| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Brawand, David, et al.
(författare)
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The genomic substrate for adaptive radiation in African cichlid fish
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 375-381
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Tidskriftsartikel (refereegranskat)abstract
- Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand themolecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.
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| 3. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 4. |
- Lange, Leslie A, et al.
(författare)
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Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 233-245
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Tidskriftsartikel (refereegranskat)abstract
- Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
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| 5. |
- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 6. |
- Arndt, D. S., et al.
(författare)
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State of the Climate in 2016
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Tidskriftsartikel (refereegranskat)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 7. |
- Chen, Yung Chih, et al.
(författare)
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Effects of neuromuscular electrical stimulation on energy expenditure and postprandial metabolism in healthy men
- 2022
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Ingår i: Applied Physiology, Nutrition and Metabolism. - : Canadian Science Publishing. - 1715-5312 .- 1715-5320. ; 47:1, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear whether neuromuscular electrical stimulation (NMES) has meaningful metabolic effects when users have the opportunity to self-select the intensity to one that can be comfortably tolerated. Nine healthy men aged 28 6 9y (mean 6 SD) with a body mass index 22.3 6 2.3 kg/m2 completed 3 trials involving a 2-h oral glucose tolerance test whilst, in a randomised counterbalanced order, (1) sitting motionless (SIT), (2) standing motionless (STAND); and (3) sitting motionless with NMES of quadriceps and calves at a self-selected tolerable intensity. The mean (95% confidence interval [CI]) total energy expenditure was greater in the NMES trial (221 [180–262] kcal/2 h) and STAND trial (178 [164–191] kcal/2 h) than during SIT (159 [150–167] kcal/2 h) (both, p < 0.05). This was primarily driven by an increase in carbohydrate oxidation in the NMES and STAND trials compared with the SIT trial (p < 0.05). Postprandial insulin iAUC was lower in both NMES and STAND compared with SIT (16.4 [7.7–25.1], 17 [7–27] and 22.6 [10.8–34.4] nmol·120 min/L, respectively; both, p < 0.05). Compared with sitting, both NMES and STAND increased energy expenditure and whole-body carbohydrate oxidation and reduced postprandial insulin concentrations in healthy men, with more pronounced effects seen with NMES. Self-selected NMES is a potential strategy for improving metabolic health. This trial is registered at ClinicalTrials.gov (ID: NCT04389736). Novelty: • NMES at a comfortable intensity enhances energy expenditure and carbohydrate oxidation, and reduces postprandial insulinemia. • Thus, self-selected NMES represents a potential strategy to improve metabolic health.
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| 8. |
- Dastani, Zari, et al.
(författare)
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Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals
- 2012
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002607-
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Tidskriftsartikel (refereegranskat)abstract
- Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P=4.5 x 10(-8)-1.2 x 10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3 x 10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p=4.3 x 10(-3), n = 22,044), increased triglycerides (p=2.6 x 10(-14), n = 93,440), increased waist-to-hip ratio (p=1.8 x 10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p=4.4 x 10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p=4.5x10(-13), n = 96,748) and decreased BMI (p= 1.4 x 10(-14), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
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| 9. |
- Diego, Jose M., et al.
(författare)
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JWST's PEARLS : Mothra, a new kaiju star at z=2.091 extremely magnified by MACS0416, and implications for dark matter models
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 679
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of Mothra, an extremely magnified monster star, likely a binary system of two supergiant stars, in one of the strongly lensed galaxies behind the galaxy cluster MACS J0416.1-2403. Mothra is in a galaxy with spectroscopic redshift z = 2.091 in a portion of the galaxy that is parsecs away from the cluster caustic. The binary star is observed only on the side of the critical curve with negative parity but has been detectable for at least eight years, implying the presence of a small lensing perturber. Microlenses alone cannot explain the earlier observations of this object made with the Hubble Space Telescope. A larger perturber with a mass of at least 10(4 )M(circle dot) offers a more satisfactory explanation. Based on the lack of perturbation on other nearby sources in the same arc, the maximum mass of the perturber is 2.5 x 10(6) M-circle dot, making this the smallest substructure constrained by lensing at z > 0.3. The existence of this millilens is fully consistent with expectations from standard cold dark matter cosmology. On the other hand, the existence of such a small substructure in a cluster environment has implications for other dark matter models. In particular, warm dark matter models with particle masses below 8.7 keV are excluded by our observations. Similarly, axion dark matter models are consistent with the observations only if the axion mass is in the range 0.5 x 10(-22) eV < m(a )< 5 x 10(-22) eV.
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| 10. |
- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 11. |
- Kenney-Lazar, Miles, et al.
(författare)
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Greening rubber? Political ecologies of plantation sustainability in Laos and Myanmar
- 2018
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Ingår i: Geoforum. - : Elsevier BV. - 0016-7185 .- 1872-9398. ; 92, s. 96-105
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Tidskriftsartikel (refereegranskat)abstract
- Over the past decade, the cultivation of rubber trees has expanded rapidly throughout the Mekong region to non-traditional rubber growing areas of Laos and Myanmar. Prompted by rising prices from 1990 to 2010 and government agro-industrialization policies, farmers and investors have rushed to plant the new boom crop. A latex price crash in 2011, however, has made it more challenging for small-scale producers to earn an income, leading to uneven social-ecological transformations and economic consequences. Several proposals have been made to address these challenges by transforming rubber into a more economically, socially, and environmentally sustainable crop. In this paper, which emerged from one such project to investigate the potential for green rubber, we argue that the sustainability of rubber is a challenging and elusive prospect - particularly in resource frontier contexts like Laos and Myanmar. Concepts like sustainability or green production are vague and malleable. They can be imbued with a variety of contradictory meanings, which often do not address the most socially and environmentally problematic aspects of cash crop expansion. Sustainable rubber, if rigorously and specifically defined, would be exceedingly difficult to reach in both countries, due to the ways in which political-economic and governance factors interact with the biophysical and social characteristics of the crop. Instead, we recommend using sustainability as a political tool for highlighting the most harmful socio-environmental impacts of rubber and generating debate concerning the best ways to address these, thus limiting unsustainable practices.
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| 12. |
- Lester, Mark, et al.
(författare)
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The Impact of Energetic Particles on the Martian Ionosphere During a Full Solar Cycle of Radar Observations: Radar Blackouts
- 2022
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Ingår i: Journal of Geophysical Research - Space Physics. - : John Wiley & Sons. - 2169-9380 .- 2169-9402. ; 127:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the first long-term characterization of ionization layers in the lower ionosphere of Mars (below ∼90 km), a region inaccessible to orbital in-situ observations, based on an analysis of radar echo blackouts observed on Mars Express and the Mars Reconnaissance Orbiter from 2006 to 2017. A blackout occurs when the expected surface reflection is partly or totally attenuated for portions of an observation. Enhanced ionization at altitudes of 60–90 km, below the main ionospheric electron density peak, leads to increased absorption of the radar signal, resulting in the blackouts. We find that (a) MARSIS, operating at frequencies between 1.8 and 5 MHz, suffered more blackouts than SHARAD, which has a higher carrier frequency (20 MHz), (b) there is a clear correlation of blackout occurrence with solar cycle, (c) there is no apparent relationship between blackout occurrence and crustal magnetic fields, and (d) blackouts occur during both nightside and dayside observations, although the peak occurrence is deep on the nightside. Analysis of Mars Atmosphere and Volatile EvolutioN Solar Energetic Particle electron counts between 20 and 200 keV demonstrates that these electrons are likely responsible for attenuating the radar signals. We investigate the minimum SEP electron fluxes required to ionize the lower atmosphere and produce measurable attenuation. When both radars experience a blackout, the SEP electron fluxes are at their highest. Based on several case studies, we find that the average SEP spectrum responsible for a blackout is particularly enhanced at its higher energy end, that is, above 70 keV.
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| 13. |
- Nabizadeh, Armin, et al.
(författare)
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A search for high-redshift direct-collapse black hole candidates in the PEARLS north ecliptic pole field
- 2024
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Direct-collapse black holes (DCBHs) of mass ∼ 104-105 M⊙ that form in HI-cooling halos in the early Universe are promising progenitors of the greater than or similar to 109 M⊙ supermassive black holes that fuel observed z greater than or similar to 7 quasars. Efficient accretion of the surrounding gas onto such DCBH seeds may render them sufficiently bright for detection with the JWST up to z ≈ 20. Additionally, the very steep and red spectral slope predicted across the ≈ 1-5 μm wavelength range of the JWST/NIRSpec instrument during their initial growth phase should make them photometrically identifiable up to very high redshifts. In this work, we present a search for such DCBH candidates across the 34 arcmin2 in the first two spokes of the JWST cycle-1 PEARLS survey of the north ecliptic pole time-domain field covering eight NIRCam filters down to a maximum depth of ∼ 29 AB mag. We identify two objects with spectral energy distributions consistent with the Pacucci et al. (2016) DCBH models. However, we also note that even with data in eight NIRCam filters, objects of this type remain degenerate with dusty galaxies and obscured active galactic nuclei over a wide range of redshifts. Follow-up spectroscopy would be required to pin down the nature of these objects. Based on our sample of DCBH candidates and assumptions on the typical duration of the DCBH steep-slope state, we set a conservative upper limit of less than or similar to 5x10-4 comoving Mpc-3 (cMpc-3) on the comoving density of host halos capable of hosting DCBHs with spectral energy distributions similar to the Pacucci et al. (2016) models at z ≈ 6-14.
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| 14. |
- Negre, Nicolas, et al.
(författare)
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A cis-regulatory map of the Drosophila genome
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 471:7339, s. 527-531
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Tidskriftsartikel (refereegranskat)abstract
- Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide(1,2) has successfully identified specific subtypes of regulatory elements(3). In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements(4), chromatin states(5), transcription factor binding sites(6-9), RNA polymerase II regulation(8) and insulator elements(10); however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships.
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| 15. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 16. |
- Peng, Xinxia, et al.
(författare)
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The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease
- 2014
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 32:12, s. 1250-U114
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Tidskriftsartikel (refereegranskat)abstract
- The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission(1-)4. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.
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| 17. |
- Russell, Aaron P., et al.
(författare)
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Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training
- 2013
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Ingår i: Journal of Physiology. - Chichester : Wiley-Blackwell. - 0022-3751 .- 1469-7793. ; 591:18, s. 4637-4653
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Tidskriftsartikel (refereegranskat)abstract
- The identification of microRNAs (miRNAs) has established new mechanisms that control skeletal muscle adaptation to exercise. The present study investigated the mRNA regulation of components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin-5), muscle enriched miRNAs, (miR-1, -133a, -133b and -206), and several miRNAs dysregulated in muscle myopathies (miR-9, -23, -29, -31 and -181). Measurements were made in muscle biopsies from nine healthy untrained males at rest, 3 h following an acute bout of moderate-intensity endurance cycling and following 10 days of endurance training. Bioinformatics analysis was used to predict potential miRNA targets. In the 3 h period following the acute exercise bout, Drosha, Dicer and Exportin-5, as well as miR-1, -133a, -133-b and -181a were all increased. In contrast miR-9, -23a, -23b and -31 were decreased. Short-term training increased miR-1 and -29b, while miR-31 remained decreased. Negative correlations were observed between miR-9 and HDAC4 protein (r=-0.71; P= 0.04), miR-31 and HDAC4 protein (r =-0.87; P= 0.026) and miR-31 and NRF1 protein (r =-0.77; P= 0.01) 3 h following exercise. miR-31 binding to the HDAC4 and NRF1 3′ untranslated region (UTR) reduced luciferase reporter activity. Exercise rapidly and transiently regulates several miRNA species in muscle. Several of these miRNAs may be involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis. Identifying endurance exercise-mediated stress signals regulating skeletal muscle miRNAs, as well as validating their targets and regulatory pathways post exercise, will advance our understanding of their potential role/s in human health. © 2013 The Authors. The Journal of Physiology © 2013 The Physiological Society.
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| 18. |
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| 19. |
- Windhorst, Rogier A., et al.
(författare)
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JWST PEARLS. Prime extragalactic areas for reionization and lensing science : project overview and first results
- 2023
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Ingår i: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 165:1
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Tidskriftsartikel (refereegranskat)abstract
- We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST “Prime Extragalactic Areas for Reionization and Lensing Science” (PEARLS) project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift protoclusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, active galactic nucleus (AGN) growth, and First Light. Five fields—the JWST NEP Time-Domain Field (TDF), IRAC Dark Field, and three lensing clusters—will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9–4.5 μm galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9–4.5 μm. PEARLS is designed to be of lasting benefit to the community.
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