| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Abbasi, R., et al.
(författare)
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Measurement of atmospheric neutrino mixing with improved IceCube DeepCore calibration and data processing
- 2023
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 108:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe a new data sample of IceCube DeepCore and report on the latest measurement of atmospheric neutrino oscillations obtained with data recorded between 2011-2019. The sample includes significant improvements in data calibration, detector simulation, and data processing, and the analysis benefits from a sophisticated treatment of systematic uncertainties, with significantly greater level of detail since our last study. By measuring the relative fluxes of neutrino flavors as a function of their reconstructed energies and arrival directions we constrain the atmospheric neutrino mixing parameters to be sin2θ23=0.51±0.05 and Δm322=2.41±0.07×10-3 eV2, assuming a normal mass ordering. The errors include both statistical and systematic uncertainties. The resulting 40% reduction in the error of both parameters with respect to our previous result makes this the most precise measurement of oscillation parameters using atmospheric neutrinos. Our results are also compatible and complementary to those obtained using neutrino beams from accelerators, which are obtained at lower neutrino energies and are subject to different sources of uncertainties.
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| 4. |
- Abbasi, R., et al.
(författare)
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Limits on Neutrino Emission from GRB 221009A from MeV to PeV Using the IceCube Neutrino Observatory
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 946:1
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Tidskriftsartikel (refereegranskat)abstract
- Gamma-ray bursts (GRBs) have long been considered a possible source of high-energy neutrinos. While no correlations have yet been detected between high-energy neutrinos and GRBs, the recent observation of GRB 221009A-the brightest GRB observed by Fermi-GBM to date and the first one to be observed above an energy of 10 TeV-provides a unique opportunity to test for hadronic emission. In this paper, we leverage the wide energy range of the IceCube Neutrino Observatory to search for neutrinos from GRB 221009A. We find no significant deviation from background expectation across event samples ranging from MeV to PeV energies, placing stringent upper limits on the neutrino emission from this source.
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| 5. |
- Abbasi, R., et al.
(författare)
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Observation of seasonal variations of the flux of high-energy atmospheric neutrinos with IceCube
- 2023
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Ingår i: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 83:9
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric muon neutrinos are produced by meson decays in cosmic-ray-induced air showers. The flux depends on meteorological quantities such as the air temperature, which affects the density of air. Competition between decay and re-interaction of those mesons in the first particle production generations gives rise to a higher neutrino flux when the air density in the stratosphere is lower, corresponding to a higher temperature. A measurement of a temperature dependence of the atmospheric νμ flux provides a novel method for constraining hadronic interaction models of air showers. It is particularly sensitive to the production of kaons. Studying this temperature dependence for the first time requires a large sample of high-energy neutrinos as well as a detailed understanding of atmospheric properties. We report the significant (>10σ) observation of a correlation between the rate of more than 260,000 neutrinos, detected by IceCube between 2012 and 2018, and atmospheric temperatures of the stratosphere, measured by the Atmospheric Infrared Sounder (AIRS) instrument aboard NASA’s AQUA satellite. For the observed 10 % seasonal change of effective atmospheric temperature we measure a 3.5(3) % change in the muon neutrino flux. This observed correlation deviates by about 2-3 standard deviations from the expected correlation of 4.3 % as obtained from theoretical predictions under the assumption of various hadronic interaction models.
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| 6. |
- Abbasi, R., et al.
(författare)
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A Search for IceCube Sub-TeV Neutrinos Correlated with Gravitational-wave Events Detected By LIGO/Virgo
- 2023
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 1538-4357 .- 0004-637X. ; 959:2
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Tidskriftsartikel (refereegranskat)abstract
- The LIGO/Virgo collaboration published the catalogs GWTC-1, GWTC-2.1, and GWTC-3 containing candidate gravitational-wave (GW) events detected during its runs O1, O2, and O3. These GW events can be possible sites of neutrino emission. In this paper, we present a search for neutrino counterparts of 90 GW candidates using IceCube DeepCore, the low-energy infill array of the IceCube Neutrino Observatory. The search is conducted using an unbinned maximum likelihood method, within a time window of 1000 s, and uses the spatial and timing information from the GW events. The neutrinos used for the search have energies ranging from a few GeV to several tens of TeV. We do not find any significant emission of neutrinos, and place upper limits on the flux and the isotropic-equivalent energy emitted in low-energy neutrinos. We also conduct a binomial test to search for source populations potentially contributing to neutrino emission. We report a nondetection of a significant neutrino-source population with this test.
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| 7. |
- Abbasi, R., et al.
(författare)
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IceCat-1: The IceCube Event Catalog of Alert Tracks
- 2023
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Ingår i: Astrophysical Journal, Supplement Series. - : IOP Publishing Ltd. - 1538-4365 .- 0067-0049. ; 269:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a catalog of likely astrophysical neutrino track-like events from the IceCube Neutrino Observatory. IceCube began reporting likely astrophysical neutrinos in 2016, and this system was updated in 2019. The catalog presented here includes events that were reported in real time since 2019, as well as events identified in archival data samples starting from 2011. We report 275 neutrino events from two selection channels as the first entries in the catalog, the IceCube Event Catalog of Alert Tracks, which will see ongoing extensions with additional alerts. The Gold and Bronze alert channels respectively provide neutrino candidates with a 50% and 30% probability of being astrophysical, on average assuming an astrophysical neutrino power-law energy spectral index of 2.19. For each neutrino alert, we provide the reconstructed energy, direction, false-alarm rate, probability of being astrophysical in origin, and likelihood contours describing the spatial uncertainty in the alert's reconstructed location. We also investigate a directional correlation of these neutrino events with gamma-ray and X-ray catalogs, including 4FGL, 3HWC, TeVCat, and Swift-BAT.
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| 8. |
- Abbasi, R., et al.
(författare)
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Search for neutrino lines from dark matter annihilation and decay with IceCube
- 2023
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Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 108:10
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Tidskriftsartikel (refereegranskat)abstract
- Dark matter particles in the Galactic Center and halo can annihilate or decay into a pair of neutrinos producing a monochromatic flux of neutrinos. The spectral feature of this signal is unique and it is not expected from any astrophysical production mechanism. Its observation would constitute a dark matter smoking gun signal. We performed the first dedicated search with a neutrino telescope for such signal, by looking at both the angular and energy information of the neutrino events. To this end, a total of five years of IceCube's DeepCore data has been used to test dark matter masses ranging from 10 GeV to 40 TeV. No significant neutrino excess was found and upper limits on the annihilation cross section, as well as lower limits on the dark matter lifetime, were set. The limits reached are of the order of 10-24 cm3/s for an annihilation and up to 1027 s for decaying dark matter. Using the same data sample we also derive limits for dark matter annihilation or decay into a pair of Standard Model charged particles.
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| 9. |
- Gilmore, G., et al.
(författare)
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The Gaia-ESO Public Spectroscopic Survey : Motivation, implementation, GIRAFFE data processing, analysis, and final data products star
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Gaia-ESO Public Spectroscopic Survey is an ambitious project designed to obtain astrophysical parameters and elemental abundances for 100 000 stars, including large representative samples of the stellar populations in the Galaxy, and a well-defined sample of 60 (plus 20 archive) open clusters. We provide internally consistent results calibrated on benchmark stars and star clusters, extending across a very wide range of abundances and ages. This provides a legacy data set of intrinsic value, and equally a large wide-ranging dataset that is of value for the homogenisation of other and future stellar surveys and Gaia's astrophysical parameters. Aims. This article provides an overview of the survey methodology, the scientific aims, and the implementation, including a description of the data processing for the GIRAFFE spectra. A companion paper introduces the survey results. Methods. Gaia-ESO aspires to quantify both random and systematic contributions to measurement uncertainties. Thus, all available spectroscopic analysis techniques are utilised, each spectrum being analysed by up to several different analysis pipelines, with considerable effort being made to homogenise and calibrate the resulting parameters. We describe here the sequence of activities up to delivery of processed data products to the ESO Science Archive Facility for open use. Results. The Gaia-ESO Survey obtained 202 000 spectra of 115 000 stars using 340 allocated VLT nights between December 2011 and January 2018 from GIRAFFE and UVES. Conclusions. The full consistently reduced final data set of spectra was released through the ESO Science Archive Facility in late 2020, with the full astrophysical parameters sets following in 2022. A companion article reviews the survey implementation, scientific highlights, the open cluster survey, and data products.
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| 10. |
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| 11. |
- Zhang, X., et al.
(författare)
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Human total, basal and activity energy expenditures are independent of ambient environmental temperature
- 2022
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Ingår i: iScience. - : Elsevier Inc.. - 2589-0042. ; 25:8
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Tidskriftsartikel (refereegranskat)abstract
- Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (−10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18–25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures.
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| 12. |
- Gehlen, J., et al.
(författare)
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First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B
- 2022
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Ingår i: Human Genetics and Genomics Advances. - : Elsevier BV. - 2666-2477. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes. © 2022 The Authors
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| 13. |
- Librado, P., et al.
(författare)
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The origins and spread of domestic horses from the Western Eurasian steppes
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 634-640
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region. Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).
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| 14. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 15. |
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| 16. |
- Mingardo, E, et al.
(författare)
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A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1203-
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Tidskriftsartikel (refereegranskat)abstract
- Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.
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| 17. |
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| 18. |
- Gialluisi, A, et al.
(författare)
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Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:7, s. 3004-3017
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Tidskriftsartikel (refereegranskat)abstract
- Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10−6) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20–25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (atpT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase;p = 8 × 10−13), bipolar disorder (1.53[1.44; 1.63];p = 1 × 10−43), schizophrenia (1.36[1.28; 1.45];p = 4 × 10−22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30];p = 3 × 10−12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96];p = 5 × 10−4), educational attainment (0.86[0.82; 0.91];p = 2 × 10−7), and intelligence (0.72[0.68; 0.76];p = 9 × 10−29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.
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| 19. |
- Carpenter, J. M., et al.
(författare)
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Neurochemical and neuroinflammatory perturbations in two Gulf War Illness models : Modulation by the immunotherapeutic LNFPIII
- 2020
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Ingår i: Neurotoxicology. - : ELSEVIER. - 0161-813X .- 1872-9711. ; 77, s. 40-50
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Tidskriftsartikel (refereegranskat)abstract
- Gulf War Illness (GWI) manifests a multitude of symptoms, including neurological and immunological, and approximately a third of the 1990-1991 Gulf War (GW) veterans suffer from it. This study sought to characterize the acute neurochemical (monoamine) and neuroinflammatory profiles of two established GWI animal models and examine the potential modulatory effects of the novel immunotherapeutic Lacto-N-fucopentaose III (LNFPIII). In Model 1, male C57BL/6J mice were treated for 10 days with pyridostigmine bromide (PB) and permethrin (PM). In Model 2, a separate cohort of mice were treated for 14 days with PB and N,N-Diethylmethylbenzamide (DEET), plus corticosterone (CORT) via drinking water on days 8-14 and diisopropylfluorophosphate (DFP) on day 15. LNFPIII was administered concurrently with GWI chemicals treatments. Brain and spleen monoamines and hippocampal inflammatory marker expression were examined by, respectively, HPLC-ECD and qPCR, 6 h post treatment cessation. Serotonergic (5-HT) and dopaminergic (DA) dyshomeostasis caused by GWI chemicals was apparent in multiple brain regions, primarily in the nucleus accumbens (5-HT) and hippocampus (5-FIT, DA) for both models. Splenic levels of 5-HT (both models) and norepinephrine (Model 2) were also disrupted by GWI chemicals. LNFPIII treatment prevented many of the GWI chemicals induced monoamine alterations. Hippocampal inflammatory cytokines were increased in both models, but the magnitude and spread of inflammation was greater in Model 2; LNFPIII was anti-inflammatory, more so in the apparently milder Model 1. Overall, in both models, GWI chemicals led to monoamine disbalance and neuroinflammation. LNFPIII co-treatment prevented many of these disruptions in both models, which is indicative of its promise as a potential GWI therapeutic.
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| 20. |
- Demichev, Vadim, et al.
(författare)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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| 21. |
- Ludwig, Sebastian, et al.
(författare)
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Transcatheter Mitral Valve Replacement versus Medical Therapy for Secondary Mitral Regurgitation: A Propensity Score-Matched Comparison.
- 2023
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Ingår i: Circulation. Cardiovascular interventions. - 1941-7632. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transcatheter mitral valve replacement (TMVR) is an emerging therapeutic alternative for patients with secondary mitral regurgitation (MR). Outcomes of TMVR versus guideline-directed medical therapy (GDMT) have not been investigated for this population. This study aimed to compare clinical outcomes of patients with secondary MR undergoing TMVR versus GDMT alone. Methods: The CHOICE-MI registry included patients with MR undergoing TMVR using dedicated devices. Patients with MR etiologies other than secondary MR were excluded. Patients treated with GDMT alone were derived from the control arm of the COAPT trial. We compared outcomes between the TMVR and GDMT groups, using propensity score (PS)-matching to adjust for baseline differences. Results: After PS-matching, 97 patient pairs undergoing TMVR (72.9±8.7 years, 60.8% male, transapical access 91.8%) versus GDMT (73.1±11.0 years, 59.8% male) were compared. At 1 and 2 years, residual MR was ≤1+ in all patients of the TMVR group compared to 6.9% and 7.7%, respectively, in those receiving GDMT alone (both p<0.001). The 2-year rate of HF hospitalization was significantly lower in the TMVR group (32.8% vs. 54.4%, HR 0.59, 95% CI 0.35-0.99; p=0.04). Among survivors, a higher proportion of patients were in NYHA functional class I or II in the TMVR group at 1 year (78.2% vs. 59.7%, p=0.03) and at 2 years (77.8% vs. 53.2%, p=0.09). Two-year mortality was similar in the two groups (TMVR vs. GDMT, 36.8% vs. 40.8%, HR 1.01, 95% CI 0.62-1.64; p=0.98). Conclusions: In this observational comparison, over 2-year follow-up, TMVR using mostly transapical devices in patients with secondary MR was associated with significant reduction of MR, symptomatic improvement, less frequent hospitalizations for HF and similar mortality compared with GDMT.
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| 22. |
- Muus, Christoph, et al.
(författare)
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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 546-559
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.
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| 23. |
- Berner, Logan T., et al.
(författare)
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The Arctic plant aboveground biomass synthesis dataset
- 2024
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.
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| 24. |
- Besse, Lenka, et al.
(författare)
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Treatment with HIV-protease inhibitor nelfinavir identifies membrane lipid composition and fluidity as a therapeutic target in advanced multiple myeloma
- 2021
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 81, s. 4581-4593
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Tidskriftsartikel (refereegranskat)abstract
- The HIV-protease inhibitor nelfinavir has shown broad anticancer activity in various preclinical and clinical contexts.In patients with advanced, proteasome inhibitor (PI)-refractory multiple myeloma, nelfinavir-based therapy resulted in 65% partial response or better, suggesting that this may be a highly active chemotherapeutic option in this setting.The broad anticancer mechanism of action of nelfinavir implies that it interferes with fundamental aspects of cancer cell biology.We combined proteome-wide affinity-purification of nelfinavir-interacting proteins with genome-wide CRISPR/Cas9-based screening to identify protein partners that interact with nelfinavir in an activity-dependent manner alongside candidate genetic contributors affecting nelfinavir cytotoxicity.Nelfinavir had multiple activity-specific binding partners embedded in lipid bilayers of mitochondria and the endoplasmic reticulum.Nelfinavir affected the fluidity and composition of lipid-rich membranes, disrupted mitochondrial respiration, blocked vesicular transport, and affected the function of membrane-embedded drug efflux transporter ABCB1, triggering the integrated stress response.Sensitivity to nelfinavir was dependent on ADIPOR2, which maintains membrane fluidity by promoting fatty acid desaturation and incorporation into phospholipids.Supplementation with fatty acids prevented the nelfinavir-induced effect on mitochondrial metabolism, drug-efflux transporters, and stress-response activation.Conversely, depletion of fatty acids/cholesterol pools by the FDAapproved drug ezetimibe showed a synergistic anticancer activity with nelfinavir in vitro.These results identify the modification of lipid-rich membranes by nelfinavir as a novel mechanism of action to achieve broad anticancer activity, which may be suitable for the treatment of PI-refractory multiple myeloma.
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| 25. |
- Brown, A. Kyle, et al.
(författare)
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Lacto-N-fucopentaose-III ameliorates acute and persisting hippocampal synaptic plasticity and transmission deficits in a Gulf War Illness mouse model
- 2021
-
Ingår i: Life Sciences. - : Elsevier. - 0024-3205 .- 1879-0631. ; 279
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The present study investigated if treatment with the immunotherapeutic, lacto-N-fucopentaose-III (LNFPIII), resulted in amelioration of acute and persisting deficits in synaptic plasticity and transmission as well as trophic factor expression along the hippocampal dorsoventral axis in a mouse model of Gulf War Illness (GWI).Main methods: Mice received either coadministered or delayed LNFPIII treatment throughout or following, respectively, exposure to a 15-day GWI induction paradigm. Subsets of animals were subsequently sacrificed 48 h, seven months, or 11 months post GWI-related (GWIR) exposure for hippocampal qPCR or in vitro electrophysiology experiments.Key findings: Progressively worsened impairments in hippocampal synaptic plasticity, as well as a biphasic effect on hippocampal synaptic transmission, were detected in GWIR-exposed animals. Dorsoventral-specific impairments in hippocampal synaptic responses became more pronounced over time, particularly in the dorsal hippocampus. Notably, delayed LNFPIII treatment ameliorated GWI-related aberrations in hippocampal synaptic plasticity and transmission seven and 11 months post-exposure, an effect that was consistent with enhanced hippocampal trophic factor expression and absence of increased interleukin 6 (IL-6) in animals treated with LNFPIII.Significance: Approximately a third of Gulf War Veterans have GWI; however, GWI therapeutics are presently limited to targeted and symptomatic treatments. As increasing evidence underscores the substantial role of persisting neuroimmune dysfunction in GWI, efficacious neuroactive immunotherapeutics hold substantial promise in yielding GWI remission. The findings in the present report indicate that LNFPIII may be an efficacious candidate for ameliorating persisting neurological abnormalities presented in GWI.
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