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The NUDIX hydrolase NUDT15 was originally implicated in sanitizing oxidized nucleotides, but was later shown to hydrolyze the active thiopurine metabolites, 6-thio-(d)GTP, thereby dictating the clinical response of this standard-of-care treatment for leukemia and inflammatory diseases. Nonetheless, its physiological roles remain elusive. Here, we sought to develop small-molecule NUDT15 inhibitors
The genetic material of viruses is protected by protein shells that are assembled from a large number of subunits in a process that is efficient and robust. Many of the mechanistic details underpinning efficient assembly of virus capsids are still unknown. The assembly mechanism of hepatitis B capsids has been intensively researched using a truncated core protein lacking the C-terminal domain resp
BACKGROUND: Alzheimer's disease (AD) is one the most common types of dementia. Plaques of amyloid beta and neurofibrillary tangles of tau are two major hallmarks of AD. Metabolism of these two proteins, in part, depends on autophagy pathways. Autophagy dysfunction and protein aggregation in AD may be involved in a vicious circle. The aim of this study was to investigate whether tau or amyloid beta
The recent debate on innovation-based structural change in Evolutionary Economic Geography is characterised by a strong focus on the rise of new industrial paths. This paper seeks to shift attention and cast light on radical innovation activities occurring within existing paths without necessarily leading to their dissolution. Departing from a systemic perspective of path development we propose a
OBJECTIVE: To evaluate the feasibility of a randomized controlled pilot study with lifestyle-promoting text messages as a treatment for hypertension in primary care.DESIGN: Randomized controlled pilot trial.SETTING: Three primary health care centers in southern Sweden.SUBJECTS: Sixty patients aged 40-80 years with hypertension were included.MAIN OUTCOME MEASURES: Feasibility of the pilot study, i.
This research investigated the liquid-phase removal of chloramphenicol (CAP), an emerging contaminant using molecularly imprinted polymers (MIPs). CAP adsorption profiles, equilibrium, and kinetics were analysed. The adsorption performance was compared between MIPs and non-imprinted polymers (NIPs), both with silica or without silica grafting. The imprinting factor (IF) values for the Si@MIPs-CAP
The number of arrangements where academia collaborates with governmental andnongovernmental organisations, as well as industries, have increased over the last decades.While research has focused on whether knowledge produced in such collaborations is genuinelyinfluenced by others than the ‘experts’, or those with the highest status and power, this reportexplores the influence of framings and re-fra
We present a local flow model approach for the transport and the decay of a roughly 50 year old perchloroethylene contamination at a former dry cleaning facility at Kv. Färgaren in Kristianstad that sits above the largest aquifer in Sweden. The study demonstrates an efficient workflow integrating ERT for conceptualising and calibrating a three dimensional transient, multi aquifer groundwater trans
Climate change is expected to be an increasingly important source of impacts on biodiversity, both directly and in combination with other activities and phenomena, such as land use change, habitat fragmentation, and biological disruption. The complexity of Biodiversity Impact Assessment under climate change is increased by the fact that the effects are difficult to generalize, given that the timin
Negative interest rates were once seen as impossible outside the realm of economic theory. However, several central banks have recently adopted negative policy rates. The Federal Reserve is coming under increasing pressure to follow suit in the wake of the coronavirus crisis. This paper investigates the actual effects of negative interest rates using the Swedish experience from 2015 to 2019. The S
Most catalytic, structural and regulatory functions of the cell are carried out by functional modules, typically complexes containing or consisting of proteins. The composition and abundance of these complexes and the quantitative distribution of specific proteins across different modules are therefore of major significance in basic and translational biology. However, detection and quantification
Abstract: Food availability sets the stage for incubation behaviour of a female bird and thereby indirectly determines the nest temperature, which in turn affects development and metabolism of avian embryos. Changes in development and metabolism in turn are known to influence offspring’s ability to adjust to environmental changes later in life. However, few studies have investigated the role of in
The Estonian Citizens’ Assembly (ECA) was initiated in late 2012 as a direct consequence of a legitimacy crisis of Estonian political parties and representative institutions. The spark igniting this crisis was the unraveling of a scheme of illegal party financing. The response from governmental institutions took the form of a democratic innovation involving public crowd‐sourcing and deliberative m
Increased incidence of narcolepsy type 1 (NT1) was observed following Pandemrix®‐vaccination, initiated as a preventive measure against the 2009 Influenza pandemic. Here, single cell analysis was conducted to suggest a lower number of CD8+CD27+ T cells among these patients. These findings provide understanding into the autoimmune pathogenesis of NT1.
Objectives: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. Methods: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in w
Understanding and quantifying the global methane (CH4) budget is important for assessing realistic pathways to mitigate climate change. Atmospheric emissions and concentrations of CH4 continue to increase, making CH4 the second most important human-influenced greenhouse gas in terms of climate forcing, after carbon dioxide (CO2). The relative importance of CH4 compared to CO2 depends on its shorte
BACKGROUND: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain
Patients with insulin resistance have high risk of cardiovascular disease such as myocardial infarction (MI). However, it is not known whether MI can initiate or aggravate insulin resistance. We observed that patients with ST-elevation MI and mice with MI had de novo hyperglycemia and features of insulin resistance, respectively. In mouse models of both myocardial and skeletal muscle injury, we ob
Inclusive ψ(2S) production is measured in p-Pb collisions at the centre-of-mass energy per nucleon-nucleon pair sNN = 8.16 TeV, using the ALICE detector at the CERN LHC. The production of ψ(2S) is studied at forward (2.03 < ycms< 3.53) and backward (−4.46 < ycms< −2.96) centre-of-mass rapidity and for transverse momentum pT< 12 GeV/c via the decay to muon pairs. In this paper, we report the integr
