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Structure and transport mechanism of P5B-ATPases

In human cells, P5B-ATPases execute the active export of physiologically important polyamines such as spermine from lysosomes to the cytosol, a function linked to a palette of disorders. Yet, the overall shape of P5B-ATPases and the mechanisms of polyamine recognition, uptake and transport remain elusive. Here we describe a series of cryo-electron microscopy structures of a yeast homolog of human

Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults

Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40–80 years f

Breast cancer cell line toxicity of a flavonoid isolated from Baccharis densiflora

Background: Flavonoids are compounds of interest in the search for new anti-cancer therapies. We have previously isolated the methoxyflavones 5,4′-dihydroxy-6,7,8,3′-tetramethoxyflavone (8-methoxycirsilineol), 5,4′-dihydroxy-6,7,8-trimethoxyflavone (xanthomicrol), and 5,4,'3′-trihydroxy-6,7,8-trimethoxyflavone (sideritoflavone) from Baccharis densiflora. Herein, we investigate the toxicity of thes

Direct contact between Plasmodium falciparum and human B-cells in a novel co-culture increases parasite growth and affects B-cell growth

Background: Plasmodium falciparum parasites cause malaria and co-exist in humans together with B-cells for long periods of time. Immunity is only achieved after repeated exposure. There has been a lack of methods to mimic the in vivo co-occurrence, where cells and parasites can be grown together for many days, and it has been difficult with long time in vitro studies. Methods and results: A new me

Forest floor fluxes drive differences in the carbon balance of contrasting boreal forest stands

The forest floor provides an important interface of soil-atmosphere CO2 exchanges but their controls and contributions to the ecosystem-scale carbon budget are uncertain due to measurement limitations. In this study, we deployed eddy covariance systems below- and above-canopy to measure the spatially integrated net forest floor CO2 exchange (NFFE) and the entire net ecosystem CO2 exchange (NEE) at

Diagnostic codes of cancer in Skåne healthcare register : a validation study using individual-level data in southern Sweden

Background: The Swedish healthcare is decentralised to 21 regions. Detailed information on all delivered care in the southernmost region, Skåne, is prospectively collected in the Skåne Healthcare Register (SHR). The data is updated daily and hence a good source for epidemiological studies. However, the diagnostic codes used to identify cancer patients in SHR have not yet been validated. Methods: W

Different approaches to selection of surgical trainees in the European Union

Background: There is an increasing global interest in selection processes for candidates to surgical training. The aim of the present study is to compare selection processes to specialist surgeon training in the European Union (EU). A secondary goal is to provide guidance for evidence-based methods by a proposed minimum standard that would align countries within the EU. Methods: Publications and g

Scientific models in legal judgements : The relationship between law and environmental science as problem-feeding

Legal decision-making often relies on scientific knowledge and information of other kinds, not least in environmental law where legal institutions use environmental modeling to, for example, project expected effects of projects when approving or denying permits. In this paper, using the problem-feeding model of interdisciplinarity, we analyze this relationship as an exchange of problems and soluti

Free silver nanoparticles doped by potassium : Work-function change in experiment and theory

The composition-dependent change in the work-function (WF) of binary silver-potassium nanoparticles has been studied experimentally by synchrotron-based x-ray photoelectron spectroscopy (PES) and theoretically using a microscopic jellium model of metals. The Ag-K particles with different K fractions were produced by letting a beam of preformed Ag particles pass through a volume with K vapor. The P

A soft x-ray probe of a titania photoelectrode sensitized with a triphenylamine dye

We present a thorough soft x-ray photoelectron spectroscopy (XPS) study of a mesoporous titanium dioxide electrode sensitized with the dye 4-(diphenylamino)phenylcyanoacrylic acid, referred to as “L0.” Supported by calculations, the suite of XPS, x-ray absorption spectroscopy, and resonant photoelectron spectroscopy allows us to examine bonding interactions between the dye and the surface and the

Finite-size shifts in simulated protein droplet phase diagrams

Computer simulation can provide valuable insight into the forces driving biomolecular liquid-liquid phase separation. However, the simulated systems have a limited size, which makes it important to minimize and control finite-size effects. Here, using a phenomenological free-energy ansatz, we investigate how the single-phase densities observed in a canonical system under coexistence conditions dep

Dual bronchodilator therapy as first-line treatment in maintenance-naïve patients with symptomatic copd : A pre-specified analysis of the emax trial

Introduction: Limited prospective evidence is available to guide selection of first-line maintenance therapy in patients with COPD. This pre-specified analysis of the EMAX trial explored the efficacy and safety of dual-versus mono-bronchodilator therapy in maintenance-naïve and maintenance-treated patients. Methods: The 24-week EMAX trial evaluated lung function, symptoms (including rescue medicat

Technological readiness and implementation of genomic-driven precision medicine for complex diseases

The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment – genomic-driven precision medicine (GDPM) – may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on tech

Separation and not residency permit restores function in resignation syndrome : a retrospective cohort study

Despite poor treatment results, a family-oriented approach and the securing of residency have been deemed essential to recovery from resignation syndrome (RS). In a retrospective cohort study, we evaluated an alternative method involving environmental therapy, with patients separated from their parents, while actively abstaining from involving the asylum process in treatment. We examined medical r

Burden of vaccine-preventable diseases, trends in vaccine coverage and current challenges in the implementation of the expanded program on immunization : A situation analysis of Cameroon

The discovery and development of vaccines remain one of the major successes of global health with millions of lives saved every year through routine vaccination. Although vaccines provide a safe and cost-effective solution to vaccine-preventable diseases (VPDs), VPDs are still a serious public health problem in most parts of the world, especially in sub-Saharan Africa (SSA) and Asia. In this revie

Network pharmacology of triptolide in cancer cells : implications for transcription factor binding

Background Triptolide is an active natural product, which inhibits cell proliferation, induces cell apoptosis, suppresses tumor metastasis and improves the effect of other therapeutic treatments in several cancer cell lines by affecting multiple molecules and signaling pathways, such as caspases, heat-shock proteins, DNA damage and NF-ĸB. Purpose We investigated the effect of triptolide towards NF

The Emerging Role of Topical Ocular Drugs to Target the Posterior Eye

The prevalence of chronic fundus diseases is increasing with the aging of the general population. The treatment of these intraocular diseases relies on invasive drug delivery because of the globular structure and multiple barriers of the eye. Frequent intraocular injections bring heavy burdens to the medical care system and patients. The use of topical drugs to treat retinal diseases has always be