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Elevated levels of amyloid beta (Aβ) peptide, hyperphosphorylation of tau protein, and inflammation are pathological hallmarks in Alzheimer's disease (AD). Phosphodiesterase 7 (PDE7) regulates the inflammatory response through the cyclic adenosine monophosphate signaling cascade, and thus plays a central role in AD. The aim of this study was to evaluate the efficacy of an inhibitor of PDE7, named

The fate of carcinogens differs among individuals who have different activities of drug-metabolizing enzymes that are important in activating and detoxifying carcinogens. A drug that profoundly alters the metabolism of the drugs and carcinogens is the anticonvulsive agent phenobarbital. To investigate why epileptic patients appear to have a low risk of cancer of the urinary bladder, and on the bas

Regulation of actomyosin dynamics by post-transcriptional modifications in cytoplasmic actin is still poorly understood. Here we demonstrate that dioxygenase ALKBH4-mediated demethylation of a monomethylated site in actin (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes such as cytokinesis and cell migration. ALKBH4-deficient cells display elevated K84me1 levels. Non-

OBJECTIVES: The purpose of this study was to assess cancer incidence and cardiovascular mortality among women with a high dietary intake of fatty fish from the Baltic Sea (on the Swedish east coast), contaminated with persistent organochlorine compounds.MATERIAL AND METHODS: Cohorts of fishermen's wives from the Swedish east (1989 subjects) and west (6605 subjects) coasts were established. The mor

Chronic respiratory diseases remain a major cause of morbidity and mortality worldwide. The only option at end-stage disease is lung transplantation, but there are not enough donor lungs to meet clinical demand. Alternative options to increase tissue availability for lung transplantation are urgently required to close the gap on this unmet clinical need. A growing number of tissue engineering appr

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease, characterized by damage of lung epithelial cells, excessive deposition of extracellular matrix in the lung interstitium, and enhanced activation and proliferation of fibroblasts. S100a4, also termed FSP-1 (fibroblast-specific protein-1), was previously considered as a marker of fibroblasts but recent findings in renal

The Na(+)- and Cl(-)-dependent GABA-betaine transporter (BGT1) has received attention mostly as a protector against osmolarity changes in the kidney and as a potential controller of the neurotransmitter GABA in the brain. Nevertheless, the cellular distribution of BGT1, and its physiological importance, is not fully understood. Here we have quantified mRNA levels using TaqMan real-time PCR, produc

Allogeneic lung transplant is limited both by the shortage of available donor lungs and by the lack of suitable long-term lung assist devices to bridge patients to lung transplantation. Avian lungs have different structure and mechanics resulting in more efficient gas exchange than mammalian lungs. Decellularized avian lungs, recellularized with human lung cells, could therefore provide a powerful

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain. Once released, it is removed from the extracellular space by cellular uptake catalyzed by GABA transporter proteins. Four GABA transporters (GAT1, GAT2, GAT3 and BGT1) have been identified. Inhibition of the GAT1 by the clinically available anti-epileptic drug tiagabine has been an effective strategy fo

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease characterized by lung epithelial cell injury, increased (myo)fibroblast activation and extracellular matrix deposition. Extracellular vesicles (EVs) regulate intercellular communication by carrying a variety of signaling mediators, including WNT proteins. The relevance of EVs in pulmonary fibrosis and their potential contribut

BACKGROUND: Different mechanical ventilation settings are known to affect lung preservation for lung transplantation. Measurement of particle flow in exhaled air may allow online assessment of the impact of ventilation before changes in the tissue can be observed. We hypothesized that by analyzing the particle flow, we could understand the impact of different ventilation parameters.METHODS: Partic

BackgroundThe time taken for epinephrine to achieve its optimal effect during local anesthesia has recently become the subject of debate. The time from injection to commencement of surgery is traditionally quoted to be 7 to 10 min, while recent reports claim that it may take 30 min to achieve maximum hypoperfusion, which would prolong the time required for surgical procedures. The discrepancy may

BackgroundHewes flap is a tarsoconjunctival eyelid flap, based at the lateral canthal tendon, and rotated and stretched to repair lateral defects in the lower eyelid commonly following tumor surgery. The aim of the present study was to monitor perfusion in a Hewes flap during reconstruction, which to the best of our knowledge, has not previously been done.MethodsA Hewes tarsoconjunctival eyelid fl

We will measure kaonic helium X-rays using transition-edge-sensor microcalorimeters, TES, in the J-PARC hadron experimental facility. To demonstrate the feasibility of the experiment, we performed a measurement of pionic carbon X-rays at PSI, where an excellent FWHM energy resolution of 7 eV at 6.4 keV was achieved. We also evaluated the expected TES performance in the kaon beam at J-PARC. The sim

Orkanen Katrina, tsunamin i Indiska oceanen, Lehmankraschen och 11-september attackerna är bara några exempel på sentida händelser som väckt frågor kring vår förmåga att förutse och förstå katastrofrisker. I efterhand är det dock lätt att glömma att vi alltid har ett oändligt antal potentiella scenarier framför oss, men bara ett förflutet, vilket kan få oss att överdriva förutsägbarheten för händeDivision of labor and trade have been prerequisites for the development of welfare societies. Ironically, this specialization has caused a fragmentation of the knowledge necessary to understand risks that may undermine societal safety. This has not only prompted a need for inter-organizational exchange and integration of disaster risk information, it has also prompted a need for understanding how

This thesis makes a contribution to the areas of deregulation, competition and consumer choice. It consists of three self-contained papers. All the research questions are examined in the context of the Swedish motor vehicle inspection market.The first paper, Competition Makes Inspectors More Lenient: Evidence from the Motor Vehicle Inspection Market, investigates whether increased competition moti

Locally Stationary Processes (LSPs) in Silverman’s sense, defined by the modulation in time of a stationary covariance function, are valuable in stochastic modelling of time-varying signals. However, for practical applications, methods to conduct reliable parameter inference from measured data are required. In this paper, we address the lack of suitable methods for estimating the parameters of the