SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Henry Brian) "

Sökning: WFRF:(Henry Brian)

  • Resultat 1-50 av 69
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
  •  
2.
  • Kanoni, Stavroula, et al. (författare)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
  •  
3.
  • The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
  • 2022
  • Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
  •  
4.
  • Weber, Michael A, et al. (författare)
  • A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension : a randomised, double-blind, placebo-controlled trial
  • 2009
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 374:9699, s. 1423-1431
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundHypertension cannot always be adequately controlled with available drugs. We investigated the blood-pressure-lowering effects of the new vasodilatory, selective endothelin type A antagonist, darusentan, in patients with treatment-resistant hypertension.MethodsThis randomised, double-blind study was undertaken in 117 sites in North and South America, Europe, New Zealand, and Australia. 379 patients with systolic blood pressure of 140 mm Hg or more (≥130 mm Hg if patient had diabetes or chronic kidney disease) who were receiving at least three blood-pressure-lowering drugs, including a diuretic, at full or maximum tolerated doses were randomly assigned to 14 weeks' treatment with placebo (n=132) or darusentan 50 mg (n=81), 100 mg (n=81), or 300 mg (n=85) taken once daily. Randomisation was made centrally via an automated telephone system, and patients and all investigators were masked to treatment assignments. The primary endpoints were changes in sitting systolic and diastolic blood pressures. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00330369.FindingsAll randomly assigned participants were analysed. The mean reductions in clinic systolic and diastolic blood pressures were 9/5 mm Hg (SD 14/8) with placebo, 17/10 mm Hg (15/9) with darusentan 50 mg, 18/10 mm Hg (16/9) with darusentan 100 mg, and 18/11 mm Hg (18/10) with darusentan 300 mg (p<0·0001 for all effects). The main adverse effects were related to fluid accumulation. Oedema or fluid retention occurred in 67 (27%) patients given darusentan compared with 19 (14%) given placebo. One patient in the placebo group died (sudden cardiac death), and five patients in the three darusentan dose groups combined had cardiac-related serious adverse events.InterpretationDarusentan provides additional reduction in blood pressure in patients who have not attained their treatment goals with three or more antihypertensive drugs. As with other vasodilatory drugs, fluid management with effective diuretic therapy might be needed.
  •  
5.
  • Zamora, Juan Carlos, et al. (författare)
  • Considerations and consequences of allowing DNA sequence data as types of fungal taxa
  • 2018
  • Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
  •  
6.
  • Aguilar-Calvo, Patricia, et al. (författare)
  • Shortening heparan sulfate chains prolongs survival and reduces parenchymal plaques in prion disease caused by mobile, ADAM10-cleaved prions
  • 2020
  • Ingår i: Acta Neuropathologica. - : SPRINGER. - 0001-6322 .- 1432-0533. ; 139:3, s. 527-546
  • Tidskriftsartikel (refereegranskat)abstract
    • Cofactors are essential for driving recombinant prion protein into pathogenic conformers. Polyanions promote prion aggregation in vitro, yet the cofactors that modulate prion assembly in vivo remain largely unknown. Here we report that the endogenous glycosaminoglycan, heparan sulfate (HS), impacts prion propagation kinetics and deposition sites in the brain. Exostosin-1 haploinsufficient (Ext1(+/-)) mice, which produce short HS chains, show a prolonged survival and a redistribution of plaques from the parenchyma to vessels when infected with fibrillar prions, and a modest delay when infected with subfibrillar prions. Notably, the fibrillar, plaque-forming prions are composed of ADAM10-cleaved prion protein lacking a glycosylphosphatidylinositol anchor, indicating that these prions are mobile and assemble extracellularly. By analyzing the prion-bound HS using liquid chromatography-mass spectrometry (LC-MS), we identified the disaccharide signature of HS differentially bound to fibrillar compared to subfibrillar prions, and found approximately 20-fold more HS bound to the fibrils. Finally, LC-MS of prion-bound HS from human patients with familial and sporadic prion disease also showed distinct HS signatures and higher HS levels associated with fibrillar prions. This study provides the first in vivo evidence of an endogenous cofactor that accelerates prion disease progression and enhances parenchymal deposition of ADAM10-cleaved, mobile prions.
  •  
7.
  • Aleynick, Mark, et al. (författare)
  • Pattern recognition receptor agonists in pathogen vaccines mediate antitumor T-cell cross-priming
  • 2023
  • Ingår i: Journal for ImmunoTherapy of Cancer. - : BMJ Publishing Group Ltd. - 2051-1426. ; 11:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Cancer immunotherapies are generallyeffective in patients whose tumors contain a prioriprimed T-cells reactive to tumor antigens (TA). Oneapproach to prime TA-reactive T-cells is to administerimmunostimulatory molecules, cells, or pathogens directlyto the tumor site, that is, in situ vaccination (ISV). Werecently described an ISV using Flt3L to expand and recruitdendritic cells (DC), radiotherapy to load DC with TA, andpattern recognition receptor agonists (PRRa) to activateTA-loaded DC. While ISV trials using synthetic PRRa haveyielded systemic tumor regressions, the optimal method toactivate DCs is unknown.Methods To discover optimal DC activators and increaseaccess to clinical grade reagents, we assessed whetherviral or bacterial components found in common pathogenvaccines are an effective source of natural PRRa(naPRRa). Using deep profiling (155-metric) of naPRRaimmunomodulatory effects and gene editing of specificPRR, we defined specific signatures and molecularmechanisms by which naPRRa potentiate T-cell priming.Results We observed that vaccine naPRRa can be evenmore potent in activating Flt3L-expanded murine andhuman DCs than synthetic PRRa, promoting cross-primingof TA-reactive T-cells. We developed a mechanisticallydiverse naPRRa combination (BCG, PedvaxHIB, Rabies)and noted more potent T-cell cross-priming than withany single naPRRa. The naPRRa triplet—as part of Flt3Lprimed ISV—induced greater intratumoral CD8 T-cellinfiltration, T-cells reactive to a newly defined tumorousneoantigen, durable tumor regressions.Conclusions This work provides rationale for thetranslation of pathogen vaccines as FDA-approved clinicalgrade DC activators which could be exploited as immunestimulants for early phase trials.
  •  
8.
  • Alimena, Juliette, et al. (författare)
  • Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
  • 2020
  • Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
  •  
9.
  •  
10.
  •  
11.
  • Bagley, Micaela B., et al. (författare)
  • A High Space Density of Luminous Ly alpha Emitters at z similar to 6.5
  • 2017
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 837:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of a systematic search for Ly alpha emitters (LAEs) at 6 less than or similar to z less than or similar to 7.6 using the HST WFC3 Infrared Spectroscopic Parallel (WISP) Survey. Our total volume over this redshift range is similar to 8 x 10(5) Mpc(3), comparable to many of the narrowband surveys despite their larger area coverage. We find two LAEs at z = 6.38 and 6.44 with line luminosities of L-Lya similar to 4.7 x 10(43) erg s(-1), putting them among the brightest LAEs discovered at these redshifts. Taking advantage of the broad spectral coverage of WISP, we are able to rule out almost all lower-redshift contaminants. The WISP LAEs have a high number density of 7.7 x 10(-6) Mpc (3). We argue that the LAEs reside in megaparsec-scale ionized bubbles that allow the Ly alpha photons to redshift out of resonance before encountering the neutral intergalactic medium. We discuss possible ionizing sources and conclude that the observed LAEs alone are not sufficient to ionize the bubbles.
  •  
12.
  • Björkman, Anne, 1981, et al. (författare)
  • Plant functional trait change across a warming tundra biome
  • 2018
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7725, s. 57-62
  • Tidskriftsartikel (refereegranskat)abstract
    • The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature–trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
  •  
13.
  • Chandramohan, Arun, et al. (författare)
  • Design-Rules for Stapled Alpha-Helical Peptides with On-Target In Vivo Activity: Application to Mdm2/X dual antagonists
  • 2023
  • Ingår i: Nature Communications. - : Cold Spring Harbor Laboratory. - 2041-1723.
  • Tidskriftsartikel (refereegranskat)abstract
    • Stapled α-helical peptides can bind to and modulate historically intractable targets while addressing the traditional liabilities associated with peptide therapeutics. However, their pipeline advancement has been impeded by the challenges of identifying peptides with sufficient cellular uptake to engage the target protein while lacking off-target toxicities. Here, we advance the field to arrive at a workflow for identifying advanced stapled peptide lead molecules with on-target in vivo activity with no off-target cell proliferation effects. Specifically, we generated a >350-member library based on ATSP-7041, a stapled peptide Mdm2(X) antagonist with validated on-target cellular effects but with significant off-target activity. Key insights from library analysis include 1) a clear correlation between lipophilicity and permeability, 2) removal of positive charge to avoid off-target toxicities, 3) judicious placement of anionic residues to enhance peptide solubility/behavior, 4) optimization of C-terminal length and helicity to enhance cell activity, 5) optimization of staple type/number to avoid polypharmacology. Incorporation of one or more of these attributes led to molecules with improved in vitro and in vivo activities (up to a >292x improved cell proliferation EC50). A subset of peptides were devoid of off-target cell proliferation effects in cell lines lacking wild-type p53 protein (up to a >3800x on-target index). This latter improvement contrasted with clinical Mdm2 antagonistic molecules. Application of these ‘design rules’ to a distinct Mdm2(X) peptide series resulted in rapid improvement in cellular activity (>150x) and removal of off-target toxicities. Overall, the detailed workflow outlined here should help researchers identify stapled α-helical peptides for therapeutic impact.
  •  
14.
  • Chandramohan, Arun, et al. (författare)
  • Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists
  • 2024
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Although stapled α-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects. Key insights include a clear correlation between lipophilicity and permeability, removal of positive charge to avoid off-target toxicities, judicious anionic residue placement to enhance solubility/behavior, optimization of C-terminal length/helicity to enhance potency, and optimization of staple type/number to avoid polypharmacology. Workflow application gives peptides with >292x improved cell proliferation potencies and no off-target cell proliferation effects ( > 3800x on-target index). Application of these ‘design rules’ to a distinct Mdm2(X) peptide series improves ( > 150x) cellular potencies and removes off-target toxicities. The outlined workflow should facilitate therapeutic impacts, especially for those targets such as Mdm2(X) that have hydrophobic interfaces and are targetable with a helical motif.
  •  
15.
  • Elsik, Christine G., et al. (författare)
  • The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
  • 2009
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
  • Tidskriftsartikel (refereegranskat)abstract
    • To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
  •  
16.
  • Fazey, Ioan, et al. (författare)
  • Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
  • 2020
  • Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
  • Tidskriftsartikel (refereegranskat)abstract
    • Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
  •  
17.
  • Fischer, Katrin, et al. (författare)
  • Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis
  • 2017
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 23:5, s. 623-630
  • Tidskriftsartikel (refereegranskat)abstract
    • Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through beta 3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1(-/-) and interleukin-4 receptor-alpha double-negative (Il4ra(-/-)) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.
  •  
18.
  • Flury, Sophia R., et al. (författare)
  • The Low-redshift Lyman Continuum Survey. I. New, Diverse Local Lyman Continuum Emitters
  • 2022
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 260:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The origins of Lyman continuum (LyC) photons responsible for the reionization of the universe are as of yet unknown and highly contested. Detecting LyC photons from the Epoch of Reionization is not possible due to absorption by the intergalactic medium, which has prompted the development of several indirect diagnostics to infer the rate at which galaxies contribute LyC photons to reionize the universe by studying lower-redshift analogs. We present the Low-redshift Lyman Continuum Survey (LzLCS) comprising measurements made with the Hubble Space Telescope Cosmic Origins Spectrograph for a z = 0.2-0.4 sample of 66 galaxies. After careful processing of the far-UV spectra, we obtain a total of 35 Lyman continuum emitters (LCEs) detected with 97.725% confidence, nearly tripling the number of known local LCEs. We estimate escape fractions from the detected LyC flux and upper limits on the undetected LyC flux, finding a range of LyC escape fractions up to 50%. Of the 35 LzLCS LCEs, 12 have LyC escape fractions greater than 5%, more than doubling the number of known local LCEs with cosmologically relevant LyC escape.
  •  
19.
  • Flury, Sophia R., et al. (författare)
  • The Low-redshift Lyman Continuum Survey. II. New Insights into LyC Diagnostics
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Lyman continuum (LyC) cannot be observed at the epoch of reionization (z greater than or similar to 6) owing to intergalactic H i absorption. To identify LyC emitters (LCEs) and infer the fraction of escaping LyC, astronomers have developed various indirect diagnostics of LyC escape. Using measurements of the LyC from the Low-redshift Lyman Continuum Survey (LzLCS), we present the first statistical test of these diagnostics. While optical depth indicators based on Ly alpha, such as peak velocity separation and equivalent width, perform well, we also find that other diagnostics, such as the [O iii]/[O ii] flux ratio and star formation rate surface density, predict whether a galaxy is an LCE. The relationship between these galaxy properties and the fraction of escaping LyC flux suggests that LyC escape depends strongly on H i column density, ionization parameter, and stellar feedback. We find that LCEs occupy a range of stellar masses, metallicities, star formation histories, and ionization parameters, which may indicate episodic and/or different physical causes of LyC escape.
  •  
20.
  • Fudamoto, Yoshinobu, et al. (författare)
  • The Extended [C II] under Construction? : Observation of the Brightest High-z Lensed Star-forming Galaxy at z=6.2
  • 2024
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 961:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present results of [C ii] 158 μm emission line observations, and report the spectroscopic redshift confirmation of a strongly lensed (μ ∼ 20) star-forming galaxy, MACS0308-zD1 at z = 6.2078 ± 0.0002. The [C ii] emission line is detected with a signal-to-noise ratio >6 within the rest-frame UV-bright clump of the lensed galaxy (zD1.1) and exhibits multiple velocity components; the narrow [C ii] has a velocity full width half maximum (FWHM) of 110 ± 20 km s−1, while broader [C ii] is seen with an FWHM of 230 ± 50 km s−1. The broader [C ii] component is blueshifted (−80 ± 20 km s−1) with respect to the narrow [C ii] component, and has a morphology that extends beyond the UV-bright clump. We find that, while the narrow [C ii] emission is most likely associated with zD1.1, the broader component is possibly associated with a physically distinct gas component from zD1.1 (e.g., outflowing or inflowing gas). Based on the nondetection of λ158μm dust continuum, we find that MACS0308-zD1's star formation activity occurs in a dust-free environment indicated by a strong upper limit of infrared luminosity ≲9 × 108L⊙. Targeting this strongly lensed faint galaxy for follow-up Atacama Large Millimeter/submillimeter Array and JWST observations will be crucial to characterize the details of typical galaxy growth in the early Universe.
  •  
21.
  • Gerostathopoulos, Ilias, et al. (författare)
  • Continuous Data-driven Software Engineering : Towards a Research Agenda
  • 2019
  • Ingår i: Software Engineering Notes. - : Association for Computing Machinery (ACM). - 0163-5948 .- 1943-5843. ; 44:3, s. 60-64
  • Tidskriftsartikel (refereegranskat)abstract
    • The rapid pace with which software needs to be built, together with the increasing need to evaluate changes for end users both quantitatively and qualitatively calls for novel software engineering approaches that focus on short release cycles, continuous deployment and delivery, experiment-driven feature development, feedback from users, and rapid tool-assisted feedback to developers. To realize these approaches there is a need for research and innovation with respect to automation and tooling, and furthermore for research into the organizational changes that support flexible data-driven decision-making in the development lifecycle. Most importantly, deep synergies are needed between software engineers, managers, and data scientists. This paper reports on the results of the joint 5th International Workshop on Rapid Continuous Software Engineering (RCoSE 2019) and the 1st International Workshop on Data-Driven Decisions, Experimentation and Evolution (DDrEE 2019), which focuses on the challenges and potential solutions in the area of continuous data-driven software engineering.   
  •  
22.
  • Gorasso, Vanessa, et al. (författare)
  • Burden of disease attributable to risk factors in European countries: a scoping literature review
  • 2023
  • Ingår i: Archives of Public Health. - 0778-7367 .- 2049-3258. ; 81:1
  • Forskningsöversikt (refereegranskat)abstract
    • Objectives: Within the framework of the burden of disease (BoD) approach, disease and injury burden estimates attributable to risk factors are a useful guide for policy formulation and priority setting in disease prevention. Considering the important differences in methods, and their impact on burden estimates, we conducted a scoping literature review to: (1) map the BoD assessments including risk factors performed across Europe; and (2) identify the methodological choices in comparative risk assessment (CRA) and risk assessment methods. Methods: We searched multiple literature databases, including grey literature websites and targeted public health agencies websites. Results: A total of 113 studies were included in the synthesis and further divided into independent BoD assessments (54 studies) and studies linked to the Global Burden of Disease (59 papers). Our results showed that the methods used to perform CRA varied substantially across independent European BoD studies. While there were some methodological choices that were more common than others, we did not observe patterns in terms of country, year or risk factor. Each methodological choice can affect the comparability of estimates between and within countries and/or risk factors, since they might significantly influence the quantification of the attributable burden. From our analysis we observed that the use of CRA was less common for some types of risk factors and outcomes. These included environmental and occupational risk factors, which are more likely to use bottom-up approaches for health outcomes where disease envelopes may not be available. Conclusions: Our review also highlighted misreporting, the lack of uncertainty analysis and the under-investigation of causal relationships in BoD studies. Development and use of guidelines for performing and reporting BoD studies will help understand differences, avoid misinterpretations thus improving comparability among estimates.
  •  
23.
  • Hammerich, Linda, et al. (författare)
  • Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination
  • 2019
  • Ingår i: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 25:5, s. 814-824
  • Tidskriftsartikel (refereegranskat)abstract
    • Indolent non-Hodgkin’s lymphomas (iNHLs) are incurable with standard therapy and are poorly responsive to checkpoint blockade. Although lymphoma cells are efficiently killed by primed T cells, in vivo priming of anti-lymphoma T cells has been elusive. Here, we demonstrate that lymphoma cells can directly prime T cells, but in vivo immunity still requires cross-presentation. To address this, we developed an in situ vaccine (ISV), combining Flt3L, radiotherapy, and a TLR3 agonist, which recruited, antigen-loaded and activated intratumoral, cross-presenting dendritic cells (DCs). ISV induced anti-tumor CD8+ T cell responses and systemic (abscopal) cancer remission in patients with advanced stage iNHL in an ongoing trial (NCT01976585). Non-responding patients developed a population of PD1+CD8+ T cells after ISV, and murine tumors became newly responsive to PD1 blockade, prompting a follow-up trial of the combined therapy. Our data substantiate that recruiting and activating intratumoral, cross-priming DCs is achievable and critical to anti-tumor T cell responses and PD1-blockade efficacy. 
  •  
24.
  • Harris, Simon R., et al. (författare)
  • Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing
  • 2012
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:4, s. 413-419
  • Tidskriftsartikel (refereegranskat)abstract
    • Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.
  •  
25.
  • Heid, Iris M, et al. (författare)
  • Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
  • Tidskriftsartikel (refereegranskat)abstract
    • Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
  •  
26.
  •  
27.
  • Hsiao, Tiger Yu-Yang, et al. (författare)
  • JWST Reveals a Possible z similar to 11 Galaxy Merger in Triply Lensed MACS0647-JD
  • 2023
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 949:2
  • Tidskriftsartikel (refereegranskat)abstract
    • MACS0647-JD is a triply lensed z similar to 11 galaxy originally discovered with the Hubble Space Telescope. The three lensed images are magnified by factors of similar to 8, 5, and 2 to AB mag 25.1, 25.6, and 26.6 at 3.5 mu m. The brightest is over a magnitude brighter than other galaxies recently discovered at similar redshifts z > 10 with JWST. Here, we report new JWST imaging that clearly resolves MACS0647-JD as having two components that are either merging galaxies or stellar complexes within a single galaxy. The brighter larger component "A" is intrinsically very blue (ss similar to-2.6 +/- 0.1), likely due to very recent star formation and no dust, and is spatially extended with an effective radius similar to 70 +/- 24 pc. The smaller component "B" (r similar to 20-+ 58 pc) appears redder (ss similar to-2 +/- 0.2), likely because it is older (100-200 Myr) with mild dust extinction (AV similar to 0.1 mag). With an estimated stellar mass ratio of roughly 2:1 and physical projected separation similar to 400 pc, we may be witnessing a galaxy merger 430 million years after the Big Bang. We identify galaxies with similar colors in a high-redshift simulation, finding their star formation histories to be dissimilar, which is also suggested by the spectral energy distribution fitting, suggesting they formed further apart. We also identify a candidate companion galaxy "C" similar to 3 kpc away, likely destined to merge with A and B. Upcoming JWST Near Infrared Spectrograph observations planned for 2023 January will deliver spectroscopic redshifts and more physical properties for these tiny magnified distant galaxies observed in the early universe.
  •  
28.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
  •  
29.
  • Khatri, C, et al. (författare)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
  •  
30.
  • Kuncarayakti, Hanindyo, et al. (författare)
  • SN 2017dio : A Type-Ic Supernova Exploding in a Hydrogen-rich Circumstellar Medium
  • 2018
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 854:1
  • Tidskriftsartikel (refereegranskat)abstract
    • SN 2017dio shows both spectral characteristics of a type-Ic supernova (SN) and signs of a hydrogen-rich circumstellar medium (CSM). Prominent, narrow emission lines of H and He are superposed on the continuum. Subsequent evolution revealed that the SN ejecta are interacting with the CSM. The initial SN Ic identification was confirmed by removing the CSM interaction component from the spectrum and comparing with known SNe Ic and, reversely, adding a CSM interaction component to the spectra of known SNe Ic and comparing them to SN 2017dio. Excellent agreement was obtained with both procedures, reinforcing the SN Ic classification. The light curve constrains the pre-interaction SN Ic peak absolute magnitude to be around M-g = -17.6 mag. No evidence of significant extinction is found, ruling out a brighter luminosity required by an SN Ia classification. These pieces of evidence support the view that SN 2017dio is an SN Ic, and therefore the first firm case of an SN Ic with signatures of hydrogen-rich CSM in the early spectrum. The CSM is unlikely to have been shaped by steady-state stellar winds. The mass loss of the progenitor star must have been intense, M similar to 0.02 (epsilon(H alpha)/0.01)(-1) (nu(wind)/500 km s(-1)) (nu(shock)/10,000 km s(-1))M--3(circle dot) yr(-1), peaking at a few decades before the SN. Such a high mass-loss rate might have been experienced by the progenitor through eruptions or binary stripping.
  •  
31.
  • Kuschel, Maxwell, et al. (författare)
  • Investigating the Dominant Environmental Quenching Process in UVCANDELS/COSMOS Groups
  • 2023
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 947:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We explore how the fraction of quenched galaxies changes in groups of galaxies with respect to the distance to the center of the group, redshift, and stellar mass to determine the dominant process of environmental quenching in 0.2 < z < 0.8 groups. We use new UV data from the UVCANDELS project in addition to existing multiband photometry to derive new galaxy physical properties of the group galaxies from the zCOSMOS 20 k group catalog. Limiting our analysis to a complete sample of log (M*/M⊙) > 10.56 group galaxies, we find that the probability of being quenched increases slowly with decreasing redshift, diverging from the stagnant field galaxy population. A corresponding analysis on how the probability of being quenched increases with time within groups suggests that the dominant environmental quenching process is characterized by slow (∼Gyr) timescales. We find a quenching time of approximately  Gyr, consistent with the slow processes of strangulation and delayed-then-rapid quenching although more data are needed to confirm this result.
  •  
32.
  • Li, Haoyuan, et al. (författare)
  • Diffraction data from aerosolized Coliphage PR772 virus particles imaged with the Linac Coherent Light Source
  • 2020
  • Ingår i: Scientific Data. - : NATURE RESEARCH. - 2052-4463. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Single Particle Imaging (SPI) with intense coherent X-ray pulses from X-ray free-electron lasers (XFELs) has the potential to produce molecular structures without the need for crystallization or freezing. Here we present a dataset of 285,944 diffraction patterns from aerosolized Coliphage PR772 virus particles injected into the femtosecond X-ray pulses of the Linac Coherent Light Source (LCLS). Additional exposures with background information are also deposited. The diffraction data were collected at the Atomic, Molecular and Optical Science Instrument (AMO) of the LCLS in 4 experimental beam times during a period of four years. The photon energy was either 1.2 or 1.7keV and the pulse energy was between 2 and 4 mJ in a focal spot of about 1.3 mu m x 1.7 mu m full width at half maximum (FWHM). The X-ray laser pulses captured the particles in random orientations. The data offer insight into aerosolised virus particles in the gas phase, contain information relevant to improving experimental parameters, and provide a basis for developing algorithms for image analysis and reconstruction.
  •  
33.
  • Lokachari, Nitin, et al. (författare)
  • A comprehensive experimental and kinetic modeling study of di-isobutylene isomers : Part 1
  • 2023
  • Ingår i: Combustion and Flame. - : Elsevier BV. - 0010-2180. ; 251
  • Tidskriftsartikel (refereegranskat)abstract
    • Di-isobutylene has received significant attention as a promising fuel blendstock, as it can be synthesized via biological routes and is a short-listed molecule from the Co-Optima initiative. Di-isobutylene is also popularly used as an alkene representative in multi-component surrogate models for engine studies of gasoline fuels. However, there is limited experimental data available in the literature for neat di-isobutylene under engine-like conditions. Hence, most existing di-isobutylene models have not been extensively validated, particularly at lower temperatures (< 1000 K). Most gasoline surrogate models include the di-isobutylene sub-mechanism published by Metcalfe et al. [1] with little or no modification. The current study is undertaken to develop a detailed kinetic model for di-isobutylene and validate the model using a wide range of relevant experimental data. Part 1 of this study exclusively focuses on the low- to intermediate temperature kinetics of di-isobutylene. An upcoming part 2 discusses the high-temperature model development and validation of the relevant experimental targets. Ignition delay time measurements for the di-isobutylene isomers were performed at pressures ranging from 15 – 30 bar at equivalence ratios of 0.5, 1.0, and 2.0 diluted in air and in the temperature range 650 – 900 K using two independent rapid compression machine facilities. In addition, measurements of species identified during the oxidation of these isomers were performed in a jet-stirred reactor and in a rapid compression machine. A detailed kinetic model for the di-isobutylene isomers is developed to capture the wide range of new experimental targets. For the first time, a comprehensive low-temperature chemistry submodel is included. The differences in the important reaction pathways for the accurate prediction of the oxidation of the two DIB isomers are compared using reaction path analysis. The most sensitive reactions controlling the ignition delay times of the DIB isomers under the pressure and temperature conditions necessary for autoignition in engines are identified.
  •  
34.
  • Lokachari, Nitin, et al. (författare)
  • A comprehensive experimental and kinetic modeling study of di-isobutylene isomers : Part 2
  • 2023
  • Ingår i: Combustion and Flame. - : Elsevier BV. - 0010-2180. ; 251
  • Tidskriftsartikel (refereegranskat)abstract
    • A wide variety of high temperature experimental data obtained in this study complement the data on the oxidation of the two di-isobutylene isomers presented in Part I and offers a basis for an extensive validation of the kinetic model developed in this study. Due to the increasing importance of unimolecular decomposition reactions in high-temperature combustion, we have investigated the di-isobutylene isomers in high dilution utilizing a pyrolysis microflow reactor and detected radical intermediates and stable products using vacuum ultraviolet (VUV) synchrotron radiation and photoelectron photoion coincidence (PEPICO) spectroscopy. Additional speciation data at oxidative conditions were also recorded utilizing a plug flow reactor at atmospheric pressure in the temperature range 725–1150 K at equivalence ratios of 1.0 and 3.0 and at residence times of 0.35 s and 0.22 s, respectively. Combustion products were analyzed using gas chromatography (GC) and mass spectrometry (MS). Ignition delay time measurements for di-isobutylene were performed at pressures of 15 and 30 bar at equivalence ratios of 0.5, 1.0, and 2.0 diluted in ‘air’ in the temperature range 900–1400 K using a high-pressure shock-tube facility. New measurements of the laminar burning velocities of di-isobutylene/air flames are also presented. The experiments were performed using the heat flux method at atmospheric pressure and initial temperatures of 298–358 K. Moreover, data consistency was assessed with the help of analysis of the temperature and pressure dependencies of laminar burning velocity measurements, which was interpreted using an empirical power-law expression. Electronic structure calculations were performed to compute the energy barriers to the formation of many of the product species formed. The predictions of the present mechanism were found to be in adequate agreement with the wide variety of experimental measurements performed.
  •  
35.
  •  
36.
  • Meyer, Esther, et al. (författare)
  • Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.
  • 2017
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49, s. 223-237
  • Tidskriftsartikel (refereegranskat)abstract
    • Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.
  •  
37.
  • Moia, Davide, et al. (författare)
  • The Role of Hole Transport between Dyes in Solid-State Dye-Sensitized Solar Cells
  • 2015
  • Ingår i: The Journal of Physical Chemistry C. - : AMER CHEMICAL SOC. - 1932-7447 .- 1932-7455. ; 119:33, s. 18975-18985
  • Tidskriftsartikel (refereegranskat)abstract
    • In dye-sensitized solar cells (DSSCs) photo-generated positive charges are normally considered to be carried away from the dyes by a separate phase of hole-transporting material (HTM). We show that there can also be significant transport within the dye monolayer itself before the hole reaches the HTM. We quantify the fraction of dye regeneration in solid-state DSSCs that can be attributed to this process. By using cyclic voltammetry and transient anisotropy spectroscopy, we demonstrate that the rate of interdye hole transport is prevented both on micrometer and nanometer length scales by reducing the dye loading on the TiO2 surface. The dye regeneration yield is quantified for films with high and low dye loadings (with and without hole percolation in the dye monolayer) infiltrated with varying levels of HTM. Interdye hole transport can account for >50% of the overall dye regeneration with low HTM pore filling. This is reduced to about 5% when the infiltration of the HTM in the pores is optimized in 2 mu m thick films. Finally, we use hole transport in the dye monolayer to characterize the spatial distribution of the HTM phase in the pores of the dyed mesoporous TiO2.
  •  
38.
  • Mychaleckyj, Josyf C., et al. (författare)
  • HLA genotyping in the international Type 1 Diabetes Genetics Consortium
  • 2010
  • Ingår i: Clinical Trials. - : SAGE Publications. - 1740-7753 .- 1740-7745. ; 7:1 suppl., s. 75-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Although human leukocyte antigen (HLA) DQ and DR loci appear to confer the strongest genetic risk for type 1 diabetes, more detailed information is required for other loci within the HLA region to understand causality and stratify additional risk factors. The Type 1 Diabetes Genetics Consortium (T1DGC) study design included high-resolution genotyping of HLA-A, B, C, DRB1, DQ, and DP loci in all affected sibling pair and trio families, and cases and controls, recruited from four networks worldwide, for analysis with clinical phenotypes and immunological markers. Purpose In this article, we present the operational strategy of training, classification, reporting, and quality control of HLA genotyping in four laboratories on three continents over nearly 5 years. Methods Methods to standardize HLA genotyping at eight loci included: central training and initial certification testing; the use of uniform reagents, protocols, instrumentation, and software versions; an automated data transfer; and the use of standardized nomenclature and allele databases. We implemented a rigorous and consistent quality control process, reinforced by repeated workshops, yearly meetings, and telephone conferences. Results A total of 15,246 samples have been HLA genotyped at eight loci to four-digit resolution; an additional 6797 samples have been HLA genotyped at two loci. The genotyping repeat rate decreased significantly over time, with an estimated unresolved Mendelian inconsistency rate of 0.21%. Annual quality control exercises tested 2192 genotypes (4384 alleles) and achieved 99.82% intra-laboratory and 99.68% inter-laboratory concordances. Limitations The chosen genotyping platform was unable to distinguish many allele combinations, which would require further multiple stepwise testing to resolve. For these combinations, a standard allele assignment was agreed upon, allowing further analysis if required. Conclusions High-resolution HLA genotyping can be performed in multiple laboratories using standard equipment, reagents, protocols, software, and communication to produce consistent and reproducible data with minimal systematic error. Many of the strategies used in this study are generally applicable to other large multi-center studies. Clinical Trials 2010; 7: S75-S87. http://ctj.sagepub.com.
  •  
39.
  • Myers, Regina M., et al. (författare)
  • Long-Term Outcomes Among 2-Year Survivors of Autologous Hematopoietic Cell Transplantation for Hodgkin and Diffuse Large B-Cell Lymphoma
  • 2018
  • Ingår i: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 124:4, s. 816-825
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Autologous hematopoietic cell transplantation (auto-HCT) is a standard therapy for relapsed classic Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL); however, long-term outcomes are not well described.METHODS: This study analyzed survival, nonrelapse mortality, late effects, and subsequent malignant neoplasms (SMNs) in 1617 patients who survived progression-free for >= 2 years after auto-HCT for cHL or DLBCL between 1990 and 2008. The median age at auto-HCT was 40 years; the median follow-up was 10.6 years.RESULTS: The 5-year overall survival rate was 90% (95% confidence interval [CI], 87%-92%) for patients with cHL and 89% (95% CI, 87%-91%) for patients with DLBCL. The risk of late mortality in comparison with the general population was 9.6-fold higher for patients with cHL (standardized mortality ratio [SMR], 9.6) and 3.4-fold higher for patients with DLBCL (SMR, 3.4). Relapse accounted for 44% of late deaths. At least 1 late effect was reported for 9% of the patients. A total of 105 SMNs were confirmed: 44 in the cHL group and 61 in the DLBCL group. According to a multivariate analysis, older age, male sex, a Karnofsky score < 90, total body irradiation (TBI) exposure, and a higher number of lines of chemotherapy before auto-HCT were risk factors for overall mortality in cHL. Risk factors in DLBCL were older age and TBI exposure. A subanalysis of 798 adolescent and young adult patients mirrored the outcomes of the overall study population.CONCLUSIONS: Despite generally favorable outcomes, 2-year survivors of auto-HCT for cHL or DLBCL have an excess late-mortality risk in comparison with the general population and experience an assortment of late complications.
  •  
40.
  • Neeland, Ian J, et al. (författare)
  • The Impact of Empagliflozin on Obstructive Sleep Apnea and Cardiovascular and Renal Outcomes: An Exploratory Analysis of the EMPA-REG OUTCOME Trial.
  • 2020
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 1935-5548 .- 0149-5992. ; 43:12, s. 3007-3015
  • Tidskriftsartikel (refereegranskat)abstract
    • To explore the effects of empagliflozin on the incidence of obstructive sleep apnea (OSA) and its effects on metabolic, cardiovascular (CV), and renal outcomes among participants with or without OSA in the EMPA-REG OUTCOME trial.Participants with diabetes and CV disease were randomized to empagliflozin (10 and 25 mg) or placebo daily in addition to standard of care. OSA was assessed by investigator report using Medical Dictionary for Regulatory Activities version 18.0, and CV outcomes were independently adjudicated. Analyses were performed using multivariable-adjusted Cox regression models.OSA was reported in 391 of 7,020 (5.6%) participants at baseline. Those with OSA were more likely to be male (83% vs. 71%) and to have moderate to severe obesity (BMI ≥35 kg/m2; 55% vs. 18%). Over a median of 3.1 years, empagliflozin had similar placebo-adjusted reductions in HbA1c, waist circumference, and systolic blood pressure, regardless of OSA status, but a larger effect on weight (adjusted mean ± SE difference at week 52: OSA vs. no OSA -2.9 ± 0.5 vs. -1.9 ± 0.1 kg). Incidence of 3-point major adverse CV events, CV death, heart failure hospitalization, and incident or worsening nephropathy in the placebo group was 1.2- to 2.0-fold higher for those with baseline OSA compared with those without. Empagliflozin significantly reduced the risk for outcomes regardless of OSA status (P-interaction all >0.05). Fifty patients reported a new diagnosis of OSA through 7 days after medication discontinuation, and this occurred less often with empagliflozin treatment (hazard ratio 0.48 [95% CI 0.27, 0.83]).In EMPA-REG OUTCOME, participants with OSA had greater comorbidity and higher frequency of CV and renal events. Empagliflozin had favorable effects on risk factors and CV and renal outcomes regardless of preexisting OSA and may also reduce the risk for new-onset OSA.
  •  
41.
  • Rhind, Nicholas, et al. (författare)
  • Comparative Functional Genomics of the Fission Yeasts
  • 2011
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 332:6032, s. 930-936
  • Tidskriftsartikel (refereegranskat)abstract
    • The fission yeast clade-comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus-occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade.
  •  
42.
  • Richards, Stephen, et al. (författare)
  • The genome of the model beetle and pest Tribolium castaneum.
  • 2008
  • Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
  •  
43.
  • Roselli, Carolina, et al. (författare)
  • Multi-ethnic genome-wide association study for atrial fibrillation
  • 2018
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
  • Tidskriftsartikel (refereegranskat)abstract
    • Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
  •  
44.
  • Rossignol, Patrick, et al. (författare)
  • Impact of eplerenone on cardiovascular outcomes in heart failure patients with hypokalaemia
  • 2017
  • Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 19:6, s. 792-799
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology Aims: Although hypokalaemia is common among patients with heart failure (HF), the prognostic significance of baseline hypokalaemia and hypokalaemia during follow-up in HF patients receiving a mineralocorticoid receptor antagonist (MRA) remains uncertain. Methods and results: Results of the EMPHASIS-HF trial in patients (n = 2737) with HF and reduced EF with mild symptoms, randomized to eplerenone or placebo, were analysed with regard to the presence or occurrence of hypokalaemia (serum K + < 4.0 mmol/L) and the risk of cardiovascular death or hospitalization for HF (primary endpoint). Median follow-up was 21 months. Baseline hypokalaemia and hypokalaemia during follow-up were common occurrences (19.6% and 40.6%, respectively). Hypokalaemia during follow-up was associated with worse outcomes in multivariable analyses [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.05–1.52, P = 0.01] without evidence of interaction with eplerenone. In contrast, baseline hypokalaemia was associated with outcomes in the placebo group (HR 1.37, 95% CI 1.05–1.79, P = 0.02) but not in the eplerenone group (HR 0.87, 95% CI 0.62–1.23, P = 0.44; P for interaction = 0.04). Concurrently, eplerenone was found to be more protective in patients with baseline hypokalaemia vs. patients without baseline hypokalaemia compared with placebo (HR 0.44, 95% 0.30–0.64, P < 0.0001 vs. 0.69, 95% CI 0.57–0.83, P = 0.0001; P for interaction = 0.04). In patients without baseline hypokalaemia, eplerenone use decreased the rate of hypokalaemia during follow-up (HR 0.69, 95% CI 0.59–0.80, P < 0.001). A potassium level > 4.0 mmol/L at 1 month after randomization mediated 26.0% (0.6–51.4%) of the eplerenone treatment effect (P = 0.04). Conclusion: In HF patients receiving optimal therapy but not treated with eplerenone, baseline hypokalaemia was associated with worse outcomes. Conversely, hypokalaemia amplified the treatment effect of eplerenone.
  •  
45.
  • Rutkowski, Michael J., et al. (författare)
  • LYMAN CONTINUUM ESCAPE FRACTION OF STAR-FORMING DWARF GALAXIES AT z similar to 1
  • 2016
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 819:1
  • Tidskriftsartikel (refereegranskat)abstract
    • To date, no direct detection of Lyman continuum emission has been measured for intermediate-redshift (z similar to 1) star-forming galaxies. We combine Hubble Space Telescope grism spectroscopy with GALEX UV and ground-based optical imaging to extend the search for escaping Lyman continuum to a large (similar to 600) sample of z similar to 1 low-mass (log((M) over bar) similar or equal to 9.3M(circle dot)), moderately star-forming ((Psi) over bar less than or similar to 10M(circle dot) yr(-1)) galaxies selected initially on H alpha emission. The characteristic escape fraction of LyC from star-forming galaxies (SFGs) that populate this parameter space remains weakly constrained by previous surveys, but these faint (sub-L-star) SFGs are assumed to play a significant role in the reionization of neutral hydrogen in the intergalactic medium (IGM) at high redshift z > 6. We do not make an unambiguous detection of escaping LyC radiation from this z similar to 1 sample, individual non-detections to constrain the absolute Lyman continuum escape fraction, f(esc) < 2.1% (3 sigma). We measure an upper limit of f(esc) < 9.6% from a sample of SFGs selected on high H alpha equivalent width (EW > 200 angstrom), which are thought to be close analogs of high redshift sources of reionization. For reference, we also present an emissivity-weighted escape fraction that is useful for measuring the general contribution SFGs to the ionizing UV background. In the discussion, we consider the implications of these intermediate redshift constraints for the reionization of hydrogen in the IGM at high (z > 6) redshift. If we assume our z similar to 1 SFGs, for which we measure this emissivity-weighted f(esc), are analogs to the high redshift sources of reionization, we find it is difficult to reconcile reionization by faint (MUV less than or similar to -13) SFGs with a low escape fraction (f(esc) < 3%), with constraints from independent high redshift observations. If f(esc) evolves with redshift, reionization by SFGs may be consistent with observations from Planck.
  •  
46.
  • Rutkowski, Michael J., et al. (författare)
  • The Lyman Continuum Escape Fraction of Emission Line-selected z similar to 2.5 Galaxies Is Less Than 15%
  • 2017
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 841:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent work suggests that strong emission line, star-forming galaxies (SFGs) may be significant Lyman continuum leakers. We combine archival Hubble Space Telescope broadband ultraviolet and optical imaging (F275W and F606W, respectively) with emission line catalogs derived from WFC3 IR G141 grism spectroscopy to search for escaping Lyman continuum (LyC) emission from homogeneously selected z similar to 2.5 SFGs. We detect no escaping Lyman continuum from SFGs selected on [O II] nebular emission (N = 208) and, within a narrow redshift range, on [O III]/[O II]. We measure 1 sigma upper limits to the LyC escape fraction relative to the non-ionizing UV continuum from [O II] emitters, f(esc) less than or similar to 5.6%, and strong [O III]/[O II] > 5 ELGs, f(esc) less than or similar to 14.0%. Our observations are not deep enough to detect f(esc) similar to 10% typical of low-redshift Lyman continuum emitters. However, we find that this population represents a small fraction of the star-forming galaxy population at z similar to 2. Thus, unless the number of extreme emission line galaxies grows substantially to z greater than or similar to 6, such galaxies may be insufficient for reionization. Deeper survey data in the rest-frame ionizing UV will be necessary to determine whether strong line ratios could be useful for pre-selecting LyC leakers at high redshift.
  •  
47.
  • Soranno, Patricia A., et al. (författare)
  • LAGOS-NE : A multi-scaled geospatial and temporal database of lake ecological context and water quality for thousands of U.S. lakes
  • 2017
  • Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 6:12, s. 1-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the factors that affect water quality and the ecological services provided by freshwater ecosystems is an urgent global environmental issue. Predicting how water quality will respond to global changes not only requires water quality data, but also information about the ecological context of individual water bodies across broad spatial extents. Because lake water quality is usually sampled in limited geographic regions, often for limited time periods, assessing the environmental controls of water quality requires compilation of many data sets across broad regions and across time into an integrated database. LAGOS-NE accomplishes this goal for lakes in the northeastern-most 17 US states. LAGOS-NE contains data for 51101 lakes and reservoirs larger than 4 ha in 17 lake-rich US states. The database includes 3 datamodules for: lake location and physical characteristics for all lakes; ecological context (i.e., the land use, geologic, climatic, and hydrologic setting of lakes) for all lakes; and in situmeasurements of lake water quality for a subset of the lakes fromthe past 3 decades for approximately 2600–12 000 lakes depending on the variable. The database contains approximately 150000 measures of total phosphorus, 200 000 measures of chlorophyll, and 900 000 measures of Secchi depth. The water quality data were compiled from87 lake water quality data sets fromfederal, state, tribal, and non-profit agencies, university researchers, and citizen scientists. This database is one of the largest andmost comprehensive databases of its type because it includes both in situmeasurements and ecological context data. Because ecological context can be used to study a variety of other questions about lakes, streams, and wetlands, this database can also be used as the foundation for other studies of freshwaters at broad spatial and ecological scales
  •  
48.
  • Spatially Resolved Stellar Populations of 0.3 < z < 6.0 Galaxies in WHL 0137–08 and MACS 0647+70 Clusters as Revealed by JWST : How Do Galaxies Grow and Quench over Cosmic Time?
  • 2023
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 945:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We study the spatially resolved stellar populations of 444 galaxies at 0.3 < z < 6.0 in two clusters (WHL 0137–08 and MACS 0647+70) and a blank field, combining imaging data from the Hubble Space Telescope and JWST to perform spatially resolved spectral energy distribution (SED) modeling using ᴘɪXᴇᴅꜰɪᴛ. The high spatial resolution of the imaging data combined with magnification from gravitational lensing in the cluster fields allows us to resolve a large fraction of our galaxies (109) to subkiloparsec scales. At redshifts around cosmic noon and higher (2.5 ≲ z ≲ 6.0), we find mass-doubling times to be independent of radius, inferred from flat specific star formation rate (sSFR) radial profiles and similarities between the half-mass and half-SFR radii. At lower redshifts (1.5 ≲ z ≲ 2.5), a significant fraction of our star-forming galaxies shows evidence for nuclear starbursts, inferred from a centrally elevated sSFR and a much smaller half-SFR radius compared to the half-mass radius. At later epochs, we find more galaxies suppress star formation in their centers but are still actively forming stars in the disk. Overall, these trends point toward a picture of inside-out galaxy growth consistent with theoretical models and simulations. We also observe a tight relationship between the central mass surface density and global stellar mass with ∼0.38 dex scatter. Our analysis demonstrates the potential of spatially resolved SED analysis with JWST data. Future analysis with larger samples will be able to further explore the assembly of galaxy mass and the growth of their structures.
  •  
49.
  • Svensson-Arvelund, Judit, 1982-, et al. (författare)
  • Expanding cross-presenting dendritic cells enhances oncolytic virotherapy and is critical for long-term anti-tumor immunity
  • 2022
  • Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunotherapies directly enhancing anti-tumor CD8(+) T cell responses have yielded measurable but limited success, highlighting the need for alternatives. Anti-tumor T cell responses critically depend on antigen presenting dendritic cells (DC), and enhancing mobilization, antigen loading and activation of these cells represent an attractive possibility to potentiate T cell based therapies. Here we show that expansion of DCs by Flt3L administration impacts in situ vaccination with oncolytic Newcastle Disease Virus (NDV). Mechanistically, NDV activates DCs and sensitizes them to dying tumor cells through upregulation of dead-cell receptors and synergizes with Flt3L to promote anti-tumor CD8(+) T cell cross-priming. In vivo, Flt3L-NDV in situ vaccination induces parallel amplification of virus- and tumor-specific T cells, including CD8(+) T cells reactive to newly-described neoepitopes, promoting long-term tumor control. Cross-presenting conventional Type 1 DCs are indispensable for the anti-tumor, but not anti-viral, T cell response, and type I IFN-dependent CD4(+) Th1 effector cells contribute to optimal anti-tumor immunity. These data demonstrate that mobilizing DCs to increase tumor antigen cross-presentation improves oncolytic virotherapy and that neoepitope-specific T cells can be induced without individualized, ex vivo manufactured vaccines. Strategies to advance T cell based immune therapies are mostly focusing on the improvement of CD8 T cell effector functions, such as cytotoxicity or recruitment to the tumor. Here authors show that by combining in situ vaccination with oncolytic Newcastle Disease Virus and Flt3L-driven dendritic cell expansion, the anti-tumor T cell response is amplified via increased antigen cross-presentation.
  •  
50.
  • Toorell, Hanna, et al. (författare)
  • Neuro-Specific and Immuno-Inflammatory Biomarkers in Umbilical Cord Blood in Neonatal Hypoxic-Ischemic Encephalopathy.
  • 2024
  • Ingår i: Neonatology. - 1661-7819. ; 121:1, s. 25-33
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to evaluate neuronal injury and immuno-inflammatory biomarkers in umbilical cord blood (UCB) at birth, in cases with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE), compared with healthy controls and to assess their ability to predict HIE.In this case-control study, term infants with perinatal asphyxia were recruited at birth. UCB was stored at delivery for batch analysis. HIE was diagnosed by clinical Sarnat staging at 24 h. Glial fibrillary acidic protein (GFAP), the neuronal biomarkers tau and neurofilament light protein (NFL), and a panel of cytokines were analyzed in a total of 150 term neonates: 50 with HIE, 50 with asphyxia without HIE (PA), and 50 controls. GFAP, tau, and NFL concentrations were measured using ultrasensitive single-molecule array (Simoa) assays, and a cytokine screening panel was applied to analyze the immuno-inflammatory and infectious markers.GFAP, tau, NFL, and several cytokines were significantly higher in newborns with moderate and severe HIE compared to a control group and provided moderate prediction of HIE II/III (AUC: 0.681-0.827). Furthermore, the levels of GFAP, tau, interleukin-6 (IL-6), and interleukin-8 (IL-8) were higher in HIE II/III cases compared with cases with PA/HIE I. IL-6 was also higher in HIE II/III compared with HIE I cases.Biomarkers of brain injury and inflammation were increased in umbilical blood in cases with asphyxia. Several biomarkers were higher in HIE II/III versus those with no HIE or HIE I, suggesting that they could assist in the prediction of HIE II/III.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 69
Typ av publikation
tidskriftsartikel (59)
forskningsöversikt (3)
konferensbidrag (2)
Typ av innehåll
refereegranskat (62)
övrigt vetenskapligt/konstnärligt (2)
Författare/redaktör
Robson, A. (6)
Davies, E. (6)
Martin, J. (6)
Campain, N (6)
Davies, RJ (6)
Silva, M. (6)
visa fler...
Moore, R. (6)
Shaw, S. (6)
Kisiel, A. (6)
Roy, C. (6)
Sharma, N. (6)
Singh, R. (6)
Costa, M. (6)
Gill, C. (6)
Mohan, M. (6)
Clark, J. (6)
Patel, P. (6)
Khan, A. (6)
Lee, M (6)
Miller, D. (6)
Ali, M (6)
Ali, S (6)
Pereira, A (6)
Singh, A (6)
Shah, S (6)
Desai, A. (6)
Evans, J. (6)
Young, R. (6)
Goyal, A. (6)
Sharma, P. (6)
Abdalla, M. (6)
Bhalla, A (6)
Murphy, S. (6)
Green, S (6)
Pereira, R (6)
Smith, L (6)
Tiwari, A (6)
James, G (6)
Ghosh, D (6)
Lawday, S (6)
Li, E (6)
Pata, F (6)
Evans, JP (6)
Jones, CS (6)
Khatri, C (6)
Gallo, G (6)
Ford, S (6)
Fiore, M (6)
Almond, M (6)
Kolias, A (6)
visa färre...
Lärosäte
Uppsala universitet (23)
Lunds universitet (17)
Karolinska Institutet (16)
Stockholms universitet (15)
Göteborgs universitet (12)
Kungliga Tekniska Högskolan (6)
visa fler...
Umeå universitet (5)
Linköpings universitet (5)
Chalmers tekniska högskola (5)
Sveriges Lantbruksuniversitet (4)
Mittuniversitetet (3)
Malmö universitet (2)
Örebro universitet (1)
Södertörns högskola (1)
Linnéuniversitetet (1)
Karlstads universitet (1)
Högskolan Dalarna (1)
Naturhistoriska riksmuseet (1)
visa färre...
Språk
Engelska (69)
Forskningsämne (UKÄ/SCB)
Naturvetenskap (34)
Medicin och hälsovetenskap (24)
Teknik (6)
Samhällsvetenskap (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy