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  • Nakanishi, Tomoko, et al. (författare)
  • Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
  • 2021
  • Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 131:23
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND. There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition. METHODS. We combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank. RESULTS. We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95% CI, 1.6-2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2-2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2-2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8-3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2-1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors. CONCLUSIONS. The major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.
  • Neddermeyer, Anne, et al. (författare)
  • A new mutant NPM1/IDH2R140- and PML-RARA-associated lncRNA MALNC plays a role in AML biology, prognosis and drug response
  • Annan publikation (övrigt vetenskapligt)abstract
    • Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by poor prognosis that requires better understanding of its disease biology and new tools for suitable risk stratification and effective treatments. Long non-coding RNAs (lncRNAs) are involved in numerous molecular mechanisms, are implicated in tumor biology and can serve as clinical biomarkers, yet their role remains mostly unclear in AML. In this study, the aim was to discover and characterize lncRNAs implicated in AML and to describe their role in AML biology. Further aims were to explore their use as prognostic or predictive biomarkers. Using whole-transcriptome analysis, a novel lncRNA, here named MALNC, was identified. MALNC had elevated expression in two large AML cohorts compared to normal CD34+ cells. Clinical correlation analyses indicated that MALNC was almost uniquely expressed in patients with PML-RARA fusion gene and with co-mutated isocitrate dehydrogenase-2 R140 and nucleophosmin-1 (IDH2R140/NPM1). MALNC expression was specifically high at the promyelocytic stage and decreased with maturation in leukemic and normal cells. High MALNC expression associated independently with better overall survival. CRISPR-Cas9-knockout in promyelocytic cell lines impaired proliferation, colony formation and all-trans retinoic acid (ATRA)-induced differentiation. Also, MALNC-knockout dramatically sensitized cells to arsenic trioxide (ATO), ATO-ATRA combinatorial and Bcl-2-inhibitor venetoclax treatment as well as associated with cyclin-dependent kinase (Cdk)-inhibitor resistance. In conclusion, MALNC is overexpressed in certain subgroups of AML and could play a role during normal and leukemic hematopoietic maturation. Furthermore, it correlates with response to anti-leukemic drugs, which suggests a role as a predictive marker to drug response and survival in AML.
  • Nightingale, A. J., et al. (författare)
  • Background and history of sustainability
  • 2019
  • Ingår i: Environment and Sustainability in a Globalizing World. Andrea J. Nightingale (red.). - New York : Routledge. - 9781317501831 ; , s. 13-34
  • Bokkapitel (övrigt vetenskapligt)abstract
    • This chapter explores how the idea of sustainability has changed over time and within different regions. The expansion of the Industrial Revolution brought environmental concerns firmly onto the political agenda and established many of the environmental—social—economic relations that continue to shape sustainability challenges. The Industrial Revolution along with colonialism brought about widespread changes in economies and environments upon which the emerging global economy depended. Steady state is used in the environmental field to indicate an ecosystem, organism, or place that is in balance. While Thomas R. Malthus maintained that population growth would eventually lead to a crisis of resources, he simultaneously believed that technological progress could postpone the inevitable need to reduce demands on resource. Neo-Malthusianism refers to a line of thought advocating population control to ensure resource availability for current and future populations. Ideas of limits to economic growth, the need for moderating human exploitation of resources, and the desirability of steady states thus have a long history. © 2019 Taylor & Francis.
  • Nightingale, A. J., et al. (författare)
  • Enacting sustainability
  • 2019
  • Ingår i: Environment and Sustainability in a Globalizing World. Andrea J. Nightingale (red.). - New York : Routledge. - 9781317501831 ; , s. 56-81
  • Bokkapitel (övrigt vetenskapligt)abstract
    • This chapter looks at the ways that narratives of sustainability have been put into practice. It deals with the idea of measuring sustainability, and examines how approaches based in the biophysical sciences may differ from those in the social sciences. Measuring sustainability and sustainable development poses a number of problems, not least of which are availability of data. Many indicators put ecology at the core of sustainability, assuming that ecological sustainability is a prerequisite for social and economic sustainability. An ecological footprint represents the amount of biologically productive land and sea area necessary to supply the resources and energy a given human population consumes and needs to dispose of its waste. Ecological science has been primarily underpinned by the idea of stability at least since Frederic Clements’ seminal text on climax vegetation in 1936. The idea of planetary boundaries has captured the imagination of sustainability communities and has helped to increase awareness of sustainability issues. © 2019 Taylor & Francis.
  • Nightingale, A. J., et al. (författare)
  • Narratives of sustainability key concepts and issues
  • 2019
  • Ingår i: Environment and Sustainability in a Globalizing World. Andrea J. Nightingale (red.). - New York : Routledge. - 9781317501831 ; , s. 35-55
  • Bokkapitel (övrigt vetenskapligt)abstract
    • This chapter reviews some of the key concepts and issues in sustainability debates in order to better understand how sustainability can be invoked for a wide range of purposes. By scrutinizing the narratives of environment and society that underpin sustainability, a wide range of conflicting conceptualizations becomes evident. The chapter deals with a discussion about the contrasting conceptualizations that underpin different narratives of sustainability. Social movements seeking to articulate competing visions of sustainability often draw upon the historically rooted value systems and ways of conceptualizing socionatures to move beyond anthropocentrism and ecocentrism. Linking society and environment ontologically through a socionatures conceptualization recognizes that entities like forests, grasslands, human bodies, even the atmosphere, are socio-natural entities. Most sustainability narratives are predicated upon some separation of society from environment. Two other narratives that are particularly important for understanding sustainability are anthropocentrism and ecocentrism. Anthropocentrism advocates often promote technical and managerial approaches to solve environmental crises. © 2019 Taylor & Francis.
  • Padma, Arvind M., et al. (författare)
  • Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning
  • 2021
  • Ingår i: Npj Regenerative Medicine. - 2057-3995. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Uterine factor infertility was considered incurable until recently when we reported the first successful live birth after uterus transplantation. However, risky donor surgery and immunosuppressive therapy are factors that may be avoided with bioengineering. For example, transplanted recellularized constructs derived from decellularized tissue restored fertility in rodent models and mandate translational studies. In this study, we decellularized whole sheep uterus with three different protocols using 0.5% sodium dodecyl sulfate, 2% sodium deoxycholate (SDC) or 2% SDC, and 1% Triton X-100. Scaffolds were then assessed for bioactivity using the dorsal root ganglion and chorioallantoic membrane assays, and we found that all the uterus scaffolds exhibited growth factor activity that promoted neurogenesis and angiogenesis. Extensive recellularization optimization was conducted using multipotent sheep fetal stem cells and we report results from the following three in vitro conditions; (a) standard cell culturing conditions, (b) constructs cultured in transwells, and (c) scaffolds preconditioned with matrix metalloproteinase 2 and 9. The recellularization efficiency was improved short-term when transwells were used compared with standard culturing conditions. However, the recellularization efficiency in scaffolds preconditioned with matrix metalloproteinases was 200-300% better than the other strategies evaluated herein, independent of decellularization protocol. Hence, a major recellularization hurdle has been overcome with the improved recellularization strategies and in vitro platforms described herein. These results are an important milestone and should facilitate the production of large bioengineered grafts suitable for future in vivo applications in the sheep, which is an essential step before considering these principles in a clinical setting.
  • Qian, Yang, et al. (författare)
  • Dimensional Stability and Water Repellency of European Aspen Improved by Oxidized Carbohydrates.
  • 2013
  • Ingår i: BioResources. - : University of North Carolina Press. - 1930-2126 .- 1930-2126. ; 8:1, s. 487-498
  • Tidskriftsartikel (refereegranskat)abstract
    • Small samples from European aspen (Populus tremula L.) were impregnated with carbohydrates oxidized by Fenton's reagent using water in a vacuum, followed by heating in an oven at 103 °C. An antiswelling efficiency (ASE) of around 45% for wood treated with oxidized glucose and 35% for wood treated with oxidized sucrose was obtained. Samples treated with oxidized carbohydrates gave water repellent effectiveness (WRE) values over 35%. The decrease in cell wall thickness during impregnation was about 18% less in the presence of oxidized glucose than samples only treated with Fenton's reagent. An ASE of 20% for the wood samples that had been treated with oxidized glucose was obtained after 7 days of soaking in water. The reasons for the improvement in dimensional stability are discussed in this work.
  • Ronquist, Fredrik, et al. (författare)
  • Completing Linnaeus’s inventory of the Swedish insect fauna: only 5,000 species left?
  • 2020
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 15:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite more than 250 years of taxonomic research, we still have only a vague idea about the true size and composition of the faunas and floras of the planet. Many biodiversity inventories provide limited insight because they focus on a small taxonomic subsample or a tiny geographic area. Here, we report on the size and composition of the Swedish insect fauna, thought to represent roughly half of the diversity of multicellular life in one of the largest European countries. Our results are based on more than a decade of data from the Swedish Taxonomy Initiative and its massive inventory of the country’s insect fauna, the Swedish Malaise Trap Project The fauna is considered one of the best known in the world, but the initiative has nevertheless revealed a surprising amount of hidden diversity: more than 3,000 new species (301 new to science) have been documented so far. Here, we use three independent methods to analyze the true size and composition of the fauna at the family or subfamily level: (1) assessments by experts who have been working on the most poorly known groups in the fauna; (2) estimates based on the proportion of new species discovered in the Malaise trap inventory; and (3) extrapolations based on species abundance and incidence data from the inventory. For the last method, we develop a new estimator, the combined non-parametric estimator, which we show is less sensitive to poor coverage of the species pool than other popular estimators. The three methods converge on similar estimates of the size and composition of the fauna, suggesting that it comprises around 33,000 species. Of those, 8,600 (26%) were unknown at the start of the inventory and 5,000 (15%) still await discovery. We analyze the taxonomic and ecological composition of the estimated fauna, and show that most of the new species belong to Hymenoptera and Diptera groups that are decomposers or parasitoids. Thus, current knowledge of the Swedish insect fauna is strongly biased taxonomically and ecologically, and we show that similar but even stronger biases have distorted our understanding of the fauna in the past. We analyze latitudinal gradients in the size and composition of known European insect faunas and show that several of the patterns contradict the Swedish data, presumably due to similar knowledge biases. Addressing these biases is critical in understanding insect biomes and the ecosystem services they provide. Our results emphasize the need to broaden the taxonomic scope of current insect monitoring efforts, a task that is all the more urgent as recent studies indicate a possible worldwide decline in insect faunas.
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