, and perhaps also to retain some 'dirtiness' that is essential to writing, the article has not been language checked throughout by a native speaker of English.
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| 8. |
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| 9. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 10. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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