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  • Vogel, Jacob W., et al. (författare)
  • Four distinct trajectories of tau deposition identified in Alzheimer’s disease
  • 2021
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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  • Docherty, Anna R, et al. (författare)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Tidskriftsartikel (refereegranskat)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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  • Tinyanont, S., et al. (författare)
  • Keck Infrared Transient Survey. I. Survey Description and Data Release 1
  • 2024
  • Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 136:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the Keck Infrared Transient Survey, a NASA Key Strategic Mission Support program to obtain near-infrared (NIR) spectra of astrophysical transients of all types, and its first data release, consisting of 105 NIR spectra of 50 transients. Such a data set is essential as we enter a new era of IR astronomy with the James Webb Space Telescope (JWST) and the upcoming Nancy Grace Roman Space Telescope (Roman). NIR spectral templates will be essential to search JWST images for stellar explosions of the first stars and to plan an effective Roman SN Ia cosmology survey, both key science objectives for mission success. Between 2022 February and 2023 July, we systematically obtained 274 NIR spectra of 146 astronomical transients, representing a significant increase in the number of available NIR spectra in the literature. Here, we describe the first release of data from the 2022A semester. We systematically observed three samples: a flux-limited sample that includes all transients <17 mag in a red optical band (usually ZTF r or ATLAS o bands); a volume-limited sample including all transients within redshift z < 0.01 (D ≈ 50 Mpc); and an SN Ia sample targeting objects at phases and light-curve parameters that had scant existing NIR data in the literature. The flux-limited sample is 39% complete (60% excluding SNe Ia), while the volume-limited sample is 54% complete and is 79% complete to z = 0.005. Transient classes observed include common Type Ia and core-collapse supernovae, tidal disruption events, luminous red novae, and the newly categorized hydrogen-free/helium-poor interacting Type Icn supernovae. We describe our observing procedures and data reduction using PypeIt, which requires minimal human interaction to ensure reproducibility.
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  • Colbourne, JK, et al. (författare)
  • The Precision Toxicology initiative
  • 2023
  • Ingår i: Toxicology letters. - 1879-3169. ; 383, s. 33-42
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Jersin, R. A., et al. (författare)
  • Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance
  • 2021
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:3, s. 680-695
  • Tidskriftsartikel (refereegranskat)abstract
    • Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.
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10.
  • Kawauchi, K., et al. (författare)
  • Validation and atmospheric exploration of the sub-Neptune TOI-2136b around a nearby M3 dwarf
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The NASA space telescope TESS is currently in the extended mission of its all-sky search for new transiting planets. Of the thousands of candidates that TESS is expected to deliver, transiting planets orbiting nearby M dwarfs are particularly interesting targets since they provide a great opportunity to characterize their atmospheres by transmission spectroscopy. Aims. We aim to validate and characterize the new sub-Neptune-sized planet candidate TOI-2136.01 orbiting a nearby M dwarf (d = 33.36 +/- 0.02 pc, T-eff = 3373 +/- 108 K) with an orbital period of 7.852 days. Methods. We use TESS data, ground-based multicolor photometry, and radial velocity measurements with the InfraRed Doppler (IRD) instrument on the Subaru Telescope to validate the planetary nature of TOI-2136.01, and estimate the stellar and planetary parameters. We also conduct high-resolution transmission spectroscopy to search for helium in its atmosphere. Results. We confirm that TOI-2136.01 (now named TOI-2136b) is a bona fide planet with a planetary radius of R-p = 2.20 +/- 0.07 R-circle plus and a mass of M-p = 4.7(-2.6)(+3.1) M-circle plus. We also search for helium 10830 angstrom absorption lines and place an upper limit on the equivalent width of <7.8 m angstrom and on the absorption signal of <1.44% with 95% confidence. Conclusions. TOI-2136b is a sub-Neptune transiting a nearby and bright star (J = 10.8 mag), and is a potentially hycean planet, which is a new class of habitable planets with large oceans under a H-2-rich atmosphere, making it an excellent target for atmospheric studies to understand the formation, evolution, and habitability of the small planets.
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