| 1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
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| 5. |
- Buchanan, E. M., et al.
(author)
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The Psychological Science Accelerator's COVID-19 rapid-response dataset
- 2023
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 10:1
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Journal article (peer-reviewed)abstract
- In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.
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| 8. |
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| 9. |
- Patel, Y., et al.
(author)
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Virtual Ontogeny of Cortical Growth Preceding Mental Illness
- 2022
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 92:4, s. 299-313
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Journal article (peer-reviewed)abstract
- Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
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| 13. |
- Evangelou, Evangelos, et al.
(author)
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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
- 2011
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
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Journal article (peer-reviewed)abstract
- Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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| 14. |
- Pilheden, M., et al.
(author)
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Duplex Sequencing Uncovers Recurrent Low-frequency Cancer-associated Mutations in Infant and Childhood KMT2A-rearranged Acute Leukemia
- 2022
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In: Hemasphere. - : Ovid Technologies (Wolters Kluwer Health). - 2572-9241. ; 6:10
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Journal article (peer-reviewed)abstract
- Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A-r leukemia and included mutations in KRAS, NRAS, FLT3, TP53, PIK3CA, PAX5, PIK3R1, and PTPN11, with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS. Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3(D835H) or NRAS(G13D/G12S) mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.
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| 15. |
- Tahmasian, Masoud, et al.
(author)
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ENIGMA-Sleep : Challenges, opportunities, and the road map
- 2021
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In: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 30:6
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Research review (peer-reviewed)abstract
- Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
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| 16. |
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| 17. |
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| 18. |
- Belyaev, I Y, et al.
(author)
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915 MHz microwaves and 50 Hz magnetic field affect chromatin conformation and 53BP1 foci in human lymphocytes from hypersensitive and healthy persons
- 2005
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In: Bioelectromagnetics. - : Wiley. - 0197-8462 .- 1521-186X. ; 26:3, s. 173-184
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Journal article (peer-reviewed)abstract
- We used exposure to microwaves from a global system for mobile communication (GSM) mobile phone (915 MHz, specific absorption rate (SAR) 37 mW/kg) and power frequency magnetic field (50 Hz, 15 mu T peak value) to investigate the response of lymphocytes from healthy subjects and from persons reporting hypersensitivity to electromagnetic field (EMF). The hypersensitive and healthy donors were matched by gender and age and the data were analyzed blind to treatment condition. The changes in chromatin conformation were measured with the method of anomalous viscosity time dependencies (AVTD). 53BP1 protein, which has been shown to colocalize in foci with DNA double strand breaks (DSBs), was analyzed by immunostaining in situ. Exposure at room temperature to either 915 MHz or 50 Hz resulted in significant condensation of chromatin, shown as AVTD changes, which was similar to the effect of heat shock at 41 degrees C. No significant differences in responses between normal and hypersensitive subjects were detected. Neither 915 MHz nor 50 Hz exposure induced 53BP1 foci. On the contrary, a distinct decrease in background level of 53BP1 signaling was observed upon these exposures as well as after heat shock treatments. This decrease correlated with the AVTD data and may indicate decrease in accessibility of 53BP1 to antibodies because of stress-induced chromatin condensation. Apoptosis was determined by morphological changes and by apoptotic fragmentation of DNA as analyzed by pulsed-field gel electrophoresis (PFGE). No apoptosis was induced by exposure to 50 Hz and 915 MHz microwaves. In conclusion, 50 Hz magnetic field and 915 MHz microwaves under specified conditions of exposure induced comparable responses in lymphocytes from healthy and hypersensitive donors that were similar but not identical to stress response induced by heat shock.
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| 19. |
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| 20. |
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| 21. |
- Stoller, R. E., et al.
(author)
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Impact of Short-Range Forces on Defect Production from High Energy Collisions
- 2016
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In: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 12:6, s. 2871-2879
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Journal article (peer-reviewed)abstract
- Primary radiation damage formation in solid materials typically involves collisions between atoms that have up to a few hundred keV of kinetic energy. Dining these collisions, the-distance between two colliding atoms can approach 0.05 nm. At such small atomic separations, force fields fitted-to equilibrium properties tend to significantly underestimate the potential-energy-of the colliding dieter. To enable molecular dynamics simulations of high-energy collisions, it is common practice to use a screened Coulomb, force field to describe the interactions and to smoothly join this to the equilibrium force field at a suitable interatomic spacing. However, there is,no accepted standard method for choosing the parameters used in the joining process, and our results prove that defect production is sensitive to how the force field's are linked. A new procedure is presented that involves the use of ab initio calculations to,determine the magnitude and spatial dependence of the pair interactions at intermediate distances, along with systematic criteria for choosing the joining parameters. Results are presented for the case of nickel, which demonstrate the use and validity of the procedure.
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| 22. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Buentke, E, et al.
(author)
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Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells
- 2011
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In: Blood Cancer Journal. - : Macmillan Publishers Limited. - 2044-5385. ; 1:e31, s. 9-
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Journal article (peer-reviewed)abstract
- Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs.
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| 28. |
- Burlakovs, Juris, 1977-, et al.
(author)
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Platinum Group Elements in Geosphere and Anthroposphere : Interplay among the Global Reserves, Urban Ores, Markets and Circular Economy
- 2020
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In: Minerals. - : MDPI. - 2075-163X. ; 10:6, s. 1-19
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Research review (peer-reviewed)abstract
- Industrial and strategic significance of platinum group elements (PGEs)-Os, Ir, Ru, Rh, Pd, Pt-makes them irreplaceable; furthermore, some PGEs are used by investors as "safe heaven" assets traded in the commodity markets. This review analyzes PGEs from various aspects: their place in the geosphere, destiny in the anthroposphere, and opportunity in the economy considering interactions among the exploration, recycling of urban ores, trade markets, speculative rhetoric, and changes required for successful technological progress towards the implementation of sustainability. The global market of PGEs is driven by several concerns: costs for extraction/recycling; logistics; the demand of industries; policies of waste management. Diversity of application and specific chemical properties, as well as improper waste management, make the recycling of PGEs complicated. The processing approach depends on composition and the amount of available waste material, and so therefore urban ores are a significant source of PGEs, especially when the supply of elements is limited by geopolitical or market tensions. Recycling potential of urban ores is particularly important in a long-term view disregarding short-term economic fluctuations, and it should influence investment flows in the advancement of innovation.
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| 29. |
- Busker, S., et al.
(author)
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Irreversible TrxR1 inhibitors block STAT3 activity and induce cancer cell death
- 2020
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:12
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Journal article (peer-reviewed)abstract
- Because of its key role in cancer development and progression, STAT3 has become an attractive target for developing new cancer therapeutics. While several STAT3 inhibitors have progressed to advanced stages of development, their underlying biology and mechanisms of action are often more complex than would be expected from specific binding to STAT3. Here, we have identified and optimized a series of compounds that block STAT3-dependent luciferase expression with nanomolar potency. Unexpectedly, our lead compounds did not bind to cellular STAT3 but to another prominent anticancer drug target, TrxR1. We further identified that TrxR1 inhibition induced Prx2 and STAT3 oxidation, which subsequently blocked STAT3-dependent transcription. Moreover, previously identified inhibitors of STAT3 were also found to inhibit TrxR1, and likewise, established TrxR1 inhibitors block STAT3-dependent transcriptional activity. These results provide new insights into the complexities of STAT3 redox regulation while highlighting a novel mechanism to block aberrant STAT3 signaling in cancer cells.
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| 30. |
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| 31. |
- Huang, Ping, et al.
(author)
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Photo-induced oxidation of a dinuclear Mn-2(II,II) complex to the Mn-2(III,IV) state by inter- and intramolecular electron transfer to Ru-III tris-bipyridine
- 2002
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In: Journal of Inorganic Biochemistry. - 0162-0134 .- 1873-3344. ; 91:1, s. 159-172
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Journal article (peer-reviewed)abstract
- To model the structural and functional parts of the water oxidizing complex in Photosystem 11, a dimeric manganese(II,11) complex (1) was linked to a ruthenium(II)tris-bipyridine (Ru-II(bpy)3) complex via a substituted L-tyrosine, to form the trinuclear complex 2 [J. Inorg. Biochem. 78 (2000) 15]. Flash photolysis of 1 and Ru-II(bpy), in aqueous solution, in the presence of an electron acceptor, resulted in the stepwise extraction of three electrons by Ru-III(bpy), from the Mn-2(II,II) dimer, which then attained the Mn-2(III,IV) oxidation state. In a similar experiment with compound 2, the dinuclear Mn complex reduced the photo-oxidized Ru moiety via intramolecular electron transfer on each photochemical event. From EPR it was seen that 2 also reached the Mn-2(III,IV) state. Our data indicate that oxidation from the Mn-2(II,II) state proceeds stepwise via intermediate formation of Mn-2(II,III) and Mn-2(III,III). In the presence of water, cyclic voltammetry showed an additional anodic peak beyond Mn-2(II,III/III,III) oxidation which was significantly lower than in neat acetonitrile. Assuming that this peak is due to oxidation to Mn-2(III,IV), this suggests that water is essential for the formation of the Mn-2(III,IV) oxidation state. Compound 2 is a structural mimic of the water oxidizing complex, in that it links a Mn complex via a tyrosine to a highly oxidizing photosensitizer. Complex 2 also mimics mechanistic aspects of Photosystem 11, in that the electron transfer to the photosensitizer is fast and results in several electron extractions from the Mn moiety.
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| 32. |
- Jung, Christian, et al.
(author)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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In: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Journal article (peer-reviewed)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 33. |
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| 34. |
- Kukli, K., et al.
(author)
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Atomic layer deposition of ZrO2 and HfO2 on deep trenched and planar silicon
- 2007
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In: Microelectronic Engineering. - : Elsevier BV. - 0167-9317 .- 1873-5568. ; 84:9-10, s. 2010-2013
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Journal article (peer-reviewed)abstract
- Conformal ZrO2 and HfO2 thin films were grown by atomic layer deposition using novel liquid cyclopentadienyl precursors at 300 degrees C or 350 degrees C on planar Si wafers and deep trenched Si with an aspect ratio of 60:1. The crystal growth and phase content in as-deposited films depended on the precursor, film thickness, and the material grown. The structural and electrical behaviour of the films were somewhat precursor-dependent, revealing better insulating properties in the films grown from oxygen-containing precursors. Also the HfO2 films showed lower leakage compared to ZrO2.
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| 35. |
- Lynch, I, et al.
(author)
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Can an InChI for Nano Address the Need for a Simplified Representation of Complex Nanomaterials across Experimental and Nanoinformatics Studies?
- 2020
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In: Nanomaterials (Basel, Switzerland). - : MDPI AG. - 2079-4991. ; 10:12
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Journal article (peer-reviewed)abstract
- Chemoinformatics has developed efficient ways of representing chemical structures for small molecules as simple text strings, simplified molecular-input line-entry system (SMILES) and the IUPAC International Chemical Identifier (InChI), which are machine-readable. In particular, InChIs have been extended to encode formalized representations of mixtures and reactions, and work is ongoing to represent polymers and other macromolecules in this way. The next frontier is encoding the multi-component structures of nanomaterials (NMs) in a machine-readable format to enable linking of datasets for nanoinformatics and regulatory applications. A workshop organized by the H2020 research infrastructure NanoCommons and the nanoinformatics project NanoSolveIT analyzed issues involved in developing an InChI for NMs (NInChI). The layers needed to capture NM structures include but are not limited to: core composition (possibly multi-layered); surface topography; surface coatings or functionalization; doping with other chemicals; and representation of impurities. NM distributions (size, shape, composition, surface properties, etc.), types of chemical linkages connecting surface functionalization and coating molecules to the core, and various crystallographic forms exhibited by NMs also need to be considered. Six case studies were conducted to elucidate requirements for unambiguous description of NMs. The suggested NInChI layers are intended to stimulate further analysis that will lead to the first version of a “nano” extension to the InChI standard.
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| 36. |
- Niinisto, Jaakko, et al.
(author)
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Advanced cyclopentadienyl precursors for atomic layer deposition of ZrO2 thin films
- 2008
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In: Journal of Materials Chemistry. - : Royal Society of Chemistry (RSC). - 0959-9428 .- 1364-5501. ; 18:28, s. 3385-3390
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Journal article (peer-reviewed)abstract
- ZrO2 thin films were grown onto silicon (100) substrates by atomic layer deposition (ALD) using novel cyclopentadienyl-type precursors, namely (CpMe)(2)ZrMe2 and (CpMe)(2)Zr(OMe) Me (Cp = cyclopentadienyl, C5H5) together with ozone as the oxygen source. Growth characteristics were studied in the temperature range of 250 to 500 degrees C. An ALD-type self-limiting growth mode was verified for both processes at 350 degrees C where highly conformal films were deposited onto high aspect ratio trenches. Signs of thermal decomposition were not observed at or below 400 degrees C, a temperature considerably exceeding the thermal decomposition temperature of the Zr-alkylamides. Processing parameters were optimised at 350 degrees C, where deposition rates of 0.55 and 0.65 angstrom cycle(-1) were obtained for (CpMe)(2)ZrMe2/O-3 and (CpMe)(2)Zr(OMe)Me/O-3, respectively. The films grown from both precursors were stoichiometric and polycrystalline with an increasing contribution from the metastable cubic phase with decreasing film thickness. In the films grown from (CpMe)(2)ZrMe2, the breakdown field did not essentially depend on the film thickness, whereas in the films grown from (CpMe)(2)Zr(OMe)Me the structural homogeneity and breakdown field increased with decreasing film thickness. The films exhibited good capacitive properties that were characteristic of insulating oxides and did not essentially depend on the precursor chemistry.
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| 37. |
- Ojagh, Houman, 1976, et al.
(author)
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Effect of Dimethyl Disulfide on Activity of NiMo Based Catalysts Used in Hydrodeoxygenation of Oleic Acid
- 2017
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In: Industrial & Engineering Chemistry Research. - : American Chemical Society (ACS). - 1520-5045 .- 0888-5885. ; 56:19, s. 5547-5557
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Journal article (peer-reviewed)abstract
- Alumina supported NiMo catalysts were synthesized. The prepared NiMo catalysts were activated by DMDS in a sulfidation process and characterized. The sulfided NiMo catalysts were next used in hydrodeoxygenation (HDO) of oleic acid in a batch reactor. Afterward, the NiMo catalysts were recovered and used in another set of HDO reactions of oleic acid under the same conditions used in the previous HDO reactions. After the HDO experiments, the active phase and deposited coke on spent catalysts were characterized. The results indicated that higher concentrations of DMDS promoted the production of heptadecane (C-17) but had no effect on the production of octadecane (C-18). Moreover, the XPS results revealed the promotional effect of DMDS concentration on maintenance of the sulfidity of the catalysts. In addition, the results for the experiments with the second run catalyst revealed a clear deactivation due to increased coke depositions. Furthermore, after two repeated experiments with first run and second run catalysts, it was observed that coke formation decreased when the concentration of DMDS was increased. These results dearly indicate a correlation between the concentration of DMDS and coke formation.
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| 38. |
- Orru, Hans, et al.
(author)
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Ozone and heat-related mortality in Europe in 2050 significantly affected by changes in climate, population and greenhouse gas emission
- 2019
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In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 14:7
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Journal article (peer-reviewed)abstract
- Climate change is expected to increase to extreme temperatures and lead to more intense formation of near-surface ozone. Higher temperatures can cause heat stress and ozone is a highly oxidative pollutant; both increase cardiorespiratory mortality. Using greenhouse gas and ozone precursor emission scenarios, global and regional climate and chemistry-transport models, epidemiological data, and population projections, we projected ozone- and heat-related health risks under a changing climate. European near-surface temperature was modelled with the regional climate model (RCA4), forced by the greenhouse gas emission scenario RCP4.5 and the global climate model EC-EARTH, and near-surface ozone was modelled with the Multi-scale Atmospheric Transport and Chemistry (MATCH) model. Two periods were compared: recent climate in 1991-2000 and future climate in 2046-2055, projecting around a 2 degrees increase in global temperatures by that time. Projections of premature mortality considered future climate, future population, and future emissions separately and jointly to understand the relative importance of their contributions. Ozone currently causes 55 000 premature deaths annually in Europe due to long-term exposure, including a proportion of the estimated 26 000 deaths per year due to short-term exposures. When only taking into account the impact of a changing climate, up to an 11% increase in ozone-associated mortality is expected in some countries in Central and Southern Europe in 2050. However, projected decreases in ozone precursor emissions are expected to result in a decrease in ozone-related mortality (-30% as EUaverage). Due to aging and increasingly susceptible populations, the decrease in 2050 would be smaller, up to -24%. During summer months, ozone risks could combine with increasing temperatures, especially during the hottest periods and in densely populated urban areas. While the heat burden is currently of the same order of magnitude as ozone, due to increasing temperatures and decreasing ozone precursor emissions, heat-related mortality could be twice as large as ozone-related mortality in 2050.
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| 39. |
- Panaretakis, T, et al.
(author)
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Interferon alpha induces nucleus-independent apoptosis by activating extracellular signal-regulated kinase 1/2 and c-Jun NH2-terminal kinase downstream of phosphatidylinositol 3-kinase and mammalian target of rapamycin
- 2008
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In: Molecular biology of the cell. - : American Society for Cell Biology (ASCB). - 1939-4586 .- 1059-1524. ; 19:1, s. 41-50
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Journal article (peer-reviewed)abstract
- Interferon (IFN)α induces apoptosis via Bak and Bax and the mitochondrial pathway. Here, we investigated the role of known IFNα-induced signaling cascades upstream of Bak activation. By pharmacological and genetic inhibition of the kinases protein kinase C (PKC)δ, extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase (JNK) in U266-1984 and RHEK-1 cells, we could demonstrate that all three enzymes are critical for the apoptosis-associated mitochondrial events and apoptotic cell death induced by IFNα, at a step downstream of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR). Furthermore, the activation of JNK was found to occur in a PKCδ/ERK-dependent manner. Inhibition of these kinases did not affect the canonical IFNα-stimulated Janus tyrosine kinase-signal transducer and activator of transcription signaling or expression of IFN-responsive genes. Therefore, enucleated cells (cytoplasts) were examined for IFNα-induced apoptosis, to test directly whether this process depends on gene transcription. Cytoplasts were found to undergo apoptosis after IFNα treatment, as analyzed by several apoptosis markers by using flow cytometry, live cell imaging, and biochemical analysis of flow-sorted cytoplasts. Furthermore, inhibition of mTOR, ERK, and JNK blocked IFNα-induced apoptosis in cytoplasts. In conclusion, IFNα-induced apoptosis requires activation of ERK1/2, PKCδ, and JNK downstream of PI3K and mTOR, and it can occur in a nucleus-independent manner, thus demonstrating for the first time that IFNα induces apoptosis in the absence of de novo transcription.
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| 40. |
- Pijuan-Galito, Sara, et al.
(author)
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Human serum-derived protein removes the need for coating in defined human pluripotent stem cell culture
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Reliable, scalable and time-efficient culture methods are required to fully realize the clinical and industrial applications of human pluripotent stem (hPS) cells. Here we present a completely defined, xeno-free medium that supports long-term propagation of hPS cells on uncoated tissue culture plastic. The medium consists of the Essential 8 (E8) formulation supplemented with inter-alpha-inhibitor (I alpha I), a human serum-derived protein, recently demonstrated to activate key pluripotency pathways in mouse PS cells. IaI efficiently induces attachment and long-term growth of both embryonic and induced hPS cell lines when added as a soluble protein to the medium at seeding. IaI supplementation efficiently supports adaptation of feeder-dependent hPS cells to xeno-free conditions, clonal growth as well as single-cell survival in the absence of Rho-associated kinase inhibitor (ROCKi). This time-efficient and simplified culture method paves the way for large-scale, high-throughput hPS cell culture, and will be valuable for both basic research and commercial applications.
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| 41. |
- Serviss, J. T., et al.
(author)
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An antisense RNA capable of modulating the expression of the tumor suppressor microRNA-34a
- 2018
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In: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:7
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Journal article (peer-reviewed)abstract
- The microRNA-34a is a well-studied tumor suppressor microRNA (miRNA) and a direct downstream target of TP53 with roles in several pathways associated with oncogenesis, such as proliferation, cellular growth, and differentiation. Due to its broad tumor suppressive activity, it is not surprising that miR34a expression is altered in a wide variety of solid tumors and hematological malignancies. However, the mechanisms by which miR34a is regulated in these cancers is largely unknown. In this study, we find that a long noncoding RNA transcribed antisense to the miR34a host gene, is critical for miR34a expression and mediation of its cellular functions in multiple types of human cancer. We name this long noncoding RNA lncTAM34a, and characterize its ability to facilitate miR34a expression under different types of cellular stress in both TP53-deficient and wild-type settings.
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| 42. |
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| 43. |
|
|
| 44. |
|
|
| 45. |
|
|
