| 1. |
- Abolfathi, Bela, et al.
(författare)
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The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
- 2018
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Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
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Tidskriftsartikel (refereegranskat)abstract
- The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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| 2. |
- Alsterholm, Mikael, 1977, et al.
(författare)
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Establishment and utility of SwedAD : a nationwide Swedish registry for patients with atopic dermatitis receiving systemic pharmacotherapy
- 2023
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 103
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Tidskriftsartikel (refereegranskat)abstract
- SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.
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| 3. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 4. |
- Ahlberg, Erik, et al.
(författare)
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Secondary organic aerosol from VOC mixtures in an oxidation flow reactor
- 2017
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 161, s. 210-220
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Tidskriftsartikel (refereegranskat)abstract
- The atmospheric organic aerosol is a tremendously complex system in terms of chemical content. Models generally treat the mixtures as ideal, something which has been questioned owing to model-measurement discrepancies. We used an oxidation flow reactor to produce secondary organic aerosol (SOA) mixtures containing oxidation products of biogenic (α-pinene, myrcene and isoprene) and anthropogenic (m-xylene) volatile organic compounds (VOCs). The resulting volume concentration and chemical composition was measured using a scanning mobility particle sizer (SMPS) and a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS), respectively. The SOA mass yield of the mixtures was compared to a partitioning model constructed from single VOC experiments. The single VOC SOA mass yields with no wall-loss correction applied are comparable to previous experiments. In the mixtures containing myrcene a higher yield than expected was produced. We attribute this to an increased condensation sink, arising from myrcene producing a significantly higher number of nucleation particles compared to the other precursors. Isoprene did not produce much mass in single VOC experiments but contributed to the mass of the mixtures. The effect of high concentrations of isoprene on the OH exposure was found to be small, even at OH reactivities that previously have been reported to significantly suppress OH exposures in oxidation flow reactors. Furthermore, isoprene shifted the particle size distribution of mixtures towards larger sizes, which could be due to a change in oxidant dynamics inside the reactor.
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| 5. |
- Bergman, Lina, et al.
(författare)
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Registered nurses' experiences of working in the intensive care unit during the COVID-19 pandemic
- 2021
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Ingår i: Nursing in Critical Care. - : John Wiley & Sons. - 1362-1017 .- 1478-5153. ; 26:6, s. 467-475
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDuring the pandemic, increased numbers of patients requiring intensive care unit (ICU) admission required an increase in ICU capacity, including ICU staffing with competence to care for critically ill patients. Consequently, nurses from acute care areas were called in to staff the ICU along with experienced intensive care nurses.Aims and objectivesTo describe Swedish registered nurses' experiences of caring for patients with COVID-19 in ICUs during the pandemic.DesignMixed method survey design.MethodsAn online questionnaire was distributed through social media to registered nurses who had been working in the ICU during the COVID-19 outbreak. Data were collected for 1 week (May 2020) and analysed using content analysis and descriptive statistics.ResultsOf the 282 nurses who participated, the majority were ICU nurses (n = 151; 54%). Half of the nurses specialized in ICU reported that they were responsible for the ICU care of three or more patients during the pandemic (n = 75; 50%). Among non-intensive care nurses, only 19% received introduction to the COVID-19 ICU (n = 26). The analysis of data regarding nurses' experiences resulted in three categories: tumbling into chaos, diminished nursing care, and transition into pandemic ICU care. Participants described how patient safety and care quality were compromised, and that nursing care was severely deprioritized during the pandemic. The situation of not being able to provide nursing care resulted in ethical stress. Furthermore, an increased workload and worsened work environment affected nurses' health and well-being.ConclusionsThe findings from the present study indicate that nurses perceived that patient safety and quality of care were compromised during the pandemic. This resulted in ethical stress among nurses, which may have affected their physical and psychosocial well-being.Relevance to clinical practiceThe COVID-19 pandemic had a severe impact on nurses' work environment, which could result in burnout and staff turnover.
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| 6. |
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| 7. |
- Castenbrandt, Helene, et al.
(författare)
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Administrating sickness: The workings of an all-female sickness fund, 1898–1931
- 2021
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Ingår i: Accounting for health: Calculation, paperwork, and medicine, 1500-2000. - : Manchester University Press. - 9781526135162 - 9781526135179 ; , s. 337-358
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Bokkapitel (refereegranskat)abstract
- This chapter investigates the characteristics of a successful voluntary sickness fund in early twentieth-century Sweden. The practices of the Seamstresses Sickness and Burial Fund reveal how a working-class organisation functioned in improving the living conditions of its members. When it was first founded in 1898, it was a small all-female and marginal sickness fund, but by the 1930s it had developed into one of the largest in the city of Gothenburg, with good financial reserves. While successfully attracting new members and retaining its old, the fund also proved to be effective in reducing the costs of long-term sickness cases, one of its greatest concerns. Moreover, the social nature of the fund, its emphasis on mutual aid, and its economic decision-making practices, which went beyond mere capital accumulation, holds much of the explanation for the fund’s success. The fund also took part in initiating discussions on maternity benefits and participated actively in the general women’s rights movement, while also playing a part in the male-dominated sickness fund movement at large. Members’ engagement and willingness to remain members was likely reinforced by how the fund in this way gave a voice for working-class women.
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| 8. |
- Falk, John, et al.
(författare)
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Immersion freezing ability of freshly emitted soot with various physico-chemical characteristics
- 2021
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Ingår i: Atmosphere. - : MDPI AG. - 2073-4433. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- The immersion freezing ability of soot particles has in previous studies been reported in the range of low/insignificant to very high. The aims of this study were to: (i) perform detailed physico-chemical characterisation of freshly produced soot particles with very different properties, (ii) investigate the immersion freezing ability of the same particles, and (iii) investigate the potential links between physico-chemical particle properties and ice-activity. A miniCAST soot generator was used to produce eight different soot samples representing a wide range of physico-chemical properties. A continuous flow diffusion chamber was used to study each sample online in immersion mode over the temperature (T) range from −41 to −32◦C, at a supersaturation of about 10% with respect to liquid water. All samples exhibited low to no heterogeneous immersion freezing. The most active sample reached ice-activated fractions (AF) of 10−3 and 10−4 at temperatures of 1.7 and 1.9 K, respectively, above the homogeneous freezing temperature. The samples were characterized online with respect to a wide range of physico-chemical properties including effective particle density, optical properties, particle surface oxidation and soot maturity. We did observe indications of increasing immersion freezing ice-activity with increasing effective particle density and increasing particulate PAH fraction . Hence, those properties, or other properties co-varying with those, could potentially enhance the immersion freezing ice-activity of the studied soot particle types. However, we found no significant correlation between the physico-chemical properties and the observed ice-nucleating ability when the particle ensemble was extended to include previously published results including more ice-active biomass combustion soot particles. We conclude that it does not appear possible in general and in any straightforward way to link observed soot particle physico-chemical properties to the ice-nucleating ability using the online instrumentation included in this study. Furthermore, our observations support that freshly produced soot particles with a wide range of physico-chemical properties have low to insignificant immersion freezing ice-nucleating ability.
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| 9. |
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| 10. |
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| 11. |
- Gren, Louise, et al.
(författare)
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Effects of renewable fuel and exhaust aftertreatment on primary and secondary emissions from a modern heavy-duty diesel engine
- 2021
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Ingår i: Journal of Aerosol Science. - : Elsevier BV. - 0021-8502. ; 156
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Tidskriftsartikel (refereegranskat)abstract
- Compared to petroleum diesel, renewable diesel fuels and exhaust aftertreatment systems can reduce primary exhaust emissions that are hazardous to human health and the environment. Secondary aerosol emissions which form upon atmospheric processing have, however, been less studied. This study aimed to quantify the impacts of replacing petroleum diesel with renewable fuels (hydrotreated vegetable oil [HVO] and rapeseed methyl ester [RME]) on primary and secondary aerosol emissions from a heavy-duty diesel engine at different stages of an exhaust aftertreatment system. Emission characterization was obtained by combining a battery of physical characterization techniques with chemical characterization using aerosol mass spectrometry. At engine-out measurements, RME and HVO reduced primary particulate matter (PM) emissions (for example equivalent black carbon [eBC]) and secondary aerosol production (studied with an oxidation flow reactor [OFR]) by mass compared to petroleum diesel. The diesel oxidation catalyst (DOC) reduced primary nucleation mode emissions, reduced the effective density of soot mode emissions, and reduced secondary particle production by mass. The DOC + a diesel particulate filter removed >99% of the particle number and eBC emissions. Volatile PM emissions (for example organic aerosol) were found to be distributed between the nucleation mode and soot mode for both primary and secondary emissions, to a degree that depends on both fuel type and aftertreatment. A high mass concentration of condensable species and a low condensation sink in the soot mode led to increased fractions of condensable species present in the nucleation mode. Aging in the OFR led to increases in particle effective density. Motoring the engine (running without combustion) showed that the nucleation mode originated primarily from lubricating oil, and nonvolatile nanoparticle emissions were identified down to 1.2 nm in particle size. In conclusion, replacing petroleum diesel with HVO and RME changes emission characteristics and can help reduce key aerosol emissions of relevance for adverse health and climate impact, especially for diesel engines with no or limited exhaust aftertreatment.
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| 12. |
- Havervall, Sebastian, et al.
(författare)
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Robust humoral and cellular immune responses and low risk for reinfection at least 8 months following asymptomatic to mild COVID-19
- 2022
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 291:1, s. 72-80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Emerging data support detectable immune responses for months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, but it is not yet established to what degree and for how long protection against reinfection lasts.Methods: We investigated SARS-CoV-2-specific humoral and cellular immune responses more than 8 months post-asymptomatic, mild and severe infection in a cohort of 1884 healthcare workers (HCW) and 51 hospitalized COVID-19 patients. Possible protection against SARS-CoV-2 reinfection was analyzed by a weekly 3-month polymerase chain reaction (PCR) screening of 252 HCW that had seroconverted 7 months prior to start of screening and 48 HCW that had remained seronegative at multiple time points.Results: All COVID-19 patients and 96% (355/370) of HCW who were anti-spike IgG positive at inclusion remained anti-spike IgG positive at the 8-month follow-up. Circulating SARS-CoV-2-specific memory T cell responses were detected in 88% (45/51) of COVID-19 patients and in 63% (233/370) of seropositive HCW. The cumulative incidence of PCR-confirmed SARS-CoV-2 infection was 1% (3/252) among anti-spike IgG positive HCW (0.13 cases per 100 weeks at risk) compared to 23% (11/48) among anti-spike IgG negative HCW (2.78 cases per 100 weeks at risk), resulting in a protective effect of 95.2% (95% CI 81.9%-99.1%).Conclusions: The vast majority of anti-spike IgG positive individuals remain anti-spike IgG positive for at least 8 months regardless of initial COVID-19 disease severity. The presence of anti-spike IgG antibodies is associated with a substantially reduced risk of reinfection up to 9 months following asymptomatic to mild COVID-19.
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| 13. |
- Kaiser, Axel
(författare)
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Architecturally Innovative Multi-Storey Timber Buildings : Methodology and Design
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This investigation applies architectural ideas of mass-customised difference and repetition, and tests them within the engineering paradigm of very tall timber buildings – taller than have ever been erected in the history of architecture. According to Edward Glaeser’s book, Triumph of the City, the cheapest way to deliver new housing (at least in the USA) is in theform of mass-produced two-storey homes, which typically cost only about $84 per square foot to erect. While building up is more costly, many of the costs – such as hiring a fancy, big-name architect – are fixed and won’t increase with the height of the building. In fact, once you’ve reached a height of about seven floors, building up has its own economic logic, since those fixed costs can be spread over more living units, writes Glaeser, before continuing: “The actual marginal cost of adding an extra square foot of living space at the topof a skyscraper in New York is typically less than $400”. If to this we add all the financial advantages of using stacked structures made from engineered timber – lower construction costs due to the simple geometry, and the speed oferection (four men built the nine stories of our primary precedent, the Stadthaus building in London, in nine weeks, reducing the entire building process from 72 weeks to 49); larger savings on the entire building (again, the Stadthaus came in at 15 percent less expensive than a concrete equivalent); and lower costs for transportation and foundations due to the lighterweight of the material – it soon becomes clear that timber developments make financial sense. Timber can also be precisely incorporated into different proprietary building systems: throughout this project, the systems of three Swedish manufacturers (Martinsons, Moelven, and Byggma) are used as structural frameworks. The trio of multi-storey timber buildings isbased on conceptual notions of stacking, cutting, and slotting, respectively. These simple formal ideas (a variation on Deleuze’s thoughts on difference and repetition) are interpreted to align with the fundamental material logic of wood, as well as with the specific ramifications of these existing timber building systems. Methodologically, these buildings utilise a primary organisational principle to inform its volumetric massing, circulatory planning, arrangement of living units, fenestration configuration, and so on, while allowing for other principles to guide further aspects so as to avoid what Reiser + Umemoto call The Abuse of the Diagram: “Any one organizational model has limits. The ambition to carry a diagram through all levels of a single architecturalproject is exhaustive and reductive. To have one model determine all aspects of design is to simplify what is in reality a richer, more heterogeneous complexity. A true multiplicity requires that many different models be coordinated. A single model relentlessly deployed at all scales emerges as merely formal.”Having said that, an initial investigation into simple formal moves at the outset of a project often yields a plethora of potential trajectories created by the self-imposed constraints that are carried through by the limiting conceptual framework we choose to adopt. There appears to be a certain psychology of limitation that are highly beneficial for devising new ideas, be theyformal, spatial, or haptically driven. As neuroscience journalist Jonah Lehrer puts it in his book Imagine: How Creativity Works: “...the imagination is unleashed by constraints. You break out of the box by stepping into shackles”. The following is a study of such a break-out attempt.
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| 14. |
- Korhonen, Kimmo, et al.
(författare)
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Ice-nucleating ability of particulate emissions from solid-biomass-fired cookstoves : An experimental study
- 2020
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:8, s. 4951-4968
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Tidskriftsartikel (refereegranskat)abstract
- This research was part of the Salutary Umeå Study of Aerosols in Biomass Cookstove Emissions (SUSTAINE) laboratory experiment campaign. We studied ice-nucleating abilities of particulate emissions from solid-fuel-burning cookstoves, using a portable ice nuclei counter, Spectrometer Ice Nuclei (SPIN). These emissions were generated from two traditional cookstove types commonly used for household cooking in sub-Saharan Africa and two advanced gasifier stoves under research to promote sustainable development alternatives. The solid fuels studied included biomass from two different African tree species, Swedish softwood and agricultural residue products relevant to the region. Measurements were performed with a modified version of the standard water boiling test on polydisperse samples from flue gas during burning and size-selected accumulation mode soot particles from a 15 m3 aerosol-storage chamber. The studied soot particle sizes in nanometers were 250, 260, 300, 350, 400, 450 and 500. From this chamber, the particles were introduced to water-supersaturated freezing conditions (-32 to-43 °C) in the SPIN. Accumulation mode soot particles generally produced an ice-activated fraction of 10-3 in temperatures 1-1.5 °C higher than that required for homogeneous freezing at fixed RHw D 115 %. In five special experiments, the combustion performance of one cookstove was intentionally modified. Two of these exhibited a significant increase in the icenucleating ability of the particles, resulting in a 10-3 ice activation at temperatures up to 5.9 °C higher than homogeneous freezing and the observed increased ice-nucleating ability. We investigated six different physico-chemical properties of the emission particles but found no clear correlation between them and increasing ice-nucleating ability. We conclude that the freshly emitted combustion aerosols form ice via immersion and condensation freezing at temperatures only moderately above homogeneous freezing conditions.
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| 15. |
- Korhonen, Kimmo, et al.
(författare)
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Particle emissions from a modern heavy-duty diesel engine as ice nuclei in immersion freezing mode: a laboratory study on fossil and renewable fuels
- 2022
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 22:23, s. 1615-1631
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Tidskriftsartikel (refereegranskat)abstract
- We studied ice-nucleating abilities of particulate emissions from a modern heavy-duty diesel engine using three different types of fuel. The polydisperse particle emissions were sampled during engine operation and introduced to a continuous-flow diffusion chamber (CFDC) instrument at a constant relative humidity RHwater=110 %, while the temperature was ramped between −43 and −32 ∘C (T scan). The tested fuels were EN 590 compliant low-sulfur fossil diesel, hydrotreated vegetable oil (HVO), and rapeseed methyl ester (RME); all were tested without blending. Sampling was carried out at different stages in the engine exhaust aftertreatment system, with and without simulated atmospheric processing using an oxidation flow reactor. In addition to ice nucleation experiments, we used supportive instrumentation to characterize the emitted particles for their physicochemical properties and presented six parameters. We found that the studied emissions contained no significant concentrations of ice-nucleating particles likely to be of atmospheric relevance. The substitution of fossil diesel with renewable fuels, using different emission aftertreatment systems such as a diesel oxidation catalyst, and photochemical aging of total exhaust had only minor effect on their ice-nucleating abilities.
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| 16. |
- Kristensen, Thomas Bjerring, et al.
(författare)
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Properties and emission factors of cloud condensation nuclei from biomass cookstoves - Observations of a strong dependency on potassium content in the fuel
- 2021
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Ingår i: Atmospheric Chemistry And Physics. - : Nicolaus Copernicus University Press. - 1680-7316 .- 1680-7324. ; 21:10, s. 8023-8044
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Tidskriftsartikel (refereegranskat)abstract
- Residential biomass combustion is a significant source of aerosol particles on regional and global scales influencing climate and human health. The main objective of the current study was to investigate the properties of cloud condensation nuclei (CCN) emitted from biomass burning of solid fuels in different cookstoves mostly of relevance to sub- Saharan east Africa.The traditional three-stone fire and a rocket stove were used for combustion of wood logs of Sesbania and Casuarina with birch used as a reference. A natural draft and a forced-draft pellet stove were used for combustion of pelletised Sesbania and pelletised Swedish softwood alone or in mixtures with pelletised coffee husk, rice husk or water hyacinth. The CCN activity and the effective density were measured for particles with mobility diameters of v65, v100 and v200 nm, respectively, and occasionally for 350 nm particles. Particle number size distributions were measured online with a fast particle analyser. The chemical composition of the fuel ash was measured by application of standard protocols.The average particle number size distributions were by number typically dominated by an ultrafine mode, and in most cases a soot mode was centred around a mobility diameter of v150 nm. The CCN activities decreased with increasing particle size for all experiments and ranged in terms of the hygroscopicity parameter, from v0:1 to v0:8 for the ultrafine mode and from v0:001 to v0:15 for the soot mode. The CCN activity of the ultrafine mode increased (i) with increasing combustion temperature for a given fuel, and (ii) it typically increased with increasing potassium concentration in the investigated fuels. The primary CCN and the estimated particulate matter (PM) emission factors were typically found to increase significantly with increasing potassium concentration in the fuel for a given stove. In order to link CCN emission factors to PM emission factors, knowledge about stove technology, stove operation and the inorganic fuel ash composition is needed. This complicates the use of ambient PM levels alone for estimation of CCN concentrations in regions dominated by biomass combustion aerosol, with the relation turning even more complex when accounting for atmospheric ageing of the aerosol.
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| 17. |
- Mastropasqua, Francesca, et al.
(författare)
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Deficiency of the Heterogeneous Nuclear Ribonucleoprotein U locus leads to delayed hindbrain neurogenesis.
- 2023
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Ingår i: Biology open. - : The Company of Biologists. - 2046-6390. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants affecting Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU) have been identified in several neurodevelopmental disorders (NDDs). HNRNPU is widely expressed in the human brain and shows the highest postnatal expression in the cerebellum. Recent studies have investigated the role of HNRNPU in cerebral cortical development, but the effects of HNRNPU deficiency on cerebellar development remain unknown. Here, we describe the molecular and cellular outcomes of HNRNPU locus deficiency during in vitro neural differentiation of patient-derived and isogenic neuroepithelial stem cells with a hindbrain profile. We demonstrate that HNRNPU deficiency leads to chromatin remodeling of A/B compartments, and transcriptional rewiring, partly by impacting exon inclusion during mRNA processing. Genomic regions affected by the chromatin restructuring and host genes of exon usage differences show a strong enrichment for genes implicated in epilepsies, intellectual disability, and autism. Lastly, we show that at the cellular level HNRNPU downregulation leads to an increased fraction of neural progenitors in the maturing neuronal population. We conclude that the HNRNPU locus is involved in delayed commitment of neural progenitors to differentiate in cell types with hindbrain profile.
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| 18. |
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