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1.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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2.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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3.
  • Almered Olsson, Gunilla, 1951, et al. (författare)
  • Food systems sustainability - For whom and by whom? : An examination of different 'food system change' viewpoints
  • 2018
  • Ingår i: Development Research Conference 2018: “Rethinking development”, 22–23 August 2018, Gothenburg, Sweden.
  • Konferensbidrag (refereegranskat)abstract
    • The United Nations identifies the food crisis as one of the primary overarching challenges facing the international community. Different stakeholders in the food system have widely different perspectives and interests, and challenging structural issues, such as the power differentials among them, remain largely unexamined. These challenges make rational discourse among food system actors from different disciplines, sectors and levels difficult. These challenges can often prevent them from working together effectively to find innovative ways to respond to food security challenges. This means that finding solutions to intractable and stuck issues, such as the food crisis often stall, not at implementation, but at the point of problem identification. Food system sustainability means very different things to different food system actors. These differences in no way undermine or discount the work carried out by these players. However, making these differences explicit is an essential activity that would serve to deepen theoretical and normative project outcomes. Would the impact and reach of different food projects differ if these differences were made explicit? The purpose of this initial part of a wider food system research project is not to search for difference or divergence, with the aim of critique, but rather to argue that by making these differences explicit, the overall food system project engagement will be made more robust, more inclusive and more encompassing. This paper starts with some discussion on the different food system perspectives, across scales, regions and sectors but focuses primarily on the design of processes used to understand these divergent and at times contradictory views of what a sustainable food system may be. This paper draws on ongoing work within the Mistra Urban Futures project, using the food system projects in cities as diverse as Cape Town, Manchester, Gothenburg and Kisumu as sites for this enquiry.
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4.
  • Arndt, D. S., et al. (författare)
  • State of the Climate in 2016
  • 2017
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
  • 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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5.
  • Arndt, D. S., et al. (författare)
  • STATE OF THE CLIMATE IN 2017
  • 2018
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
  • Forskningsöversikt (refereegranskat)
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6.
  • Asselbergs, Folkert W., et al. (författare)
  • Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
  • 2012
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
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7.
  • Bassett, Andrew R., et al. (författare)
  • Understanding functional miRNA-target interactions in vivo by site-specific genome engineering
  • 2014
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4640-
  • Tidskriftsartikel (refereegranskat)abstract
    • MicroRNA (miRNA) target recognition is largely dictated by short 'seed' sequences, and single miRNAs therefore have the potential to regulate a large number of genes. Understanding the contribution of specific miRNA-target interactions to the regulation of biological processes in vivo remains challenging. Here we use transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technologies to interrogate the functional relevance of predicted miRNA response elements (MREs) to post-transcriptional silencing in zebrafish and Drosophila. We also demonstrate an effective strategy that uses CRISPR-mediated homology-directed repair with short oligonucleotide donors for the assessment of MRE activity in human cells. These methods facilitate analysis of the direct phenotypic consequences resulting from blocking specific miRNA-MRE interactions at any point during development.
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8.
  • Blunden, Jessica, et al. (författare)
  • State of the Climate in 2012
  • 2013
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
  • Tidskriftsartikel (refereegranskat)abstract
    • For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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9.
  • Boudry-Labis, Elise, et al. (författare)
  • A novel microdeletion syndrome at 9q21.13 characterised by mental retardation, speech delay, epilepsy and characteristic facial features
  • 2013
  • Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 56:3, s. 163-170
  • Tidskriftsartikel (refereegranskat)abstract
    • The increased use of array-CGH and SNP-arrays for genetic diagnosis has led to the identification of new microdeletion/microduplication syndromes and enabled genotype-phenotype correlations to be made. In this study, nine patients with 9q21 deletions were investigated and compared with four previously Decipher reported patients. Genotype-phenotype comparisons of 13 patients revealed several common major characteristics including significant developmental delay, epilepsy, neuro-behavioural disorders and recognizable facial features including hypertelorism, feature-less philtrum, and a thin upper lip. The molecular investigation identified deletions with different breakpoints and of variable lengths, but the 750 kb smallest overlapping deleted region includes four genes. Among these genes, RORB is a strong candidate for a neurological phenotype. To our knowledge, this is the first published report of 9q21 microdeletions and our observations strongly suggest that these deletions are responsible for a new genetic syndrome characterised by mental retardation with speech delay, epilepsy, autistic behaviour and moderate facial dysmorphy. 
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10.
  • Brout, Dillon, et al. (författare)
  • The Pantheon+ analysis : cosmological constraints
  • 2022
  • Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 938:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present constraints on cosmological parameters from the Pantheon+ analysis of 1701 light curves of 1550 distinct Type Ia supernovae (SNe Ia) ranging in redshift from z = 0.001 to 2.26. This work features an increased sample size from the addition of multiple cross-calibrated photometric systems of SNe covering an increased redshift span, and improved treatments of systematic uncertainties in comparison to the original Pantheon analysis, which together result in a factor of 2 improvement in cosmological constraining power. For a flat ΛCDM model, we find ΩM = 0.334 ± 0.018 from SNe Ia alone. For a flat w0CDM model, we measure w0 = −0.90 ± 0.14 from SNe Ia alone, H0 = 73.5 ± 1.1 km s−1 Mpc−1 when including the Cepheid host distances and covariance (SH0ES), and w0 = -0.978-+0.0310.024 when combining the SN likelihood with Planck constraints from the cosmic microwave background (CMB) and baryon acoustic oscillations (BAO); both w0 values are consistent with a cosmological constant. We also present the most precise measurements to date on the evolution of dark energy in a flat w0waCDM universe, and measure wa = -0.1-+2.00.9 from Pantheon+ SNe Ia alone, H0 = 73.3 ± 1.1 km s−1 Mpc−1 when including SH0ES Cepheid distances, and wa = -0.65-+0.320.28 when combining Pantheon+ SNe Ia with CMB and BAO data. Finally, we find that systematic uncertainties in the use of SNe Ia along the distance ladder comprise less than one-third of the total uncertainty in the measurement of H0 and cannot explain the present “Hubble tension” between local measurements and early universe predictions from the cosmological model.
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11.
  • Brout, Dillon, et al. (författare)
  • The Pantheon+ analysis : supercal-fragilistic cross calibration, retrained SALT2 light-curve model, and calibration systematic uncertainty
  • 2022
  • Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 938:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a recalibration of the photometric systems in the Pantheon+ sample of Type Ia supernovae (SNe Ia) including those in the SH0ES distance-ladder measurement of H0. We utilize the large and uniform sky coverage of the public Pan-STARRS stellar photometry catalog to cross calibrate against tertiary standards released by individual SN Ia surveys. The most significant updates over the “SuperCal” cross calibration used for the previous Pantheon and SH0ES analyses are: (1) expansion of the number of photometric systems (now 25) and filters (now 105), (2) solving for all filter offsets in all systems simultaneously to produce a calibration uncertainty covariance matrix for cosmological-model constraints, and (3) accounting for the change in the fundamental flux calibration of the Hubble Space Telescope CALSPEC standards from previous versions on the order of 1.5% over a Δλ of 4000 Å. We retrain the SALT2 model and find that our new model coupled with the new calibration of the light curves themselves causes a net distance modulus change (dμ/dz) of 0.04 mag over the redshift range 0 < z < 1. We introduce a new formalism to determine the systematic impact on cosmological inference by propagating the covariance in the fitted calibration offsets through retraining simultaneously with light-curve fitting and find a total calibration uncertainty impact of σw = 0.013; roughly half the size of the sample statistical uncertainty. Similarly, we find the systematic SN calibration contribution to the SH0ES H0 uncertainty is less than 0.2 km s−1 Mpc−1, suggesting that SN Ia calibration cannot resolve the current level of the “Hubble Tension.”
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12.
  • Connolly, Stuart J., et al. (författare)
  • Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage
  • 2024
  • Ingår i: New England Journal of Medicine. - 0028-4793. ; 390:19, s. 1745-1755
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. Methods We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. Results A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P=0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P=0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. Conclusions Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).
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13.
  • Cuni-Sanchez, Aida, et al. (författare)
  • High aboveground carbon stock of African tropical montane forests
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7873, s. 536-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Tropical forests store 40–50per cent of terrestrial vegetation carbon. However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests. Owing to climatic and soil changes with increasing elevation, AGC stocks are lower in tropical montane forests compared with lowland forests. Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4megagrams of carbon per hectare (95% confidence interval 137.1–164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network4 and about 70per cent and 32per cent higher than averages from plot networks in montane and lowland forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa8. We find that the low stem density and high abundance of large trees of African lowland forests is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to helpto guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse and carbon-rich ecosystems.
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14.
  • 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.
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15.
  • Falck-Ytter, Terje, et al. (författare)
  • The Babytwins Study Sweden (BATSS): A Multi-Method Infant Twin Study of Genetic and Environmental Factors Influencing Infant Brain and Behavioral Development
  • 2021
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 24:4, s. 217-227
  • Tidskriftsartikel (refereegranskat)abstract
    • Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5-36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years.
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16.
  • Figueiredo, Vandre C., et al. (författare)
  • Genetic and epigenetic regulation of skeletal muscle ribosome biogenesis with exercise
  • 2021
  • Ingår i: Journal of Physiology. - : Wiley-Blackwell. - 0022-3751 .- 1469-7793. ; 599:13, s. 3363-3384
  • Tidskriftsartikel (refereegranskat)abstract
    • Key points Ribosome biogenesis and MYC transcription are associated with acute resistance exercise (RE) and are distinct from endurance exercise in human skeletal muscle throughout a 24 h time course of recovery. A PCR-based method for relative ribosomal DNA (rDNA) copy number estimation was validated by whole genome sequencing and revealed that rDNA dosage is positively correlated with ribosome biogenesis in response to RE. Acute RE modifies rDNA methylation patterns in enhancer, intergenic spacer and non-canonical MYC-associated regions, but not the promoter. Myonuclear-specific rDNA methylation patterns with acute mechanical overload in mice corroborate and expand on rDNA findings with RE in humans. A genetic predisposition for hypertrophic responsiveness may exist based on rDNA gene dosage. Ribosomes are the macromolecular engines of protein synthesis. Skeletal muscle ribosome biogenesis is stimulated by exercise, although the contribution of ribosomal DNA (rDNA) copy number and methylation to exercise-induced rDNA transcription is unclear. To investigate the genetic and epigenetic regulation of ribosome biogenesis with exercise, a time course of skeletal muscle biopsies was obtained from 30 participants (18 men and 12 women; 31 +/- 8 years, 25 +/- 4 kg m(-2)) at rest and 30 min, 3 h, 8 h and 24 h after acute endurance (n = 10, 45 min cycling, 70% V?O2max) or resistance exercise (n = 10, 4 x 7 x 2 exercises); 10 control participants underwent biopsies without exercise. rDNA transcription and dosage were assessed using quantitative PCR and whole genome sequencing. rDNA promoter methylation was investigated using massARRAY EpiTYPER and global rDNA CpG methylation was assessed using reduced-representation bisulphite sequencing. Ribosome biogenesis and MYC transcription were associated primarily with resistance but not endurance exercise, indicating preferential up-regulation during hypertrophic processes. With resistance exercise, ribosome biogenesis was associated with rDNA gene dosage, as well as epigenetic changes in enhancer and non-canonical MYC-associated areas in rDNA, but not the promoter. A mouse model of in vivo metabolic RNA labelling and genetic myonuclear fluorescence labelling validated the effects of an acute hypertrophic stimulus on ribosome biogenesis and Myc transcription, and also corroborated rDNA enhancer and Myc-associated methylation alterations specifically in myonuclei. The present study provides the first information on skeletal muscle genetic and rDNA gene-wide epigenetic regulation of ribosome biogenesis in response to exercise, revealing novel roles for rDNA dosage and CpG methylation.
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17.
  • Ganesh, Santhi K., et al. (författare)
  • Loci influencing blood pressure identified using a cardiovascular gene-centric array
  • 2013
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
  • Tidskriftsartikel (refereegranskat)abstract
    • Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
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18.
  • Goetz, Charlotte, et al. (författare)
  • Solar Wind Protons in the Diamagnetic Cavity at Comet 67P/Churyumov-Gerasimenko
  • 2023
  • Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 128:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The plasma environment at a comet can be divided into different regions with distinct plasma characteristics. Two such regions are the solar wind ion cavity, which refers to the part of the outer coma that does not contain any solar wind ions anymore; and the diamagnetic cavity, which is the region of unmagnetized plasma in the innermost coma. From theory and previous observations, it was thought that under usual circumstances no solar wind ion should be observable near or inside of the diamagnetic cavity. For the first time, we report on five observations that show that protons near solar wind energies can also be found inside the diamagnetic cavity. We characterize these proton signatures, where and when they occur, and discuss possible mechanisms that could lead to protons penetrating the inner coma and traversing the diamagnetic cavity boundary. By understanding these observations, we hope to better understand the interaction region of the comet with the solar wind under nonstandard conditions. The protons detected inside the diamagnetic cavity have directions and energies consistent with protons of solar wind origin. The five events occur only at intermediate gas production rates and low cometocentric distances. Charge transfer reactions, high solar wind dynamic pressure and a neutral gas outburst can be ruled out as causes. We suggest that the anomalous appearance of protons in the diamagnetic cavity is due to a specific solar wind configuration where the solar wind velocity is parallel to the interplanetary magnetic field, thus inhibiting mass-loading and deflection.
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19.
  • Goetz, Charlotte, et al. (författare)
  • The plasma environment of comet 67P/Churyumov-Gerasimenko
  • 2022
  • Ingår i: Space Science Reviews. - : Springer. - 0038-6308 .- 1572-9672. ; 218:8
  • Forskningsöversikt (refereegranskat)abstract
    • The environment of a comet is a fascinating and unique laboratory to study plasma processes and the formation of structures such as shocks and discontinuities from electron scales to ion scales and above. The European Space Agency's Rosetta mission collected data for more than two years, from the rendezvous with comet 67P/Churyumov-Gerasimenko in August 2014 until the final touch-down of the spacecraft end of September 2016. This escort phase spanned a large arc of the comet's orbit around the Sun, including its perihelion and corresponding to heliocentric distances between 3.8 AU and 1.24 AU. The length of the active mission together with this span in heliocentric and cometocentric distances make the Rosetta data set unique and much richer than sets obtained with previous cometary probes. Here, we review the results from the Rosetta mission that pertain to the plasma environment. We detail all known sources and losses of the plasma and typical processes within it. The findings from in-situ plasma measurements are complemented by remote observations of emissions from the plasma. Overviews of the methods and instruments used in the study are given as well as a short review of the Rosetta mission. The long duration of the Rosetta mission provides the opportunity to better understand how the importance of these processes changes depending on parameters like the outgassing rate and the solar wind conditions. We discuss how the shape and existence of large scale structures depend on these parameters and how the plasma within different regions of the plasma environment can be characterised. We end with a non-exhaustive list of still open questions, as well as suggestions on how to answer them in the future.
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20.
  • Goetz, Charlotte, et al. (författare)
  • Warm protons at comet 67P/Churyumov-Gerasimenko-implications for the infant bow shock
  • 2021
  • Ingår i: Annales Geophysicae. - : European Geosciences Union (EGU). - 0992-7689 .- 1432-0576. ; 39:3, s. 379-396
  • Tidskriftsartikel (refereegranskat)abstract
    • The plasma around comet 67P/Churyumov-Gerasimenko showed remarkable variability throughout the entire Rosetta mission. Plasma boundaries such as the diamagnetic cavity, solar wind ion cavity and infant bow shock separate regions with distinct plasma parameters from each other. Here, we focus on a particular feature in the plasma: warm, slow solar wind protons. We investigate this particular proton population further by focusing on the proton behaviour and surveying all of the Rosetta comet phase data. We find over 300 events where Rosetta transited from a region with fast, cold protons into a region with warm, slow protons. We investigate the properties of the plasma and magnetic field at this boundary and the location where it can be found. We find that the protons are preferentially detected at intermediate gas production rates with a slight trend towards larger cometocentric distances for higher gas production rates. The events can mostly be found in the positive convective electric field hemisphere. These results agree well with simulations of the infant bow shock (IBS), an asymmetric structure in the plasma environment previously detected on only 2 d during the comet phase. The properties of the plasma on both sides of this structure are harder to constrain, but there is a trend towards higher electron flux, lower magnetic field, higher magnetic field power spectral density and higher density in the region that contains the warm protons. This is in partial agreement with the previous IBS definitions; however, it also indicates that the plasma and this structure are highly non-stationary. For future research, Comet Interceptor, with its multi-point measurements, can help to disentangle the spatial and temporal effects and give more clarity on the influence of changing upstream conditions on the movement of boundaries in this unusual environment.
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21.
  • Grasselli, Giacomo, et al. (författare)
  • ESICM guidelines on acute respiratory distress syndrome : definition, phenotyping and respiratory support strategies
  • 2023
  • Ingår i: Intensive Care Medicine. - : Springer Nature. - 0342-4642 .- 1432-1238. ; 49, s. 727-759
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
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22.
  • Haycock, Philip C., et al. (författare)
  • Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
  • 2017
  • Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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23.
  • Haysom, Gareth, et al. (författare)
  • Food systems sustainability: An examination of different viewpoints on food system change
  • 2019
  • Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Global food insecurity levels remain stubbornly high. One of the surest ways to grasp the scale and consequence of global inequality is through a food systems lens. In a predominantly urban world, urban food systems present a useful lens to engage a wide variety of urban (and global) challenges—so called ‘wicked problems.’ This paper describes a collaborative research project between four urban food system research units, two European and two African. The project purpose was to seek out solutions to what lay between, across and within the different approaches applied in the understanding of each city’s food system challenges. Contextual differences and immediate (perceived) needs resulted in very different views on the nature of the challenge and the solutions required. Value positions of individuals and their disciplinary “enclaves” presented further boundaries. The paper argues that finding consensus provides false solutions. Rather the identification of novel approaches to such wicked problems is contingent of these differences being brought to the fore, being part of the conversation, as devices through which common positions can be discovered, where spaces are created for the realisation of new perspectives, but also, where difference is celebrated as opposed to censored.
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24.
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25.
  • Li, Chen, et al. (författare)
  • Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
  • 2020
  • Ingår i: American Journal of Human Genetics. - : CELL PRESS. - 0002-9297 .- 1537-6605. ; 106:3, s. 389-404
  • Tidskriftsartikel (refereegranskat)abstract
    • Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
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26.
  • Löfstrand, Stefan D., et al. (författare)
  • Phylogenetic relationships, infrageneric classification and species limits in the Neotropical genus Faramea (Coussareeae: Rubiaceae)
  • 2021
  • Ingår i: Botanical journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4074 .- 1095-8339. ; 197, s. 478-497
  • Tidskriftsartikel (refereegranskat)abstract
    • Faramea is characterized by white or blue, tetramerous corollas and blue-black, fleshy fruits with a single, large pyrene. Both infrageneric relationships and species boundaries are poorly understood in the genus. This study represents the first broad-scale phylogenetic study of Faramea, with 80 of the c. 170 species sampled, 24 by two or more specimens. We aimed to include specimens representing the entire geographical, morphological and ecological ranges of the genus. Morphological characters historically utilized to delimit infrageneric sections in Faramea (e.g. bract and pyrene forms) were also evaluated. Only one of the currently accepted infrageneric sections was recovered as monophyletic (within a complex of species from other sections) and none of the morphological features traditionally utilized to determine infrageneric relationships in the genus was found to be uniquely diagnostic of a larger clade. Some Faramea lineages appear to be geographically isolated, with several clades containing solely specimens collected in the Atlantic Forest biomes. Of the 24 species represented by at least two specimens, 11 were supported as monophyletic, ten as non-monophyletic and three were not resolved as either monophyletic nor non-monophyletic. The results of the present study constitute a good basis for future studies of taxonomy, biogeography and ecology of Faramea.
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27.
  • Manns, Ulrika, et al. (författare)
  • HISTORICAL BIOGEOGRAPHY OF THE PREDOMINANTLY NEOTROPICAL SUBFAMILY CINCHONOIDEAE (RUBIACEAE) : INTO OR OUT OF AMERICA?
  • 2012
  • Ingår i: International journal of plant sciences. - : University of Chicago Press. - 1058-5893 .- 1537-5315. ; 173:3, s. 261-289
  • Tidskriftsartikel (refereegranskat)abstract
    • The Rubiaceae is the fifth largest plant family and is found on all continents, mostly in (sub-)tropical regions. Despite a large representation of Rubiaceae in the Paleotropics, the subfamily Cinchonoideae has its primary distribution in the Neotropics. Within the Cinchonoideae only two tribes, Naucleeae and Hymenodictyeae, have Paleotropical centers of distribution. In this study, we used information from five chloroplast DNA markers and fossil data to investigate when the subfamily was established in the Neotropics as well as major subsequent dispersal events within and out of the Neotropics and within the Paleotropics. Our results show that the ancestor of Cinchonoideae and its sister, Ixoroideae, was present in South America during the Late Cretaceous. Dispersal to Central America was estimated to occur during the Early Paleocene, and subsequent dispersals to the Caribbean islands occurred during the Oligocene-Miocene. The ancestor of Naucleeae and Hymenodictyeae dispersed to the Paleotropics no later than the Eocene, and the findings of fossils of Cephalanthus in Europe and western Siberia support its presence in the boreotropical forests. Long-distance, trans-Pacific dispersal during the Miocene was indicated for the remaining Paleotropical Cinchonoideae.
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28.
  • Mollenhauer, Brit, et al. (författare)
  • Antibody-based methods for the measurement of α-synuclein concentration in human cerebrospinal fluid - method comparison and round robin study.
  • 2019
  • Ingår i: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 149:1, s. 126-138
  • Tidskriftsartikel (refereegranskat)abstract
    • α-Synuclein is the major component of Lewy bodies and a candidate biomarker for neurodegenerative diseases in which Lewy bodies are common, including Parkinson's disease and dementia with Lewy bodies. A large body of literature suggests that these disorders are characterized by reduced concentrations of α-synuclein in cerebrospinal fluid (CSF), with overlapping concentrations compared to healthy controls and variability across studies. Several reasons can account for this variability, including technical ones, such as inter-assay and inter-laboratory variation (reproducibility). We compared four immunochemical methods for the quantification of α-synuclein concentration in 50 unique CSF samples. All methods were designed to capture most of the existing α-synuclein forms in CSF ('total' α-synuclein). Each of the four methods showed high analytical precision, excellent correlation between laboratories (R2 0.83-0.99), and good correlation with each other (R2 0.64-0.93), although the slopes of the regression lines were different between the four immunoassays. The use of common reference CSF samples decreased the differences in α-synuclein concentration between detection methods and technologies. Pilot data on an immunoprecipitation mass spectrometry (IP-MS) method isalso presented. Our results suggest that the four immunochemical methods and the IP-MS method measure similarforms of α-synuclein and that a common reference materialwould allow harmonization of results between immunoassays.
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29.
  • Nguyen, Thanh N, et al. (författare)
  • Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
  • 2023
  • Ingår i: Neurology. - 1526-632X. ; 100:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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30.
  • Pérez-Izquierdo, Leticia, et al. (författare)
  • Fire severity as a key determinant of aboveground and belowground biological community recovery in managed even-aged boreal forests
  • 2023
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 13:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Changes in fire regime of boreal forests in response to climate warming are expected to impact postfire recovery. However, quantitative data on how managed forests sustain and recover from recent fire disturbance are limited.Two years after a large wildfire in managed even-aged boreal forests in Sweden, we investigated how recovery of aboveground and belowground communities, that is, understory vegetation and soil microbial and faunal communities, responded to variation in the severity of soil (i.e., consumption of soil organic matter) and canopy fires (i.e., tree mortality).While fire overall enhanced diversity of understory vegetation through colonization of fire adapted plant species, it reduced the abundance and diversity of soil biota. We observed contrasting effects of tree- and soil-related fire severity on survival and recovery of understory vegetation and soil biological communities. Severe fires that killed overstory Pinus sylvestris promoted a successional stage dominated by the mosses Ceratodon purpureus and Polytrichum juniperinum, but reduced regeneration of tree seedlings and disfavored the ericaceous dwarf-shrub Vaccinium vitis-idaea and the grass Deschampsia flexuosa. Moreover, high tree mortality from fire reduced fungal biomass and changed fungal community composition, in particular that of ectomycorrhizal fungi, and reduced the fungivorous soil Oribatida. In contrast, soil-related fire severity had little impact on vegetation composition, fungal communities, and soil animals. Bacterial communities responded to both tree- and soil-related fire severity.Synthesis: Our results 2 years postfire suggest that a change in fire regime from a historically low-severity ground fire regime, with fires that mainly burns into the soil organic layer, to a stand-replacing fire regime with a high degree of tree mortality, as may be expected with climate change, is likely to impact the short-term recovery of stand structure and above- and belowground species composition of even-aged P. sylvestris boreal forests.
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31.
  • Portugal, Ana Maria, et al. (författare)
  • Infants' looking preferences for social versus non-social objects reflect genetic variation
  • 2024
  • Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 8:1, s. 115-124
  • Tidskriftsartikel (refereegranskat)abstract
    • To what extent do individual differences in infants’ early preference for faces versus non-facial objects reflect genetic and environmental factors? Here in a sample of 536 5-month-old same-sex twins, we assessed attention to faces using eye tracking in two ways: initial orienting to faces at the start of the trial (thought to reflect subcortical processing) and sustained face preference throughout the trial (thought to reflect emerging attention control). Twin model fitting suggested an influence of genetic and unique environmental effects, but there was no evidence for an effect of shared environment. The heritability of face orienting and preference were 0.19 (95% confidence interval (CI) 0.04 to 0.33) and 0.46 (95% CI 0.33 to 0.57), respectively. Face preference was associated positively with later parent-reported verbal competence (β = 0.14, 95% CI 0.03 to 0.25, P = 0.014, R2 = 0.018, N = 420). This study suggests that individual differences in young infants’ selection of perceptual input—social versus non-social—are heritable, providing a developmental perspective on gene–environment interplay occurring at the level of eye movements.
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32.
  • Portugal, Ana Maria, et al. (författare)
  • Pupil size and pupillary light reflex in early infancy : heritability and link to genetic liability to schizophrenia
  • 2022
  • Ingår i: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 63:9, s. 1068-1077
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Measures based on pupillometry, such as the pupillary light reflex (PLR) and baseline pupil size, reflect physiological responses linked to specific neural circuits that have been implicated as atypical in some psychiatric and neurodevelopmental conditions.MethodsWe investigated the contribution of genetic and environmental factors to the baseline pupil size and the PLR in 510 infant twins assessed at 5?months of age (281 monozygotic and 229 dizygotic pairs), and its associations with common genetic variants associated with neurodevelopmental (autism spectrum disorder and attention deficit hyperactivity disorder) and mental health (bipolar disorder, major depressive disorder and schizophrenia) conditions using genome-wide polygenic scores (GPSs).ResultsUnivariate twin modelling showed high heritability at 5?months for both pupil size (h2?=?.64) and constriction in response to light (h2?=?.62), and bivariate twin modeling indicated substantial independence between the genetic factors influencing each (rG?=?.38). A statistically significant positive association between infant tonic pupil size and the GPS for schizophrenia was found (??=?.15, p?=?.024), while there was no significant association with the GPS for autism or any other GPSs.ConclusionsThis study shows that some pupil measures are highly heritable in early infancy, although substantially independent in their genetic etiologies, and associated with common genetic variants linked to schizophrenia. It illustrates how genetically informed studies of infants may help us understand early physiological responses associated with psychiatric disorders which emerge much later in life.
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33.
  • Razafimandimbison, Sylvain G., et al. (författare)
  • PHYLOGENY AND GENERIC LIMITS IN THE SISTER TRIBES PSYCHOTRIEAE AND PALICOUREEAE (RUBIACEAE) : EVOLUTION OF SCHIZOCARPS IN PSYCHOTRIA AND ORIGINS OF BACTERIAL LEAF NODULES OF THE MALAGASY SPECIES
  • 2014
  • Ingår i: American Journal of Botany. - : Wiley. - 0002-9122 .- 1537-2197. ; 101:7, s. 1102-1126
  • Tidskriftsartikel (refereegranskat)abstract
    • Premise of the study: The pantropical, species-rich Psychotrieae and Palicoureeae are sister tribes of mostly drupe-bearing and nonbacterial leaf-nodulating species with problematic generic limits. This problem is more complicated in Psychotrieae due to the paraphyly of the genus Psychotria, the lack of diagnostic characters for some major lineages, and the poor sampling from some biodiversity hotspots. Schizocarps and bacterial leaf nodules have been used for recognizing formal groups in Psychotrieae, but their evolution and taxonomic value have not been studied using a robust phylogeny of the tribe. Methods: We analyzed 287 samples from the entire ranges of the tribes, with particular emphasis on the Western Indian Ocean region, with the Bayesian Markov chain Monte Carlo method. Key results: All allied Psychotria genera investigated are nested within a paraphyletic Psychotria. Schizocarps evolved independently two times within Psychotria, and one reversal back to the drupaceous condition is inferred. The Malagasy leaf-nodulated Psychotrieae (except Apomuria bullata) and the Comorian non-leaf-nodulated Psychotria conocarpa are nested within the (African) leaf-nodulated clade. Within Palicoureeae, Chassalia is paraphyletic with respect to Geophila sensu stricto, and the Malagasy Geophila gerrardii and the African Hymenocoleus are closely related. Conclusions: A widely circumscribed Psychotria encompassing the entire Psychotrieae is supported. Within Psychotria, two separate origins of schizocarps from drupes, one reversal back to the drupaceous condition, and two independent origins of the Malagasy leafnodulated species are inferred. A new genus Puffia is described to accommodate Geophila gerrardii, and a narrow circumscription of Chassalia is adopted. Thirty-two new combinations, two lectotypifications, and 25 new names are presented.
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34.
  • Ruggeri, Kai, et al. (författare)
  • The globalizability of temporal discounting
  • 2022
  • Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 6:10, s. 1386-1397
  • Tidskriftsartikel (refereegranskat)abstract
    • Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns. Ruggeri et al. find in a study of 61 countries that temporal discounting patterns are globally generalizable. Worse financial environments, greater inequality and high inflation are associated with extreme or inconsistent long-term decisions.
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35.
  • Shukla, Neerav, et al. (författare)
  • Proteasome Addiction Defined in Ewing Sarcoma Is Effectively Targeted by a Novel Class of 19S Proteasome Inhibitors
  • 2016
  • Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 76:15, s. 4525-4534
  • Tidskriftsartikel (refereegranskat)abstract
    • Ewing sarcoma is a primitive round cell sarcoma with a peak incidence in adolescence that is driven by a chimeric oncogene created from the fusion of the EWSR1 gene with a member of the ETS family of genes. Patients with metastatic and recurrent disease have dismal outcomes and need better therapeutic options. We screened a library of 309,989 chemical compounds for growth inhibition of Ewing sarcoma cells to provide the basis for the development of novel therapies and to discover vulnerable pathways that might broaden our understanding of the pathobiology of this aggressive sarcoma. This screening campaign identified a class of benzyl-4-piperidone compounds that selectively inhibit the growth of Ewing sarcoma cell lines by inducing apoptosis. These agents disrupt 19S proteasome function through inhibition of the deubiquitinating enzymes USP14 and UCHL5. Functional genomic data from a genome-wide shRNA screen in Ewing sarcoma cells also identified the proteasome as a node of vulnerability in Ewing sarcoma cells, providing orthologous confirmation of the chemical screen findings. Furthermore, shRNA-mediated silencing of USP14 or UCHL5 in Ewing sarcoma cells produced significant growth inhibition. Finally, treatment of a xenograft mouse model of Ewing sarcoma with VLX1570, a benzyl-4-piperidone compound derivative currently in clinical trials for relapsed multiple myeloma, significantly inhibited in vivo tumor growth. Overall, our results offer a preclinical proof of concept for the use of 19S proteasome inhibitors as a novel therapeutic strategy for Ewing sarcoma. (C) 2016 AACR.
  •  
36.
  • Taylor, Charlotte, et al. (författare)
  • Eumachia expanded, a tropical genus distinct from Psychotria (Rubiaceae, Palicoureeae)
  • 2017
  • Ingår i: Candollea. - : Society of Conservatoire at Jardin Botaniques de la Ville de Geneve. - 0373-2967 .- 2235-3658. ; 72, s. 289-318
  • Tidskriftsartikel (refereegranskat)abstract
    • The pantropical genus Margaritopsis C. Wright (Rubiaceae, Palicoureeae) was recently separated from Psychotria L. and transferred to a different tribe, Palicoureeae, based on both molecular and morphological data. Margaritopsis has been studied in the Neotropics, and in Africa as Chazaliella E.M.A. Petit & Verdc. ; the species that belong to this group in the Pacific are enumerated for the first time here. Recently Eumachia DC. was found to be an older name for this group, and a few species of Margaritopsis have been transferred nomenclaturally to that genus. Here Eumachia is surveyed comprehensively for the first time, with a list of species and an overview of morphological characteristics. The remaining species of Margaritopsis are nomenclaturally transferred here to Eumachia, along with one species of Hodgkinsonia F. Müll., one species of Mapouria Aubl., and several species of Psychotria from Asia, Australia, New Guinea, and the Pacific region. In this new circumscription Eumachia includes 83 species, and is characterized within Palicoureeae by a yellowish green drying color ; stipules that are persistent or fall by fragmentation and are generally glandular when young and hardened when old ; green to whitened inflorescence axes ; white to cream or yellowish green, often rather small corollas ; orange to red fruits ; pyrenes with marginal pre-formed germination slits and no ethanol-soluble pigments ; and non-ruminate endosperm. Eumachia includes 20 species, 8 subspecies, and 7 varieties in Africa, 27 species in the Neotropics, and 36 species and 6 varieties in Asia, Australasia, and the Pacific region. Here we publish 81 new nomenclatural combinations in Eumachia and two new synonymies for Neotropical names, and 11 names from various regions are lectotypified.
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37.
  • Taylor, Charlotte M., et al. (författare)
  • Rubiacearum Americanarum Magna Hama Pars XXVIII: New Taxa, New Combinations, New Names, and Lectotypification for Several Species Found in Mexico and Central America
  • 2011
  • Ingår i: Novon. - : Missouri Botanical Garden Press. - 1055-3177. ; 21:1, s. 133-148
  • Tidskriftsartikel (refereegranskat)abstract
    • The Neotropical genus Borojoa Cuatrec. (Rubiaceae) is now considered a synonym of Alibertia A. Rich. ex DC. Consequently, three species named in Borojoa and found in Costa Rica and Panama are transferred to Alibertia with these corresponding nomenclatural changes: the new combination A. atlantica (Dwyer) Delprete & C. H. Perss. is based on B. atlantica Dwyer, the new name A. dwyeri Delprete & C. H. Perss. is provided for B. panamensis Dwyer, and the new combination A. patinoi (Cuatrec.) Delprete & C. H. Perss. is provided for B. patinoi Cuatrec. Additionally, the species A. premontana C. M. Taylor is reduced to a variety of A. (quits (Rich.) A. Rich. ex DC., as A. edulis var. premontana (C. M. Taylor) Delprete & C. H. Perss. A lectotype is selected for A. edulis. The recent publication of Arachnothryx chimalaparam Lorence ex Borhidi designated a holotype deposited at MO, but no such specimen has been located; a lectotype is here chosen based on a duplicate of the holotype deposited at MEXU. The new species Notopleura recondita Hammel & C. M. Taylor of the Osa Peninsula of Costa Rica can be distinguished from polyphlebia (Donn. Sm.) C. M. Taylor by its leaf blades with the secondary veins plane on the adaxial surface and its short cymose or paniculiform inflorescences. The new species Palicourea matamana C. M. Taylor of premontane forests of central-eastern Costa Rica can be separated from P. orosiana C. M. Taylor by its larger stipules, longer calyx lobes, and hirsute pubescence. The new species P. providenciana J. Sanchez-Gonz. & C. M. Taylor of montane forests in south-central Costa Rica can be separated from P. hammelii C. M. Taylor by its longer lanceolate stipule lobes, dark purple or yellow-flushed inflorescences, and shorter calyx lobes. The Panamanian plants treated previously as Psychotria acuminata subsp. boraginoides Dwyer are here considered to differ at the species level from P. acuminata Benth., and accordingly the new combination P. boraginoides (Dwyer) C. M. Taylor is here published for this species. Clarification of the identity of Cephaelis croatii Dwyer shows that it is a distinct species of Psychotria, and the new combination P. croatii (Dwyer) C. M. Taylor is published here for this species. The new species P. herrerana C. M. Taylor of central Costa Rica can be recognized by its combination of large, sessile, elliptic leaves, its large paniculiform inflorescences, and its relatively small corollas. Study of the Costa Rican plants previously called Rudgea thyrsiflora Donn. Sm. shows that these do not have the characters of Rudgea, but are similar to Psychotria racemosa Rich, and better included in this latter genus; the new name P. tsakiana C. M. Taylor is here published for this species. The new combination Simira panamensis (Dwyer) C. M. Taylor is published here based on the name Bathysa panamensis Dwyer, which has priority over the name S. darienensis Dwyer; both of the names Dwyer published are based on the same type specimen, thus the later name S. darienensis is illegitimate.
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38.
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39.
  • Vechetti, Ivan J. Jr., et al. (författare)
  • Mechanical overload-induced muscle-derived extracellular vesicles promote adipose tissue lipolysis
  • 2021
  • Ingår i: The FASEB Journal. - : WILEY. - 0892-6638 .- 1530-6860. ; 35:6
  • Tidskriftsartikel (refereegranskat)abstract
    • How regular physical activity is able to improve health remains poorly understood. The release of factors from skeletal muscle following exercise has been proposed as a possible mechanism mediating such systemic benefits. We describe a mechanism wherein skeletal muscle, in response to a hypertrophic stimulus induced by mechanical overload (MOV), released extracellular vesicles (EVs) containing muscle-specific miR-1 that were preferentially taken up by epidydimal white adipose tissue (eWAT). In eWAT, miR-1 promoted adrenergic signaling and lipolysis by targeting Tfap2 alpha, a known repressor of Adr beta 3 expression. Inhibiting EV release prevented the MOV-induced increase in eWAT miR-1 abundance and expression of lipolytic genes. Resistance exercise decreased skeletal muscle miR-1 expression with a concomitant increase in plasma EV miR-1 abundance, suggesting a similar mechanism may be operative in humans. Altogether, these findings demonstrate that skeletal muscle promotes metabolic adaptations in adipose tissue in response to MOV via EV-mediated delivery of miR-1.
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40.
  • Viktorsson, Charlotte, et al. (författare)
  • Infants’ sense of approximate numerosity : Heritability and link to other concurrent traits
  • 2023
  • Ingår i: Developmental Science. - : John Wiley & Sons. - 1363-755X .- 1467-7687. ; 26:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract The ability to perceive approximate numerosity is present in many animal species, and emerges early in human infants. Later in life, it is moderately heritable and associated with mathematical abilities, but the etiology of the Approximate Number System (ANS) and its degree of independence from other cognitive abilities in infancy is unknown. Here, we assessed the phenotypic specificity as well as the influence of genetic and environmental factors on the ANS in a sample of 5-month-old twins (N = 514). We found a small-to-moderate but statistically significant effects of genetic factors on ANS acuity (heritability = 0.18, 95% CI: 0.02, 0.33), but only when differences in numerosity were relatively large (1:4 ratio). Non-verbal ability assessed with the Mullen Scales of Early Learning (MSEL) was found to be heritable (0.47; 95% CI: 0.34, 0.57) and the phenotypic association between ANS acuity and non-verbal ability performance was close to zero. Similarly, we found no association between ANS acuity and general attention during the task. An unexpected weak but statistically significant negative association between ANS auity and scores on the receptive language scale of the MSEL was found. These results suggest that early ANS function may be largely independent from other aspects of non-verbal development. Further, variability in ANS in infancy seems to, to some extent, reflect genotypic differences in the population. Assessing 514 infant twins with eye tracking, we found that infant’s sense of approximate numerosity is heritable and not positively associated with concurrent attentional, cognitive or motor abilities. These results have implications for our understanding of development of mathematical ability and the link between cognitive abilities early in postnatal life.
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41.
  • Viktorsson, Charlotte, et al. (författare)
  • Preferential looking to eyes versus mouth in early infancy : heritability and link to concurrent and later development
  • 2023
  • Ingår i: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 64:2, s. 311-319
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundFrom birth, infants orient preferentially to faces, and when looking at the face, they attend primarily to eyes and mouth. These areas convey different types of information, and earlier research suggests that genetic factors influence the preference for one or the other in young children. MethodsIn a sample of 535 5-month-old infant twins, we assessed eye (relative to mouth) preference in early infancy, i.e., before neural systems for social communication and language are fully developed. We investigated the contribution of genetic and environmental factors to the preference for looking at eyes, and the association with concurrent traits and follow-up measures. ResultsEye preference was independent from all other concurrent traits measured, and had a moderate-to-high contribution from genetic influences (A = 0.57; 95% CI: 0.45, 0.66). Preference for eyes at 5 months was associated with higher parent ratings of receptive vocabulary at 14 months. No statistically significant association with later autistic traits was found. Preference for eyes was strikingly stable across different stimulus types (e.g., dynamic vs. still), suggesting that infants' preference at this age does not reflect sensitivity to low-level visual cues. ConclusionsThese results suggest that individual differences in infants' preferential looking to eyes versus mouth to a substantial degree reflect genetic variation. The findings provide new leads on both the perceptual basis and the developmental consequences of these attentional biases.
  •  
42.
  • Viktorsson, Charlotte, et al. (författare)
  • Sustained looking at faces at 5 months of age is associated with socio-communicative skills in the second year of life
  • 2024
  • Ingår i: Infancy. - : John Wiley & Sons. - 1525-0008 .- 1532-7078.
  • Tidskriftsartikel (refereegranskat)abstract
    • Efficiently processing information from faces in infancy is foundational for nonverbal communication. We studied individual differences in 5-month-old infants' (N = 517) sustained attention to faces and preference for emotional faces. We assessed the contribution of genetic and environmental influences to individual differences in these gaze behaviors, and the association between these traits and other concurrent and later phenotypes. We found an association between the mean duration of looking at a face (before looking away from it) at 5 months and socio-communicative abilities at 14 months (β = 0.17, 95% CI: 0.08; 0.26, p < 0.001). Sustained attention to faces predicted socio-communicative abilities over and above variance captured by mean fixation duration. We also found a statistically significant but weak tendency to prefer looking at smiling faces (relative to neutral faces), but no indication that variability in this behavior was explained by genetic effects. Moderate heritability was found for sustained attention to faces (A = 0.23, CI: 0.06; 0.38), while shared environmental influences were non-significant for both phenotypes. These findings suggest that sustained looking at individual faces before looking away is a developmentally significant ‘social attention’ phenotype in infancy, characterized by moderate heritability and a specific relation to later socio-communicative abilities.
  •  
43.
  • Wardlaw, Joanna M., et al. (författare)
  • ESO Guideline on covert cerebral small vessel disease
  • 2021
  • Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 6:2
  • Tidskriftsartikel (refereegranskat)abstract
    • ‘Covert’ cerebral small vessel disease (ccSVD) is common on neuroimaging in persons without overt neurological manifestations, and increases the risk of future stroke, cognitive impairment, dependency, and death. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist with clinical decisions about management of ccSVD, specifically white matter hyperintensities and lacunes, to prevent adverse clinical outcomes. The guidelines were developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We prioritised the clinical outcomes of stroke, cognitive decline or dementia, dependency, death, mobility and mood disorders, and interventions of blood pressure lowering, antiplatelet drugs, lipid lowering, lifestyle modifications, glucose lowering and conventional treatments for dementia. We systematically reviewed the literature, assessed the evidence, formulated evidence-based recommendations where feasible, and expert consensus statements. We found little direct evidence, mostly of low quality. We recommend patients with ccSVD and hypertension to have their blood pressure well controlled; lower blood pressure targets may reduce ccSVD progression. We do not recommend antiplatelet drugs such as aspirin in ccSVD. We found little evidence on lipid lowering in ccSVD. Smoking cessation is a health priority. We recommend regular exercise which may benefit cognition, and a healthy diet, good sleep habits, avoiding obesity and stress for general health reasons. In ccSVD, we found no evidence for glucose control in the absence of diabetes or for conventional Alzheimer dementia treatments. Randomised controlled trials with clinical endpoints are a priority for ccSVD.
  •  
44.
  • Yoneyama, Sachiko, et al. (författare)
  • Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:9, s. 2498-2510
  • Tidskriftsartikel (refereegranskat)abstract
    • Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBIs Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 2080 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes 50 000 cosmopolitan tagged SNPs across 2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P 2.4 10(6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR ( SE, 0.048 0.008, P 7.7 10(9)) as was rs7302703-G in HOXC10 ( 0.044 0.008, P 2.9 10(7)) and rs936108-C in PEMT ( 0.035 0.007, P 1.9 10(6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 ( 0.10 0.02, P 1.9 10(6)) and rs1037575-A in ATBDB4 ( 0.046 0.01, P 2.2 10(6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.
  •  
45.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
  •  
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