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- Sainio, M. T., et al.
(författare)
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Neurofilament Light Regulates Axon Caliber, Synaptic Activity, and Organelle Trafficking in Cultured Human Motor Neurons
- 2022
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Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media SA. - 2296-634X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light (NFL) is one of the proteins forming multimeric neuron-specific intermediate filaments, neurofilaments, which fill the axonal cytoplasm, establish caliber growth, and provide structural support. Dominant missense mutations and recessive nonsense mutations in the neurofilament light gene (NEFL) are among the causes of Charcot-Marie-Tooth (CMT) neuropathy, which affects the peripheral nerves with the longest axons. We previously demonstrated that a neuropathy-causing homozygous nonsense mutation in NEFL led to the absence of NFL in patient-specific neurons. To understand the disease-causing mechanisms, we investigate here the functional effects of NFL loss in human motor neurons differentiated from induced pluripotent stem cells (iPSC). We used genome editing to generate NEFL knockouts and compared them to patient-specific nonsense mutants and isogenic controls. iPSC lacking NFL differentiated efficiently into motor neurons with normal axon growth and regrowth after mechanical axotomy and contained neurofilaments. Electrophysiological analysis revealed that motor neurons without NFL fired spontaneous and evoked action potentials with similar characteristics as controls. However, we found that, in the absence of NFL, human motor neurons 1) had reduced axonal caliber, 2) the amplitude of miniature excitatory postsynaptic currents (mEPSC) was decreased, 3) neurofilament heavy (NFH) levels were reduced and no compensatory increases in other filament subunits were observed, and 4) the movement of mitochondria and to a lesser extent lysosomes was increased. Our findings elaborate the functional roles of NFL in human motor neurons. NFL is not only a structural protein forming neurofilaments and filling the axonal cytoplasm, but our study supports the role of NFL in the regulation of synaptic transmission and organelle trafficking. To rescue the NFL deficiency in the patient-specific nonsense mutant motor neurons, we used three drugs, amlexanox, ataluren (PTC-124), and gentamicin to induce translational read-through or inhibit nonsense-mediated decay. However, the drugs failed to increase the amount of NFL protein to detectable levels and were toxic to iPSC-derived motor neurons.
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- Sepponen, K., et al.
(författare)
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Steroidogenic factor 1 (NR5A1) induces multiple transcriptional changes during differentiation of human gonadal-like cells
- 2022
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Ingår i: Differentiation. - : Elsevier BV. - 0301-4681. ; 128:Nov-Dec, s. 83-100
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear receptor subfamily 5 group A member 1 (NR5A1) encodes steroidogenic factor 1 (SF1), a key regulatory factor that determines gonadal development and coordinates endocrine functions. Here, we have established a stem cell-based model of human gonadal development and applied it to evaluate the effects of NR5A1 during the transition from bipotential gonad to testicular cells. We combined directed differentiation of human induced pluripotent stem cells (46,XY) with activation of endogenous NR5A1 expression by conditionally-inducible CRISPR activation. The resulting male gonadal-like cells expressed several Sertoli cell transcripts, secreted anti-Müllerian hormone and responded to follicle-stimulating hormone by producing sex steroid intermediates. These characteristics were not induced without NR5A1 activation. A total of 2691 differentially expressed genetic elements, including both coding and non-coding RNAs, were detected immediately following activation of NR5A1 expression. Of those, we identified novel gonad-related putative NR5A1 targets, such as SCARA5, which we validated also by immunocytochemistry. In addition, NR5A1 activation was associated with dynamic expression of multiple gonad- and infertility-related differentially expressed genes. In conclusion, by combining targeted differentiation and endogenous activation of NR5A1 we have for the first time, been able to examine in detail the effects of NR5A1 in early human gonadal cells. The model and results obtained provide a useful resource for future investigations exploring the causative reasons for gonadal dysgenesis and infertility in humans. © 2022 The Authors
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- Hokkanen, S., et al.
(författare)
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Adsorption of Ni2+, Cd2+, PO4 3- and NO3 - from aqueous solutions by nanostructured microfibrillated cellulose modified with carbonated hydroxyapatite
- 2014
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Ingår i: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947. ; 252, s. 64-74
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption of Ni2+, Cd2+, PO4 3- and NO3 - by carbonated hydroxyapatite (CHA) modified microfibrillated cellulose (MFC) was studied in the aqueous solution. The modified adsorbent was characterized using elemental analysis, FTIR, SEM and EDAX analysis. The adsorption studies were conducted in batch mode. The effects of pH, contact time, the concentration of metals and the regeneration efficiency were studied. The removal of Ni2+, Cd2+, PO4 3- and NO3 - was not pH dependent. The maximum removal capacities of the CHA/MFC adsorbent for Ni2+, Cd2+, PO4 3- and NO3 - were 2.021, 1.224, 0.843 and 0.209mmol/g, respectively. The Langmuir and Sips models were representative to simulate adsorption isotherms. The results of adsorption kinetic indicate that adsorption was very fast for all studied compounds.
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- Zucca, M., et al.
(författare)
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Metrology for Inductive Charging of Electric Vehicles (MICEV)
- 2019
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Ingår i: 2019 AEIT International Conference of Electrical and Electronic Technologies for Automotive (AEIT AUTOMOTIVE). ; , s. 1-6
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Konferensbidrag (refereegranskat)abstract
- The European Union funded project MICEV aims at improving the traceability of electrical and magnetic measurement at charging stations and to better assess the safety of this technology with respect to human exposure. The paper describes some limits of the instrumentation used for electrical measurements in the charging stations, and briefly presents two new calibration facilities for magnetic field meters and electric power meters. Modeling approaches for the efficiency and human exposure assessment are proposed. In the latter case, electromagnetic computational codes have been combined with dosimetric computational codes making use of highly detailed human anatomical phantoms in order to establish human exposure modeling real charging stations. Detailed results are presented for light vehicles where, according to our calculations, the concern towards human exposure is limited. Currently, the project has reached half way point (about 18 months) and will end in August 2020.
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- Alenius, M, et al.
(författare)
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Cognitive Performance among Cognitively Healthy Adults Aged 30-100 Years
- 2019
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Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 9:1, s. 11-23
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> To detect cognitive decline in older adults, measures of verbal fluency and verbal memory are widely used. Less is known about performance in these measures in younger persons or according to education level and gender. We investigated cognitive performance according to age, education and gender among cognitively healthy adults aged 30–100 years. <b><i>Methods:</i></b> The study population comprised 4,174 cognitively healthy persons participating in the nationally representative Finnish Health 2011 survey. Cognitive assessment included verbal fluency, word list memory, word list recall and word list savings from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery. <b><i>Results:</i></b> Total variance in the cognitive test performance explained by age, education and gender varied from 12.3 to 31.2%. A decreasing trend in cognitive performance existed in all subtests by advancing age, with differences appearing between 50 and 55 years. Persons with the highest-education level performed best for all measures. For the participants < 55 years, education explained part of the variance, while age and gender did not. <b><i>Conclusions:</i></b> When assessing cognition, age and education should be accounted for in more detail in research and clinical practice. Additionally, the cohort effect and its potential impact on the renewal cycle of future normative values for cognitive tests should be considered.
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