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Intersubunit bridge formation governs agonist efficacy at nicotinic acetylcholine α4β2 receptors : unique role of halogen bonding revealed

The α4β2 subtype of the nicotinic acetylcholine receptor has been pursued as a drug target for treatment of psychiatric and neurodegenerative disorders and smoking cessation aids for decades. Still, a thorough understanding of structure-function relationships of α4β2 agonists is lacking. Using binding experiments, electrophysiology and x-ray crystallography we have investigated a consecutive serie

Thermodynamics and structural analysis of positive allosteric modulation of the ionotropic glutamate receptor GluA2

Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimer's disease. These modulators bind within the dimer interface of the LBD (ligand-binding domain) and stabilize the agonist-bound conformation slowing receptor desensitization and/or deactivation. In the present study, we employ isothermal titr

The reversibility of the snuff-induced lesion : an experimental study in the rat

Snuff lesions were induced in 30 rats. Ten of the snuff-exposed rats were killed immediately after 13 months snuff exposure, as were the 10 control animals. Ten rats were killed 1 month and 10 rats 4 months after the snuff administration had ceased. The rats exposed to snuff for 13 months exhibited hyperplastic, hyperorthokeratotic epithelium with focal mild atypia, focal ulcerations and marked su

Amputations due to lower-limb ischemia. Analysis of a 3-year series

Lower-limb amputation was performed on 261 patients from a catchment population of 232,500 in 1984-1986, and 253 of the amputees were retrospectively followed up. In 241 cases amputation was performed because of threatening or manifest gangrene, 95 of them without preceding consultation with vascular surgeons. In 19 cases amputation followed thromboembolectomy. Of the 127 patients seen by vascular

An integrated approach to design site specific distributed electrical hubs combining optimization, multi-criterion assessment and decision making

An integrated approach is presented in this study to design electrical hubs combining optimization, multi-criterion assessment and decision making. Levelized Energy Cost (LEC), Initial Capital Cost (ICC), Grid Integration Level (GI), Levelized CO2 emission (LCO2), utilization of renewable energy, flexibility of the system, loss of load probability (LOLP) are considered as criteria used to assess t

The Plasmodium serine-type SERA proteases display distinct expression patterns and non-essential in vivo roles during life cycle progression of the malaria parasite

Parasite proteases play key roles in several fundamental steps of the Plasmodium life cycle, including haemoglobin degradation, host cell invasion and parasite egress. Plasmodium exit from infected host cells appears to be mediated by a class of papain-like cysteine proteases called 'serine repeat antigens' (SERAs). A SERA subfamily, represented by Plasmodium falciparum SERA5, contains an atypical

Expression and processing of Plasmodium berghei SERA3 during liver stages

Cysteine proteases mediate liberation of Plasmodium berghei merozoites from infected hepatocytes. In an attempt to identify the responsible parasite proteases, we screened the genome of P. berghei for cysteine protease-encoding genes. RT-PCR analyses revealed that transcription of four out of five P. berghei serine repeat antigen (PbSERA) genes was strongly upregulated in late liver stages briefly

The liver stage of Plasmodium berghei inhibits host cell apoptosis

Plasmodium berghei is the causative agent of rodent malaria and is widely used as a model system to study the liver stage of Plasmodium parasites. The entry of P. berghei sporozoites into hepatocytes has extensively been studied, but little is known about parasite-host interaction during later developmental stages of the intracellular parasite. Growth of the parasite far beyond the normal size of

Nano-Micro Tubes & Fibers for Biomedical Applications

Polymer based nanometer to micrometer size fibers and tubes are the bases for a wide range of industrial and medical applications and various research branches. They are capable of guiding light, carrying electricity and liquid or exchanging heat. Two production systems were established and built. These systems enable us to produce a wide range of tiny tubes & fibers. Light, nano-micro tubes &

Soluble urokinase-plasminogen activator receptor (suPAR) and natural phosphorylcholine IgM antibodies in patients at clinical onset of diabetes mellitus

We have studied the presence of novel inflammatory markers as soluble urokinase plasminogen activator receptor (suPAR) and natural IgM antibodies directed against phosphorylcholine (αPC-IgM) in Swedish diabetic patients (n = 164) and in healthy control subjects (n = 41). SuPAR is expressed by several types of immune cells and has been shown to be a marker of disease severity and predict mortality

Clinical use of C-peptide and β-cell specific autoantibodies during gestational diabetes mellitus

Gestational diabetes mellitus (GDM) confers a risk for developing type 2 diabetes later in life, but the risk of developing type 1 diabetes is also increased. In this study we have evaluated the clinical use of C-peptide and β-cell specific autoantibodies during pregnancy with GDM as predictors for later development of diabetes. C-peptide levels were measured 2 hours after glucose intake in pregn